Antimicrobial Stewardship - Summa Health System/media/Files/SummaMeded/CME... · 2012-11-27 ·...
Transcript of Antimicrobial Stewardship - Summa Health System/media/Files/SummaMeded/CME... · 2012-11-27 ·...
Antimicrobial Stewardship: Strategies for Appropriate
Antimicrobial Use
Thomas M. File, Jr, MD, MSc, MACP
Chair, Infectious Disease Division
Summa Health System;
Professor of Internal Medicine, Master
Teacher, Chair ID Section NEOMED
IDSA Call-to-Action: Bad Bugs, No Drugs
IDSA. Infectious Diseases Soc. Of Am. Bad Bugs, No Drugs.
Available at: www.idsociety.org/badbugsnodrugs.html.
As resistance increases . . . number of new antimicrobials diminishes
No
. o
f n
ew a
nti
mic
rob
ials
‘Drug resistance follows the drug like a faithful
shadow’. Paul Erhlich 1854-1915
“It is not difficult to make microbes resistant to penicillin in
the laboratory by exposing them to concentrations not
sufficient to kill them….there is the danger that the
ignorant man may easily underdose himself and
by exposing his microbes to non-lethal quantities
of the drug make them resistant.” Alexander Fleming Nobel Prize lecture Dec 11, 1945
Clin Infect Dis. 2011 “Antimicrobial resistance is a major public health crisis.” Clin Infect Dis 2011
Antibiotics Should Be Assigned to a Special Drug Class to
Preserve Their Power, Says Alliance for the Prudent Use of
Antibiotics S. Levy 2010
The Impact of Antimicrobial Resistance
File TM, Jr. Chest. 1999;115(suppl):3S-8S.
Affects clinical outcomes
Associated with higher mortality
Results in higher healthcare costs
Leads to prolonged hospitalization
Increase challenge for appropriate
management
Empiric therapy
Directed therapy
Clinical Practice Guidelines
"Clinical practice guidelines are systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances" (Institute of Medicine, 1990).
Bringing scientific evidence into daily clinical routines
“Evidence-based”
IDSA > 50 guidelines (www.idsociety.org)
“…guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment…” (IDSA guidelines)
From Pirates of the Caribbean Curse of the Black Pearl 2003
Jack Sparrow: I thought you were supposed to keep to the code
(referring to the pirates code that “Any man that falls behind stays behind”… when the Black Pearl waits for him to escape)
Mr. Gibb: We figured they were more like guidelines rather than actual rules
CMS Measures and Stewardship
Core Measures--Effort to improve care of
patients1
Based on Process of care recommendations (within control of HCP) or
outcomes
Should be complementary to Stewardship
• Unintended consequences
Effects reimbursement
Stewardship Strategies Avoid Antimicrobials if not warranted Stop in not warranted
Appropriate agent (based on susceptibility) Stop MRSA therapy if no MRSA
Avoid discordant therapy Reduce Duration
De-escalation Dose Optimization
Switch to oral ID consult
1. File TM Jr. et al. Clin Infect Dis. 2011; 53: S15-S22
2. File TM Jr, Gross PA. Clin Infect Dis. 2007;44:942-944;
Link Between Evidence-based Guidelines, Core Measures, & Outcomes
Actual
Practice
Ideal
Practice
GAP Individual
factors justify
variance
of care
CORE MEASURES
& GUIDELINES Reduce variance
Improve care
Reasons to Target Antimicrobials
Increased rates of bacterial resistance result in part
from antimicrobial drug use
50% antimicrobial use is inappropriate
Improvements in antimicrobial use have been shown
to improve patient outcomes and reduce rates of
resistance
Pt with resistant infection is 15% more likely to die
Stimulus for Antimicrobial Stewardship
“The primary goal of antimicrobial stewardship is to optimize clinical
outcomes while minimizing unintended consequences of antimicrobial
use, including toxicity, the selection of pathogenic organisms (such as
Clostridium difficile), and the emergence of resistance…..Effective
antimicrobial stewardship programs can be financially self-supporting
and improve patient care. ….”
