Post on 06-Oct-2020
Managing resistant bacterial infections
Professor Mark Wilcox
Head of Medical MicrobiologyClinical Director of Pathology
Leeds Teaching Hospitals amp University of Leeds UK
Lead on Clostridium difficile infectionHealth Protection Agency
Thanks Robin
amp Kevin
Carbapenem
Piperacillin tazobactam
3GC
Quinolone
Tigecycline
Spectrum of activity of broad-spectrum agents
Excludes ertapenem which has no Pseudomonas coverageAlthough tigecycline has demonstrated in vitro activity against atypicals these organisms are not implicated in cIAI and cSSTI the two current licensed indications for tigecycline
ANO2 PseudoAtypicalResistant Gram-
negative
Gram-negative
Gram-positive
Resistant Gram-
positive
The whole picturehellip
Selection risks associated with major antimicrobial classes
Cao B et al J Hosp Infect 200457112-18 Gerding DN Clin Infect Dis 199725(Suppl 2)S206-10Padiglione AA et al Antimicrob Agents Chemother 2003472492-8
Carsenti-Etesse H et al Clin Microbiol Infect 20017144-51Paterson DL Clin Infect Dis 200438(Suppl 4)S341-5 Carmeli Y et al Emerg Infect Dis 20028802-7
C difficile
Fluoroquinolones
3GC
Piperacillin tazobactam
Carbapenems
MDR pseudo
ESBLVREMRSA
Tigecycline and MDR Enterobacteriaceae
bull Systematic review microbiological activity and clinical effectiveness of tigecycline for multidrug-resistant (MDR) Enterobacteriaceae
bull 26 microbiological amp 10 clinical studies were identified
bull FDA (MIC lt2 mgL) or EUCAST (lt1 mgL) breakpoints
Kelesidis T et al J Antimicrob Chemother 200862895-904
Kelesidis T et al J Antimicrob Chemother 200862895-904
Tigecycline and MDR Enterobacteriaceae
bull In clinical studies 697 of the 33 reported patients treated with tigecycline achieved resolution of an infection caused by a carbapenem-resistant or ESBL-producing or MDR Enterobacteriaceae
Kelesidis T et al J Antimicrob Chemother 200862895-904
Fosfomycin and MDR Enterobacteriaceae
bull Systematic review microbiological activity and clinical effectiveness of tigecycline for multidrug-resistant (MDR) Enterobacteriaceae
bull 17 microbiological studies n=5057 isolates including 4448 ESBL +ve
bull 11 of the 17 studies reported that at least 90 of the isolates were susceptible to fosfomycin
bull Using a provisional MIC breakpoint lt64 mgLE coli (n=1657) 968 susceptibleKlebsiella spp (n=748) 813 susceptible
Falagas M et al Lancet Infect Dis 20101043-50
Fosfomycin and MDR Enterobacteriaceae
bull In two clinical studies oral treatment with fosfomycin-trometamol was clinically effective against complicated or uncomplicated lower UTIs caused by ESBL-producing E coli in 75 (938) of 80 patients
Falagas M et al Lancet Infect Dis 20101043-50
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull Italian hospital with increased prevalence of Proteus mirabilis strains producing acquired AmpC-type beta-lactamases (CBLs)
bull 43 CBL-positive isolates were obtained from hospitalised (n=22) and non-hospitalised (n=21) patients (median age 788 years) ndash usually UTIs
bull Treatment with amikacin or carbapenems was consistently effective
bull Piperacillintazobactam produced a clinical response in seven of nine cases
Luzarro F et al int J Antimicrob Agents 200933328-33
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull Italian hospital with increased prevalence of Proteus mirabilis strains producing acquired AmpC-type beta-lactamases (CBLs)
bull 43 CBL-positive isolates were obtained from hospitalised (n=22) and non-hospitalised (n=21) patients (median age 788 years) ndash usually UTIs
bull Treatment with amikacin or carbapenems was consistently effective
bull Piperacillintazobactam produced a clinical response in seven of nine cases
Luzarro F et al int J Antimicrob Agents 200933328-33
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull b-lactamndashb-lactamase inhibitor agents on patients infected with ESBL-producing strains of E coli and Klebsiella spp
bull 7 medical centres across North Americabull 148 patient records reviewedbull 30 rcvd FQ 18 carbapenem 16 pip-tazo 9 other b-
lactams 7 ampndashsul 6 aminogly 6 co-trimoxbull 83 given monotherapybull 23 rcvd pip-tazo (17 infections outside the urinary tract)bull For infections with pathogen MIC of pip-tazo lt16 mgfrasl L
successful outcome was reported in 1415 (1011 non-UTIs)bull Only 15 non-UTIs responded when pip-tazo MIC gt16 mgfrasl Lbull Meropenem therapy was successful in 24 pip-tazo resistant
infectionsGavin PJ et al int J Antimicrob Agents Chemother 2006502244-7
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull 43 episodes of E coli bacteraemia caused by ESBL-producing strains (primarily CTX-M-14)
bullbull Mortality was lower when patients were given a b-lactamndashb-
lactamase inhibitor combination or carbapenem as compared with either a cephalosporin or FQ
(9vs 35 p 005)bullbull E coli 100 susceptible to meropenem 95 to piperacillinndash
tazobactam 26 to ciprofloxacin and 0 to cephalosporins
Rodrıguez-Bano J et al Clin Infect Dis 2006431407-14
Tigecycline for MDR A baumanniiMetan G et al Clinical experience with tigecycline in the treatment of carbapenem-resistant Acinetobacter infections J Chemother 2010 Apr22(2)110-4
Gordon NC Wareham DW A review of clinical and microbiological outcomes following treatment of infections involving multidrug-resistant Acinetobacterbaumannii with tigecycline J AntimicrobChemother 2009 Apr63(4)775-80
Curcio D et al Tigecycline in the treatment of Ventilator-Associated Pneumonia experience from the Latin American Tigecycline Use Registry Infez Med 2010 Mar18(1)27-34
Tigecycline for MDR A baumanniibull Retrospective study of patients who received tigecycline for
tige-S carbapenem-R Acb-complex infections 2008-09bull 21 patients (median age 48 years) median duration tige 14 dbull 18 patients were treated with tigecycline as the sole pathogenbull Most common indication for tigecycline was SSI (VAP)bull Tigecycline was the sole antibiotic in 7 patientsbull 2 patients died within 14 days 4 died within 30 daysbull 1721 lsquohad successful clinical outcomesrsquo BUT 1421 had
microbiological failurebull Poor correlation between micro and clinical responsebull Clinical failure was more common in patients with VAPbull Patients with bacteraemia or VAP more likely to have
microbiological failureMetan G et al J Chemother 201022110-4
Colistin for MDR A baumanniibull 166 consecutive patients infected or colonised with
carbapenem- and MDR A Baumannii
bull 18 hospitals (London UK) 141 belonged to OXA-23 clone 1
bull Only colistin and tigecycline retained good in vitro activity with 994 and 819 of isolates susceptible respectively
bull 62 patients in ICU or HDU 84 (506) infected
bull Survival rates among infected and colonised patients were 68 and 67 indicating little attributable mortality
Livermore D et al Int J Antimicrob Agents 20103519-24
Colistin for MDR A baumanniibull Univariate and multivariate analyses
ndash poorer outcomes among ICU-infected patients pulmonary infection or bacteraemia
ndash trauma patients had significantly better outcomebull Outcomes varied by hospital (multivariate analysis) CASE MIXbull Poor association between outcome and therapy with colistin
(andor tigecycline)bull Patients with respiratory infection 1215 treated with
intravenous colistin alone had poor outcome compared with 18 whose therapy include nebulised colistin (P=0003)
BUT the patients receiving nebulised drug were mostly younger included trauma cases and were at a hospital with good outcomes
Livermore D et al Int J Antimicrob Agents 20103519-24
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
APACHE Acute Physiology and Chronic Health EvaluationSOFA Sequential Organ Failure Assessment
Enterococcus durans
Enterobacter cloacae
Enterococcus casseliflavus or Enterococcus gallinarum
Burkholderia cepacia
Acinetobacter baumannii
Enterococci species not determined
MRSA
Enterococcus faecalis
Infection of unknown origin
Strenotrophomonas maltophilia
VRE
Enterococcus faecium
Microorganism
1 (1)
1 (1)
1 (1) 1 (1)
1 (1)
4 (6) 4 (6)
7 (10)
11 (16)
13 (19)
15 (21)
26 (37)
Infections n ()
bull APACHE II scores 27 plusmn 10 SOFA 12 plusmn 3bull Overall mortality 30
n=70 withindication
0
10
20
30
40
50
60cIAI
cSSTI
Mixed
Other
bull Mean duration of tigecycline therapy was 9 +- 4 daysbull 76 of patients received tigecycline in combination
(64 second line)bull APACHE score and renal replacement were identified
as predictive factors for mortalitybull AUTHOR CONCLUSIONS lsquoTigecycline treatment of
critically ill SICU patients with severe sepsis or septic shock appeared to result in remarkably low mortality Tigecycline may be an important treatment option for septic patients with infections resistant to other available agentsrsquo
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
Antibiotics and risk of CDI
Evidence to supportthe restriction
of these as a controlmeasure for CDI
CDI may still occur
Need to minimise all antibiotic use polypharmacy and duration
Medium risk Low riskHigh risk
CephalosporinsClindamycin
AmpicillinamoxycillinCo-trimoxazole
MacrolidesFluoroquinolones
AminoglycosidesMetronidazole
Anti-pseudomonal penicillins +
β-lactamase inhibitorsTetracyclinesRifampicin
Vancomycin
Baines SD et al J Antimicrob Chemother 200555974-82Baines SD et al J Antimicrob Chemother 2006581062-5
Induction of C difficile toxin production
Tigecycline and C difficilebull Tigecycline is highly active (MIC=006 mgL) against C difficile
Baines SD et al J Antimicrob Chemother 2006581062-5
bull No in vitro evidence of increased risk of tigecycline-induced CDIBaines SD et al J Antimicrob Chemother 2006581062-5
bull No in vivo evidence of increased risk of tigecycline-induced CDIWilcox MH Clin Microbiol Infect 200713949-52
bull Some evidence that tigecycline could be used to treat CDI (THIS IS NOT A LICENSED INDICATION)Herpers BL et al Clin Infect Dis 2009481732-5
Lu CL et al Int J Antimicrob Agents 201035311-2
The missing care bundle antibiotic prescribing in hospitalsCooke FJ Holmes AHInt J Antimicrob Agents 20073025-9Department of Infectious Diseases and Immunology Hammersmith Hospitals NHS Trust Imperial CollegeDu Cane Road London W12 0HS UK
The care bundle involves grouping together key elements of care for procedures and the management of specific diagnoses in order to provide a systematic method to improve and monitor the delivery of clinical care processes In short care bundles aim to ensure that all patients consistently receive the best care or treatment all of the time This approach has been successfully applied to the management of various conditions particularly in the critical care setting The Institute for Healthcare Improvements 100K lives campaign consisted of six care bundles three of which have addressed preventing hospital-acquired infection The UK Department of Healths delivery programme to reduce healthcare-associated infections (HCAIs) including methicillin-resistant Staphylococcus aureus (MRSA) includes six high-impact interventions which are care bundles to reduce HCAIs However we suggest that one key intervention is missing and consider this intervention will be increasingly important if hospitals are to address the rising incidence of Clostridium difficile to tackle antibiotic resistance and to improve patient care The missing intervention addresses the process of antibiotic prescribing We propose that the time is right to consider the application of the care bundle approach to improve the prescribing of antibiotics both for treatment and prophylaxis
The antibiotic prescribing bundle
bull Use monotherapy whenever possible for initial (empiric) treatment
bull Optimise dose and duration
bull Perform a regular risk assessment
ndash For each patient
ndash Impact of the programme
Aminoglycosides
Glycopeptides
LipopeptidesOxazolidinones
Monotherapy or
combinationCarbapenems
BLICsCephalosporins
Fluoroquinolones
Tigecycline
Empiric choice Empiric choice 2nd 3rd line Final option
Low resistance risk and minimal
complexity
Increased resistance risk
and complexity
Treatment failure
[Cef Met prophylaxis]
Not if intravascular infectionNot in VAP as monotherapy
Antibiotic choice in high-risk patients
bull Capacity to cover resistant pathogens
bull Proven efficacy in MDR infection
bull Pharmacokinetic and pharmacodynamic profile
bull Safety profile
bull Capacity not to induce lsquoovergrowthrsquo eg CDI
bull Low potential for inducible resistance
bull Capacity not to select for resistant pathogens
Should consider measures to reduce use of 3GCs FQs amp carbapenems
Increased reliance on carbapenemsmay accelerate emergence of completely resistant isolates
Thanks Robin
amp Kevin
Carbapenem
Piperacillin tazobactam
3GC
Quinolone
Tigecycline
Spectrum of activity of broad-spectrum agents
Excludes ertapenem which has no Pseudomonas coverageAlthough tigecycline has demonstrated in vitro activity against atypicals these organisms are not implicated in cIAI and cSSTI the two current licensed indications for tigecycline
ANO2 PseudoAtypicalResistant Gram-
negative
Gram-negative
Gram-positive
Resistant Gram-
positive
The whole picturehellip
Selection risks associated with major antimicrobial classes
Cao B et al J Hosp Infect 200457112-18 Gerding DN Clin Infect Dis 199725(Suppl 2)S206-10Padiglione AA et al Antimicrob Agents Chemother 2003472492-8
Carsenti-Etesse H et al Clin Microbiol Infect 20017144-51Paterson DL Clin Infect Dis 200438(Suppl 4)S341-5 Carmeli Y et al Emerg Infect Dis 20028802-7
C difficile
Fluoroquinolones
3GC
Piperacillin tazobactam
Carbapenems
MDR pseudo
ESBLVREMRSA
Tigecycline and MDR Enterobacteriaceae
bull Systematic review microbiological activity and clinical effectiveness of tigecycline for multidrug-resistant (MDR) Enterobacteriaceae
bull 26 microbiological amp 10 clinical studies were identified
bull FDA (MIC lt2 mgL) or EUCAST (lt1 mgL) breakpoints
Kelesidis T et al J Antimicrob Chemother 200862895-904
Kelesidis T et al J Antimicrob Chemother 200862895-904
Tigecycline and MDR Enterobacteriaceae
bull In clinical studies 697 of the 33 reported patients treated with tigecycline achieved resolution of an infection caused by a carbapenem-resistant or ESBL-producing or MDR Enterobacteriaceae
Kelesidis T et al J Antimicrob Chemother 200862895-904
Fosfomycin and MDR Enterobacteriaceae
bull Systematic review microbiological activity and clinical effectiveness of tigecycline for multidrug-resistant (MDR) Enterobacteriaceae
bull 17 microbiological studies n=5057 isolates including 4448 ESBL +ve
bull 11 of the 17 studies reported that at least 90 of the isolates were susceptible to fosfomycin
bull Using a provisional MIC breakpoint lt64 mgLE coli (n=1657) 968 susceptibleKlebsiella spp (n=748) 813 susceptible
Falagas M et al Lancet Infect Dis 20101043-50
Fosfomycin and MDR Enterobacteriaceae
bull In two clinical studies oral treatment with fosfomycin-trometamol was clinically effective against complicated or uncomplicated lower UTIs caused by ESBL-producing E coli in 75 (938) of 80 patients
Falagas M et al Lancet Infect Dis 20101043-50
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull Italian hospital with increased prevalence of Proteus mirabilis strains producing acquired AmpC-type beta-lactamases (CBLs)
bull 43 CBL-positive isolates were obtained from hospitalised (n=22) and non-hospitalised (n=21) patients (median age 788 years) ndash usually UTIs
bull Treatment with amikacin or carbapenems was consistently effective
bull Piperacillintazobactam produced a clinical response in seven of nine cases
Luzarro F et al int J Antimicrob Agents 200933328-33
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull Italian hospital with increased prevalence of Proteus mirabilis strains producing acquired AmpC-type beta-lactamases (CBLs)
bull 43 CBL-positive isolates were obtained from hospitalised (n=22) and non-hospitalised (n=21) patients (median age 788 years) ndash usually UTIs
bull Treatment with amikacin or carbapenems was consistently effective
bull Piperacillintazobactam produced a clinical response in seven of nine cases
Luzarro F et al int J Antimicrob Agents 200933328-33
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull b-lactamndashb-lactamase inhibitor agents on patients infected with ESBL-producing strains of E coli and Klebsiella spp
bull 7 medical centres across North Americabull 148 patient records reviewedbull 30 rcvd FQ 18 carbapenem 16 pip-tazo 9 other b-
lactams 7 ampndashsul 6 aminogly 6 co-trimoxbull 83 given monotherapybull 23 rcvd pip-tazo (17 infections outside the urinary tract)bull For infections with pathogen MIC of pip-tazo lt16 mgfrasl L
successful outcome was reported in 1415 (1011 non-UTIs)bull Only 15 non-UTIs responded when pip-tazo MIC gt16 mgfrasl Lbull Meropenem therapy was successful in 24 pip-tazo resistant
infectionsGavin PJ et al int J Antimicrob Agents Chemother 2006502244-7
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull 43 episodes of E coli bacteraemia caused by ESBL-producing strains (primarily CTX-M-14)
bullbull Mortality was lower when patients were given a b-lactamndashb-
lactamase inhibitor combination or carbapenem as compared with either a cephalosporin or FQ
(9vs 35 p 005)bullbull E coli 100 susceptible to meropenem 95 to piperacillinndash
tazobactam 26 to ciprofloxacin and 0 to cephalosporins
Rodrıguez-Bano J et al Clin Infect Dis 2006431407-14
Tigecycline for MDR A baumanniiMetan G et al Clinical experience with tigecycline in the treatment of carbapenem-resistant Acinetobacter infections J Chemother 2010 Apr22(2)110-4
Gordon NC Wareham DW A review of clinical and microbiological outcomes following treatment of infections involving multidrug-resistant Acinetobacterbaumannii with tigecycline J AntimicrobChemother 2009 Apr63(4)775-80
Curcio D et al Tigecycline in the treatment of Ventilator-Associated Pneumonia experience from the Latin American Tigecycline Use Registry Infez Med 2010 Mar18(1)27-34
Tigecycline for MDR A baumanniibull Retrospective study of patients who received tigecycline for
tige-S carbapenem-R Acb-complex infections 2008-09bull 21 patients (median age 48 years) median duration tige 14 dbull 18 patients were treated with tigecycline as the sole pathogenbull Most common indication for tigecycline was SSI (VAP)bull Tigecycline was the sole antibiotic in 7 patientsbull 2 patients died within 14 days 4 died within 30 daysbull 1721 lsquohad successful clinical outcomesrsquo BUT 1421 had
microbiological failurebull Poor correlation between micro and clinical responsebull Clinical failure was more common in patients with VAPbull Patients with bacteraemia or VAP more likely to have
microbiological failureMetan G et al J Chemother 201022110-4
Colistin for MDR A baumanniibull 166 consecutive patients infected or colonised with
carbapenem- and MDR A Baumannii
bull 18 hospitals (London UK) 141 belonged to OXA-23 clone 1
bull Only colistin and tigecycline retained good in vitro activity with 994 and 819 of isolates susceptible respectively
bull 62 patients in ICU or HDU 84 (506) infected
bull Survival rates among infected and colonised patients were 68 and 67 indicating little attributable mortality
Livermore D et al Int J Antimicrob Agents 20103519-24
Colistin for MDR A baumanniibull Univariate and multivariate analyses
ndash poorer outcomes among ICU-infected patients pulmonary infection or bacteraemia
ndash trauma patients had significantly better outcomebull Outcomes varied by hospital (multivariate analysis) CASE MIXbull Poor association between outcome and therapy with colistin
(andor tigecycline)bull Patients with respiratory infection 1215 treated with
intravenous colistin alone had poor outcome compared with 18 whose therapy include nebulised colistin (P=0003)
BUT the patients receiving nebulised drug were mostly younger included trauma cases and were at a hospital with good outcomes
Livermore D et al Int J Antimicrob Agents 20103519-24
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
APACHE Acute Physiology and Chronic Health EvaluationSOFA Sequential Organ Failure Assessment
Enterococcus durans
Enterobacter cloacae
Enterococcus casseliflavus or Enterococcus gallinarum
Burkholderia cepacia
Acinetobacter baumannii
Enterococci species not determined
MRSA
Enterococcus faecalis
Infection of unknown origin
Strenotrophomonas maltophilia
VRE
Enterococcus faecium
Microorganism
1 (1)
1 (1)
1 (1) 1 (1)
1 (1)
4 (6) 4 (6)
7 (10)
11 (16)
13 (19)
15 (21)
26 (37)
Infections n ()
bull APACHE II scores 27 plusmn 10 SOFA 12 plusmn 3bull Overall mortality 30
n=70 withindication
0
10
20
30
40
50
60cIAI
cSSTI
Mixed
Other
bull Mean duration of tigecycline therapy was 9 +- 4 daysbull 76 of patients received tigecycline in combination
(64 second line)bull APACHE score and renal replacement were identified
as predictive factors for mortalitybull AUTHOR CONCLUSIONS lsquoTigecycline treatment of
critically ill SICU patients with severe sepsis or septic shock appeared to result in remarkably low mortality Tigecycline may be an important treatment option for septic patients with infections resistant to other available agentsrsquo
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
Antibiotics and risk of CDI
Evidence to supportthe restriction
of these as a controlmeasure for CDI
CDI may still occur
Need to minimise all antibiotic use polypharmacy and duration
Medium risk Low riskHigh risk
CephalosporinsClindamycin
AmpicillinamoxycillinCo-trimoxazole
MacrolidesFluoroquinolones
AminoglycosidesMetronidazole
Anti-pseudomonal penicillins +
β-lactamase inhibitorsTetracyclinesRifampicin
Vancomycin
Baines SD et al J Antimicrob Chemother 200555974-82Baines SD et al J Antimicrob Chemother 2006581062-5
Induction of C difficile toxin production
Tigecycline and C difficilebull Tigecycline is highly active (MIC=006 mgL) against C difficile
Baines SD et al J Antimicrob Chemother 2006581062-5
bull No in vitro evidence of increased risk of tigecycline-induced CDIBaines SD et al J Antimicrob Chemother 2006581062-5
bull No in vivo evidence of increased risk of tigecycline-induced CDIWilcox MH Clin Microbiol Infect 200713949-52
bull Some evidence that tigecycline could be used to treat CDI (THIS IS NOT A LICENSED INDICATION)Herpers BL et al Clin Infect Dis 2009481732-5
Lu CL et al Int J Antimicrob Agents 201035311-2
The missing care bundle antibiotic prescribing in hospitalsCooke FJ Holmes AHInt J Antimicrob Agents 20073025-9Department of Infectious Diseases and Immunology Hammersmith Hospitals NHS Trust Imperial CollegeDu Cane Road London W12 0HS UK
The care bundle involves grouping together key elements of care for procedures and the management of specific diagnoses in order to provide a systematic method to improve and monitor the delivery of clinical care processes In short care bundles aim to ensure that all patients consistently receive the best care or treatment all of the time This approach has been successfully applied to the management of various conditions particularly in the critical care setting The Institute for Healthcare Improvements 100K lives campaign consisted of six care bundles three of which have addressed preventing hospital-acquired infection The UK Department of Healths delivery programme to reduce healthcare-associated infections (HCAIs) including methicillin-resistant Staphylococcus aureus (MRSA) includes six high-impact interventions which are care bundles to reduce HCAIs However we suggest that one key intervention is missing and consider this intervention will be increasingly important if hospitals are to address the rising incidence of Clostridium difficile to tackle antibiotic resistance and to improve patient care The missing intervention addresses the process of antibiotic prescribing We propose that the time is right to consider the application of the care bundle approach to improve the prescribing of antibiotics both for treatment and prophylaxis
The antibiotic prescribing bundle
bull Use monotherapy whenever possible for initial (empiric) treatment
bull Optimise dose and duration
bull Perform a regular risk assessment
ndash For each patient
ndash Impact of the programme
Aminoglycosides
Glycopeptides
LipopeptidesOxazolidinones
Monotherapy or
combinationCarbapenems
BLICsCephalosporins
Fluoroquinolones
Tigecycline
Empiric choice Empiric choice 2nd 3rd line Final option
Low resistance risk and minimal
complexity
Increased resistance risk
and complexity
Treatment failure
[Cef Met prophylaxis]
Not if intravascular infectionNot in VAP as monotherapy
Antibiotic choice in high-risk patients
bull Capacity to cover resistant pathogens
bull Proven efficacy in MDR infection
bull Pharmacokinetic and pharmacodynamic profile
bull Safety profile
bull Capacity not to induce lsquoovergrowthrsquo eg CDI
bull Low potential for inducible resistance
bull Capacity not to select for resistant pathogens
Should consider measures to reduce use of 3GCs FQs amp carbapenems
Increased reliance on carbapenemsmay accelerate emergence of completely resistant isolates
Carbapenem
Piperacillin tazobactam
3GC
Quinolone
Tigecycline
Spectrum of activity of broad-spectrum agents
Excludes ertapenem which has no Pseudomonas coverageAlthough tigecycline has demonstrated in vitro activity against atypicals these organisms are not implicated in cIAI and cSSTI the two current licensed indications for tigecycline
ANO2 PseudoAtypicalResistant Gram-
negative
Gram-negative
Gram-positive
Resistant Gram-
positive
The whole picturehellip
Selection risks associated with major antimicrobial classes