Guidelines for Developing an Institutional Program to Enhance Antimicrobial
Stewardship: Dellit T et al. Clin Infect Dis. 2007;44:159-77
Appropriate antimicrobial usage: For optimal outcomes and reduce resistance
‘Antimicrobial Avoidance’ when not
indicated
3 ‘Ds’
Right DRUG
• Guidelines
• Local resistance patterns
• Patient risk stratification
Right DOSE
• Pharmacokinetics/Pharmacodynamics (PK/PD)
Right DURATION
• Compliance
Who of the following patients are likely to warrant antibacterial therapy?
1. 35 year old afebrile, non-smoking male with
mild nasal congestion and non-productive
cough for three days
2. 20 year old afebrile college student with non-
exudative acute sore throat
3. 35 year old afebrile female with signs of acute
sinusitis of three days duration
4. 55 year old smoking male with diabetes and
acute fever cough and localised rhonchi
5. All of the above
1MacKay DN. J Gen Inter Med. 1996;11:557-562. 2Bent S, et al. Am J Med.
1999;107:62-67. 3. Smith et al. Cochrane Systematic Review 2012
9 studies reviewed (placebo versus ATMB)1 – Antibiotics had no benefit
– Albuterol better than antibiotics (2 studies)
– “Treating a condition that is largely viral in origin with antibiotics” promotes
resistance
Meta-analysis, 8 studies2 – “Small” benefit (? clinically significant)
– “As the benefit must be weighed against the risk of side effects and the
societal cost of increasing antibiotic resistance, we believe that the use of
antibiotics is not justified in these patients”
– Cochrane systematic review (2012)3 – “the current update provides clearer evidence on the lack of effectiveness of
antibiotics for acute bronchitis.”
Antibiotics and Acute Bronchitis
File TM Jr. Up-To-Date 2012
Clinical
Cough (50% scant sputum; often green or yellow); occasional
wheezing, chest wall discomfort; assoc with common cold
Procalcitonin-low if viral
Etiology
90% viral; 10%-Mycoplasma, Chlamydophila; B. pertussis
CXR-negative
Therapy
No antimicrobials for viral
Antimicrobial only if bacterial (Pertussis > 3 wks cough; treatment to
reduce transmission, not for acute resolution)
Symptomatic
NSAIDS, Aspirin, Ipratroprium (Atrovent)
Delayed prescription
Acute Bronchitis
Procalcitonin for Antimicrobial
Stewardship for RTIs
File TM Jr. Clin Cherst Med. 2011; modified from
Schuetz P. et al. Eur Respir J 2011;37(2): 384–92.
PCT < 0.1
ug/ml
Bacterial
Infection
VERY
UNLIKELY
NO
ANTIMICROBIALS
Consider repeat 6-24hrs
based on clinical status
PCT 0.1-
0.25 ug/ml
Bacterial
infection
UNLIKELY
NO
ANTIMICROBIALS
Use of ABX based on
clinical status (‘unstable’) &
judgment
PCT > 0.25-
0.5 ug/ml
Bacterial
infection
LIKELY
YES
ANTIMICROBIALS
Repeat PCT day 3, 5, 7 (for
Duration)
PCT > 0.5
ug/ml
Bacterial
infection
VERY LIKELY
YES
ANTIMICROBIALS
CONSIDER STOP ABX
when 80=90% decrease; if
PCT remains high consdier
treatment failure
NQF PERFORMANCE MEASURE: ACUTE BRONCHITIS
NQF=National Quality Forum
www.qualtiyforum.org/Measures_List.aspx
Acute respiratory infection
Case: 40-year-old male with non-productive
cough x 4 days; non-smoker;
no comorbidity
Exam: Afebrile; P-72; R-20; lungs –
no localized findings
Survey of PCPs:
No Yes
Should antibiotics be used? 90% 10%
Would antibiotics be used? 12% 88%
Antimicrobials for Colds—Why?