Cao B et al J Hosp Infect 200457112-18 Gerding DN Clin Infect Dis 199725(Suppl 2)S206-10Padiglione AA et al Antimicrob Agents Chemother 2003472492-8
Carsenti-Etesse H et al Clin Microbiol Infect 20017144-51Paterson DL Clin Infect Dis 200438(Suppl 4)S341-5 Carmeli Y et al Emerg Infect Dis 20028802-7
C difficile
Fluoroquinolones
3GC
Piperacillin tazobactam
Carbapenems
MDR pseudo
ESBLVREMRSA
Tigecycline and MDR Enterobacteriaceae
bull Systematic review microbiological activity and clinical effectiveness of tigecycline for multidrug-resistant (MDR) Enterobacteriaceae
bull 26 microbiological amp 10 clinical studies were identified
bull FDA (MIC lt2 mgL) or EUCAST (lt1 mgL) breakpoints
Kelesidis T et al J Antimicrob Chemother 200862895-904
Kelesidis T et al J Antimicrob Chemother 200862895-904
Tigecycline and MDR Enterobacteriaceae
bull In clinical studies 697 of the 33 reported patients treated with tigecycline achieved resolution of an infection caused by a carbapenem-resistant or ESBL-producing or MDR Enterobacteriaceae
Kelesidis T et al J Antimicrob Chemother 200862895-904
Fosfomycin and MDR Enterobacteriaceae
bull Systematic review microbiological activity and clinical effectiveness of tigecycline for multidrug-resistant (MDR) Enterobacteriaceae
bull 17 microbiological studies n=5057 isolates including 4448 ESBL +ve
bull 11 of the 17 studies reported that at least 90 of the isolates were susceptible to fosfomycin
bull Using a provisional MIC breakpoint lt64 mgLE coli (n=1657) 968 susceptibleKlebsiella spp (n=748) 813 susceptible
Falagas M et al Lancet Infect Dis 20101043-50
Fosfomycin and MDR Enterobacteriaceae
bull In two clinical studies oral treatment with fosfomycin-trometamol was clinically effective against complicated or uncomplicated lower UTIs caused by ESBL-producing E coli in 75 (938) of 80 patients
Falagas M et al Lancet Infect Dis 20101043-50
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull Italian hospital with increased prevalence of Proteus mirabilis strains producing acquired AmpC-type beta-lactamases (CBLs)
bull 43 CBL-positive isolates were obtained from hospitalised (n=22) and non-hospitalised (n=21) patients (median age 788 years) ndash usually UTIs
bull Treatment with amikacin or carbapenems was consistently effective
bull Piperacillintazobactam produced a clinical response in seven of nine cases
Luzarro F et al int J Antimicrob Agents 200933328-33
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull Italian hospital with increased prevalence of Proteus mirabilis strains producing acquired AmpC-type beta-lactamases (CBLs)
bull 43 CBL-positive isolates were obtained from hospitalised (n=22) and non-hospitalised (n=21) patients (median age 788 years) ndash usually UTIs
bull Treatment with amikacin or carbapenems was consistently effective
bull Piperacillintazobactam produced a clinical response in seven of nine cases
Luzarro F et al int J Antimicrob Agents 200933328-33
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull b-lactamndashb-lactamase inhibitor agents on patients infected with ESBL-producing strains of E coli and Klebsiella spp
bull 7 medical centres across North Americabull 148 patient records reviewedbull 30 rcvd FQ 18 carbapenem 16 pip-tazo 9 other b-
lactams 7 ampndashsul 6 aminogly 6 co-trimoxbull 83 given monotherapybull 23 rcvd pip-tazo (17 infections outside the urinary tract)bull For infections with pathogen MIC of pip-tazo lt16 mgfrasl L
successful outcome was reported in 1415 (1011 non-UTIs)bull Only 15 non-UTIs responded when pip-tazo MIC gt16 mgfrasl Lbull Meropenem therapy was successful in 24 pip-tazo resistant
infectionsGavin PJ et al int J Antimicrob Agents Chemother 2006502244-7
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull 43 episodes of E coli bacteraemia caused by ESBL-producing strains (primarily CTX-M-14)
bullbull Mortality was lower when patients were given a b-lactamndashb-
lactamase inhibitor combination or carbapenem as compared with either a cephalosporin or FQ
(9vs 35 p 005)bullbull E coli 100 susceptible to meropenem 95 to piperacillinndash
tazobactam 26 to ciprofloxacin and 0 to cephalosporins
Rodrıguez-Bano J et al Clin Infect Dis 2006431407-14
Tigecycline for MDR A baumanniiMetan G et al Clinical experience with tigecycline in the treatment of carbapenem-resistant Acinetobacter infections J Chemother 2010 Apr22(2)110-4
Gordon NC Wareham DW A review of clinical and microbiological outcomes following treatment of infections involving multidrug-resistant Acinetobacterbaumannii with tigecycline J AntimicrobChemother 2009 Apr63(4)775-80
Curcio D et al Tigecycline in the treatment of Ventilator-Associated Pneumonia experience from the Latin American Tigecycline Use Registry Infez Med 2010 Mar18(1)27-34
Tigecycline for MDR A baumanniibull Retrospective study of patients who received tigecycline for
tige-S carbapenem-R Acb-complex infections 2008-09bull 21 patients (median age 48 years) median duration tige 14 dbull 18 patients were treated with tigecycline as the sole pathogenbull Most common indication for tigecycline was SSI (VAP)bull Tigecycline was the sole antibiotic in 7 patientsbull 2 patients died within 14 days 4 died within 30 daysbull 1721 lsquohad successful clinical outcomesrsquo BUT 1421 had
microbiological failurebull Poor correlation between micro and clinical responsebull Clinical failure was more common in patients with VAPbull Patients with bacteraemia or VAP more likely to have
microbiological failureMetan G et al J Chemother 201022110-4
Colistin for MDR A baumanniibull 166 consecutive patients infected or colonised with
carbapenem- and MDR A Baumannii
bull 18 hospitals (London UK) 141 belonged to OXA-23 clone 1
bull Only colistin and tigecycline retained good in vitro activity with 994 and 819 of isolates susceptible respectively
bull 62 patients in ICU or HDU 84 (506) infected
bull Survival rates among infected and colonised patients were 68 and 67 indicating little attributable mortality
Livermore D et al Int J Antimicrob Agents 20103519-24
Colistin for MDR A baumanniibull Univariate and multivariate analyses
ndash poorer outcomes among ICU-infected patients pulmonary infection or bacteraemia
ndash trauma patients had significantly better outcomebull Outcomes varied by hospital (multivariate analysis) CASE MIXbull Poor association between outcome and therapy with colistin
(andor tigecycline)bull Patients with respiratory infection 1215 treated with
intravenous colistin alone had poor outcome compared with 18 whose therapy include nebulised colistin (P=0003)
BUT the patients receiving nebulised drug were mostly younger included trauma cases and were at a hospital with good outcomes
Livermore D et al Int J Antimicrob Agents 20103519-24
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
APACHE Acute Physiology and Chronic Health EvaluationSOFA Sequential Organ Failure Assessment
Enterococcus durans
Enterobacter cloacae
Enterococcus casseliflavus or Enterococcus gallinarum
Burkholderia cepacia
Acinetobacter baumannii
Enterococci species not determined
MRSA
Enterococcus faecalis
Infection of unknown origin
Strenotrophomonas maltophilia
VRE
Enterococcus faecium
Microorganism
1 (1)
1 (1)
1 (1) 1 (1)
1 (1)
4 (6) 4 (6)
7 (10)
11 (16)
13 (19)
15 (21)
26 (37)
Infections n ()
bull APACHE II scores 27 plusmn 10 SOFA 12 plusmn 3bull Overall mortality 30
n=70 withindication
0
10
20
30
40
50
60cIAI
cSSTI
Mixed
Other
bull Mean duration of tigecycline therapy was 9 +- 4 daysbull 76 of patients received tigecycline in combination
(64 second line)bull APACHE score and renal replacement were identified
as predictive factors for mortalitybull AUTHOR CONCLUSIONS lsquoTigecycline treatment of
critically ill SICU patients with severe sepsis or septic shock appeared to result in remarkably low mortality Tigecycline may be an important treatment option for septic patients with infections resistant to other available agentsrsquo
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
Antibiotics and risk of CDI
Evidence to supportthe restriction
of these as a controlmeasure for CDI
CDI may still occur
Need to minimise all antibiotic use polypharmacy and duration
Medium risk Low riskHigh risk
CephalosporinsClindamycin
AmpicillinamoxycillinCo-trimoxazole
MacrolidesFluoroquinolones
AminoglycosidesMetronidazole
Anti-pseudomonal penicillins +
β-lactamase inhibitorsTetracyclinesRifampicin
Vancomycin
Baines SD et al J Antimicrob Chemother 200555974-82Baines SD et al J Antimicrob Chemother 2006581062-5
Induction of C difficile toxin production
Tigecycline and C difficilebull Tigecycline is highly active (MIC=006 mgL) against C difficile
Baines SD et al J Antimicrob Chemother 2006581062-5
bull No in vitro evidence of increased risk of tigecycline-induced CDIBaines SD et al J Antimicrob Chemother 2006581062-5
bull No in vivo evidence of increased risk of tigecycline-induced CDIWilcox MH Clin Microbiol Infect 200713949-52
bull Some evidence that tigecycline could be used to treat CDI (THIS IS NOT A LICENSED INDICATION)Herpers BL et al Clin Infect Dis 2009481732-5
Lu CL et al Int J Antimicrob Agents 201035311-2
The missing care bundle antibiotic prescribing in hospitalsCooke FJ Holmes AHInt J Antimicrob Agents 20073025-9Department of Infectious Diseases and Immunology Hammersmith Hospitals NHS Trust Imperial CollegeDu Cane Road London W12 0HS UK
The care bundle involves grouping together key elements of care for procedures and the management of specific diagnoses in order to provide a systematic method to improve and monitor the delivery of clinical care processes In short care bundles aim to ensure that all patients consistently receive the best care or treatment all of the time This approach has been successfully applied to the management of various conditions particularly in the critical care setting The Institute for Healthcare Improvements 100K lives campaign consisted of six care bundles three of which have addressed preventing hospital-acquired infection The UK Department of Healths delivery programme to reduce healthcare-associated infections (HCAIs) including methicillin-resistant Staphylococcus aureus (MRSA) includes six high-impact interventions which are care bundles to reduce HCAIs However we suggest that one key intervention is missing and consider this intervention will be increasingly important if hospitals are to address the rising incidence of Clostridium difficile to tackle antibiotic resistance and to improve patient care The missing intervention addresses the process of antibiotic prescribing We propose that the time is right to consider the application of the care bundle approach to improve the prescribing of antibiotics both for treatment and prophylaxis
The antibiotic prescribing bundle
bull Use monotherapy whenever possible for initial (empiric) treatment
bull Optimise dose and duration
bull Perform a regular risk assessment
ndash For each patient
ndash Impact of the programme
Aminoglycosides
Glycopeptides
LipopeptidesOxazolidinones
Monotherapy or
combinationCarbapenems
BLICsCephalosporins
Fluoroquinolones
Tigecycline
Empiric choice Empiric choice 2nd 3rd line Final option
Low resistance risk and minimal
complexity
Increased resistance risk
and complexity
Treatment failure
[Cef Met prophylaxis]
Not if intravascular infectionNot in VAP as monotherapy
Antibiotic choice in high-risk patients
bull Capacity to cover resistant pathogens
bull Proven efficacy in MDR infection
bull Pharmacokinetic and pharmacodynamic profile
bull Safety profile
bull Capacity not to induce lsquoovergrowthrsquo eg CDI
bull Low potential for inducible resistance
bull Capacity not to select for resistant pathogens
Should consider measures to reduce use of 3GCs FQs amp carbapenems
Increased reliance on carbapenemsmay accelerate emergence of completely resistant isolates
The whole picturehellip
Selection risks associated with major antimicrobial classes
Cao B et al J Hosp Infect 200457112-18 Gerding DN Clin Infect Dis 199725(Suppl 2)S206-10Padiglione AA et al Antimicrob Agents Chemother 2003472492-8
Carsenti-Etesse H et al Clin Microbiol Infect 20017144-51Paterson DL Clin Infect Dis 200438(Suppl 4)S341-5 Carmeli Y et al Emerg Infect Dis 20028802-7
C difficile
Fluoroquinolones
3GC
Piperacillin tazobactam
Carbapenems
MDR pseudo
ESBLVREMRSA
Tigecycline and MDR Enterobacteriaceae
bull Systematic review microbiological activity and clinical effectiveness of tigecycline for multidrug-resistant (MDR) Enterobacteriaceae
bull 26 microbiological amp 10 clinical studies were identified
bull FDA (MIC lt2 mgL) or EUCAST (lt1 mgL) breakpoints
Kelesidis T et al J Antimicrob Chemother 200862895-904
Kelesidis T et al J Antimicrob Chemother 200862895-904
Tigecycline and MDR Enterobacteriaceae
bull In clinical studies 697 of the 33 reported patients treated with tigecycline achieved resolution of an infection caused by a carbapenem-resistant or ESBL-producing or MDR Enterobacteriaceae
Kelesidis T et al J Antimicrob Chemother 200862895-904
Fosfomycin and MDR Enterobacteriaceae
bull Systematic review microbiological activity and clinical effectiveness of tigecycline for multidrug-resistant (MDR) Enterobacteriaceae
bull 17 microbiological studies n=5057 isolates including 4448 ESBL +ve
bull 11 of the 17 studies reported that at least 90 of the isolates were susceptible to fosfomycin
bull Using a provisional MIC breakpoint lt64 mgLE coli (n=1657) 968 susceptibleKlebsiella spp (n=748) 813 susceptible
Falagas M et al Lancet Infect Dis 20101043-50
Fosfomycin and MDR Enterobacteriaceae
bull In two clinical studies oral treatment with fosfomycin-trometamol was clinically effective against complicated or uncomplicated lower UTIs caused by ESBL-producing E coli in 75 (938) of 80 patients
Falagas M et al Lancet Infect Dis 20101043-50
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull Italian hospital with increased prevalence of Proteus mirabilis strains producing acquired AmpC-type beta-lactamases (CBLs)
bull 43 CBL-positive isolates were obtained from hospitalised (n=22) and non-hospitalised (n=21) patients (median age 788 years) ndash usually UTIs
bull Treatment with amikacin or carbapenems was consistently effective
bull Piperacillintazobactam produced a clinical response in seven of nine cases
Luzarro F et al int J Antimicrob Agents 200933328-33
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull Italian hospital with increased prevalence of Proteus mirabilis strains producing acquired AmpC-type beta-lactamases (CBLs)
bull 43 CBL-positive isolates were obtained from hospitalised (n=22) and non-hospitalised (n=21) patients (median age 788 years) ndash usually UTIs
bull Treatment with amikacin or carbapenems was consistently effective
bull Piperacillintazobactam produced a clinical response in seven of nine cases
Luzarro F et al int J Antimicrob Agents 200933328-33
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull b-lactamndashb-lactamase inhibitor agents on patients infected with ESBL-producing strains of E coli and Klebsiella spp
bull 7 medical centres across North Americabull 148 patient records reviewedbull 30 rcvd FQ 18 carbapenem 16 pip-tazo 9 other b-
lactams 7 ampndashsul 6 aminogly 6 co-trimoxbull 83 given monotherapybull 23 rcvd pip-tazo (17 infections outside the urinary tract)bull For infections with pathogen MIC of pip-tazo lt16 mgfrasl L
successful outcome was reported in 1415 (1011 non-UTIs)bull Only 15 non-UTIs responded when pip-tazo MIC gt16 mgfrasl Lbull Meropenem therapy was successful in 24 pip-tazo resistant
infectionsGavin PJ et al int J Antimicrob Agents Chemother 2006502244-7
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull 43 episodes of E coli bacteraemia caused by ESBL-producing strains (primarily CTX-M-14)
bullbull Mortality was lower when patients were given a b-lactamndashb-
lactamase inhibitor combination or carbapenem as compared with either a cephalosporin or FQ
(9vs 35 p 005)bullbull E coli 100 susceptible to meropenem 95 to piperacillinndash
tazobactam 26 to ciprofloxacin and 0 to cephalosporins
Rodrıguez-Bano J et al Clin Infect Dis 2006431407-14
Tigecycline for MDR A baumanniiMetan G et al Clinical experience with tigecycline in the treatment of carbapenem-resistant Acinetobacter infections J Chemother 2010 Apr22(2)110-4
Gordon NC Wareham DW A review of clinical and microbiological outcomes following treatment of infections involving multidrug-resistant Acinetobacterbaumannii with tigecycline J AntimicrobChemother 2009 Apr63(4)775-80
Curcio D et al Tigecycline in the treatment of Ventilator-Associated Pneumonia experience from the Latin American Tigecycline Use Registry Infez Med 2010 Mar18(1)27-34
Tigecycline for MDR A baumanniibull Retrospective study of patients who received tigecycline for
tige-S carbapenem-R Acb-complex infections 2008-09bull 21 patients (median age 48 years) median duration tige 14 dbull 18 patients were treated with tigecycline as the sole pathogenbull Most common indication for tigecycline was SSI (VAP)bull Tigecycline was the sole antibiotic in 7 patientsbull 2 patients died within 14 days 4 died within 30 daysbull 1721 lsquohad successful clinical outcomesrsquo BUT 1421 had
microbiological failurebull Poor correlation between micro and clinical responsebull Clinical failure was more common in patients with VAPbull Patients with bacteraemia or VAP more likely to have
microbiological failureMetan G et al J Chemother 201022110-4
Colistin for MDR A baumanniibull 166 consecutive patients infected or colonised with
carbapenem- and MDR A Baumannii
bull 18 hospitals (London UK) 141 belonged to OXA-23 clone 1
bull Only colistin and tigecycline retained good in vitro activity with 994 and 819 of isolates susceptible respectively
bull 62 patients in ICU or HDU 84 (506) infected
bull Survival rates among infected and colonised patients were 68 and 67 indicating little attributable mortality
Livermore D et al Int J Antimicrob Agents 20103519-24
Colistin for MDR A baumanniibull Univariate and multivariate analyses
ndash poorer outcomes among ICU-infected patients pulmonary infection or bacteraemia
ndash trauma patients had significantly better outcomebull Outcomes varied by hospital (multivariate analysis) CASE MIXbull Poor association between outcome and therapy with colistin
(andor tigecycline)bull Patients with respiratory infection 1215 treated with
intravenous colistin alone had poor outcome compared with 18 whose therapy include nebulised colistin (P=0003)
BUT the patients receiving nebulised drug were mostly younger included trauma cases and were at a hospital with good outcomes
Livermore D et al Int J Antimicrob Agents 20103519-24
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
APACHE Acute Physiology and Chronic Health EvaluationSOFA Sequential Organ Failure Assessment
Enterococcus durans
Enterobacter cloacae
Enterococcus casseliflavus or Enterococcus gallinarum
Burkholderia cepacia
Acinetobacter baumannii
Enterococci species not determined
MRSA
Enterococcus faecalis
Infection of unknown origin
Strenotrophomonas maltophilia
VRE
Enterococcus faecium
Microorganism
1 (1)
1 (1)
1 (1) 1 (1)
1 (1)
4 (6) 4 (6)
7 (10)
11 (16)
13 (19)
15 (21)
26 (37)
Infections n ()
bull APACHE II scores 27 plusmn 10 SOFA 12 plusmn 3bull Overall mortality 30
n=70 withindication
0
10
20
30
40
50
60cIAI
cSSTI
Mixed
Other
bull Mean duration of tigecycline therapy was 9 +- 4 daysbull 76 of patients received tigecycline in combination
(64 second line)bull APACHE score and renal replacement were identified
as predictive factors for mortalitybull AUTHOR CONCLUSIONS lsquoTigecycline treatment of
critically ill SICU patients with severe sepsis or septic shock appeared to result in remarkably low mortality Tigecycline may be an important treatment option for septic patients with infections resistant to other available agentsrsquo
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
Antibiotics and risk of CDI
Evidence to supportthe restriction
of these as a controlmeasure for CDI
CDI may still occur
Need to minimise all antibiotic use polypharmacy and duration
Medium risk Low riskHigh risk
CephalosporinsClindamycin
AmpicillinamoxycillinCo-trimoxazole
MacrolidesFluoroquinolones
AminoglycosidesMetronidazole
Anti-pseudomonal penicillins +
β-lactamase inhibitorsTetracyclinesRifampicin
Vancomycin
Baines SD et al J Antimicrob Chemother 200555974-82Baines SD et al J Antimicrob Chemother 2006581062-5
Induction of C difficile toxin production
Tigecycline and C difficilebull Tigecycline is highly active (MIC=006 mgL) against C difficile
Baines SD et al J Antimicrob Chemother 2006581062-5
bull No in vitro evidence of increased risk of tigecycline-induced CDIBaines SD et al J Antimicrob Chemother 2006581062-5
bull No in vivo evidence of increased risk of tigecycline-induced CDIWilcox MH Clin Microbiol Infect 200713949-52
bull Some evidence that tigecycline could be used to treat CDI (THIS IS NOT A LICENSED INDICATION)Herpers BL et al Clin Infect Dis 2009481732-5
Lu CL et al Int J Antimicrob Agents 201035311-2
The missing care bundle antibiotic prescribing in hospitalsCooke FJ Holmes AHInt J Antimicrob Agents 20073025-9Department of Infectious Diseases and Immunology Hammersmith Hospitals NHS Trust Imperial CollegeDu Cane Road London W12 0HS UK
The care bundle involves grouping together key elements of care for procedures and the management of specific diagnoses in order to provide a systematic method to improve and monitor the delivery of clinical care processes In short care bundles aim to ensure that all patients consistently receive the best care or treatment all of the time This approach has been successfully applied to the management of various conditions particularly in the critical care setting The Institute for Healthcare Improvements 100K lives campaign consisted of six care bundles three of which have addressed preventing hospital-acquired infection The UK Department of Healths delivery programme to reduce healthcare-associated infections (HCAIs) including methicillin-resistant Staphylococcus aureus (MRSA) includes six high-impact interventions which are care bundles to reduce HCAIs However we suggest that one key intervention is missing and consider this intervention will be increasingly important if hospitals are to address the rising incidence of Clostridium difficile to tackle antibiotic resistance and to improve patient care The missing intervention addresses the process of antibiotic prescribing We propose that the time is right to consider the application of the care bundle approach to improve the prescribing of antibiotics both for treatment and prophylaxis
The antibiotic prescribing bundle
bull Use monotherapy whenever possible for initial (empiric) treatment
bull Optimise dose and duration
bull Perform a regular risk assessment
ndash For each patient
ndash Impact of the programme
Aminoglycosides
Glycopeptides
LipopeptidesOxazolidinones
Monotherapy or
combinationCarbapenems
BLICsCephalosporins
Fluoroquinolones
Tigecycline
Empiric choice Empiric choice 2nd 3rd line Final option
Low resistance risk and minimal
complexity
Increased resistance risk
and complexity
Treatment failure
[Cef Met prophylaxis]
Not if intravascular infectionNot in VAP as monotherapy
Antibiotic choice in high-risk patients
bull Capacity to cover resistant pathogens
bull Proven efficacy in MDR infection
bull Pharmacokinetic and pharmacodynamic profile
bull Safety profile
bull Capacity not to induce lsquoovergrowthrsquo eg CDI
bull Low potential for inducible resistance
bull Capacity not to select for resistant pathogens
Should consider measures to reduce use of 3GCs FQs amp carbapenems
Increased reliance on carbapenemsmay accelerate emergence of completely resistant isolates
Selection risks associated with major antimicrobial classes
Cao B et al J Hosp Infect 200457112-18 Gerding DN Clin Infect Dis 199725(Suppl 2)S206-10Padiglione AA et al Antimicrob Agents Chemother 2003472492-8
Carsenti-Etesse H et al Clin Microbiol Infect 20017144-51Paterson DL Clin Infect Dis 200438(Suppl 4)S341-5 Carmeli Y et al Emerg Infect Dis 20028802-7
C difficile
Fluoroquinolones
3GC
Piperacillin tazobactam
Carbapenems
MDR pseudo
ESBLVREMRSA
Tigecycline and MDR Enterobacteriaceae
bull Systematic review microbiological activity and clinical effectiveness of tigecycline for multidrug-resistant (MDR) Enterobacteriaceae
bull 26 microbiological amp 10 clinical studies were identified
bull FDA (MIC lt2 mgL) or EUCAST (lt1 mgL) breakpoints
Kelesidis T et al J Antimicrob Chemother 200862895-904
Kelesidis T et al J Antimicrob Chemother 200862895-904
Tigecycline and MDR Enterobacteriaceae
bull In clinical studies 697 of the 33 reported patients treated with tigecycline achieved resolution of an infection caused by a carbapenem-resistant or ESBL-producing or MDR Enterobacteriaceae
Kelesidis T et al J Antimicrob Chemother 200862895-904
Fosfomycin and MDR Enterobacteriaceae
bull Systematic review microbiological activity and clinical effectiveness of tigecycline for multidrug-resistant (MDR) Enterobacteriaceae
bull 17 microbiological studies n=5057 isolates including 4448 ESBL +ve
bull 11 of the 17 studies reported that at least 90 of the isolates were susceptible to fosfomycin
bull Using a provisional MIC breakpoint lt64 mgLE coli (n=1657) 968 susceptibleKlebsiella spp (n=748) 813 susceptible
Falagas M et al Lancet Infect Dis 20101043-50
Fosfomycin and MDR Enterobacteriaceae
bull In two clinical studies oral treatment with fosfomycin-trometamol was clinically effective against complicated or uncomplicated lower UTIs caused by ESBL-producing E coli in 75 (938) of 80 patients
Falagas M et al Lancet Infect Dis 20101043-50
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull Italian hospital with increased prevalence of Proteus mirabilis strains producing acquired AmpC-type beta-lactamases (CBLs)
bull 43 CBL-positive isolates were obtained from hospitalised (n=22) and non-hospitalised (n=21) patients (median age 788 years) ndash usually UTIs
bull Treatment with amikacin or carbapenems was consistently effective
bull Piperacillintazobactam produced a clinical response in seven of nine cases
Luzarro F et al int J Antimicrob Agents 200933328-33
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull Italian hospital with increased prevalence of Proteus mirabilis strains producing acquired AmpC-type beta-lactamases (CBLs)
bull 43 CBL-positive isolates were obtained from hospitalised (n=22) and non-hospitalised (n=21) patients (median age 788 years) ndash usually UTIs
bull Treatment with amikacin or carbapenems was consistently effective
bull Piperacillintazobactam produced a clinical response in seven of nine cases
Luzarro F et al int J Antimicrob Agents 200933328-33
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull b-lactamndashb-lactamase inhibitor agents on patients infected with ESBL-producing strains of E coli and Klebsiella spp
bull 7 medical centres across North Americabull 148 patient records reviewedbull 30 rcvd FQ 18 carbapenem 16 pip-tazo 9 other b-
lactams 7 ampndashsul 6 aminogly 6 co-trimoxbull 83 given monotherapybull 23 rcvd pip-tazo (17 infections outside the urinary tract)bull For infections with pathogen MIC of pip-tazo lt16 mgfrasl L
successful outcome was reported in 1415 (1011 non-UTIs)bull Only 15 non-UTIs responded when pip-tazo MIC gt16 mgfrasl Lbull Meropenem therapy was successful in 24 pip-tazo resistant
infectionsGavin PJ et al int J Antimicrob Agents Chemother 2006502244-7
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull 43 episodes of E coli bacteraemia caused by ESBL-producing strains (primarily CTX-M-14)
bullbull Mortality was lower when patients were given a b-lactamndashb-
lactamase inhibitor combination or carbapenem as compared with either a cephalosporin or FQ
(9vs 35 p 005)bullbull E coli 100 susceptible to meropenem 95 to piperacillinndash
tazobactam 26 to ciprofloxacin and 0 to cephalosporins
Rodrıguez-Bano J et al Clin Infect Dis 2006431407-14
Tigecycline for MDR A baumanniiMetan G et al Clinical experience with tigecycline in the treatment of carbapenem-resistant Acinetobacter infections J Chemother 2010 Apr22(2)110-4
Gordon NC Wareham DW A review of clinical and microbiological outcomes following treatment of infections involving multidrug-resistant Acinetobacterbaumannii with tigecycline J AntimicrobChemother 2009 Apr63(4)775-80
Curcio D et al Tigecycline in the treatment of Ventilator-Associated Pneumonia experience from the Latin American Tigecycline Use Registry Infez Med 2010 Mar18(1)27-34
Tigecycline for MDR A baumanniibull Retrospective study of patients who received tigecycline for
tige-S carbapenem-R Acb-complex infections 2008-09bull 21 patients (median age 48 years) median duration tige 14 dbull 18 patients were treated with tigecycline as the sole pathogenbull Most common indication for tigecycline was SSI (VAP)bull Tigecycline was the sole antibiotic in 7 patientsbull 2 patients died within 14 days 4 died within 30 daysbull 1721 lsquohad successful clinical outcomesrsquo BUT 1421 had
microbiological failurebull Poor correlation between micro and clinical responsebull Clinical failure was more common in patients with VAPbull Patients with bacteraemia or VAP more likely to have
microbiological failureMetan G et al J Chemother 201022110-4
Colistin for MDR A baumanniibull 166 consecutive patients infected or colonised with
carbapenem- and MDR A Baumannii
bull 18 hospitals (London UK) 141 belonged to OXA-23 clone 1
bull Only colistin and tigecycline retained good in vitro activity with 994 and 819 of isolates susceptible respectively
bull 62 patients in ICU or HDU 84 (506) infected
bull Survival rates among infected and colonised patients were 68 and 67 indicating little attributable mortality
Livermore D et al Int J Antimicrob Agents 20103519-24
Colistin for MDR A baumanniibull Univariate and multivariate analyses
ndash poorer outcomes among ICU-infected patients pulmonary infection or bacteraemia
ndash trauma patients had significantly better outcomebull Outcomes varied by hospital (multivariate analysis) CASE MIXbull Poor association between outcome and therapy with colistin
(andor tigecycline)bull Patients with respiratory infection 1215 treated with
intravenous colistin alone had poor outcome compared with 18 whose therapy include nebulised colistin (P=0003)
BUT the patients receiving nebulised drug were mostly younger included trauma cases and were at a hospital with good outcomes
Livermore D et al Int J Antimicrob Agents 20103519-24
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
APACHE Acute Physiology and Chronic Health EvaluationSOFA Sequential Organ Failure Assessment
Enterococcus durans
Enterobacter cloacae
Enterococcus casseliflavus or Enterococcus gallinarum
Burkholderia cepacia
Acinetobacter baumannii
Enterococci species not determined
MRSA
Enterococcus faecalis
Infection of unknown origin
Strenotrophomonas maltophilia
VRE
Enterococcus faecium
Microorganism
1 (1)
1 (1)
1 (1) 1 (1)
1 (1)
4 (6) 4 (6)
7 (10)
11 (16)
13 (19)
15 (21)
26 (37)
Infections n ()
bull APACHE II scores 27 plusmn 10 SOFA 12 plusmn 3bull Overall mortality 30
n=70 withindication
0
10
20
30
40
50
60cIAI
cSSTI
Mixed
Other
bull Mean duration of tigecycline therapy was 9 +- 4 daysbull 76 of patients received tigecycline in combination
(64 second line)bull APACHE score and renal replacement were identified
as predictive factors for mortalitybull AUTHOR CONCLUSIONS lsquoTigecycline treatment of
critically ill SICU patients with severe sepsis or septic shock appeared to result in remarkably low mortality Tigecycline may be an important treatment option for septic patients with infections resistant to other available agentsrsquo
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
Antibiotics and risk of CDI
Evidence to supportthe restriction
of these as a controlmeasure for CDI
CDI may still occur
Need to minimise all antibiotic use polypharmacy and duration
Medium risk Low riskHigh risk
CephalosporinsClindamycin
AmpicillinamoxycillinCo-trimoxazole
MacrolidesFluoroquinolones
AminoglycosidesMetronidazole
Anti-pseudomonal penicillins +
β-lactamase inhibitorsTetracyclinesRifampicin
Vancomycin
Baines SD et al J Antimicrob Chemother 200555974-82Baines SD et al J Antimicrob Chemother 2006581062-5
Induction of C difficile toxin production
Tigecycline and C difficilebull Tigecycline is highly active (MIC=006 mgL) against C difficile
Baines SD et al J Antimicrob Chemother 2006581062-5
bull No in vitro evidence of increased risk of tigecycline-induced CDIBaines SD et al J Antimicrob Chemother 2006581062-5
bull No in vivo evidence of increased risk of tigecycline-induced CDIWilcox MH Clin Microbiol Infect 200713949-52
bull Some evidence that tigecycline could be used to treat CDI (THIS IS NOT A LICENSED INDICATION)Herpers BL et al Clin Infect Dis 2009481732-5
Lu CL et al Int J Antimicrob Agents 201035311-2
The missing care bundle antibiotic prescribing in hospitalsCooke FJ Holmes AHInt J Antimicrob Agents 20073025-9Department of Infectious Diseases and Immunology Hammersmith Hospitals NHS Trust Imperial CollegeDu Cane Road London W12 0HS UK
The care bundle involves grouping together key elements of care for procedures and the management of specific diagnoses in order to provide a systematic method to improve and monitor the delivery of clinical care processes In short care bundles aim to ensure that all patients consistently receive the best care or treatment all of the time This approach has been successfully applied to the management of various conditions particularly in the critical care setting The Institute for Healthcare Improvements 100K lives campaign consisted of six care bundles three of which have addressed preventing hospital-acquired infection The UK Department of Healths delivery programme to reduce healthcare-associated infections (HCAIs) including methicillin-resistant Staphylococcus aureus (MRSA) includes six high-impact interventions which are care bundles to reduce HCAIs However we suggest that one key intervention is missing and consider this intervention will be increasingly important if hospitals are to address the rising incidence of Clostridium difficile to tackle antibiotic resistance and to improve patient care The missing intervention addresses the process of antibiotic prescribing We propose that the time is right to consider the application of the care bundle approach to improve the prescribing of antibiotics both for treatment and prophylaxis
The antibiotic prescribing bundle
bull Use monotherapy whenever possible for initial (empiric) treatment
bull Optimise dose and duration
bull Perform a regular risk assessment
ndash For each patient
ndash Impact of the programme
Aminoglycosides
Glycopeptides
LipopeptidesOxazolidinones
Monotherapy or
combinationCarbapenems
BLICsCephalosporins
Fluoroquinolones
Tigecycline
Empiric choice Empiric choice 2nd 3rd line Final option
Low resistance risk and minimal
complexity
Increased resistance risk
and complexity
Treatment failure
[Cef Met prophylaxis]
Not if intravascular infectionNot in VAP as monotherapy
Antibiotic choice in high-risk patients
bull Capacity to cover resistant pathogens
bull Proven efficacy in MDR infection
bull Pharmacokinetic and pharmacodynamic profile
bull Safety profile
bull Capacity not to induce lsquoovergrowthrsquo eg CDI
bull Low potential for inducible resistance
bull Capacity not to select for resistant pathogens
Should consider measures to reduce use of 3GCs FQs amp carbapenems
Increased reliance on carbapenemsmay accelerate emergence of completely resistant isolates
Tigecycline and MDR Enterobacteriaceae
bull Systematic review microbiological activity and clinical effectiveness of tigecycline for multidrug-resistant (MDR) Enterobacteriaceae
bull 26 microbiological amp 10 clinical studies were identified
bull FDA (MIC lt2 mgL) or EUCAST (lt1 mgL) breakpoints
Kelesidis T et al J Antimicrob Chemother 200862895-904
Kelesidis T et al J Antimicrob Chemother 200862895-904
Tigecycline and MDR Enterobacteriaceae
bull In clinical studies 697 of the 33 reported patients treated with tigecycline achieved resolution of an infection caused by a carbapenem-resistant or ESBL-producing or MDR Enterobacteriaceae
Kelesidis T et al J Antimicrob Chemother 200862895-904
Fosfomycin and MDR Enterobacteriaceae
bull Systematic review microbiological activity and clinical effectiveness of tigecycline for multidrug-resistant (MDR) Enterobacteriaceae
bull 17 microbiological studies n=5057 isolates including 4448 ESBL +ve
bull 11 of the 17 studies reported that at least 90 of the isolates were susceptible to fosfomycin
bull Using a provisional MIC breakpoint lt64 mgLE coli (n=1657) 968 susceptibleKlebsiella spp (n=748) 813 susceptible
Falagas M et al Lancet Infect Dis 20101043-50
Fosfomycin and MDR Enterobacteriaceae
bull In two clinical studies oral treatment with fosfomycin-trometamol was clinically effective against complicated or uncomplicated lower UTIs caused by ESBL-producing E coli in 75 (938) of 80 patients
Falagas M et al Lancet Infect Dis 20101043-50
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull Italian hospital with increased prevalence of Proteus mirabilis strains producing acquired AmpC-type beta-lactamases (CBLs)
bull 43 CBL-positive isolates were obtained from hospitalised (n=22) and non-hospitalised (n=21) patients (median age 788 years) ndash usually UTIs
bull Treatment with amikacin or carbapenems was consistently effective
bull Piperacillintazobactam produced a clinical response in seven of nine cases
Luzarro F et al int J Antimicrob Agents 200933328-33
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull Italian hospital with increased prevalence of Proteus mirabilis strains producing acquired AmpC-type beta-lactamases (CBLs)
bull 43 CBL-positive isolates were obtained from hospitalised (n=22) and non-hospitalised (n=21) patients (median age 788 years) ndash usually UTIs
bull Treatment with amikacin or carbapenems was consistently effective
bull Piperacillintazobactam produced a clinical response in seven of nine cases
Luzarro F et al int J Antimicrob Agents 200933328-33
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull b-lactamndashb-lactamase inhibitor agents on patients infected with ESBL-producing strains of E coli and Klebsiella spp
bull 7 medical centres across North Americabull 148 patient records reviewedbull 30 rcvd FQ 18 carbapenem 16 pip-tazo 9 other b-
lactams 7 ampndashsul 6 aminogly 6 co-trimoxbull 83 given monotherapybull 23 rcvd pip-tazo (17 infections outside the urinary tract)bull For infections with pathogen MIC of pip-tazo lt16 mgfrasl L
successful outcome was reported in 1415 (1011 non-UTIs)bull Only 15 non-UTIs responded when pip-tazo MIC gt16 mgfrasl Lbull Meropenem therapy was successful in 24 pip-tazo resistant
infectionsGavin PJ et al int J Antimicrob Agents Chemother 2006502244-7
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull 43 episodes of E coli bacteraemia caused by ESBL-producing strains (primarily CTX-M-14)
bullbull Mortality was lower when patients were given a b-lactamndashb-
lactamase inhibitor combination or carbapenem as compared with either a cephalosporin or FQ
(9vs 35 p 005)bullbull E coli 100 susceptible to meropenem 95 to piperacillinndash
tazobactam 26 to ciprofloxacin and 0 to cephalosporins
Rodrıguez-Bano J et al Clin Infect Dis 2006431407-14
Tigecycline for MDR A baumanniiMetan G et al Clinical experience with tigecycline in the treatment of carbapenem-resistant Acinetobacter infections J Chemother 2010 Apr22(2)110-4
Gordon NC Wareham DW A review of clinical and microbiological outcomes following treatment of infections involving multidrug-resistant Acinetobacterbaumannii with tigecycline J AntimicrobChemother 2009 Apr63(4)775-80
Curcio D et al Tigecycline in the treatment of Ventilator-Associated Pneumonia experience from the Latin American Tigecycline Use Registry Infez Med 2010 Mar18(1)27-34
Tigecycline for MDR A baumanniibull Retrospective study of patients who received tigecycline for
tige-S carbapenem-R Acb-complex infections 2008-09bull 21 patients (median age 48 years) median duration tige 14 dbull 18 patients were treated with tigecycline as the sole pathogenbull Most common indication for tigecycline was SSI (VAP)bull Tigecycline was the sole antibiotic in 7 patientsbull 2 patients died within 14 days 4 died within 30 daysbull 1721 lsquohad successful clinical outcomesrsquo BUT 1421 had
microbiological failurebull Poor correlation between micro and clinical responsebull Clinical failure was more common in patients with VAPbull Patients with bacteraemia or VAP more likely to have
microbiological failureMetan G et al J Chemother 201022110-4
Colistin for MDR A baumanniibull 166 consecutive patients infected or colonised with
carbapenem- and MDR A Baumannii
bull 18 hospitals (London UK) 141 belonged to OXA-23 clone 1
bull Only colistin and tigecycline retained good in vitro activity with 994 and 819 of isolates susceptible respectively
bull 62 patients in ICU or HDU 84 (506) infected
bull Survival rates among infected and colonised patients were 68 and 67 indicating little attributable mortality
Livermore D et al Int J Antimicrob Agents 20103519-24
Colistin for MDR A baumanniibull Univariate and multivariate analyses
ndash poorer outcomes among ICU-infected patients pulmonary infection or bacteraemia
ndash trauma patients had significantly better outcomebull Outcomes varied by hospital (multivariate analysis) CASE MIXbull Poor association between outcome and therapy with colistin
(andor tigecycline)bull Patients with respiratory infection 1215 treated with
intravenous colistin alone had poor outcome compared with 18 whose therapy include nebulised colistin (P=0003)
BUT the patients receiving nebulised drug were mostly younger included trauma cases and were at a hospital with good outcomes
Livermore D et al Int J Antimicrob Agents 20103519-24
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
APACHE Acute Physiology and Chronic Health EvaluationSOFA Sequential Organ Failure Assessment
Enterococcus durans
Enterobacter cloacae
Enterococcus casseliflavus or Enterococcus gallinarum
Burkholderia cepacia
Acinetobacter baumannii
Enterococci species not determined
MRSA
Enterococcus faecalis
Infection of unknown origin
Strenotrophomonas maltophilia
VRE
Enterococcus faecium
Microorganism
1 (1)
1 (1)
1 (1) 1 (1)
1 (1)
4 (6) 4 (6)
7 (10)
11 (16)
13 (19)
15 (21)
26 (37)
Infections n ()
bull APACHE II scores 27 plusmn 10 SOFA 12 plusmn 3bull Overall mortality 30
n=70 withindication
0
10
20
30
40
50
60cIAI
cSSTI
Mixed
Other
bull Mean duration of tigecycline therapy was 9 +- 4 daysbull 76 of patients received tigecycline in combination
(64 second line)bull APACHE score and renal replacement were identified
as predictive factors for mortalitybull AUTHOR CONCLUSIONS lsquoTigecycline treatment of
critically ill SICU patients with severe sepsis or septic shock appeared to result in remarkably low mortality Tigecycline may be an important treatment option for septic patients with infections resistant to other available agentsrsquo
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
Antibiotics and risk of CDI
Evidence to supportthe restriction
of these as a controlmeasure for CDI
CDI may still occur
Need to minimise all antibiotic use polypharmacy and duration
Medium risk Low riskHigh risk
CephalosporinsClindamycin
AmpicillinamoxycillinCo-trimoxazole
MacrolidesFluoroquinolones
AminoglycosidesMetronidazole
Anti-pseudomonal penicillins +
β-lactamase inhibitorsTetracyclinesRifampicin
Vancomycin
Baines SD et al J Antimicrob Chemother 200555974-82Baines SD et al J Antimicrob Chemother 2006581062-5
Induction of C difficile toxin production
Tigecycline and C difficilebull Tigecycline is highly active (MIC=006 mgL) against C difficile
Baines SD et al J Antimicrob Chemother 2006581062-5
bull No in vitro evidence of increased risk of tigecycline-induced CDIBaines SD et al J Antimicrob Chemother 2006581062-5
bull No in vivo evidence of increased risk of tigecycline-induced CDIWilcox MH Clin Microbiol Infect 200713949-52
bull Some evidence that tigecycline could be used to treat CDI (THIS IS NOT A LICENSED INDICATION)Herpers BL et al Clin Infect Dis 2009481732-5
Lu CL et al Int J Antimicrob Agents 201035311-2
The missing care bundle antibiotic prescribing in hospitalsCooke FJ Holmes AHInt J Antimicrob Agents 20073025-9Department of Infectious Diseases and Immunology Hammersmith Hospitals NHS Trust Imperial CollegeDu Cane Road London W12 0HS UK
The care bundle involves grouping together key elements of care for procedures and the management of specific diagnoses in order to provide a systematic method to improve and monitor the delivery of clinical care processes In short care bundles aim to ensure that all patients consistently receive the best care or treatment all of the time This approach has been successfully applied to the management of various conditions particularly in the critical care setting The Institute for Healthcare Improvements 100K lives campaign consisted of six care bundles three of which have addressed preventing hospital-acquired infection The UK Department of Healths delivery programme to reduce healthcare-associated infections (HCAIs) including methicillin-resistant Staphylococcus aureus (MRSA) includes six high-impact interventions which are care bundles to reduce HCAIs However we suggest that one key intervention is missing and consider this intervention will be increasingly important if hospitals are to address the rising incidence of Clostridium difficile to tackle antibiotic resistance and to improve patient care The missing intervention addresses the process of antibiotic prescribing We propose that the time is right to consider the application of the care bundle approach to improve the prescribing of antibiotics both for treatment and prophylaxis
The antibiotic prescribing bundle
bull Use monotherapy whenever possible for initial (empiric) treatment
bull Optimise dose and duration
bull Perform a regular risk assessment
ndash For each patient
ndash Impact of the programme
Aminoglycosides
Glycopeptides
LipopeptidesOxazolidinones
Monotherapy or
combinationCarbapenems
BLICsCephalosporins
Fluoroquinolones
Tigecycline
Empiric choice Empiric choice 2nd 3rd line Final option
Low resistance risk and minimal
complexity
Increased resistance risk
and complexity
Treatment failure
[Cef Met prophylaxis]
Not if intravascular infectionNot in VAP as monotherapy
Antibiotic choice in high-risk patients
bull Capacity to cover resistant pathogens
bull Proven efficacy in MDR infection
bull Pharmacokinetic and pharmacodynamic profile
bull Safety profile
bull Capacity not to induce lsquoovergrowthrsquo eg CDI
bull Low potential for inducible resistance
bull Capacity not to select for resistant pathogens
Should consider measures to reduce use of 3GCs FQs amp carbapenems
Increased reliance on carbapenemsmay accelerate emergence of completely resistant isolates
Kelesidis T et al J Antimicrob Chemother 200862895-904
Tigecycline and MDR Enterobacteriaceae
bull In clinical studies 697 of the 33 reported patients treated with tigecycline achieved resolution of an infection caused by a carbapenem-resistant or ESBL-producing or MDR Enterobacteriaceae
Kelesidis T et al J Antimicrob Chemother 200862895-904
Fosfomycin and MDR Enterobacteriaceae
bull Systematic review microbiological activity and clinical effectiveness of tigecycline for multidrug-resistant (MDR) Enterobacteriaceae
bull 17 microbiological studies n=5057 isolates including 4448 ESBL +ve
bull 11 of the 17 studies reported that at least 90 of the isolates were susceptible to fosfomycin
bull Using a provisional MIC breakpoint lt64 mgLE coli (n=1657) 968 susceptibleKlebsiella spp (n=748) 813 susceptible
Falagas M et al Lancet Infect Dis 20101043-50
Fosfomycin and MDR Enterobacteriaceae
bull In two clinical studies oral treatment with fosfomycin-trometamol was clinically effective against complicated or uncomplicated lower UTIs caused by ESBL-producing E coli in 75 (938) of 80 patients
Falagas M et al Lancet Infect Dis 20101043-50
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull Italian hospital with increased prevalence of Proteus mirabilis strains producing acquired AmpC-type beta-lactamases (CBLs)
bull 43 CBL-positive isolates were obtained from hospitalised (n=22) and non-hospitalised (n=21) patients (median age 788 years) ndash usually UTIs
bull Treatment with amikacin or carbapenems was consistently effective
bull Piperacillintazobactam produced a clinical response in seven of nine cases
Luzarro F et al int J Antimicrob Agents 200933328-33
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull Italian hospital with increased prevalence of Proteus mirabilis strains producing acquired AmpC-type beta-lactamases (CBLs)
bull 43 CBL-positive isolates were obtained from hospitalised (n=22) and non-hospitalised (n=21) patients (median age 788 years) ndash usually UTIs
bull Treatment with amikacin or carbapenems was consistently effective
bull Piperacillintazobactam produced a clinical response in seven of nine cases
Luzarro F et al int J Antimicrob Agents 200933328-33
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull b-lactamndashb-lactamase inhibitor agents on patients infected with ESBL-producing strains of E coli and Klebsiella spp
bull 7 medical centres across North Americabull 148 patient records reviewedbull 30 rcvd FQ 18 carbapenem 16 pip-tazo 9 other b-
lactams 7 ampndashsul 6 aminogly 6 co-trimoxbull 83 given monotherapybull 23 rcvd pip-tazo (17 infections outside the urinary tract)bull For infections with pathogen MIC of pip-tazo lt16 mgfrasl L
successful outcome was reported in 1415 (1011 non-UTIs)bull Only 15 non-UTIs responded when pip-tazo MIC gt16 mgfrasl Lbull Meropenem therapy was successful in 24 pip-tazo resistant
infectionsGavin PJ et al int J Antimicrob Agents Chemother 2006502244-7
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull 43 episodes of E coli bacteraemia caused by ESBL-producing strains (primarily CTX-M-14)
bullbull Mortality was lower when patients were given a b-lactamndashb-
lactamase inhibitor combination or carbapenem as compared with either a cephalosporin or FQ
(9vs 35 p 005)bullbull E coli 100 susceptible to meropenem 95 to piperacillinndash
tazobactam 26 to ciprofloxacin and 0 to cephalosporins
Rodrıguez-Bano J et al Clin Infect Dis 2006431407-14
Tigecycline for MDR A baumanniiMetan G et al Clinical experience with tigecycline in the treatment of carbapenem-resistant Acinetobacter infections J Chemother 2010 Apr22(2)110-4
Gordon NC Wareham DW A review of clinical and microbiological outcomes following treatment of infections involving multidrug-resistant Acinetobacterbaumannii with tigecycline J AntimicrobChemother 2009 Apr63(4)775-80