“Patient pressures”
Patient satisfaction correlates with
quality of patient-doctor
intervention,
not prescription1 “Prevent bacterial superinfection”
Several controlled studies showed
no benefit for URI/colds2
1Hamm RM, et al. J Fam Pract. 1996;43:56-62.
2Rosenstein N, et al. Pediatrics. 1998;101:181-184.
Overuse of antibiotics
Receiving an antibiotic reinforces the
patients’ belief that antibiotics are warranted
when a similar situation arises
Patients may continue to consult for acute
RTIs and expect antibiotics to be prescribed
Doctors may also prescribe antibiotics rather
than educate patients
Most patients and many doctors view
‘unnecessary’ antibiotic prescribing as a
neutral intervention that is, one that cannot harm but may help
File T. Curr Opin Infect Dis. 2002;15:149–50
Reduce use by reducing demand
Primary care: acute bronchitis (> 200 patients)
Antibiotics used by:
Prescription alone (no leaflet) 62% (P = 0.04)
Prescription plus explanatory leaflet 47%
Macfarlane et al. BMJ 2002; 324:1–6
Primary care: acute bronchitis (> 2,000 patients)
Decline in antibiotic use associated with
education of patient and prescriber
(74% to 48%, P = 0.003) Gonzales et al. JAMA 1999; 281:1512–1519
Restricting antibiotics reduces resistance
Finland – reduced erythromycin use led to
reduced Streptococcus pyogenes
resistance1
Iceland – reduced antibiotic use led to
reduced penicillin-nonsusceptible S.
pneumoniae2
Alaska – reduced antibiotic use led to
reduced penicillin-resistant S. pneumoniae3
1 Seppala et al. N Engl J Med. 1997; 337:441–446 2 Arason et al. BMJ 1996; 313:387–391
3 Petersen et al. 37th IDSA Meeting 1999 [Abstract 62]
Hospital Antimicrobial Stewardship:
Dellit T, et al. Clin Infect Dis. 2007;44:159-177.
Definition “An ongoing effort…to optimize antimicrobial use in
order to improve patient outcomes, ensure cost-
effective therapy, and reduce adverse sequelae of
antimicrobial use (including antimicrobial resistance)”
Common interventions in pilot programs at SUMMA
Avoid Antimicrobials if not warranted
Appropriate agent (based on susceptibility)
Avoid discordant therapy
Dose Optimization
Based on renal function, weight, MIC
De-escalation
Stop if no antimicrobial warranted
Stop MRSA therapy if no MRSA
Reduce duration
Switch to oral
a. Trimethoprim/Sulfamethoxazole (e.g.
Septra, Bactrim) three DS tablets as a
single dose
b. Ciprofloxacin (Cipro) 250 mg po b.i.d. for
6 doses
c. Nitrofurantoin (e.g. Macrobid) 100 mg po
b.i.d. for three days
d. None of the above; no therapy is required
What is appropriate therapy for a 55
year old asymptomatic diabetic
female with >105 E. coli in urine
culture?
ASYMPTOMATIC BACTERIURIA
SCREENING AND TREATMENT NOT INDICATED
Premenopausal, Nonpregnant or Diabetic Women1
Older persons whether living in Nursing Homes or in the
community 2
Spinal cord Injury 2
Catheterized patients 2
1 ACOG Bulletin #91. Obstet Gynecol 2008;111:785
2 Nicolle et al. IDSA Guidelines. Clin Infect Dis 2005;40:643-50.
ASYMPTOMATIC BACTERIURIA
DEFINITION
Single Catheter Specimen with > 105 Bacteria
Women: 2 CCU Specimens with same Bacteria (> 105 )
Men: Single CCU specimen with > 105 Bacteria
SCREENING AND TREATMENT INDICATED
Urologic Surgery (Including TURP)
Pregnancy
Nicolle et al. IDSA Guidelines. Clin Infect Dis 2005;40:643-50
Prevalence of Asymptomatic
Bacteriuria Population Prevalence
Healthy premenopausal women 1-5%
Pregnant women 2-10%
Postmenopausal women (50-70) 3-9%
Diabetic women/men 9-27/4-19%
Elderly (>70) in community: W/M 25-50/15-40%
Spinal cord injuries 23-90%
Indwelling catheters
short term 9-23%
Long term 100%
Nicolle L et al. Clin Infect Dis 2005; 40: 643-54
(IDSA Guidelines for asymptomatic bacteriuria in adults)
ASYMPTOMATIC BACTERIURIA
in Young Women RCT of 673 young women (18-40)
No therapy vs antimicrobial (based on culture)
RESULT:
Recurrence: No therapy 13% vs Therapy 47% (p<
0.001)
CONCLUSION: No benefit to treat. AB should not
be treated in young women and it may play a
protective role in preventing symptomatic
recurrence
Cai T et al. Clin Infect Dis 2012; early access July
82 y/o female transferred from LTCF with chest pain; has acute MI. Has foley catheter. Afebrile; + pyuria; Culture: 105 Klebsiella pneumoniae
Course of action?
A. Start antimicrobial
B. Await
susceptibility test
and chose most
cost effective
agent for therapy
C. No antimicrobial
therapy warranted
D. Methenamine
UTI in LTCF
CULTURE SHOULD NOT BE PERFORMED FOR
ASYMPTOMATIC RESIDENTS!!!!![A-I]1
10-50% or residents have >105 cfu/ml
Prospective studies have shown no benefit to treat
In catheterized patients, reserve U/A and culture
for those with symptoms [A-II] 1
Pyuria or positive dipstick for leukocyte esterase not
helpful unless negative
Methenamine not recommended in patients with long-
term catheterization2
1. High K. et al. Clin Infect dis. 2009; 48: 149-71; can access via www.idsociety.org
2. Hooton et al. Clin Infect Dis. 2010
82 y/o female transferred from LTCF with fever, decrease mental status; WBC-15,000. Exam unremarkable. Has long-term foley catheter: + pyuria; Treated initially with ciprofloxacin. Day #3 lab reports culture with > 100,000 E. coli resistant to ciprofloxacin but susceptible to all other agents tested. What is the appropriate choice now? Stop ciprofloxacin and start:
A. Cefepime
B. Ampicillin
C. Piperacillin/tazobactam
D. Imipenem
De-escalation
• Susceptibility results used to more specifically target
microbiological results; narrowing the antibiotic
spectrum by changing from a broad spectrum agent to
a narrow spectrum agent or by eliminating a drug from
combination therapy.
• Should ideally occur as soon as possible, but within 48
hours of the availability of culture results.
• Benefits include
• reduced bacterial resistance,
• decreased incidence of bacterial, viral, and fungal superinfections,
• limited exposure to unnecessary drug therapy and the associated
risks
• decreased costs.
52 y/o male in ICU; 5 days post abdominal surgery
Develops fever, pulmonary infiltrates, purulent sputum, leukocytosis
Principles: Nosocomial Pneumonia* Recognise variability in bacteriology from
hospital to hospital, and customise therapy to local data
Avoid untreated or inadequately treated patients by using prompt and appropriate therapy
Avoid the overuse of antibiotics: accurate diagnosis, tailor therapy to culture data, shorten duration of therapy as much as possible (7-8 days unless Pseudomonas)
• De-escalation
Case Study: Nososcomial Pneumonia
CXR courtesy of T File
* ATS/IDSA Guidelines Am J Resp Crit Care Med. 2005
VAP: Empiric Treatment Patient at Risk for MDR*
Potential Pathogens
Core pathogens +
MDR pathogens
P. aeruginosa
ESBL
Acinetobacter spp
MRSA
Legionella
Combination Therapy
Antipseudomonal cephalosporin (cefepime, ceftazidime) or Antipseudomonal carbapenem (imipenem, meropenem) or Piperacillin-tazobactam PLUS Antipseudomonal fluoroquinolone (levofloxacin, ciprofloxacin) or aminoglycoside PLUS linezolid or vancomycin (if MRSA risk)
*Multidrug Resistance; Adapt to local patterns of resistance.