Curcio D et al Tigecycline in the treatment of Ventilator-Associated Pneumonia experience from the Latin American Tigecycline Use Registry Infez Med 2010 Mar18(1)27-34
Tigecycline for MDR A baumanniibull Retrospective study of patients who received tigecycline for
tige-S carbapenem-R Acb-complex infections 2008-09bull 21 patients (median age 48 years) median duration tige 14 dbull 18 patients were treated with tigecycline as the sole pathogenbull Most common indication for tigecycline was SSI (VAP)bull Tigecycline was the sole antibiotic in 7 patientsbull 2 patients died within 14 days 4 died within 30 daysbull 1721 lsquohad successful clinical outcomesrsquo BUT 1421 had
microbiological failurebull Poor correlation between micro and clinical responsebull Clinical failure was more common in patients with VAPbull Patients with bacteraemia or VAP more likely to have
microbiological failureMetan G et al J Chemother 201022110-4
Colistin for MDR A baumanniibull 166 consecutive patients infected or colonised with
carbapenem- and MDR A Baumannii
bull 18 hospitals (London UK) 141 belonged to OXA-23 clone 1
bull Only colistin and tigecycline retained good in vitro activity with 994 and 819 of isolates susceptible respectively
bull 62 patients in ICU or HDU 84 (506) infected
bull Survival rates among infected and colonised patients were 68 and 67 indicating little attributable mortality
Livermore D et al Int J Antimicrob Agents 20103519-24
Colistin for MDR A baumanniibull Univariate and multivariate analyses
ndash poorer outcomes among ICU-infected patients pulmonary infection or bacteraemia
ndash trauma patients had significantly better outcomebull Outcomes varied by hospital (multivariate analysis) CASE MIXbull Poor association between outcome and therapy with colistin
(andor tigecycline)bull Patients with respiratory infection 1215 treated with
intravenous colistin alone had poor outcome compared with 18 whose therapy include nebulised colistin (P=0003)
BUT the patients receiving nebulised drug were mostly younger included trauma cases and were at a hospital with good outcomes
Livermore D et al Int J Antimicrob Agents 20103519-24
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
APACHE Acute Physiology and Chronic Health EvaluationSOFA Sequential Organ Failure Assessment
Enterococcus durans
Enterobacter cloacae
Enterococcus casseliflavus or Enterococcus gallinarum
Burkholderia cepacia
Acinetobacter baumannii
Enterococci species not determined
MRSA
Enterococcus faecalis
Infection of unknown origin
Strenotrophomonas maltophilia
VRE
Enterococcus faecium
Microorganism
1 (1)
1 (1)
1 (1) 1 (1)
1 (1)
4 (6) 4 (6)
7 (10)
11 (16)
13 (19)
15 (21)
26 (37)
Infections n ()
bull APACHE II scores 27 plusmn 10 SOFA 12 plusmn 3bull Overall mortality 30
n=70 withindication
0
10
20
30
40
50
60cIAI
cSSTI
Mixed
Other
bull Mean duration of tigecycline therapy was 9 +- 4 daysbull 76 of patients received tigecycline in combination
(64 second line)bull APACHE score and renal replacement were identified
as predictive factors for mortalitybull AUTHOR CONCLUSIONS lsquoTigecycline treatment of
critically ill SICU patients with severe sepsis or septic shock appeared to result in remarkably low mortality Tigecycline may be an important treatment option for septic patients with infections resistant to other available agentsrsquo
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
Antibiotics and risk of CDI
Evidence to supportthe restriction
of these as a controlmeasure for CDI
CDI may still occur
Need to minimise all antibiotic use polypharmacy and duration
Medium risk Low riskHigh risk
CephalosporinsClindamycin
AmpicillinamoxycillinCo-trimoxazole
MacrolidesFluoroquinolones
AminoglycosidesMetronidazole
Anti-pseudomonal penicillins +
β-lactamase inhibitorsTetracyclinesRifampicin
Vancomycin
Baines SD et al J Antimicrob Chemother 200555974-82Baines SD et al J Antimicrob Chemother 2006581062-5
Induction of C difficile toxin production
Tigecycline and C difficilebull Tigecycline is highly active (MIC=006 mgL) against C difficile
Baines SD et al J Antimicrob Chemother 2006581062-5
bull No in vitro evidence of increased risk of tigecycline-induced CDIBaines SD et al J Antimicrob Chemother 2006581062-5
bull No in vivo evidence of increased risk of tigecycline-induced CDIWilcox MH Clin Microbiol Infect 200713949-52
bull Some evidence that tigecycline could be used to treat CDI (THIS IS NOT A LICENSED INDICATION)Herpers BL et al Clin Infect Dis 2009481732-5
Lu CL et al Int J Antimicrob Agents 201035311-2
The missing care bundle antibiotic prescribing in hospitalsCooke FJ Holmes AHInt J Antimicrob Agents 20073025-9Department of Infectious Diseases and Immunology Hammersmith Hospitals NHS Trust Imperial CollegeDu Cane Road London W12 0HS UK
The care bundle involves grouping together key elements of care for procedures and the management of specific diagnoses in order to provide a systematic method to improve and monitor the delivery of clinical care processes In short care bundles aim to ensure that all patients consistently receive the best care or treatment all of the time This approach has been successfully applied to the management of various conditions particularly in the critical care setting The Institute for Healthcare Improvements 100K lives campaign consisted of six care bundles three of which have addressed preventing hospital-acquired infection The UK Department of Healths delivery programme to reduce healthcare-associated infections (HCAIs) including methicillin-resistant Staphylococcus aureus (MRSA) includes six high-impact interventions which are care bundles to reduce HCAIs However we suggest that one key intervention is missing and consider this intervention will be increasingly important if hospitals are to address the rising incidence of Clostridium difficile to tackle antibiotic resistance and to improve patient care The missing intervention addresses the process of antibiotic prescribing We propose that the time is right to consider the application of the care bundle approach to improve the prescribing of antibiotics both for treatment and prophylaxis
The antibiotic prescribing bundle
bull Use monotherapy whenever possible for initial (empiric) treatment
bull Optimise dose and duration
bull Perform a regular risk assessment
ndash For each patient
ndash Impact of the programme
Aminoglycosides
Glycopeptides
LipopeptidesOxazolidinones
Monotherapy or
combinationCarbapenems
BLICsCephalosporins
Fluoroquinolones
Tigecycline
Empiric choice Empiric choice 2nd 3rd line Final option
Low resistance risk and minimal
complexity
Increased resistance risk
and complexity
Treatment failure
[Cef Met prophylaxis]
Not if intravascular infectionNot in VAP as monotherapy
Antibiotic choice in high-risk patients
bull Capacity to cover resistant pathogens
bull Proven efficacy in MDR infection
bull Pharmacokinetic and pharmacodynamic profile
bull Safety profile
bull Capacity not to induce lsquoovergrowthrsquo eg CDI
bull Low potential for inducible resistance
bull Capacity not to select for resistant pathogens
Should consider measures to reduce use of 3GCs FQs amp carbapenems
Increased reliance on carbapenemsmay accelerate emergence of completely resistant isolates
Tigecycline and MDR Enterobacteriaceae
bull In clinical studies 697 of the 33 reported patients treated with tigecycline achieved resolution of an infection caused by a carbapenem-resistant or ESBL-producing or MDR Enterobacteriaceae
Kelesidis T et al J Antimicrob Chemother 200862895-904
Fosfomycin and MDR Enterobacteriaceae
bull Systematic review microbiological activity and clinical effectiveness of tigecycline for multidrug-resistant (MDR) Enterobacteriaceae
bull 17 microbiological studies n=5057 isolates including 4448 ESBL +ve
bull 11 of the 17 studies reported that at least 90 of the isolates were susceptible to fosfomycin
bull Using a provisional MIC breakpoint lt64 mgLE coli (n=1657) 968 susceptibleKlebsiella spp (n=748) 813 susceptible
Falagas M et al Lancet Infect Dis 20101043-50
Fosfomycin and MDR Enterobacteriaceae
bull In two clinical studies oral treatment with fosfomycin-trometamol was clinically effective against complicated or uncomplicated lower UTIs caused by ESBL-producing E coli in 75 (938) of 80 patients
Falagas M et al Lancet Infect Dis 20101043-50
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull Italian hospital with increased prevalence of Proteus mirabilis strains producing acquired AmpC-type beta-lactamases (CBLs)
bull 43 CBL-positive isolates were obtained from hospitalised (n=22) and non-hospitalised (n=21) patients (median age 788 years) ndash usually UTIs
bull Treatment with amikacin or carbapenems was consistently effective
bull Piperacillintazobactam produced a clinical response in seven of nine cases
Luzarro F et al int J Antimicrob Agents 200933328-33
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull Italian hospital with increased prevalence of Proteus mirabilis strains producing acquired AmpC-type beta-lactamases (CBLs)
bull 43 CBL-positive isolates were obtained from hospitalised (n=22) and non-hospitalised (n=21) patients (median age 788 years) ndash usually UTIs
bull Treatment with amikacin or carbapenems was consistently effective
bull Piperacillintazobactam produced a clinical response in seven of nine cases
Luzarro F et al int J Antimicrob Agents 200933328-33
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull b-lactamndashb-lactamase inhibitor agents on patients infected with ESBL-producing strains of E coli and Klebsiella spp
bull 7 medical centres across North Americabull 148 patient records reviewedbull 30 rcvd FQ 18 carbapenem 16 pip-tazo 9 other b-
lactams 7 ampndashsul 6 aminogly 6 co-trimoxbull 83 given monotherapybull 23 rcvd pip-tazo (17 infections outside the urinary tract)bull For infections with pathogen MIC of pip-tazo lt16 mgfrasl L
successful outcome was reported in 1415 (1011 non-UTIs)bull Only 15 non-UTIs responded when pip-tazo MIC gt16 mgfrasl Lbull Meropenem therapy was successful in 24 pip-tazo resistant
infectionsGavin PJ et al int J Antimicrob Agents Chemother 2006502244-7
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull 43 episodes of E coli bacteraemia caused by ESBL-producing strains (primarily CTX-M-14)
bullbull Mortality was lower when patients were given a b-lactamndashb-
lactamase inhibitor combination or carbapenem as compared with either a cephalosporin or FQ
(9vs 35 p 005)bullbull E coli 100 susceptible to meropenem 95 to piperacillinndash
tazobactam 26 to ciprofloxacin and 0 to cephalosporins
Rodrıguez-Bano J et al Clin Infect Dis 2006431407-14
Tigecycline for MDR A baumanniiMetan G et al Clinical experience with tigecycline in the treatment of carbapenem-resistant Acinetobacter infections J Chemother 2010 Apr22(2)110-4
Gordon NC Wareham DW A review of clinical and microbiological outcomes following treatment of infections involving multidrug-resistant Acinetobacterbaumannii with tigecycline J AntimicrobChemother 2009 Apr63(4)775-80
Curcio D et al Tigecycline in the treatment of Ventilator-Associated Pneumonia experience from the Latin American Tigecycline Use Registry Infez Med 2010 Mar18(1)27-34
Tigecycline for MDR A baumanniibull Retrospective study of patients who received tigecycline for
tige-S carbapenem-R Acb-complex infections 2008-09bull 21 patients (median age 48 years) median duration tige 14 dbull 18 patients were treated with tigecycline as the sole pathogenbull Most common indication for tigecycline was SSI (VAP)bull Tigecycline was the sole antibiotic in 7 patientsbull 2 patients died within 14 days 4 died within 30 daysbull 1721 lsquohad successful clinical outcomesrsquo BUT 1421 had
microbiological failurebull Poor correlation between micro and clinical responsebull Clinical failure was more common in patients with VAPbull Patients with bacteraemia or VAP more likely to have
microbiological failureMetan G et al J Chemother 201022110-4
Colistin for MDR A baumanniibull 166 consecutive patients infected or colonised with
carbapenem- and MDR A Baumannii
bull 18 hospitals (London UK) 141 belonged to OXA-23 clone 1
bull Only colistin and tigecycline retained good in vitro activity with 994 and 819 of isolates susceptible respectively
bull 62 patients in ICU or HDU 84 (506) infected
bull Survival rates among infected and colonised patients were 68 and 67 indicating little attributable mortality
Livermore D et al Int J Antimicrob Agents 20103519-24
Colistin for MDR A baumanniibull Univariate and multivariate analyses
ndash poorer outcomes among ICU-infected patients pulmonary infection or bacteraemia
ndash trauma patients had significantly better outcomebull Outcomes varied by hospital (multivariate analysis) CASE MIXbull Poor association between outcome and therapy with colistin
(andor tigecycline)bull Patients with respiratory infection 1215 treated with
intravenous colistin alone had poor outcome compared with 18 whose therapy include nebulised colistin (P=0003)
BUT the patients receiving nebulised drug were mostly younger included trauma cases and were at a hospital with good outcomes
Livermore D et al Int J Antimicrob Agents 20103519-24
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
APACHE Acute Physiology and Chronic Health EvaluationSOFA Sequential Organ Failure Assessment
Enterococcus durans
Enterobacter cloacae
Enterococcus casseliflavus or Enterococcus gallinarum
Burkholderia cepacia
Acinetobacter baumannii
Enterococci species not determined
MRSA
Enterococcus faecalis
Infection of unknown origin
Strenotrophomonas maltophilia
VRE
Enterococcus faecium
Microorganism
1 (1)
1 (1)
1 (1) 1 (1)
1 (1)
4 (6) 4 (6)
7 (10)
11 (16)
13 (19)
15 (21)
26 (37)
Infections n ()
bull APACHE II scores 27 plusmn 10 SOFA 12 plusmn 3bull Overall mortality 30
n=70 withindication
0
10
20
30
40
50
60cIAI
cSSTI
Mixed
Other
bull Mean duration of tigecycline therapy was 9 +- 4 daysbull 76 of patients received tigecycline in combination
(64 second line)bull APACHE score and renal replacement were identified
as predictive factors for mortalitybull AUTHOR CONCLUSIONS lsquoTigecycline treatment of
critically ill SICU patients with severe sepsis or septic shock appeared to result in remarkably low mortality Tigecycline may be an important treatment option for septic patients with infections resistant to other available agentsrsquo
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
Antibiotics and risk of CDI
Evidence to supportthe restriction
of these as a controlmeasure for CDI
CDI may still occur
Need to minimise all antibiotic use polypharmacy and duration
Medium risk Low riskHigh risk
CephalosporinsClindamycin
AmpicillinamoxycillinCo-trimoxazole
MacrolidesFluoroquinolones
AminoglycosidesMetronidazole
Anti-pseudomonal penicillins +
β-lactamase inhibitorsTetracyclinesRifampicin
Vancomycin
Baines SD et al J Antimicrob Chemother 200555974-82Baines SD et al J Antimicrob Chemother 2006581062-5
Induction of C difficile toxin production
Tigecycline and C difficilebull Tigecycline is highly active (MIC=006 mgL) against C difficile
Baines SD et al J Antimicrob Chemother 2006581062-5
bull No in vitro evidence of increased risk of tigecycline-induced CDIBaines SD et al J Antimicrob Chemother 2006581062-5
bull No in vivo evidence of increased risk of tigecycline-induced CDIWilcox MH Clin Microbiol Infect 200713949-52
bull Some evidence that tigecycline could be used to treat CDI (THIS IS NOT A LICENSED INDICATION)Herpers BL et al Clin Infect Dis 2009481732-5
Lu CL et al Int J Antimicrob Agents 201035311-2
The missing care bundle antibiotic prescribing in hospitalsCooke FJ Holmes AHInt J Antimicrob Agents 20073025-9Department of Infectious Diseases and Immunology Hammersmith Hospitals NHS Trust Imperial CollegeDu Cane Road London W12 0HS UK
The care bundle involves grouping together key elements of care for procedures and the management of specific diagnoses in order to provide a systematic method to improve and monitor the delivery of clinical care processes In short care bundles aim to ensure that all patients consistently receive the best care or treatment all of the time This approach has been successfully applied to the management of various conditions particularly in the critical care setting The Institute for Healthcare Improvements 100K lives campaign consisted of six care bundles three of which have addressed preventing hospital-acquired infection The UK Department of Healths delivery programme to reduce healthcare-associated infections (HCAIs) including methicillin-resistant Staphylococcus aureus (MRSA) includes six high-impact interventions which are care bundles to reduce HCAIs However we suggest that one key intervention is missing and consider this intervention will be increasingly important if hospitals are to address the rising incidence of Clostridium difficile to tackle antibiotic resistance and to improve patient care The missing intervention addresses the process of antibiotic prescribing We propose that the time is right to consider the application of the care bundle approach to improve the prescribing of antibiotics both for treatment and prophylaxis
The antibiotic prescribing bundle
bull Use monotherapy whenever possible for initial (empiric) treatment
bull Optimise dose and duration
bull Perform a regular risk assessment
ndash For each patient
ndash Impact of the programme
Aminoglycosides
Glycopeptides
LipopeptidesOxazolidinones
Monotherapy or
combinationCarbapenems
BLICsCephalosporins
Fluoroquinolones
Tigecycline
Empiric choice Empiric choice 2nd 3rd line Final option
Low resistance risk and minimal
complexity
Increased resistance risk
and complexity
Treatment failure
[Cef Met prophylaxis]
Not if intravascular infectionNot in VAP as monotherapy
Antibiotic choice in high-risk patients
bull Capacity to cover resistant pathogens
bull Proven efficacy in MDR infection
bull Pharmacokinetic and pharmacodynamic profile
bull Safety profile
bull Capacity not to induce lsquoovergrowthrsquo eg CDI
bull Low potential for inducible resistance
bull Capacity not to select for resistant pathogens
Should consider measures to reduce use of 3GCs FQs amp carbapenems
Increased reliance on carbapenemsmay accelerate emergence of completely resistant isolates
Fosfomycin and MDR Enterobacteriaceae
bull Systematic review microbiological activity and clinical effectiveness of tigecycline for multidrug-resistant (MDR) Enterobacteriaceae
bull 17 microbiological studies n=5057 isolates including 4448 ESBL +ve
bull 11 of the 17 studies reported that at least 90 of the isolates were susceptible to fosfomycin
bull Using a provisional MIC breakpoint lt64 mgLE coli (n=1657) 968 susceptibleKlebsiella spp (n=748) 813 susceptible
Falagas M et al Lancet Infect Dis 20101043-50
Fosfomycin and MDR Enterobacteriaceae
bull In two clinical studies oral treatment with fosfomycin-trometamol was clinically effective against complicated or uncomplicated lower UTIs caused by ESBL-producing E coli in 75 (938) of 80 patients
Falagas M et al Lancet Infect Dis 20101043-50
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull Italian hospital with increased prevalence of Proteus mirabilis strains producing acquired AmpC-type beta-lactamases (CBLs)
bull 43 CBL-positive isolates were obtained from hospitalised (n=22) and non-hospitalised (n=21) patients (median age 788 years) ndash usually UTIs
bull Treatment with amikacin or carbapenems was consistently effective
bull Piperacillintazobactam produced a clinical response in seven of nine cases
Luzarro F et al int J Antimicrob Agents 200933328-33
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull Italian hospital with increased prevalence of Proteus mirabilis strains producing acquired AmpC-type beta-lactamases (CBLs)
bull 43 CBL-positive isolates were obtained from hospitalised (n=22) and non-hospitalised (n=21) patients (median age 788 years) ndash usually UTIs
bull Treatment with amikacin or carbapenems was consistently effective
bull Piperacillintazobactam produced a clinical response in seven of nine cases
Luzarro F et al int J Antimicrob Agents 200933328-33
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull b-lactamndashb-lactamase inhibitor agents on patients infected with ESBL-producing strains of E coli and Klebsiella spp
bull 7 medical centres across North Americabull 148 patient records reviewedbull 30 rcvd FQ 18 carbapenem 16 pip-tazo 9 other b-
lactams 7 ampndashsul 6 aminogly 6 co-trimoxbull 83 given monotherapybull 23 rcvd pip-tazo (17 infections outside the urinary tract)bull For infections with pathogen MIC of pip-tazo lt16 mgfrasl L
successful outcome was reported in 1415 (1011 non-UTIs)bull Only 15 non-UTIs responded when pip-tazo MIC gt16 mgfrasl Lbull Meropenem therapy was successful in 24 pip-tazo resistant
infectionsGavin PJ et al int J Antimicrob Agents Chemother 2006502244-7
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull 43 episodes of E coli bacteraemia caused by ESBL-producing strains (primarily CTX-M-14)
bullbull Mortality was lower when patients were given a b-lactamndashb-
lactamase inhibitor combination or carbapenem as compared with either a cephalosporin or FQ
(9vs 35 p 005)bullbull E coli 100 susceptible to meropenem 95 to piperacillinndash
tazobactam 26 to ciprofloxacin and 0 to cephalosporins
Rodrıguez-Bano J et al Clin Infect Dis 2006431407-14
Tigecycline for MDR A baumanniiMetan G et al Clinical experience with tigecycline in the treatment of carbapenem-resistant Acinetobacter infections J Chemother 2010 Apr22(2)110-4
Gordon NC Wareham DW A review of clinical and microbiological outcomes following treatment of infections involving multidrug-resistant Acinetobacterbaumannii with tigecycline J AntimicrobChemother 2009 Apr63(4)775-80
Curcio D et al Tigecycline in the treatment of Ventilator-Associated Pneumonia experience from the Latin American Tigecycline Use Registry Infez Med 2010 Mar18(1)27-34
Tigecycline for MDR A baumanniibull Retrospective study of patients who received tigecycline for
tige-S carbapenem-R Acb-complex infections 2008-09bull 21 patients (median age 48 years) median duration tige 14 dbull 18 patients were treated with tigecycline as the sole pathogenbull Most common indication for tigecycline was SSI (VAP)bull Tigecycline was the sole antibiotic in 7 patientsbull 2 patients died within 14 days 4 died within 30 daysbull 1721 lsquohad successful clinical outcomesrsquo BUT 1421 had
microbiological failurebull Poor correlation between micro and clinical responsebull Clinical failure was more common in patients with VAPbull Patients with bacteraemia or VAP more likely to have
microbiological failureMetan G et al J Chemother 201022110-4
Colistin for MDR A baumanniibull 166 consecutive patients infected or colonised with
carbapenem- and MDR A Baumannii
bull 18 hospitals (London UK) 141 belonged to OXA-23 clone 1
bull Only colistin and tigecycline retained good in vitro activity with 994 and 819 of isolates susceptible respectively
bull 62 patients in ICU or HDU 84 (506) infected
bull Survival rates among infected and colonised patients were 68 and 67 indicating little attributable mortality
Livermore D et al Int J Antimicrob Agents 20103519-24
Colistin for MDR A baumanniibull Univariate and multivariate analyses
ndash poorer outcomes among ICU-infected patients pulmonary infection or bacteraemia
ndash trauma patients had significantly better outcomebull Outcomes varied by hospital (multivariate analysis) CASE MIXbull Poor association between outcome and therapy with colistin
(andor tigecycline)bull Patients with respiratory infection 1215 treated with
intravenous colistin alone had poor outcome compared with 18 whose therapy include nebulised colistin (P=0003)
BUT the patients receiving nebulised drug were mostly younger included trauma cases and were at a hospital with good outcomes
Livermore D et al Int J Antimicrob Agents 20103519-24
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
APACHE Acute Physiology and Chronic Health EvaluationSOFA Sequential Organ Failure Assessment
Enterococcus durans
Enterobacter cloacae
Enterococcus casseliflavus or Enterococcus gallinarum
Burkholderia cepacia
Acinetobacter baumannii
Enterococci species not determined
MRSA
Enterococcus faecalis
Infection of unknown origin
Strenotrophomonas maltophilia
VRE
Enterococcus faecium
Microorganism
1 (1)
1 (1)
1 (1) 1 (1)
1 (1)
4 (6) 4 (6)
7 (10)
11 (16)
13 (19)
15 (21)
26 (37)
Infections n ()
bull APACHE II scores 27 plusmn 10 SOFA 12 plusmn 3bull Overall mortality 30
n=70 withindication
0
10
20
30
40
50
60cIAI
cSSTI
Mixed
Other
bull Mean duration of tigecycline therapy was 9 +- 4 daysbull 76 of patients received tigecycline in combination
(64 second line)bull APACHE score and renal replacement were identified
as predictive factors for mortalitybull AUTHOR CONCLUSIONS lsquoTigecycline treatment of
critically ill SICU patients with severe sepsis or septic shock appeared to result in remarkably low mortality Tigecycline may be an important treatment option for septic patients with infections resistant to other available agentsrsquo
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
Antibiotics and risk of CDI
Evidence to supportthe restriction
of these as a controlmeasure for CDI
CDI may still occur
Need to minimise all antibiotic use polypharmacy and duration
Medium risk Low riskHigh risk
CephalosporinsClindamycin
AmpicillinamoxycillinCo-trimoxazole
MacrolidesFluoroquinolones
AminoglycosidesMetronidazole
Anti-pseudomonal penicillins +
β-lactamase inhibitorsTetracyclinesRifampicin