American Thoracic Society, Infectious Diseases Society of America. Am J Respir Crit Care Med. 2005;171:388-416.
Case Study: Patient Initially Treated with Cefepime and Vancomycin. Day #3 Patient Improved and ETA culture reveals Klebsiella sp. (pan susceptible). What therapy?
1. Continue present therapy
2. Continue cefepime; stop
vancomycin
3. Continue cefepime; add
gentamicin
4. De-escalate to cefazolin or
ceftriaxone
ETA: endotracheal aspirate.
Strategy for Optimization:
De-escalation De-escalation in ICU1
20 ICUs; 398 pts with VAP (MRSA, Pseudomonas most frequent pathogens)
Mortality • No De-escalation (62%): 24%
• Escalation 43%
• DE-ESCALATION 17% (P=0.001)
De-escalation for VAP in Surgical ICU2
Retrospective evaluation
138 of 1596 patients (8.7%) developed VAP
Mortality • De-escalation: 35.1; No de-escalation: 42.1% (P=0.324)
IMPORTANCE OF CULTURE
1. Kollef MH et al. Chest. 2006;129:1210-1218. 2. Eachempati SR et al. J Trauma. 2009;66:1343-1348.
72 y/o male in ICU on ventilator; New Fever, Purulent ET secretions, Leukocytosis
Endotracheal aspirate culture reveals: MRSA (vancomycin MIC 1.5 μg/mL by E-test) and Acinetobacter:
Gentamicin-R; Amikacin-R; Cipro-R;
Cefepime-R; Amp/Sulb-
R;Pip/tazob-R
Ertapenem-R; Meropenem-R;
Doripenem-R
VAP: Case Study, Senerio 2
CXR Courtesy of T File
Resistant Gram Negative Infections: Treatment Options
Optimize PK/PD
Extended infusion; Continuous Infusion; Higher doses for Beta-lactams (e.g., Cefepime, Amp/sulb)1-3
Use of old drugs: colistin IV
New drugs: (tigecycline; doripenem)
Combination therapy
Variable combinations (colistin, carbapenems, tigecycline, rifampin….)
Aerosolized drugs (aminoglycosides, colistin)4
1.Lodise TP Jr et al. Clin Infect Dis. 2007;44:357-363. 3. Chastre J et al. Crit Care Med. 2008;36:1089-1096; 4 Betrosian AP et al. Scand J Infect
Dis. 2007;39(1):38-43 ; 4 Palmer L . Curr Opin Crit Care 2009
Optimizing Beta-lactam Therapy: Maximizing Percent T>MIC
Increased duration of infusion Prolonged infusion
• Same dose and dosing interval, 100-250 mL, however, change duration of infusion (0.5 hr 3-4hr)
Co
nce
ntr
atio
n
(mg
/L)
Time Since Start of Infusion (h)
MIC
32
16
8
4
2
1 0 6 4 2 8 10 12
Slide courtesy of D Nicolau
Empiric Therapy
CrCl > 40 ml/min – Piperacillin/tazobactam 4.5 g IV over 3 hrs every 6 hrs CrCl 20-40 ml/min – Piperacillin/tazobactam 4.5 g IV over 4 hrs every 8 hrs CrCl < 20 ml/min (inc. intermittent HD) – Piperacillin/tazobactam 2.25 g IV over 3 hrs every 6 hrs CRRT patients (ie. CVVHD) – Piperacillin/tazobactam 4.5 g IV over 4 hrs every 8 hrs
CrCl > 20 ml/min – Piperacillin/tazobactam 3.375 g IV over 4 hrs every 8 hrs CrCl < 20 (inc. intermittent HD) – Piperacillin/tazobactam 3.375 g IV over 4 hrs every 12 hrs CRRT patients (i.e. CVVHD) – Piperacillin/tazobactam 3.375 g IV over 4 hrs every 8 hrs