Vancomycin
Baines SD et al J Antimicrob Chemother 200555974-82Baines SD et al J Antimicrob Chemother 2006581062-5
Induction of C difficile toxin production
Tigecycline and C difficilebull Tigecycline is highly active (MIC=006 mgL) against C difficile
Baines SD et al J Antimicrob Chemother 2006581062-5
bull No in vitro evidence of increased risk of tigecycline-induced CDIBaines SD et al J Antimicrob Chemother 2006581062-5
bull No in vivo evidence of increased risk of tigecycline-induced CDIWilcox MH Clin Microbiol Infect 200713949-52
bull Some evidence that tigecycline could be used to treat CDI (THIS IS NOT A LICENSED INDICATION)Herpers BL et al Clin Infect Dis 2009481732-5
Lu CL et al Int J Antimicrob Agents 201035311-2
The missing care bundle antibiotic prescribing in hospitalsCooke FJ Holmes AHInt J Antimicrob Agents 20073025-9Department of Infectious Diseases and Immunology Hammersmith Hospitals NHS Trust Imperial CollegeDu Cane Road London W12 0HS UK
The care bundle involves grouping together key elements of care for procedures and the management of specific diagnoses in order to provide a systematic method to improve and monitor the delivery of clinical care processes In short care bundles aim to ensure that all patients consistently receive the best care or treatment all of the time This approach has been successfully applied to the management of various conditions particularly in the critical care setting The Institute for Healthcare Improvements 100K lives campaign consisted of six care bundles three of which have addressed preventing hospital-acquired infection The UK Department of Healths delivery programme to reduce healthcare-associated infections (HCAIs) including methicillin-resistant Staphylococcus aureus (MRSA) includes six high-impact interventions which are care bundles to reduce HCAIs However we suggest that one key intervention is missing and consider this intervention will be increasingly important if hospitals are to address the rising incidence of Clostridium difficile to tackle antibiotic resistance and to improve patient care The missing intervention addresses the process of antibiotic prescribing We propose that the time is right to consider the application of the care bundle approach to improve the prescribing of antibiotics both for treatment and prophylaxis
The antibiotic prescribing bundle
bull Use monotherapy whenever possible for initial (empiric) treatment
bull Optimise dose and duration
bull Perform a regular risk assessment
ndash For each patient
ndash Impact of the programme
Aminoglycosides
Glycopeptides
LipopeptidesOxazolidinones
Monotherapy or
combinationCarbapenems
BLICsCephalosporins
Fluoroquinolones
Tigecycline
Empiric choice Empiric choice 2nd 3rd line Final option
Low resistance risk and minimal
complexity
Increased resistance risk
and complexity
Treatment failure
[Cef Met prophylaxis]
Not if intravascular infectionNot in VAP as monotherapy
Antibiotic choice in high-risk patients
bull Capacity to cover resistant pathogens
bull Proven efficacy in MDR infection
bull Pharmacokinetic and pharmacodynamic profile
bull Safety profile
bull Capacity not to induce lsquoovergrowthrsquo eg CDI
bull Low potential for inducible resistance
bull Capacity not to select for resistant pathogens
Should consider measures to reduce use of 3GCs FQs amp carbapenems
Increased reliance on carbapenemsmay accelerate emergence of completely resistant isolates
Fosfomycin and MDR Enterobacteriaceae
bull In two clinical studies oral treatment with fosfomycin-trometamol was clinically effective against complicated or uncomplicated lower UTIs caused by ESBL-producing E coli in 75 (938) of 80 patients
Falagas M et al Lancet Infect Dis 20101043-50
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull Italian hospital with increased prevalence of Proteus mirabilis strains producing acquired AmpC-type beta-lactamases (CBLs)
bull 43 CBL-positive isolates were obtained from hospitalised (n=22) and non-hospitalised (n=21) patients (median age 788 years) ndash usually UTIs
bull Treatment with amikacin or carbapenems was consistently effective
bull Piperacillintazobactam produced a clinical response in seven of nine cases
Luzarro F et al int J Antimicrob Agents 200933328-33
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull Italian hospital with increased prevalence of Proteus mirabilis strains producing acquired AmpC-type beta-lactamases (CBLs)
bull 43 CBL-positive isolates were obtained from hospitalised (n=22) and non-hospitalised (n=21) patients (median age 788 years) ndash usually UTIs
bull Treatment with amikacin or carbapenems was consistently effective
bull Piperacillintazobactam produced a clinical response in seven of nine cases
Luzarro F et al int J Antimicrob Agents 200933328-33
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull b-lactamndashb-lactamase inhibitor agents on patients infected with ESBL-producing strains of E coli and Klebsiella spp
bull 7 medical centres across North Americabull 148 patient records reviewedbull 30 rcvd FQ 18 carbapenem 16 pip-tazo 9 other b-
lactams 7 ampndashsul 6 aminogly 6 co-trimoxbull 83 given monotherapybull 23 rcvd pip-tazo (17 infections outside the urinary tract)bull For infections with pathogen MIC of pip-tazo lt16 mgfrasl L
successful outcome was reported in 1415 (1011 non-UTIs)bull Only 15 non-UTIs responded when pip-tazo MIC gt16 mgfrasl Lbull Meropenem therapy was successful in 24 pip-tazo resistant
infectionsGavin PJ et al int J Antimicrob Agents Chemother 2006502244-7
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull 43 episodes of E coli bacteraemia caused by ESBL-producing strains (primarily CTX-M-14)
bullbull Mortality was lower when patients were given a b-lactamndashb-
lactamase inhibitor combination or carbapenem as compared with either a cephalosporin or FQ
(9vs 35 p 005)bullbull E coli 100 susceptible to meropenem 95 to piperacillinndash
tazobactam 26 to ciprofloxacin and 0 to cephalosporins
Rodrıguez-Bano J et al Clin Infect Dis 2006431407-14
Tigecycline for MDR A baumanniiMetan G et al Clinical experience with tigecycline in the treatment of carbapenem-resistant Acinetobacter infections J Chemother 2010 Apr22(2)110-4
Gordon NC Wareham DW A review of clinical and microbiological outcomes following treatment of infections involving multidrug-resistant Acinetobacterbaumannii with tigecycline J AntimicrobChemother 2009 Apr63(4)775-80
Curcio D et al Tigecycline in the treatment of Ventilator-Associated Pneumonia experience from the Latin American Tigecycline Use Registry Infez Med 2010 Mar18(1)27-34
Tigecycline for MDR A baumanniibull Retrospective study of patients who received tigecycline for
tige-S carbapenem-R Acb-complex infections 2008-09bull 21 patients (median age 48 years) median duration tige 14 dbull 18 patients were treated with tigecycline as the sole pathogenbull Most common indication for tigecycline was SSI (VAP)bull Tigecycline was the sole antibiotic in 7 patientsbull 2 patients died within 14 days 4 died within 30 daysbull 1721 lsquohad successful clinical outcomesrsquo BUT 1421 had
microbiological failurebull Poor correlation between micro and clinical responsebull Clinical failure was more common in patients with VAPbull Patients with bacteraemia or VAP more likely to have
microbiological failureMetan G et al J Chemother 201022110-4
Colistin for MDR A baumanniibull 166 consecutive patients infected or colonised with
carbapenem- and MDR A Baumannii
bull 18 hospitals (London UK) 141 belonged to OXA-23 clone 1
bull Only colistin and tigecycline retained good in vitro activity with 994 and 819 of isolates susceptible respectively
bull 62 patients in ICU or HDU 84 (506) infected
bull Survival rates among infected and colonised patients were 68 and 67 indicating little attributable mortality
Livermore D et al Int J Antimicrob Agents 20103519-24
Colistin for MDR A baumanniibull Univariate and multivariate analyses
ndash poorer outcomes among ICU-infected patients pulmonary infection or bacteraemia
ndash trauma patients had significantly better outcomebull Outcomes varied by hospital (multivariate analysis) CASE MIXbull Poor association between outcome and therapy with colistin
(andor tigecycline)bull Patients with respiratory infection 1215 treated with
intravenous colistin alone had poor outcome compared with 18 whose therapy include nebulised colistin (P=0003)
BUT the patients receiving nebulised drug were mostly younger included trauma cases and were at a hospital with good outcomes
Livermore D et al Int J Antimicrob Agents 20103519-24
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
APACHE Acute Physiology and Chronic Health EvaluationSOFA Sequential Organ Failure Assessment
Enterococcus durans
Enterobacter cloacae
Enterococcus casseliflavus or Enterococcus gallinarum
Burkholderia cepacia
Acinetobacter baumannii
Enterococci species not determined
MRSA
Enterococcus faecalis
Infection of unknown origin
Strenotrophomonas maltophilia
VRE
Enterococcus faecium
Microorganism
1 (1)
1 (1)
1 (1) 1 (1)
1 (1)
4 (6) 4 (6)
7 (10)
11 (16)
13 (19)
15 (21)
26 (37)
Infections n ()
bull APACHE II scores 27 plusmn 10 SOFA 12 plusmn 3bull Overall mortality 30
n=70 withindication
0
10
20
30
40
50
60cIAI
cSSTI
Mixed
Other
bull Mean duration of tigecycline therapy was 9 +- 4 daysbull 76 of patients received tigecycline in combination
(64 second line)bull APACHE score and renal replacement were identified
as predictive factors for mortalitybull AUTHOR CONCLUSIONS lsquoTigecycline treatment of
critically ill SICU patients with severe sepsis or septic shock appeared to result in remarkably low mortality Tigecycline may be an important treatment option for septic patients with infections resistant to other available agentsrsquo
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
Antibiotics and risk of CDI
Evidence to supportthe restriction
of these as a controlmeasure for CDI
CDI may still occur
Need to minimise all antibiotic use polypharmacy and duration
Medium risk Low riskHigh risk
CephalosporinsClindamycin
AmpicillinamoxycillinCo-trimoxazole
MacrolidesFluoroquinolones
AminoglycosidesMetronidazole
Anti-pseudomonal penicillins +
β-lactamase inhibitorsTetracyclinesRifampicin
Vancomycin
Baines SD et al J Antimicrob Chemother 200555974-82Baines SD et al J Antimicrob Chemother 2006581062-5
Induction of C difficile toxin production
Tigecycline and C difficilebull Tigecycline is highly active (MIC=006 mgL) against C difficile
Baines SD et al J Antimicrob Chemother 2006581062-5
bull No in vitro evidence of increased risk of tigecycline-induced CDIBaines SD et al J Antimicrob Chemother 2006581062-5
bull No in vivo evidence of increased risk of tigecycline-induced CDIWilcox MH Clin Microbiol Infect 200713949-52
bull Some evidence that tigecycline could be used to treat CDI (THIS IS NOT A LICENSED INDICATION)Herpers BL et al Clin Infect Dis 2009481732-5
Lu CL et al Int J Antimicrob Agents 201035311-2
The missing care bundle antibiotic prescribing in hospitalsCooke FJ Holmes AHInt J Antimicrob Agents 20073025-9Department of Infectious Diseases and Immunology Hammersmith Hospitals NHS Trust Imperial CollegeDu Cane Road London W12 0HS UK
The care bundle involves grouping together key elements of care for procedures and the management of specific diagnoses in order to provide a systematic method to improve and monitor the delivery of clinical care processes In short care bundles aim to ensure that all patients consistently receive the best care or treatment all of the time This approach has been successfully applied to the management of various conditions particularly in the critical care setting The Institute for Healthcare Improvements 100K lives campaign consisted of six care bundles three of which have addressed preventing hospital-acquired infection The UK Department of Healths delivery programme to reduce healthcare-associated infections (HCAIs) including methicillin-resistant Staphylococcus aureus (MRSA) includes six high-impact interventions which are care bundles to reduce HCAIs However we suggest that one key intervention is missing and consider this intervention will be increasingly important if hospitals are to address the rising incidence of Clostridium difficile to tackle antibiotic resistance and to improve patient care The missing intervention addresses the process of antibiotic prescribing We propose that the time is right to consider the application of the care bundle approach to improve the prescribing of antibiotics both for treatment and prophylaxis
The antibiotic prescribing bundle
bull Use monotherapy whenever possible for initial (empiric) treatment
bull Optimise dose and duration
bull Perform a regular risk assessment
ndash For each patient
ndash Impact of the programme
Aminoglycosides
Glycopeptides
LipopeptidesOxazolidinones
Monotherapy or
combinationCarbapenems
BLICsCephalosporins
Fluoroquinolones
Tigecycline
Empiric choice Empiric choice 2nd 3rd line Final option
Low resistance risk and minimal
complexity
Increased resistance risk
and complexity
Treatment failure
[Cef Met prophylaxis]
Not if intravascular infectionNot in VAP as monotherapy
Antibiotic choice in high-risk patients
bull Capacity to cover resistant pathogens
bull Proven efficacy in MDR infection
bull Pharmacokinetic and pharmacodynamic profile
bull Safety profile
bull Capacity not to induce lsquoovergrowthrsquo eg CDI
bull Low potential for inducible resistance
bull Capacity not to select for resistant pathogens
Should consider measures to reduce use of 3GCs FQs amp carbapenems
Increased reliance on carbapenemsmay accelerate emergence of completely resistant isolates
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull Italian hospital with increased prevalence of Proteus mirabilis strains producing acquired AmpC-type beta-lactamases (CBLs)
bull 43 CBL-positive isolates were obtained from hospitalised (n=22) and non-hospitalised (n=21) patients (median age 788 years) ndash usually UTIs
bull Treatment with amikacin or carbapenems was consistently effective
bull Piperacillintazobactam produced a clinical response in seven of nine cases
Luzarro F et al int J Antimicrob Agents 200933328-33
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull Italian hospital with increased prevalence of Proteus mirabilis strains producing acquired AmpC-type beta-lactamases (CBLs)
bull 43 CBL-positive isolates were obtained from hospitalised (n=22) and non-hospitalised (n=21) patients (median age 788 years) ndash usually UTIs
bull Treatment with amikacin or carbapenems was consistently effective
bull Piperacillintazobactam produced a clinical response in seven of nine cases
Luzarro F et al int J Antimicrob Agents 200933328-33
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull b-lactamndashb-lactamase inhibitor agents on patients infected with ESBL-producing strains of E coli and Klebsiella spp
bull 7 medical centres across North Americabull 148 patient records reviewedbull 30 rcvd FQ 18 carbapenem 16 pip-tazo 9 other b-
lactams 7 ampndashsul 6 aminogly 6 co-trimoxbull 83 given monotherapybull 23 rcvd pip-tazo (17 infections outside the urinary tract)bull For infections with pathogen MIC of pip-tazo lt16 mgfrasl L
successful outcome was reported in 1415 (1011 non-UTIs)bull Only 15 non-UTIs responded when pip-tazo MIC gt16 mgfrasl Lbull Meropenem therapy was successful in 24 pip-tazo resistant
infectionsGavin PJ et al int J Antimicrob Agents Chemother 2006502244-7
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull 43 episodes of E coli bacteraemia caused by ESBL-producing strains (primarily CTX-M-14)
bullbull Mortality was lower when patients were given a b-lactamndashb-
lactamase inhibitor combination or carbapenem as compared with either a cephalosporin or FQ
(9vs 35 p 005)bullbull E coli 100 susceptible to meropenem 95 to piperacillinndash
tazobactam 26 to ciprofloxacin and 0 to cephalosporins
Rodrıguez-Bano J et al Clin Infect Dis 2006431407-14
Tigecycline for MDR A baumanniiMetan G et al Clinical experience with tigecycline in the treatment of carbapenem-resistant Acinetobacter infections J Chemother 2010 Apr22(2)110-4
Gordon NC Wareham DW A review of clinical and microbiological outcomes following treatment of infections involving multidrug-resistant Acinetobacterbaumannii with tigecycline J AntimicrobChemother 2009 Apr63(4)775-80
Curcio D et al Tigecycline in the treatment of Ventilator-Associated Pneumonia experience from the Latin American Tigecycline Use Registry Infez Med 2010 Mar18(1)27-34
Tigecycline for MDR A baumanniibull Retrospective study of patients who received tigecycline for
tige-S carbapenem-R Acb-complex infections 2008-09bull 21 patients (median age 48 years) median duration tige 14 dbull 18 patients were treated with tigecycline as the sole pathogenbull Most common indication for tigecycline was SSI (VAP)bull Tigecycline was the sole antibiotic in 7 patientsbull 2 patients died within 14 days 4 died within 30 daysbull 1721 lsquohad successful clinical outcomesrsquo BUT 1421 had
microbiological failurebull Poor correlation between micro and clinical responsebull Clinical failure was more common in patients with VAPbull Patients with bacteraemia or VAP more likely to have
microbiological failureMetan G et al J Chemother 201022110-4
Colistin for MDR A baumanniibull 166 consecutive patients infected or colonised with
carbapenem- and MDR A Baumannii
bull 18 hospitals (London UK) 141 belonged to OXA-23 clone 1
bull Only colistin and tigecycline retained good in vitro activity with 994 and 819 of isolates susceptible respectively
bull 62 patients in ICU or HDU 84 (506) infected
bull Survival rates among infected and colonised patients were 68 and 67 indicating little attributable mortality
Livermore D et al Int J Antimicrob Agents 20103519-24
Colistin for MDR A baumanniibull Univariate and multivariate analyses
ndash poorer outcomes among ICU-infected patients pulmonary infection or bacteraemia
ndash trauma patients had significantly better outcomebull Outcomes varied by hospital (multivariate analysis) CASE MIXbull Poor association between outcome and therapy with colistin
(andor tigecycline)bull Patients with respiratory infection 1215 treated with
intravenous colistin alone had poor outcome compared with 18 whose therapy include nebulised colistin (P=0003)
BUT the patients receiving nebulised drug were mostly younger included trauma cases and were at a hospital with good outcomes
Livermore D et al Int J Antimicrob Agents 20103519-24
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
APACHE Acute Physiology and Chronic Health EvaluationSOFA Sequential Organ Failure Assessment
Enterococcus durans
Enterobacter cloacae
Enterococcus casseliflavus or Enterococcus gallinarum
Burkholderia cepacia
Acinetobacter baumannii
Enterococci species not determined
MRSA
Enterococcus faecalis
Infection of unknown origin
Strenotrophomonas maltophilia
VRE
Enterococcus faecium
Microorganism
1 (1)
1 (1)
1 (1) 1 (1)
1 (1)
4 (6) 4 (6)
7 (10)
11 (16)
13 (19)
15 (21)
26 (37)
Infections n ()
bull APACHE II scores 27 plusmn 10 SOFA 12 plusmn 3bull Overall mortality 30
n=70 withindication
0
10
20
30
40
50
60cIAI
cSSTI
Mixed
Other
bull Mean duration of tigecycline therapy was 9 +- 4 daysbull 76 of patients received tigecycline in combination
(64 second line)bull APACHE score and renal replacement were identified
as predictive factors for mortalitybull AUTHOR CONCLUSIONS lsquoTigecycline treatment of
critically ill SICU patients with severe sepsis or septic shock appeared to result in remarkably low mortality Tigecycline may be an important treatment option for septic patients with infections resistant to other available agentsrsquo
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
Antibiotics and risk of CDI
Evidence to supportthe restriction
of these as a controlmeasure for CDI
CDI may still occur
Need to minimise all antibiotic use polypharmacy and duration
Medium risk Low riskHigh risk
CephalosporinsClindamycin
AmpicillinamoxycillinCo-trimoxazole
MacrolidesFluoroquinolones
AminoglycosidesMetronidazole
Anti-pseudomonal penicillins +
β-lactamase inhibitorsTetracyclinesRifampicin
Vancomycin
Baines SD et al J Antimicrob Chemother 200555974-82Baines SD et al J Antimicrob Chemother 2006581062-5
Induction of C difficile toxin production
Tigecycline and C difficilebull Tigecycline is highly active (MIC=006 mgL) against C difficile
Baines SD et al J Antimicrob Chemother 2006581062-5
bull No in vitro evidence of increased risk of tigecycline-induced CDIBaines SD et al J Antimicrob Chemother 2006581062-5
bull No in vivo evidence of increased risk of tigecycline-induced CDIWilcox MH Clin Microbiol Infect 200713949-52
bull Some evidence that tigecycline could be used to treat CDI (THIS IS NOT A LICENSED INDICATION)Herpers BL et al Clin Infect Dis 2009481732-5
Lu CL et al Int J Antimicrob Agents 201035311-2
The missing care bundle antibiotic prescribing in hospitalsCooke FJ Holmes AHInt J Antimicrob Agents 20073025-9Department of Infectious Diseases and Immunology Hammersmith Hospitals NHS Trust Imperial CollegeDu Cane Road London W12 0HS UK
The care bundle involves grouping together key elements of care for procedures and the management of specific diagnoses in order to provide a systematic method to improve and monitor the delivery of clinical care processes In short care bundles aim to ensure that all patients consistently receive the best care or treatment all of the time This approach has been successfully applied to the management of various conditions particularly in the critical care setting The Institute for Healthcare Improvements 100K lives campaign consisted of six care bundles three of which have addressed preventing hospital-acquired infection The UK Department of Healths delivery programme to reduce healthcare-associated infections (HCAIs) including methicillin-resistant Staphylococcus aureus (MRSA) includes six high-impact interventions which are care bundles to reduce HCAIs However we suggest that one key intervention is missing and consider this intervention will be increasingly important if hospitals are to address the rising incidence of Clostridium difficile to tackle antibiotic resistance and to improve patient care The missing intervention addresses the process of antibiotic prescribing We propose that the time is right to consider the application of the care bundle approach to improve the prescribing of antibiotics both for treatment and prophylaxis
The antibiotic prescribing bundle
bull Use monotherapy whenever possible for initial (empiric) treatment
bull Optimise dose and duration
bull Perform a regular risk assessment
ndash For each patient
ndash Impact of the programme
Aminoglycosides
Glycopeptides
LipopeptidesOxazolidinones
Monotherapy or
combinationCarbapenems
BLICsCephalosporins
Fluoroquinolones
Tigecycline
Empiric choice Empiric choice 2nd 3rd line Final option
Low resistance risk and minimal
complexity
Increased resistance risk
and complexity
Treatment failure
[Cef Met prophylaxis]
Not if intravascular infectionNot in VAP as monotherapy
Antibiotic choice in high-risk patients
bull Capacity to cover resistant pathogens
bull Proven efficacy in MDR infection
bull Pharmacokinetic and pharmacodynamic profile
bull Safety profile
bull Capacity not to induce lsquoovergrowthrsquo eg CDI
bull Low potential for inducible resistance
bull Capacity not to select for resistant pathogens
Should consider measures to reduce use of 3GCs FQs amp carbapenems
Increased reliance on carbapenemsmay accelerate emergence of completely resistant isolates
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull Italian hospital with increased prevalence of Proteus mirabilis strains producing acquired AmpC-type beta-lactamases (CBLs)
bull 43 CBL-positive isolates were obtained from hospitalised (n=22) and non-hospitalised (n=21) patients (median age 788 years) ndash usually UTIs
bull Treatment with amikacin or carbapenems was consistently effective
bull Piperacillintazobactam produced a clinical response in seven of nine cases
Luzarro F et al int J Antimicrob Agents 200933328-33
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull b-lactamndashb-lactamase inhibitor agents on patients infected with ESBL-producing strains of E coli and Klebsiella spp
bull 7 medical centres across North Americabull 148 patient records reviewedbull 30 rcvd FQ 18 carbapenem 16 pip-tazo 9 other b-
lactams 7 ampndashsul 6 aminogly 6 co-trimoxbull 83 given monotherapybull 23 rcvd pip-tazo (17 infections outside the urinary tract)bull For infections with pathogen MIC of pip-tazo lt16 mgfrasl L
successful outcome was reported in 1415 (1011 non-UTIs)bull Only 15 non-UTIs responded when pip-tazo MIC gt16 mgfrasl Lbull Meropenem therapy was successful in 24 pip-tazo resistant
infectionsGavin PJ et al int J Antimicrob Agents Chemother 2006502244-7
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull 43 episodes of E coli bacteraemia caused by ESBL-producing strains (primarily CTX-M-14)
bullbull Mortality was lower when patients were given a b-lactamndashb-
lactamase inhibitor combination or carbapenem as compared with either a cephalosporin or FQ
(9vs 35 p 005)bullbull E coli 100 susceptible to meropenem 95 to piperacillinndash
tazobactam 26 to ciprofloxacin and 0 to cephalosporins
Rodrıguez-Bano J et al Clin Infect Dis 2006431407-14
Tigecycline for MDR A baumanniiMetan G et al Clinical experience with tigecycline in the treatment of carbapenem-resistant Acinetobacter infections J Chemother 2010 Apr22(2)110-4