CrCl > 40 ml/min – Piperacillin/tazobactam 4.5 g IV over 30 min every 6 hrs CrCl 20-40 ml/min – Piperacillin/tazobactam 4.5 g IV over 30 min every 8 hrs CrCl < 20 ml/min (inc. intermittent HD) – Piperacillin/tazobactam 2.25 g IV over 30 min every 6 hrs CRRT patients (ie. CVVHD) – Piperacillin/tazobactam 4.5 g IV over 30 min every 8 hrs
MIC 32
MIC 8**
Summa Health System Pharmacodynamic Dose Optimization for Pip/tazob
CrCl > 40 ml/min – Piperacillin/tazobactam 4.5 g IV over 3 hrs every 6 hrs CrCl 20-40 ml/min – Piperacillin/tazobactam 4.5 g IV over 4 hrs every 8 hrs CrCl < 20 ml/min (inc. intermittent HD) – Piperacillin/tazobactam 2.25 g IV over 3 hrs every 6 hrs CRRT patients (ie. CVVHD) – Piperacillin/tazobactam 4.5 g IV over 4 hrs every 8 hrs
MIC <16
8/2010 – Ref: Shea KM, et al. Annals of Pharmacother 2009;43:1747-54. Kim A, et al. Pharmacother 2007;27:1490-97.
CrCl > 20 ml/min – Piperacillin/tazobactam 4.5 g IV over 30 min every 8 hrs CrCl < 20 ml/min (inc. intermittent HD) – Piperacillin/tazobactam 2.25 g IV over 30 min every 6 hrs CRRT patients (ie. CVVHD) – Piperacillin/tazobactam 4.5 g IV over 30 min every 8 hrs
MIC < 4** ** Only If no IV access for extended infusion
Case Study SENARIO 2a: Pt on Cefepime, Vancomycin, gentamicin. ETA culture reveals Heavy growth MSSA. You D/C cefepime and gentamicin. Choice of therapy for MSSA?
1. Vancomycin 15 mg/kg q 8-12 h
2. Vancomycin + rifampin
3. Linezolid
4. Nafcillin
Outcomes in MSSA Bacteremia Nafcillin vs Vancomycin
5
10
15
20
25
Persistent
>3 but ≤7 Days
Persistent
>7 Days
Relapse Bacteriologic
Failure
Nafcillin (n=18)
Vancomycin (n=70)
6
21
0
11
0
7
0
19
Chang et al. Medicine (Baltimore). 2003;82:333-339.
Prospective Observational Study With 6 Months Follow-up
Duration: 8 vs 15 days of ABX for VAP
Prospective, R,D-B RCT in 51 French ICUs
401 pts diagnosed by quant culture results
Results Mortality: 8 vs 15 no difference (18.8% vs 17.2%)
Recurrent infections: No difference (28.9% vs 26.0%)
Antibiotic-free days less with 8 d; Resistance LESS
NO difference in # ventilator-days, Organ dysfunction
Infection caused by non-fermenting GNR had higher pulm-infection-recurrence
Conclusion: Comparable clinical effectiveness against VAP was obtained. Reduction in days of antibiotics could help control costs and contain the emergence of resistance
Chastre et al. JAMA Med 2003; 290: 2588-2598
2013 Measures and Timing: 20 Measures for FFY 2013
Weighted
70%
Experience of Care
Measures Encompassing 8
Key Topics
• Communication with nurses
• Communication with
doctors
• Responsiveness of staff
• Pain management
• Communication about meds
• Cleanliness and quietness
of hospital environment
• Discharge information • Overall rating of hospital
Weighted
30%
FFY, Federal Fiscal Year.
Medicare Program; Hospital Inpatient Value-Based Purchasing Program. Available at:
https://www.federalregister.gov/articles/2011/05/06/2011-10568/medicare-program-hospital-inpatient-value-based-
purchasing-program. Accessed June 5, 2012.
17 Clinical Process
Measures
• Acute Myocardial
Infection
• Heart Failure
• Pneumonia
• SCIP (SCIP 1,2,3 and
4 considered HAI)