Gordon NC Wareham DW A review of clinical and microbiological outcomes following treatment of infections involving multidrug-resistant Acinetobacterbaumannii with tigecycline J AntimicrobChemother 2009 Apr63(4)775-80
Curcio D et al Tigecycline in the treatment of Ventilator-Associated Pneumonia experience from the Latin American Tigecycline Use Registry Infez Med 2010 Mar18(1)27-34
Tigecycline for MDR A baumanniibull Retrospective study of patients who received tigecycline for
tige-S carbapenem-R Acb-complex infections 2008-09bull 21 patients (median age 48 years) median duration tige 14 dbull 18 patients were treated with tigecycline as the sole pathogenbull Most common indication for tigecycline was SSI (VAP)bull Tigecycline was the sole antibiotic in 7 patientsbull 2 patients died within 14 days 4 died within 30 daysbull 1721 lsquohad successful clinical outcomesrsquo BUT 1421 had
microbiological failurebull Poor correlation between micro and clinical responsebull Clinical failure was more common in patients with VAPbull Patients with bacteraemia or VAP more likely to have
microbiological failureMetan G et al J Chemother 201022110-4
Colistin for MDR A baumanniibull 166 consecutive patients infected or colonised with
carbapenem- and MDR A Baumannii
bull 18 hospitals (London UK) 141 belonged to OXA-23 clone 1
bull Only colistin and tigecycline retained good in vitro activity with 994 and 819 of isolates susceptible respectively
bull 62 patients in ICU or HDU 84 (506) infected
bull Survival rates among infected and colonised patients were 68 and 67 indicating little attributable mortality
Livermore D et al Int J Antimicrob Agents 20103519-24
Colistin for MDR A baumanniibull Univariate and multivariate analyses
ndash poorer outcomes among ICU-infected patients pulmonary infection or bacteraemia
ndash trauma patients had significantly better outcomebull Outcomes varied by hospital (multivariate analysis) CASE MIXbull Poor association between outcome and therapy with colistin
(andor tigecycline)bull Patients with respiratory infection 1215 treated with
intravenous colistin alone had poor outcome compared with 18 whose therapy include nebulised colistin (P=0003)
BUT the patients receiving nebulised drug were mostly younger included trauma cases and were at a hospital with good outcomes
Livermore D et al Int J Antimicrob Agents 20103519-24
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
APACHE Acute Physiology and Chronic Health EvaluationSOFA Sequential Organ Failure Assessment
Enterococcus durans
Enterobacter cloacae
Enterococcus casseliflavus or Enterococcus gallinarum
Burkholderia cepacia
Acinetobacter baumannii
Enterococci species not determined
MRSA
Enterococcus faecalis
Infection of unknown origin
Strenotrophomonas maltophilia
VRE
Enterococcus faecium
Microorganism
1 (1)
1 (1)
1 (1) 1 (1)
1 (1)
4 (6) 4 (6)
7 (10)
11 (16)
13 (19)
15 (21)
26 (37)
Infections n ()
bull APACHE II scores 27 plusmn 10 SOFA 12 plusmn 3bull Overall mortality 30
n=70 withindication
0
10
20
30
40
50
60cIAI
cSSTI
Mixed
Other
bull Mean duration of tigecycline therapy was 9 +- 4 daysbull 76 of patients received tigecycline in combination
(64 second line)bull APACHE score and renal replacement were identified
as predictive factors for mortalitybull AUTHOR CONCLUSIONS lsquoTigecycline treatment of
critically ill SICU patients with severe sepsis or septic shock appeared to result in remarkably low mortality Tigecycline may be an important treatment option for septic patients with infections resistant to other available agentsrsquo
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
Antibiotics and risk of CDI
Evidence to supportthe restriction
of these as a controlmeasure for CDI
CDI may still occur
Need to minimise all antibiotic use polypharmacy and duration
Medium risk Low riskHigh risk
CephalosporinsClindamycin
AmpicillinamoxycillinCo-trimoxazole
MacrolidesFluoroquinolones
AminoglycosidesMetronidazole
Anti-pseudomonal penicillins +
β-lactamase inhibitorsTetracyclinesRifampicin
Vancomycin
Baines SD et al J Antimicrob Chemother 200555974-82Baines SD et al J Antimicrob Chemother 2006581062-5
Induction of C difficile toxin production
Tigecycline and C difficilebull Tigecycline is highly active (MIC=006 mgL) against C difficile
Baines SD et al J Antimicrob Chemother 2006581062-5
bull No in vitro evidence of increased risk of tigecycline-induced CDIBaines SD et al J Antimicrob Chemother 2006581062-5
bull No in vivo evidence of increased risk of tigecycline-induced CDIWilcox MH Clin Microbiol Infect 200713949-52
bull Some evidence that tigecycline could be used to treat CDI (THIS IS NOT A LICENSED INDICATION)Herpers BL et al Clin Infect Dis 2009481732-5
Lu CL et al Int J Antimicrob Agents 201035311-2
The missing care bundle antibiotic prescribing in hospitalsCooke FJ Holmes AHInt J Antimicrob Agents 20073025-9Department of Infectious Diseases and Immunology Hammersmith Hospitals NHS Trust Imperial CollegeDu Cane Road London W12 0HS UK
The care bundle involves grouping together key elements of care for procedures and the management of specific diagnoses in order to provide a systematic method to improve and monitor the delivery of clinical care processes In short care bundles aim to ensure that all patients consistently receive the best care or treatment all of the time This approach has been successfully applied to the management of various conditions particularly in the critical care setting The Institute for Healthcare Improvements 100K lives campaign consisted of six care bundles three of which have addressed preventing hospital-acquired infection The UK Department of Healths delivery programme to reduce healthcare-associated infections (HCAIs) including methicillin-resistant Staphylococcus aureus (MRSA) includes six high-impact interventions which are care bundles to reduce HCAIs However we suggest that one key intervention is missing and consider this intervention will be increasingly important if hospitals are to address the rising incidence of Clostridium difficile to tackle antibiotic resistance and to improve patient care The missing intervention addresses the process of antibiotic prescribing We propose that the time is right to consider the application of the care bundle approach to improve the prescribing of antibiotics both for treatment and prophylaxis
The antibiotic prescribing bundle
bull Use monotherapy whenever possible for initial (empiric) treatment
bull Optimise dose and duration
bull Perform a regular risk assessment
ndash For each patient
ndash Impact of the programme
Aminoglycosides
Glycopeptides
LipopeptidesOxazolidinones
Monotherapy or
combinationCarbapenems
BLICsCephalosporins
Fluoroquinolones
Tigecycline
Empiric choice Empiric choice 2nd 3rd line Final option
Low resistance risk and minimal
complexity
Increased resistance risk
and complexity
Treatment failure
[Cef Met prophylaxis]
Not if intravascular infectionNot in VAP as monotherapy
Antibiotic choice in high-risk patients
bull Capacity to cover resistant pathogens
bull Proven efficacy in MDR infection
bull Pharmacokinetic and pharmacodynamic profile
bull Safety profile
bull Capacity not to induce lsquoovergrowthrsquo eg CDI
bull Low potential for inducible resistance
bull Capacity not to select for resistant pathogens
Should consider measures to reduce use of 3GCs FQs amp carbapenems
Increased reliance on carbapenemsmay accelerate emergence of completely resistant isolates
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull b-lactamndashb-lactamase inhibitor agents on patients infected with ESBL-producing strains of E coli and Klebsiella spp
bull 7 medical centres across North Americabull 148 patient records reviewedbull 30 rcvd FQ 18 carbapenem 16 pip-tazo 9 other b-
lactams 7 ampndashsul 6 aminogly 6 co-trimoxbull 83 given monotherapybull 23 rcvd pip-tazo (17 infections outside the urinary tract)bull For infections with pathogen MIC of pip-tazo lt16 mgfrasl L
successful outcome was reported in 1415 (1011 non-UTIs)bull Only 15 non-UTIs responded when pip-tazo MIC gt16 mgfrasl Lbull Meropenem therapy was successful in 24 pip-tazo resistant
infectionsGavin PJ et al int J Antimicrob Agents Chemother 2006502244-7
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull 43 episodes of E coli bacteraemia caused by ESBL-producing strains (primarily CTX-M-14)
bullbull Mortality was lower when patients were given a b-lactamndashb-
lactamase inhibitor combination or carbapenem as compared with either a cephalosporin or FQ
(9vs 35 p 005)bullbull E coli 100 susceptible to meropenem 95 to piperacillinndash
tazobactam 26 to ciprofloxacin and 0 to cephalosporins
Rodrıguez-Bano J et al Clin Infect Dis 2006431407-14
Tigecycline for MDR A baumanniiMetan G et al Clinical experience with tigecycline in the treatment of carbapenem-resistant Acinetobacter infections J Chemother 2010 Apr22(2)110-4
Gordon NC Wareham DW A review of clinical and microbiological outcomes following treatment of infections involving multidrug-resistant Acinetobacterbaumannii with tigecycline J AntimicrobChemother 2009 Apr63(4)775-80
Curcio D et al Tigecycline in the treatment of Ventilator-Associated Pneumonia experience from the Latin American Tigecycline Use Registry Infez Med 2010 Mar18(1)27-34
Tigecycline for MDR A baumanniibull Retrospective study of patients who received tigecycline for
tige-S carbapenem-R Acb-complex infections 2008-09bull 21 patients (median age 48 years) median duration tige 14 dbull 18 patients were treated with tigecycline as the sole pathogenbull Most common indication for tigecycline was SSI (VAP)bull Tigecycline was the sole antibiotic in 7 patientsbull 2 patients died within 14 days 4 died within 30 daysbull 1721 lsquohad successful clinical outcomesrsquo BUT 1421 had
microbiological failurebull Poor correlation between micro and clinical responsebull Clinical failure was more common in patients with VAPbull Patients with bacteraemia or VAP more likely to have
microbiological failureMetan G et al J Chemother 201022110-4
Colistin for MDR A baumanniibull 166 consecutive patients infected or colonised with
carbapenem- and MDR A Baumannii
bull 18 hospitals (London UK) 141 belonged to OXA-23 clone 1
bull Only colistin and tigecycline retained good in vitro activity with 994 and 819 of isolates susceptible respectively
bull 62 patients in ICU or HDU 84 (506) infected
bull Survival rates among infected and colonised patients were 68 and 67 indicating little attributable mortality
Livermore D et al Int J Antimicrob Agents 20103519-24
Colistin for MDR A baumanniibull Univariate and multivariate analyses
ndash poorer outcomes among ICU-infected patients pulmonary infection or bacteraemia
ndash trauma patients had significantly better outcomebull Outcomes varied by hospital (multivariate analysis) CASE MIXbull Poor association between outcome and therapy with colistin
(andor tigecycline)bull Patients with respiratory infection 1215 treated with
intravenous colistin alone had poor outcome compared with 18 whose therapy include nebulised colistin (P=0003)
BUT the patients receiving nebulised drug were mostly younger included trauma cases and were at a hospital with good outcomes
Livermore D et al Int J Antimicrob Agents 20103519-24
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
APACHE Acute Physiology and Chronic Health EvaluationSOFA Sequential Organ Failure Assessment
Enterococcus durans
Enterobacter cloacae
Enterococcus casseliflavus or Enterococcus gallinarum
Burkholderia cepacia
Acinetobacter baumannii
Enterococci species not determined
MRSA
Enterococcus faecalis
Infection of unknown origin
Strenotrophomonas maltophilia
VRE
Enterococcus faecium
Microorganism
1 (1)
1 (1)
1 (1) 1 (1)
1 (1)
4 (6) 4 (6)
7 (10)
11 (16)
13 (19)
15 (21)
26 (37)
Infections n ()
bull APACHE II scores 27 plusmn 10 SOFA 12 plusmn 3bull Overall mortality 30
n=70 withindication
0
10
20
30
40
50
60cIAI
cSSTI
Mixed
Other
bull Mean duration of tigecycline therapy was 9 +- 4 daysbull 76 of patients received tigecycline in combination
(64 second line)bull APACHE score and renal replacement were identified
as predictive factors for mortalitybull AUTHOR CONCLUSIONS lsquoTigecycline treatment of
critically ill SICU patients with severe sepsis or septic shock appeared to result in remarkably low mortality Tigecycline may be an important treatment option for septic patients with infections resistant to other available agentsrsquo
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
Antibiotics and risk of CDI
Evidence to supportthe restriction
of these as a controlmeasure for CDI
CDI may still occur
Need to minimise all antibiotic use polypharmacy and duration
Medium risk Low riskHigh risk
CephalosporinsClindamycin
AmpicillinamoxycillinCo-trimoxazole
MacrolidesFluoroquinolones
AminoglycosidesMetronidazole
Anti-pseudomonal penicillins +
β-lactamase inhibitorsTetracyclinesRifampicin
Vancomycin
Baines SD et al J Antimicrob Chemother 200555974-82Baines SD et al J Antimicrob Chemother 2006581062-5
Induction of C difficile toxin production
Tigecycline and C difficilebull Tigecycline is highly active (MIC=006 mgL) against C difficile
Baines SD et al J Antimicrob Chemother 2006581062-5
bull No in vitro evidence of increased risk of tigecycline-induced CDIBaines SD et al J Antimicrob Chemother 2006581062-5
bull No in vivo evidence of increased risk of tigecycline-induced CDIWilcox MH Clin Microbiol Infect 200713949-52
bull Some evidence that tigecycline could be used to treat CDI (THIS IS NOT A LICENSED INDICATION)Herpers BL et al Clin Infect Dis 2009481732-5
Lu CL et al Int J Antimicrob Agents 201035311-2
The missing care bundle antibiotic prescribing in hospitalsCooke FJ Holmes AHInt J Antimicrob Agents 20073025-9Department of Infectious Diseases and Immunology Hammersmith Hospitals NHS Trust Imperial CollegeDu Cane Road London W12 0HS UK
The care bundle involves grouping together key elements of care for procedures and the management of specific diagnoses in order to provide a systematic method to improve and monitor the delivery of clinical care processes In short care bundles aim to ensure that all patients consistently receive the best care or treatment all of the time This approach has been successfully applied to the management of various conditions particularly in the critical care setting The Institute for Healthcare Improvements 100K lives campaign consisted of six care bundles three of which have addressed preventing hospital-acquired infection The UK Department of Healths delivery programme to reduce healthcare-associated infections (HCAIs) including methicillin-resistant Staphylococcus aureus (MRSA) includes six high-impact interventions which are care bundles to reduce HCAIs However we suggest that one key intervention is missing and consider this intervention will be increasingly important if hospitals are to address the rising incidence of Clostridium difficile to tackle antibiotic resistance and to improve patient care The missing intervention addresses the process of antibiotic prescribing We propose that the time is right to consider the application of the care bundle approach to improve the prescribing of antibiotics both for treatment and prophylaxis
The antibiotic prescribing bundle
bull Use monotherapy whenever possible for initial (empiric) treatment
bull Optimise dose and duration
bull Perform a regular risk assessment
ndash For each patient
ndash Impact of the programme
Aminoglycosides
Glycopeptides
LipopeptidesOxazolidinones
Monotherapy or
combinationCarbapenems
BLICsCephalosporins
Fluoroquinolones
Tigecycline
Empiric choice Empiric choice 2nd 3rd line Final option
Low resistance risk and minimal
complexity
Increased resistance risk
and complexity
Treatment failure
[Cef Met prophylaxis]
Not if intravascular infectionNot in VAP as monotherapy
Antibiotic choice in high-risk patients
bull Capacity to cover resistant pathogens
bull Proven efficacy in MDR infection
bull Pharmacokinetic and pharmacodynamic profile
bull Safety profile
bull Capacity not to induce lsquoovergrowthrsquo eg CDI
bull Low potential for inducible resistance
bull Capacity not to select for resistant pathogens
Should consider measures to reduce use of 3GCs FQs amp carbapenems
Increased reliance on carbapenemsmay accelerate emergence of completely resistant isolates
Piperacillin-tazobactam and MDR Enterobacteriaceae
bull 43 episodes of E coli bacteraemia caused by ESBL-producing strains (primarily CTX-M-14)
bullbull Mortality was lower when patients were given a b-lactamndashb-
lactamase inhibitor combination or carbapenem as compared with either a cephalosporin or FQ
(9vs 35 p 005)bullbull E coli 100 susceptible to meropenem 95 to piperacillinndash
tazobactam 26 to ciprofloxacin and 0 to cephalosporins
Rodrıguez-Bano J et al Clin Infect Dis 2006431407-14
Tigecycline for MDR A baumanniiMetan G et al Clinical experience with tigecycline in the treatment of carbapenem-resistant Acinetobacter infections J Chemother 2010 Apr22(2)110-4
Gordon NC Wareham DW A review of clinical and microbiological outcomes following treatment of infections involving multidrug-resistant Acinetobacterbaumannii with tigecycline J AntimicrobChemother 2009 Apr63(4)775-80
Curcio D et al Tigecycline in the treatment of Ventilator-Associated Pneumonia experience from the Latin American Tigecycline Use Registry Infez Med 2010 Mar18(1)27-34
Tigecycline for MDR A baumanniibull Retrospective study of patients who received tigecycline for
tige-S carbapenem-R Acb-complex infections 2008-09bull 21 patients (median age 48 years) median duration tige 14 dbull 18 patients were treated with tigecycline as the sole pathogenbull Most common indication for tigecycline was SSI (VAP)bull Tigecycline was the sole antibiotic in 7 patientsbull 2 patients died within 14 days 4 died within 30 daysbull 1721 lsquohad successful clinical outcomesrsquo BUT 1421 had
microbiological failurebull Poor correlation between micro and clinical responsebull Clinical failure was more common in patients with VAPbull Patients with bacteraemia or VAP more likely to have
microbiological failureMetan G et al J Chemother 201022110-4
Colistin for MDR A baumanniibull 166 consecutive patients infected or colonised with
carbapenem- and MDR A Baumannii
bull 18 hospitals (London UK) 141 belonged to OXA-23 clone 1
bull Only colistin and tigecycline retained good in vitro activity with 994 and 819 of isolates susceptible respectively
bull 62 patients in ICU or HDU 84 (506) infected
bull Survival rates among infected and colonised patients were 68 and 67 indicating little attributable mortality
Livermore D et al Int J Antimicrob Agents 20103519-24
Colistin for MDR A baumanniibull Univariate and multivariate analyses
ndash poorer outcomes among ICU-infected patients pulmonary infection or bacteraemia
ndash trauma patients had significantly better outcomebull Outcomes varied by hospital (multivariate analysis) CASE MIXbull Poor association between outcome and therapy with colistin
(andor tigecycline)bull Patients with respiratory infection 1215 treated with
intravenous colistin alone had poor outcome compared with 18 whose therapy include nebulised colistin (P=0003)
BUT the patients receiving nebulised drug were mostly younger included trauma cases and were at a hospital with good outcomes
Livermore D et al Int J Antimicrob Agents 20103519-24
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
APACHE Acute Physiology and Chronic Health EvaluationSOFA Sequential Organ Failure Assessment
Enterococcus durans
Enterobacter cloacae
Enterococcus casseliflavus or Enterococcus gallinarum
Burkholderia cepacia
Acinetobacter baumannii
Enterococci species not determined
MRSA
Enterococcus faecalis
Infection of unknown origin
Strenotrophomonas maltophilia
VRE
Enterococcus faecium
Microorganism
1 (1)
1 (1)
1 (1) 1 (1)
1 (1)
4 (6) 4 (6)
7 (10)
11 (16)
13 (19)
15 (21)
26 (37)
Infections n ()
bull APACHE II scores 27 plusmn 10 SOFA 12 plusmn 3bull Overall mortality 30
n=70 withindication
0
10
20
30
40
50
60cIAI
cSSTI
Mixed
Other
bull Mean duration of tigecycline therapy was 9 +- 4 daysbull 76 of patients received tigecycline in combination
(64 second line)bull APACHE score and renal replacement were identified
as predictive factors for mortalitybull AUTHOR CONCLUSIONS lsquoTigecycline treatment of
critically ill SICU patients with severe sepsis or septic shock appeared to result in remarkably low mortality Tigecycline may be an important treatment option for septic patients with infections resistant to other available agentsrsquo
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
Antibiotics and risk of CDI
Evidence to supportthe restriction
of these as a controlmeasure for CDI
CDI may still occur
Need to minimise all antibiotic use polypharmacy and duration
Medium risk Low riskHigh risk
CephalosporinsClindamycin
AmpicillinamoxycillinCo-trimoxazole
MacrolidesFluoroquinolones
AminoglycosidesMetronidazole
Anti-pseudomonal penicillins +
β-lactamase inhibitorsTetracyclinesRifampicin
Vancomycin
Baines SD et al J Antimicrob Chemother 200555974-82Baines SD et al J Antimicrob Chemother 2006581062-5
Induction of C difficile toxin production
Tigecycline and C difficilebull Tigecycline is highly active (MIC=006 mgL) against C difficile
Baines SD et al J Antimicrob Chemother 2006581062-5
bull No in vitro evidence of increased risk of tigecycline-induced CDIBaines SD et al J Antimicrob Chemother 2006581062-5
bull No in vivo evidence of increased risk of tigecycline-induced CDIWilcox MH Clin Microbiol Infect 200713949-52
bull Some evidence that tigecycline could be used to treat CDI (THIS IS NOT A LICENSED INDICATION)Herpers BL et al Clin Infect Dis 2009481732-5
Lu CL et al Int J Antimicrob Agents 201035311-2
The missing care bundle antibiotic prescribing in hospitalsCooke FJ Holmes AHInt J Antimicrob Agents 20073025-9Department of Infectious Diseases and Immunology Hammersmith Hospitals NHS Trust Imperial CollegeDu Cane Road London W12 0HS UK
The care bundle involves grouping together key elements of care for procedures and the management of specific diagnoses in order to provide a systematic method to improve and monitor the delivery of clinical care processes In short care bundles aim to ensure that all patients consistently receive the best care or treatment all of the time This approach has been successfully applied to the management of various conditions particularly in the critical care setting The Institute for Healthcare Improvements 100K lives campaign consisted of six care bundles three of which have addressed preventing hospital-acquired infection The UK Department of Healths delivery programme to reduce healthcare-associated infections (HCAIs) including methicillin-resistant Staphylococcus aureus (MRSA) includes six high-impact interventions which are care bundles to reduce HCAIs However we suggest that one key intervention is missing and consider this intervention will be increasingly important if hospitals are to address the rising incidence of Clostridium difficile to tackle antibiotic resistance and to improve patient care The missing intervention addresses the process of antibiotic prescribing We propose that the time is right to consider the application of the care bundle approach to improve the prescribing of antibiotics both for treatment and prophylaxis
The antibiotic prescribing bundle
bull Use monotherapy whenever possible for initial (empiric) treatment
bull Optimise dose and duration
bull Perform a regular risk assessment
ndash For each patient
ndash Impact of the programme
Aminoglycosides
Glycopeptides
LipopeptidesOxazolidinones
Monotherapy or
combinationCarbapenems
BLICsCephalosporins
Fluoroquinolones
Tigecycline
Empiric choice Empiric choice 2nd 3rd line Final option
Low resistance risk and minimal
complexity
Increased resistance risk
and complexity
Treatment failure
[Cef Met prophylaxis]
Not if intravascular infectionNot in VAP as monotherapy
Antibiotic choice in high-risk patients
bull Capacity to cover resistant pathogens
bull Proven efficacy in MDR infection
bull Pharmacokinetic and pharmacodynamic profile
bull Safety profile
bull Capacity not to induce lsquoovergrowthrsquo eg CDI
bull Low potential for inducible resistance
bull Capacity not to select for resistant pathogens
Should consider measures to reduce use of 3GCs FQs amp carbapenems
Increased reliance on carbapenemsmay accelerate emergence of completely resistant isolates
Tigecycline for MDR A baumanniiMetan G et al Clinical experience with tigecycline in the treatment of carbapenem-resistant Acinetobacter infections J Chemother 2010 Apr22(2)110-4
Gordon NC Wareham DW A review of clinical and microbiological outcomes following treatment of infections involving multidrug-resistant Acinetobacterbaumannii with tigecycline J AntimicrobChemother 2009 Apr63(4)775-80
Curcio D et al Tigecycline in the treatment of Ventilator-Associated Pneumonia experience from the Latin American Tigecycline Use Registry Infez Med 2010 Mar18(1)27-34
Tigecycline for MDR A baumanniibull Retrospective study of patients who received tigecycline for
tige-S carbapenem-R Acb-complex infections 2008-09bull 21 patients (median age 48 years) median duration tige 14 dbull 18 patients were treated with tigecycline as the sole pathogenbull Most common indication for tigecycline was SSI (VAP)bull Tigecycline was the sole antibiotic in 7 patientsbull 2 patients died within 14 days 4 died within 30 daysbull 1721 lsquohad successful clinical outcomesrsquo BUT 1421 had
microbiological failurebull Poor correlation between micro and clinical responsebull Clinical failure was more common in patients with VAPbull Patients with bacteraemia or VAP more likely to have
microbiological failureMetan G et al J Chemother 201022110-4
Colistin for MDR A baumanniibull 166 consecutive patients infected or colonised with
carbapenem- and MDR A Baumannii
bull 18 hospitals (London UK) 141 belonged to OXA-23 clone 1
bull Only colistin and tigecycline retained good in vitro activity with 994 and 819 of isolates susceptible respectively
bull 62 patients in ICU or HDU 84 (506) infected
bull Survival rates among infected and colonised patients were 68 and 67 indicating little attributable mortality
Livermore D et al Int J Antimicrob Agents 20103519-24
Colistin for MDR A baumanniibull Univariate and multivariate analyses
ndash poorer outcomes among ICU-infected patients pulmonary infection or bacteraemia
ndash trauma patients had significantly better outcomebull Outcomes varied by hospital (multivariate analysis) CASE MIXbull Poor association between outcome and therapy with colistin
(andor tigecycline)bull Patients with respiratory infection 1215 treated with
intravenous colistin alone had poor outcome compared with 18 whose therapy include nebulised colistin (P=0003)
BUT the patients receiving nebulised drug were mostly younger included trauma cases and were at a hospital with good outcomes
Livermore D et al Int J Antimicrob Agents 20103519-24
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
APACHE Acute Physiology and Chronic Health EvaluationSOFA Sequential Organ Failure Assessment
Enterococcus durans
Enterobacter cloacae
Enterococcus casseliflavus or Enterococcus gallinarum
Burkholderia cepacia
Acinetobacter baumannii
Enterococci species not determined
MRSA
Enterococcus faecalis
Infection of unknown origin
Strenotrophomonas maltophilia
VRE
Enterococcus faecium
Microorganism
1 (1)
1 (1)
1 (1) 1 (1)
1 (1)
4 (6) 4 (6)
7 (10)
11 (16)
13 (19)
15 (21)
26 (37)
Infections n ()
bull APACHE II scores 27 plusmn 10 SOFA 12 plusmn 3bull Overall mortality 30
n=70 withindication
0
10
20
30
40
50
60cIAI
cSSTI
Mixed
Other
bull Mean duration of tigecycline therapy was 9 +- 4 daysbull 76 of patients received tigecycline in combination
(64 second line)bull APACHE score and renal replacement were identified
as predictive factors for mortalitybull AUTHOR CONCLUSIONS lsquoTigecycline treatment of
critically ill SICU patients with severe sepsis or septic shock appeared to result in remarkably low mortality Tigecycline may be an important treatment option for septic patients with infections resistant to other available agentsrsquo
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
Antibiotics and risk of CDI
Evidence to supportthe restriction
of these as a controlmeasure for CDI
CDI may still occur
Need to minimise all antibiotic use polypharmacy and duration
Medium risk Low riskHigh risk
CephalosporinsClindamycin
AmpicillinamoxycillinCo-trimoxazole
MacrolidesFluoroquinolones
AminoglycosidesMetronidazole
Anti-pseudomonal penicillins +
β-lactamase inhibitorsTetracyclinesRifampicin
Vancomycin
Baines SD et al J Antimicrob Chemother 200555974-82Baines SD et al J Antimicrob Chemother 2006581062-5
Induction of C difficile toxin production
Tigecycline and C difficilebull Tigecycline is highly active (MIC=006 mgL) against C difficile
Baines SD et al J Antimicrob Chemother 2006581062-5
bull No in vitro evidence of increased risk of tigecycline-induced CDIBaines SD et al J Antimicrob Chemother 2006581062-5
bull No in vivo evidence of increased risk of tigecycline-induced CDIWilcox MH Clin Microbiol Infect 200713949-52
bull Some evidence that tigecycline could be used to treat CDI (THIS IS NOT A LICENSED INDICATION)Herpers BL et al Clin Infect Dis 2009481732-5
Lu CL et al Int J Antimicrob Agents 201035311-2
The missing care bundle antibiotic prescribing in hospitalsCooke FJ Holmes AHInt J Antimicrob Agents 20073025-9Department of Infectious Diseases and Immunology Hammersmith Hospitals NHS Trust Imperial CollegeDu Cane Road London W12 0HS UK
The care bundle involves grouping together key elements of care for procedures and the management of specific diagnoses in order to provide a systematic method to improve and monitor the delivery of clinical care processes In short care bundles aim to ensure that all patients consistently receive the best care or treatment all of the time This approach has been successfully applied to the management of various conditions particularly in the critical care setting The Institute for Healthcare Improvements 100K lives campaign consisted of six care bundles three of which have addressed preventing hospital-acquired infection The UK Department of Healths delivery programme to reduce healthcare-associated infections (HCAIs) including methicillin-resistant Staphylococcus aureus (MRSA) includes six high-impact interventions which are care bundles to reduce HCAIs However we suggest that one key intervention is missing and consider this intervention will be increasingly important if hospitals are to address the rising incidence of Clostridium difficile to tackle antibiotic resistance and to improve patient care The missing intervention addresses the process of antibiotic prescribing We propose that the time is right to consider the application of the care bundle approach to improve the prescribing of antibiotics both for treatment and prophylaxis
The antibiotic prescribing bundle
bull Use monotherapy whenever possible for initial (empiric) treatment
bull Optimise dose and duration
bull Perform a regular risk assessment
ndash For each patient
ndash Impact of the programme
Aminoglycosides
Glycopeptides
LipopeptidesOxazolidinones
Monotherapy or
combinationCarbapenems
BLICsCephalosporins
Fluoroquinolones
Tigecycline
Empiric choice Empiric choice 2nd 3rd line Final option
Low resistance risk and minimal
complexity
Increased resistance risk
and complexity
Treatment failure
[Cef Met prophylaxis]
Not if intravascular infectionNot in VAP as monotherapy
Antibiotic choice in high-risk patients
bull Capacity to cover resistant pathogens
bull Proven efficacy in MDR infection
bull Pharmacokinetic and pharmacodynamic profile
bull Safety profile
bull Capacity not to induce lsquoovergrowthrsquo eg CDI
bull Low potential for inducible resistance
bull Capacity not to select for resistant pathogens
Should consider measures to reduce use of 3GCs FQs amp carbapenems
Increased reliance on carbapenemsmay accelerate emergence of completely resistant isolates
Tigecycline for MDR A baumanniibull Retrospective study of patients who received tigecycline for
tige-S carbapenem-R Acb-complex infections 2008-09bull 21 patients (median age 48 years) median duration tige 14 dbull 18 patients were treated with tigecycline as the sole pathogenbull Most common indication for tigecycline was SSI (VAP)bull Tigecycline was the sole antibiotic in 7 patientsbull 2 patients died within 14 days 4 died within 30 daysbull 1721 lsquohad successful clinical outcomesrsquo BUT 1421 had
microbiological failurebull Poor correlation between micro and clinical responsebull Clinical failure was more common in patients with VAPbull Patients with bacteraemia or VAP more likely to have
microbiological failureMetan G et al J Chemother 201022110-4
Colistin for MDR A baumanniibull 166 consecutive patients infected or colonised with
carbapenem- and MDR A Baumannii
bull 18 hospitals (London UK) 141 belonged to OXA-23 clone 1
bull Only colistin and tigecycline retained good in vitro activity with 994 and 819 of isolates susceptible respectively
bull 62 patients in ICU or HDU 84 (506) infected
bull Survival rates among infected and colonised patients were 68 and 67 indicating little attributable mortality
Livermore D et al Int J Antimicrob Agents 20103519-24
Colistin for MDR A baumanniibull Univariate and multivariate analyses
ndash poorer outcomes among ICU-infected patients pulmonary infection or bacteraemia
ndash trauma patients had significantly better outcomebull Outcomes varied by hospital (multivariate analysis) CASE MIXbull Poor association between outcome and therapy with colistin
(andor tigecycline)bull Patients with respiratory infection 1215 treated with
intravenous colistin alone had poor outcome compared with 18 whose therapy include nebulised colistin (P=0003)
BUT the patients receiving nebulised drug were mostly younger included trauma cases and were at a hospital with good outcomes
Livermore D et al Int J Antimicrob Agents 20103519-24
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
APACHE Acute Physiology and Chronic Health EvaluationSOFA Sequential Organ Failure Assessment
Enterococcus durans
Enterobacter cloacae
Enterococcus casseliflavus or Enterococcus gallinarum
Burkholderia cepacia
Acinetobacter baumannii
Enterococci species not determined
MRSA
Enterococcus faecalis
Infection of unknown origin
Strenotrophomonas maltophilia
VRE
Enterococcus faecium
Microorganism
1 (1)
1 (1)
1 (1) 1 (1)
1 (1)
4 (6) 4 (6)
7 (10)
11 (16)
13 (19)
15 (21)
26 (37)
Infections n ()
bull APACHE II scores 27 plusmn 10 SOFA 12 plusmn 3bull Overall mortality 30
n=70 withindication
0
10
20
30
40
50
60cIAI
cSSTI
Mixed
Other
bull Mean duration of tigecycline therapy was 9 +- 4 daysbull 76 of patients received tigecycline in combination
(64 second line)bull APACHE score and renal replacement were identified
as predictive factors for mortalitybull AUTHOR CONCLUSIONS lsquoTigecycline treatment of
critically ill SICU patients with severe sepsis or septic shock appeared to result in remarkably low mortality Tigecycline may be an important treatment option for septic patients with infections resistant to other available agentsrsquo
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
Antibiotics and risk of CDI
Evidence to supportthe restriction
of these as a controlmeasure for CDI
CDI may still occur
Need to minimise all antibiotic use polypharmacy and duration
Medium risk Low riskHigh risk
CephalosporinsClindamycin
AmpicillinamoxycillinCo-trimoxazole
MacrolidesFluoroquinolones
AminoglycosidesMetronidazole
Anti-pseudomonal penicillins +
β-lactamase inhibitorsTetracyclinesRifampicin
Vancomycin
Baines SD et al J Antimicrob Chemother 200555974-82Baines SD et al J Antimicrob Chemother 2006581062-5
Induction of C difficile toxin production
Tigecycline and C difficilebull Tigecycline is highly active (MIC=006 mgL) against C difficile
Baines SD et al J Antimicrob Chemother 2006581062-5
bull No in vitro evidence of increased risk of tigecycline-induced CDIBaines SD et al J Antimicrob Chemother 2006581062-5
bull No in vivo evidence of increased risk of tigecycline-induced CDIWilcox MH Clin Microbiol Infect 200713949-52
bull Some evidence that tigecycline could be used to treat CDI (THIS IS NOT A LICENSED INDICATION)Herpers BL et al Clin Infect Dis 2009481732-5
Lu CL et al Int J Antimicrob Agents 201035311-2
The missing care bundle antibiotic prescribing in hospitalsCooke FJ Holmes AHInt J Antimicrob Agents 20073025-9Department of Infectious Diseases and Immunology Hammersmith Hospitals NHS Trust Imperial CollegeDu Cane Road London W12 0HS UK
The care bundle involves grouping together key elements of care for procedures and the management of specific diagnoses in order to provide a systematic method to improve and monitor the delivery of clinical care processes In short care bundles aim to ensure that all patients consistently receive the best care or treatment all of the time This approach has been successfully applied to the management of various conditions particularly in the critical care setting The Institute for Healthcare Improvements 100K lives campaign consisted of six care bundles three of which have addressed preventing hospital-acquired infection The UK Department of Healths delivery programme to reduce healthcare-associated infections (HCAIs) including methicillin-resistant Staphylococcus aureus (MRSA) includes six high-impact interventions which are care bundles to reduce HCAIs However we suggest that one key intervention is missing and consider this intervention will be increasingly important if hospitals are to address the rising incidence of Clostridium difficile to tackle antibiotic resistance and to improve patient care The missing intervention addresses the process of antibiotic prescribing We propose that the time is right to consider the application of the care bundle approach to improve the prescribing of antibiotics both for treatment and prophylaxis
The antibiotic prescribing bundle
bull Use monotherapy whenever possible for initial (empiric) treatment
bull Optimise dose and duration
bull Perform a regular risk assessment
ndash For each patient
ndash Impact of the programme
Aminoglycosides
Glycopeptides
LipopeptidesOxazolidinones
Monotherapy or
combinationCarbapenems
BLICsCephalosporins
Fluoroquinolones
Tigecycline
Empiric choice Empiric choice 2nd 3rd line Final option
Low resistance risk and minimal
complexity
Increased resistance risk
and complexity
Treatment failure
[Cef Met prophylaxis]
Not if intravascular infectionNot in VAP as monotherapy
Antibiotic choice in high-risk patients
bull Capacity to cover resistant pathogens
bull Proven efficacy in MDR infection
bull Pharmacokinetic and pharmacodynamic profile
bull Safety profile
bull Capacity not to induce lsquoovergrowthrsquo eg CDI
bull Low potential for inducible resistance
bull Capacity not to select for resistant pathogens
Should consider measures to reduce use of 3GCs FQs amp carbapenems
Increased reliance on carbapenemsmay accelerate emergence of completely resistant isolates
Colistin for MDR A baumanniibull 166 consecutive patients infected or colonised with
carbapenem- and MDR A Baumannii
bull 18 hospitals (London UK) 141 belonged to OXA-23 clone 1
bull Only colistin and tigecycline retained good in vitro activity with 994 and 819 of isolates susceptible respectively
bull 62 patients in ICU or HDU 84 (506) infected
bull Survival rates among infected and colonised patients were 68 and 67 indicating little attributable mortality
Livermore D et al Int J Antimicrob Agents 20103519-24
Colistin for MDR A baumanniibull Univariate and multivariate analyses
ndash poorer outcomes among ICU-infected patients pulmonary infection or bacteraemia
ndash trauma patients had significantly better outcomebull Outcomes varied by hospital (multivariate analysis) CASE MIXbull Poor association between outcome and therapy with colistin
(andor tigecycline)bull Patients with respiratory infection 1215 treated with
intravenous colistin alone had poor outcome compared with 18 whose therapy include nebulised colistin (P=0003)
BUT the patients receiving nebulised drug were mostly younger included trauma cases and were at a hospital with good outcomes
Livermore D et al Int J Antimicrob Agents 20103519-24
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
APACHE Acute Physiology and Chronic Health EvaluationSOFA Sequential Organ Failure Assessment
Enterococcus durans
Enterobacter cloacae
Enterococcus casseliflavus or Enterococcus gallinarum
Burkholderia cepacia
Acinetobacter baumannii
Enterococci species not determined
MRSA
Enterococcus faecalis
Infection of unknown origin
Strenotrophomonas maltophilia
VRE
Enterococcus faecium
Microorganism
1 (1)
1 (1)
1 (1) 1 (1)
1 (1)
4 (6) 4 (6)
7 (10)
11 (16)
13 (19)
15 (21)
26 (37)
Infections n ()
bull APACHE II scores 27 plusmn 10 SOFA 12 plusmn 3bull Overall mortality 30
n=70 withindication
0
10
20
30
40
50
60cIAI
cSSTI
Mixed
Other
bull Mean duration of tigecycline therapy was 9 +- 4 daysbull 76 of patients received tigecycline in combination
(64 second line)bull APACHE score and renal replacement were identified
as predictive factors for mortalitybull AUTHOR CONCLUSIONS lsquoTigecycline treatment of
critically ill SICU patients with severe sepsis or septic shock appeared to result in remarkably low mortality Tigecycline may be an important treatment option for septic patients with infections resistant to other available agentsrsquo
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
Antibiotics and risk of CDI
Evidence to supportthe restriction
of these as a controlmeasure for CDI
CDI may still occur
Need to minimise all antibiotic use polypharmacy and duration
Medium risk Low riskHigh risk
CephalosporinsClindamycin
AmpicillinamoxycillinCo-trimoxazole
MacrolidesFluoroquinolones
AminoglycosidesMetronidazole
Anti-pseudomonal penicillins +
β-lactamase inhibitorsTetracyclinesRifampicin
Vancomycin
Baines SD et al J Antimicrob Chemother 200555974-82Baines SD et al J Antimicrob Chemother 2006581062-5
Induction of C difficile toxin production
Tigecycline and C difficilebull Tigecycline is highly active (MIC=006 mgL) against C difficile
Baines SD et al J Antimicrob Chemother 2006581062-5
bull No in vitro evidence of increased risk of tigecycline-induced CDIBaines SD et al J Antimicrob Chemother 2006581062-5
bull No in vivo evidence of increased risk of tigecycline-induced CDIWilcox MH Clin Microbiol Infect 200713949-52
bull Some evidence that tigecycline could be used to treat CDI (THIS IS NOT A LICENSED INDICATION)Herpers BL et al Clin Infect Dis 2009481732-5
Lu CL et al Int J Antimicrob Agents 201035311-2
The missing care bundle antibiotic prescribing in hospitalsCooke FJ Holmes AHInt J Antimicrob Agents 20073025-9Department of Infectious Diseases and Immunology Hammersmith Hospitals NHS Trust Imperial CollegeDu Cane Road London W12 0HS UK
The care bundle involves grouping together key elements of care for procedures and the management of specific diagnoses in order to provide a systematic method to improve and monitor the delivery of clinical care processes In short care bundles aim to ensure that all patients consistently receive the best care or treatment all of the time This approach has been successfully applied to the management of various conditions particularly in the critical care setting The Institute for Healthcare Improvements 100K lives campaign consisted of six care bundles three of which have addressed preventing hospital-acquired infection The UK Department of Healths delivery programme to reduce healthcare-associated infections (HCAIs) including methicillin-resistant Staphylococcus aureus (MRSA) includes six high-impact interventions which are care bundles to reduce HCAIs However we suggest that one key intervention is missing and consider this intervention will be increasingly important if hospitals are to address the rising incidence of Clostridium difficile to tackle antibiotic resistance and to improve patient care The missing intervention addresses the process of antibiotic prescribing We propose that the time is right to consider the application of the care bundle approach to improve the prescribing of antibiotics both for treatment and prophylaxis
The antibiotic prescribing bundle
bull Use monotherapy whenever possible for initial (empiric) treatment
bull Optimise dose and duration
bull Perform a regular risk assessment
ndash For each patient
ndash Impact of the programme
Aminoglycosides
Glycopeptides
LipopeptidesOxazolidinones
Monotherapy or
combinationCarbapenems
BLICsCephalosporins
Fluoroquinolones
Tigecycline
Empiric choice Empiric choice 2nd 3rd line Final option
Low resistance risk and minimal
complexity
Increased resistance risk
and complexity
Treatment failure
[Cef Met prophylaxis]
Not if intravascular infectionNot in VAP as monotherapy
Antibiotic choice in high-risk patients
bull Capacity to cover resistant pathogens
bull Proven efficacy in MDR infection
bull Pharmacokinetic and pharmacodynamic profile
bull Safety profile
bull Capacity not to induce lsquoovergrowthrsquo eg CDI
bull Low potential for inducible resistance
bull Capacity not to select for resistant pathogens
Should consider measures to reduce use of 3GCs FQs amp carbapenems
Increased reliance on carbapenemsmay accelerate emergence of completely resistant isolates
Colistin for MDR A baumanniibull Univariate and multivariate analyses
ndash poorer outcomes among ICU-infected patients pulmonary infection or bacteraemia
ndash trauma patients had significantly better outcomebull Outcomes varied by hospital (multivariate analysis) CASE MIXbull Poor association between outcome and therapy with colistin
(andor tigecycline)bull Patients with respiratory infection 1215 treated with
intravenous colistin alone had poor outcome compared with 18 whose therapy include nebulised colistin (P=0003)
BUT the patients receiving nebulised drug were mostly younger included trauma cases and were at a hospital with good outcomes
Livermore D et al Int J Antimicrob Agents 20103519-24
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
APACHE Acute Physiology and Chronic Health EvaluationSOFA Sequential Organ Failure Assessment
Enterococcus durans
Enterobacter cloacae
Enterococcus casseliflavus or Enterococcus gallinarum
Burkholderia cepacia
Acinetobacter baumannii
Enterococci species not determined
MRSA
Enterococcus faecalis
Infection of unknown origin
Strenotrophomonas maltophilia
VRE
Enterococcus faecium
Microorganism
1 (1)
1 (1)
1 (1) 1 (1)
1 (1)
4 (6) 4 (6)
7 (10)
11 (16)
13 (19)
15 (21)
26 (37)
Infections n ()
bull APACHE II scores 27 plusmn 10 SOFA 12 plusmn 3bull Overall mortality 30
n=70 withindication
0
10
20
30
40
50
60cIAI
cSSTI
Mixed
Other
bull Mean duration of tigecycline therapy was 9 +- 4 daysbull 76 of patients received tigecycline in combination
(64 second line)bull APACHE score and renal replacement were identified
as predictive factors for mortalitybull AUTHOR CONCLUSIONS lsquoTigecycline treatment of
critically ill SICU patients with severe sepsis or septic shock appeared to result in remarkably low mortality Tigecycline may be an important treatment option for septic patients with infections resistant to other available agentsrsquo
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
Antibiotics and risk of CDI
Evidence to supportthe restriction
of these as a controlmeasure for CDI
CDI may still occur
Need to minimise all antibiotic use polypharmacy and duration
Medium risk Low riskHigh risk
CephalosporinsClindamycin
AmpicillinamoxycillinCo-trimoxazole
MacrolidesFluoroquinolones
AminoglycosidesMetronidazole
Anti-pseudomonal penicillins +
β-lactamase inhibitorsTetracyclinesRifampicin
Vancomycin
Baines SD et al J Antimicrob Chemother 200555974-82Baines SD et al J Antimicrob Chemother 2006581062-5
Induction of C difficile toxin production
Tigecycline and C difficilebull Tigecycline is highly active (MIC=006 mgL) against C difficile
Baines SD et al J Antimicrob Chemother 2006581062-5
bull No in vitro evidence of increased risk of tigecycline-induced CDIBaines SD et al J Antimicrob Chemother 2006581062-5
bull No in vivo evidence of increased risk of tigecycline-induced CDIWilcox MH Clin Microbiol Infect 200713949-52
bull Some evidence that tigecycline could be used to treat CDI (THIS IS NOT A LICENSED INDICATION)Herpers BL et al Clin Infect Dis 2009481732-5
Lu CL et al Int J Antimicrob Agents 201035311-2
The missing care bundle antibiotic prescribing in hospitalsCooke FJ Holmes AHInt J Antimicrob Agents 20073025-9Department of Infectious Diseases and Immunology Hammersmith Hospitals NHS Trust Imperial CollegeDu Cane Road London W12 0HS UK
The care bundle involves grouping together key elements of care for procedures and the management of specific diagnoses in order to provide a systematic method to improve and monitor the delivery of clinical care processes In short care bundles aim to ensure that all patients consistently receive the best care or treatment all of the time This approach has been successfully applied to the management of various conditions particularly in the critical care setting The Institute for Healthcare Improvements 100K lives campaign consisted of six care bundles three of which have addressed preventing hospital-acquired infection The UK Department of Healths delivery programme to reduce healthcare-associated infections (HCAIs) including methicillin-resistant Staphylococcus aureus (MRSA) includes six high-impact interventions which are care bundles to reduce HCAIs However we suggest that one key intervention is missing and consider this intervention will be increasingly important if hospitals are to address the rising incidence of Clostridium difficile to tackle antibiotic resistance and to improve patient care The missing intervention addresses the process of antibiotic prescribing We propose that the time is right to consider the application of the care bundle approach to improve the prescribing of antibiotics both for treatment and prophylaxis
The antibiotic prescribing bundle
bull Use monotherapy whenever possible for initial (empiric) treatment
bull Optimise dose and duration
bull Perform a regular risk assessment
ndash For each patient
ndash Impact of the programme
Aminoglycosides
Glycopeptides
LipopeptidesOxazolidinones
Monotherapy or
combinationCarbapenems
BLICsCephalosporins
Fluoroquinolones
Tigecycline
Empiric choice Empiric choice 2nd 3rd line Final option
Low resistance risk and minimal
complexity
Increased resistance risk
and complexity
Treatment failure
[Cef Met prophylaxis]
Not if intravascular infectionNot in VAP as monotherapy
Antibiotic choice in high-risk patients
bull Capacity to cover resistant pathogens
bull Proven efficacy in MDR infection
bull Pharmacokinetic and pharmacodynamic profile
bull Safety profile
bull Capacity not to induce lsquoovergrowthrsquo eg CDI
bull Low potential for inducible resistance
bull Capacity not to select for resistant pathogens
Should consider measures to reduce use of 3GCs FQs amp carbapenems
Increased reliance on carbapenemsmay accelerate emergence of completely resistant isolates
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
APACHE Acute Physiology and Chronic Health EvaluationSOFA Sequential Organ Failure Assessment
Enterococcus durans
Enterobacter cloacae
Enterococcus casseliflavus or Enterococcus gallinarum
Burkholderia cepacia
Acinetobacter baumannii
Enterococci species not determined
MRSA
Enterococcus faecalis
Infection of unknown origin
Strenotrophomonas maltophilia
VRE
Enterococcus faecium
Microorganism
1 (1)
1 (1)
1 (1) 1 (1)
1 (1)
4 (6) 4 (6)
7 (10)
11 (16)
13 (19)
15 (21)
26 (37)
Infections n ()
bull APACHE II scores 27 plusmn 10 SOFA 12 plusmn 3bull Overall mortality 30
n=70 withindication
0
10
20
30
40
50
60cIAI
cSSTI
Mixed
Other
bull Mean duration of tigecycline therapy was 9 +- 4 daysbull 76 of patients received tigecycline in combination
(64 second line)bull APACHE score and renal replacement were identified
as predictive factors for mortalitybull AUTHOR CONCLUSIONS lsquoTigecycline treatment of
critically ill SICU patients with severe sepsis or septic shock appeared to result in remarkably low mortality Tigecycline may be an important treatment option for septic patients with infections resistant to other available agentsrsquo
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
Antibiotics and risk of CDI
Evidence to supportthe restriction
of these as a controlmeasure for CDI
CDI may still occur
Need to minimise all antibiotic use polypharmacy and duration
Medium risk Low riskHigh risk
CephalosporinsClindamycin
AmpicillinamoxycillinCo-trimoxazole
MacrolidesFluoroquinolones
AminoglycosidesMetronidazole
Anti-pseudomonal penicillins +
β-lactamase inhibitorsTetracyclinesRifampicin
Vancomycin
Baines SD et al J Antimicrob Chemother 200555974-82Baines SD et al J Antimicrob Chemother 2006581062-5
Induction of C difficile toxin production
Tigecycline and C difficilebull Tigecycline is highly active (MIC=006 mgL) against C difficile
Baines SD et al J Antimicrob Chemother 2006581062-5
bull No in vitro evidence of increased risk of tigecycline-induced CDIBaines SD et al J Antimicrob Chemother 2006581062-5
bull No in vivo evidence of increased risk of tigecycline-induced CDIWilcox MH Clin Microbiol Infect 200713949-52
bull Some evidence that tigecycline could be used to treat CDI (THIS IS NOT A LICENSED INDICATION)Herpers BL et al Clin Infect Dis 2009481732-5
Lu CL et al Int J Antimicrob Agents 201035311-2
The missing care bundle antibiotic prescribing in hospitalsCooke FJ Holmes AHInt J Antimicrob Agents 20073025-9Department of Infectious Diseases and Immunology Hammersmith Hospitals NHS Trust Imperial CollegeDu Cane Road London W12 0HS UK
The care bundle involves grouping together key elements of care for procedures and the management of specific diagnoses in order to provide a systematic method to improve and monitor the delivery of clinical care processes In short care bundles aim to ensure that all patients consistently receive the best care or treatment all of the time This approach has been successfully applied to the management of various conditions particularly in the critical care setting The Institute for Healthcare Improvements 100K lives campaign consisted of six care bundles three of which have addressed preventing hospital-acquired infection The UK Department of Healths delivery programme to reduce healthcare-associated infections (HCAIs) including methicillin-resistant Staphylococcus aureus (MRSA) includes six high-impact interventions which are care bundles to reduce HCAIs However we suggest that one key intervention is missing and consider this intervention will be increasingly important if hospitals are to address the rising incidence of Clostridium difficile to tackle antibiotic resistance and to improve patient care The missing intervention addresses the process of antibiotic prescribing We propose that the time is right to consider the application of the care bundle approach to improve the prescribing of antibiotics both for treatment and prophylaxis
The antibiotic prescribing bundle
bull Use monotherapy whenever possible for initial (empiric) treatment
bull Optimise dose and duration
bull Perform a regular risk assessment
ndash For each patient
ndash Impact of the programme
Aminoglycosides
Glycopeptides
LipopeptidesOxazolidinones
Monotherapy or
combinationCarbapenems
BLICsCephalosporins
Fluoroquinolones
Tigecycline
Empiric choice Empiric choice 2nd 3rd line Final option
Low resistance risk and minimal
complexity
Increased resistance risk
and complexity
Treatment failure
[Cef Met prophylaxis]
Not if intravascular infectionNot in VAP as monotherapy
Antibiotic choice in high-risk patients
bull Capacity to cover resistant pathogens
bull Proven efficacy in MDR infection
bull Pharmacokinetic and pharmacodynamic profile
bull Safety profile
bull Capacity not to induce lsquoovergrowthrsquo eg CDI
bull Low potential for inducible resistance
bull Capacity not to select for resistant pathogens
Should consider measures to reduce use of 3GCs FQs amp carbapenems
Increased reliance on carbapenemsmay accelerate emergence of completely resistant isolates
bull Mean duration of tigecycline therapy was 9 +- 4 daysbull 76 of patients received tigecycline in combination
(64 second line)bull APACHE score and renal replacement were identified
as predictive factors for mortalitybull AUTHOR CONCLUSIONS lsquoTigecycline treatment of
critically ill SICU patients with severe sepsis or septic shock appeared to result in remarkably low mortality Tigecycline may be an important treatment option for septic patients with infections resistant to other available agentsrsquo
Tigecycline in ICU setting
Swoboda et al J Antimicrob Chemother 2008
Antibiotics and risk of CDI
Evidence to supportthe restriction
of these as a controlmeasure for CDI
CDI may still occur
Need to minimise all antibiotic use polypharmacy and duration
Medium risk Low riskHigh risk
CephalosporinsClindamycin
AmpicillinamoxycillinCo-trimoxazole
MacrolidesFluoroquinolones
AminoglycosidesMetronidazole
Anti-pseudomonal penicillins +
β-lactamase inhibitorsTetracyclinesRifampicin
Vancomycin
Baines SD et al J Antimicrob Chemother 200555974-82Baines SD et al J Antimicrob Chemother 2006581062-5
Induction of C difficile toxin production
Tigecycline and C difficilebull Tigecycline is highly active (MIC=006 mgL) against C difficile
Baines SD et al J Antimicrob Chemother 2006581062-5
bull No in vitro evidence of increased risk of tigecycline-induced CDIBaines SD et al J Antimicrob Chemother 2006581062-5
bull No in vivo evidence of increased risk of tigecycline-induced CDIWilcox MH Clin Microbiol Infect 200713949-52
bull Some evidence that tigecycline could be used to treat CDI (THIS IS NOT A LICENSED INDICATION)Herpers BL et al Clin Infect Dis 2009481732-5
Lu CL et al Int J Antimicrob Agents 201035311-2
The missing care bundle antibiotic prescribing in hospitalsCooke FJ Holmes AHInt J Antimicrob Agents 20073025-9Department of Infectious Diseases and Immunology Hammersmith Hospitals NHS Trust Imperial CollegeDu Cane Road London W12 0HS UK
The care bundle involves grouping together key elements of care for procedures and the management of specific diagnoses in order to provide a systematic method to improve and monitor the delivery of clinical care processes In short care bundles aim to ensure that all patients consistently receive the best care or treatment all of the time This approach has been successfully applied to the management of various conditions particularly in the critical care setting The Institute for Healthcare Improvements 100K lives campaign consisted of six care bundles three of which have addressed preventing hospital-acquired infection The UK Department of Healths delivery programme to reduce healthcare-associated infections (HCAIs) including methicillin-resistant Staphylococcus aureus (MRSA) includes six high-impact interventions which are care bundles to reduce HCAIs However we suggest that one key intervention is missing and consider this intervention will be increasingly important if hospitals are to address the rising incidence of Clostridium difficile to tackle antibiotic resistance and to improve patient care The missing intervention addresses the process of antibiotic prescribing We propose that the time is right to consider the application of the care bundle approach to improve the prescribing of antibiotics both for treatment and prophylaxis
The antibiotic prescribing bundle
bull Use monotherapy whenever possible for initial (empiric) treatment
bull Optimise dose and duration
bull Perform a regular risk assessment
ndash For each patient
ndash Impact of the programme
Aminoglycosides
Glycopeptides
LipopeptidesOxazolidinones
Monotherapy or
combinationCarbapenems
BLICsCephalosporins
Fluoroquinolones
Tigecycline
Empiric choice Empiric choice 2nd 3rd line Final option
Low resistance risk and minimal
complexity
Increased resistance risk
and complexity
Treatment failure
[Cef Met prophylaxis]
Not if intravascular infectionNot in VAP as monotherapy
Antibiotic choice in high-risk patients
bull Capacity to cover resistant pathogens
bull Proven efficacy in MDR infection
bull Pharmacokinetic and pharmacodynamic profile
bull Safety profile
bull Capacity not to induce lsquoovergrowthrsquo eg CDI
bull Low potential for inducible resistance
bull Capacity not to select for resistant pathogens
Should consider measures to reduce use of 3GCs FQs amp carbapenems
Increased reliance on carbapenemsmay accelerate emergence of completely resistant isolates
Antibiotics and risk of CDI
Evidence to supportthe restriction
of these as a controlmeasure for CDI
CDI may still occur
Need to minimise all antibiotic use polypharmacy and duration
Medium risk Low riskHigh risk
CephalosporinsClindamycin
AmpicillinamoxycillinCo-trimoxazole
MacrolidesFluoroquinolones
AminoglycosidesMetronidazole
Anti-pseudomonal penicillins +
β-lactamase inhibitorsTetracyclinesRifampicin
Vancomycin
Baines SD et al J Antimicrob Chemother 200555974-82Baines SD et al J Antimicrob Chemother 2006581062-5
Induction of C difficile toxin production
Tigecycline and C difficilebull Tigecycline is highly active (MIC=006 mgL) against C difficile
Baines SD et al J Antimicrob Chemother 2006581062-5
bull No in vitro evidence of increased risk of tigecycline-induced CDIBaines SD et al J Antimicrob Chemother 2006581062-5
bull No in vivo evidence of increased risk of tigecycline-induced CDIWilcox MH Clin Microbiol Infect 200713949-52
bull Some evidence that tigecycline could be used to treat CDI (THIS IS NOT A LICENSED INDICATION)Herpers BL et al Clin Infect Dis 2009481732-5
Lu CL et al Int J Antimicrob Agents 201035311-2
The missing care bundle antibiotic prescribing in hospitalsCooke FJ Holmes AHInt J Antimicrob Agents 20073025-9Department of Infectious Diseases and Immunology Hammersmith Hospitals NHS Trust Imperial CollegeDu Cane Road London W12 0HS UK
The care bundle involves grouping together key elements of care for procedures and the management of specific diagnoses in order to provide a systematic method to improve and monitor the delivery of clinical care processes In short care bundles aim to ensure that all patients consistently receive the best care or treatment all of the time This approach has been successfully applied to the management of various conditions particularly in the critical care setting The Institute for Healthcare Improvements 100K lives campaign consisted of six care bundles three of which have addressed preventing hospital-acquired infection The UK Department of Healths delivery programme to reduce healthcare-associated infections (HCAIs) including methicillin-resistant Staphylococcus aureus (MRSA) includes six high-impact interventions which are care bundles to reduce HCAIs However we suggest that one key intervention is missing and consider this intervention will be increasingly important if hospitals are to address the rising incidence of Clostridium difficile to tackle antibiotic resistance and to improve patient care The missing intervention addresses the process of antibiotic prescribing We propose that the time is right to consider the application of the care bundle approach to improve the prescribing of antibiotics both for treatment and prophylaxis
The antibiotic prescribing bundle
bull Use monotherapy whenever possible for initial (empiric) treatment
bull Optimise dose and duration
bull Perform a regular risk assessment
ndash For each patient
ndash Impact of the programme
Aminoglycosides
Glycopeptides
LipopeptidesOxazolidinones
Monotherapy or
combinationCarbapenems
BLICsCephalosporins
Fluoroquinolones
Tigecycline
Empiric choice Empiric choice 2nd 3rd line Final option
Low resistance risk and minimal
complexity
Increased resistance risk
and complexity
Treatment failure
[Cef Met prophylaxis]
Not if intravascular infectionNot in VAP as monotherapy
Antibiotic choice in high-risk patients
bull Capacity to cover resistant pathogens
bull Proven efficacy in MDR infection
bull Pharmacokinetic and pharmacodynamic profile
bull Safety profile
bull Capacity not to induce lsquoovergrowthrsquo eg CDI
bull Low potential for inducible resistance
bull Capacity not to select for resistant pathogens
Should consider measures to reduce use of 3GCs FQs amp carbapenems
Increased reliance on carbapenemsmay accelerate emergence of completely resistant isolates
Baines SD et al J Antimicrob Chemother 200555974-82Baines SD et al J Antimicrob Chemother 2006581062-5
Induction of C difficile toxin production
Tigecycline and C difficilebull Tigecycline is highly active (MIC=006 mgL) against C difficile
Baines SD et al J Antimicrob Chemother 2006581062-5
bull No in vitro evidence of increased risk of tigecycline-induced CDIBaines SD et al J Antimicrob Chemother 2006581062-5
bull No in vivo evidence of increased risk of tigecycline-induced CDIWilcox MH Clin Microbiol Infect 200713949-52
bull Some evidence that tigecycline could be used to treat CDI (THIS IS NOT A LICENSED INDICATION)Herpers BL et al Clin Infect Dis 2009481732-5
Lu CL et al Int J Antimicrob Agents 201035311-2
The missing care bundle antibiotic prescribing in hospitalsCooke FJ Holmes AHInt J Antimicrob Agents 20073025-9Department of Infectious Diseases and Immunology Hammersmith Hospitals NHS Trust Imperial CollegeDu Cane Road London W12 0HS UK
The care bundle involves grouping together key elements of care for procedures and the management of specific diagnoses in order to provide a systematic method to improve and monitor the delivery of clinical care processes In short care bundles aim to ensure that all patients consistently receive the best care or treatment all of the time This approach has been successfully applied to the management of various conditions particularly in the critical care setting The Institute for Healthcare Improvements 100K lives campaign consisted of six care bundles three of which have addressed preventing hospital-acquired infection The UK Department of Healths delivery programme to reduce healthcare-associated infections (HCAIs) including methicillin-resistant Staphylococcus aureus (MRSA) includes six high-impact interventions which are care bundles to reduce HCAIs However we suggest that one key intervention is missing and consider this intervention will be increasingly important if hospitals are to address the rising incidence of Clostridium difficile to tackle antibiotic resistance and to improve patient care The missing intervention addresses the process of antibiotic prescribing We propose that the time is right to consider the application of the care bundle approach to improve the prescribing of antibiotics both for treatment and prophylaxis
The antibiotic prescribing bundle
bull Use monotherapy whenever possible for initial (empiric) treatment
bull Optimise dose and duration
bull Perform a regular risk assessment
ndash For each patient
ndash Impact of the programme
Aminoglycosides
Glycopeptides
LipopeptidesOxazolidinones
Monotherapy or
combinationCarbapenems
BLICsCephalosporins
Fluoroquinolones
Tigecycline
Empiric choice Empiric choice 2nd 3rd line Final option
Low resistance risk and minimal
complexity
Increased resistance risk
and complexity
Treatment failure
[Cef Met prophylaxis]
Not if intravascular infectionNot in VAP as monotherapy
Antibiotic choice in high-risk patients
bull Capacity to cover resistant pathogens
bull Proven efficacy in MDR infection
bull Pharmacokinetic and pharmacodynamic profile
bull Safety profile
bull Capacity not to induce lsquoovergrowthrsquo eg CDI
bull Low potential for inducible resistance
bull Capacity not to select for resistant pathogens
Should consider measures to reduce use of 3GCs FQs amp carbapenems
Increased reliance on carbapenemsmay accelerate emergence of completely resistant isolates
Tigecycline and C difficilebull Tigecycline is highly active (MIC=006 mgL) against C difficile
Baines SD et al J Antimicrob Chemother 2006581062-5
bull No in vitro evidence of increased risk of tigecycline-induced CDIBaines SD et al J Antimicrob Chemother 2006581062-5
bull No in vivo evidence of increased risk of tigecycline-induced CDIWilcox MH Clin Microbiol Infect 200713949-52
bull Some evidence that tigecycline could be used to treat CDI (THIS IS NOT A LICENSED INDICATION)Herpers BL et al Clin Infect Dis 2009481732-5
Lu CL et al Int J Antimicrob Agents 201035311-2
The missing care bundle antibiotic prescribing in hospitalsCooke FJ Holmes AHInt J Antimicrob Agents 20073025-9Department of Infectious Diseases and Immunology Hammersmith Hospitals NHS Trust Imperial CollegeDu Cane Road London W12 0HS UK
The care bundle involves grouping together key elements of care for procedures and the management of specific diagnoses in order to provide a systematic method to improve and monitor the delivery of clinical care processes In short care bundles aim to ensure that all patients consistently receive the best care or treatment all of the time This approach has been successfully applied to the management of various conditions particularly in the critical care setting The Institute for Healthcare Improvements 100K lives campaign consisted of six care bundles three of which have addressed preventing hospital-acquired infection The UK Department of Healths delivery programme to reduce healthcare-associated infections (HCAIs) including methicillin-resistant Staphylococcus aureus (MRSA) includes six high-impact interventions which are care bundles to reduce HCAIs However we suggest that one key intervention is missing and consider this intervention will be increasingly important if hospitals are to address the rising incidence of Clostridium difficile to tackle antibiotic resistance and to improve patient care The missing intervention addresses the process of antibiotic prescribing We propose that the time is right to consider the application of the care bundle approach to improve the prescribing of antibiotics both for treatment and prophylaxis
The antibiotic prescribing bundle
bull Use monotherapy whenever possible for initial (empiric) treatment
bull Optimise dose and duration
bull Perform a regular risk assessment
ndash For each patient
ndash Impact of the programme
Aminoglycosides
Glycopeptides
LipopeptidesOxazolidinones
Monotherapy or
combinationCarbapenems
BLICsCephalosporins
Fluoroquinolones
Tigecycline
Empiric choice Empiric choice 2nd 3rd line Final option
Low resistance risk and minimal
complexity
Increased resistance risk
and complexity
Treatment failure
[Cef Met prophylaxis]
Not if intravascular infectionNot in VAP as monotherapy
Antibiotic choice in high-risk patients
bull Capacity to cover resistant pathogens
bull Proven efficacy in MDR infection
bull Pharmacokinetic and pharmacodynamic profile
bull Safety profile
bull Capacity not to induce lsquoovergrowthrsquo eg CDI
bull Low potential for inducible resistance
bull Capacity not to select for resistant pathogens
Should consider measures to reduce use of 3GCs FQs amp carbapenems
Increased reliance on carbapenemsmay accelerate emergence of completely resistant isolates
The missing care bundle antibiotic prescribing in hospitalsCooke FJ Holmes AHInt J Antimicrob Agents 20073025-9Department of Infectious Diseases and Immunology Hammersmith Hospitals NHS Trust Imperial CollegeDu Cane Road London W12 0HS UK
The care bundle involves grouping together key elements of care for procedures and the management of specific diagnoses in order to provide a systematic method to improve and monitor the delivery of clinical care processes In short care bundles aim to ensure that all patients consistently receive the best care or treatment all of the time This approach has been successfully applied to the management of various conditions particularly in the critical care setting The Institute for Healthcare Improvements 100K lives campaign consisted of six care bundles three of which have addressed preventing hospital-acquired infection The UK Department of Healths delivery programme to reduce healthcare-associated infections (HCAIs) including methicillin-resistant Staphylococcus aureus (MRSA) includes six high-impact interventions which are care bundles to reduce HCAIs However we suggest that one key intervention is missing and consider this intervention will be increasingly important if hospitals are to address the rising incidence of Clostridium difficile to tackle antibiotic resistance and to improve patient care The missing intervention addresses the process of antibiotic prescribing We propose that the time is right to consider the application of the care bundle approach to improve the prescribing of antibiotics both for treatment and prophylaxis
The antibiotic prescribing bundle
bull Use monotherapy whenever possible for initial (empiric) treatment
bull Optimise dose and duration
bull Perform a regular risk assessment
ndash For each patient
ndash Impact of the programme
Aminoglycosides
Glycopeptides
LipopeptidesOxazolidinones
Monotherapy or
combinationCarbapenems
BLICsCephalosporins
Fluoroquinolones
Tigecycline
Empiric choice Empiric choice 2nd 3rd line Final option
Low resistance risk and minimal
complexity
Increased resistance risk
and complexity
Treatment failure
[Cef Met prophylaxis]
Not if intravascular infectionNot in VAP as monotherapy
Antibiotic choice in high-risk patients
bull Capacity to cover resistant pathogens
bull Proven efficacy in MDR infection
bull Pharmacokinetic and pharmacodynamic profile
bull Safety profile
bull Capacity not to induce lsquoovergrowthrsquo eg CDI
bull Low potential for inducible resistance
bull Capacity not to select for resistant pathogens
Should consider measures to reduce use of 3GCs FQs amp carbapenems
Increased reliance on carbapenemsmay accelerate emergence of completely resistant isolates
The antibiotic prescribing bundle
bull Use monotherapy whenever possible for initial (empiric) treatment
bull Optimise dose and duration
bull Perform a regular risk assessment
ndash For each patient
ndash Impact of the programme
Aminoglycosides
Glycopeptides
LipopeptidesOxazolidinones
Monotherapy or
combinationCarbapenems
BLICsCephalosporins
Fluoroquinolones
Tigecycline
Empiric choice Empiric choice 2nd 3rd line Final option
Low resistance risk and minimal
complexity
Increased resistance risk
and complexity
Treatment failure
[Cef Met prophylaxis]
Not if intravascular infectionNot in VAP as monotherapy
Antibiotic choice in high-risk patients
bull Capacity to cover resistant pathogens
bull Proven efficacy in MDR infection
bull Pharmacokinetic and pharmacodynamic profile
bull Safety profile
bull Capacity not to induce lsquoovergrowthrsquo eg CDI
bull Low potential for inducible resistance
bull Capacity not to select for resistant pathogens
Should consider measures to reduce use of 3GCs FQs amp carbapenems
Increased reliance on carbapenemsmay accelerate emergence of completely resistant isolates
Aminoglycosides
Glycopeptides
LipopeptidesOxazolidinones
Monotherapy or
combinationCarbapenems
BLICsCephalosporins
Fluoroquinolones
Tigecycline
Empiric choice Empiric choice 2nd 3rd line Final option
Low resistance risk and minimal
complexity
Increased resistance risk
and complexity
Treatment failure
[Cef Met prophylaxis]
Not if intravascular infectionNot in VAP as monotherapy
Antibiotic choice in high-risk patients
bull Capacity to cover resistant pathogens
bull Proven efficacy in MDR infection
bull Pharmacokinetic and pharmacodynamic profile
bull Safety profile
bull Capacity not to induce lsquoovergrowthrsquo eg CDI
bull Low potential for inducible resistance
bull Capacity not to select for resistant pathogens
Should consider measures to reduce use of 3GCs FQs amp carbapenems
Increased reliance on carbapenemsmay accelerate emergence of completely resistant isolates
Antibiotic choice in high-risk patients
bull Capacity to cover resistant pathogens
bull Proven efficacy in MDR infection
bull Pharmacokinetic and pharmacodynamic profile
bull Safety profile
bull Capacity not to induce lsquoovergrowthrsquo eg CDI
bull Low potential for inducible resistance
bull Capacity not to select for resistant pathogens
Should consider measures to reduce use of 3GCs FQs amp carbapenems
Increased reliance on carbapenemsmay accelerate emergence of completely resistant isolates