The foundation of SEIMC ESCMID Online Lecture Library © by ...

The foundation of SEIMC

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The Paular Meeting

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My mentors

Prof. José María Segovia de Arana

Prof. Juan Martínez López de Letona

Prof. Manuel Moreno López

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My mentors

Prof. William HewittProf Sidney FinegoldProf Lowell S. YoungProf Colin JordanProf William MartinProf Richard D. MeyerProf Lamar Johnson

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The beginning

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The institutions of my life

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The institutions of my life

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The life-long colleagues

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Part of my team

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ESCMID

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Since 1968: Carmen and our family

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The Central Venous Catheter, is a link between clinicians and microbiologists

Emilio BouzaHospital Gregorio MarañónUniversity of Madrid. Spain

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Day D: French CoastDay D: French Coast

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PathogenesisPathogenesis

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Pathogenesis

65% 65%

30%30%

Skin and subcut

65% 65%

30%30%

Skin and subcut

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EpidemiologyEpidemiology

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US Data

Mermel L. C.I.D. 2009

150.000.000 devices

20,000,000 with I.V. therapy

5,000,000 central v. cath.

250,000 catheter's infections

120,000 bloodstream infections

Extra cost/case

Mean stay 7 - 21 days

8.000 to 40.000 $ more

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European Data

Bouza E. C.M.I. 2004

ESGNI 5

ESGNI 6Muñoz P. C.M.I. 2004

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European Data

Bouza E. C.M.I. 2004

ESGNI 5 and 6

Muñoz P. C.M.I. 2004

ICU38%

Medical27%

Other7%

Surgical26%

Pediatrics (non ICU)

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Epidemiology

Attributable mortality 12-25%Attributable mortality 12-25%

Prolongation of hospitalization 10-40 dProlongation of hospitalization 10-40 d

Extra cost 8,000 to 40,000 $ episodeExtra cost 8,000 to 40,000 $ episode

Pittet D. JAMA 1994; Smith RL. Chest 1991

Pittet D. JAMA 1994; Digiovine B. A.J.R.C.C.M. 1999

Mermel LA. Ann.Intern.Med. 2002; Arnow PM. C.I.D. 1993

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Evolution and etiologic shift of catheter‐related bloodstream infection in a whole institution. Can the microbiology department act as a watchtower?

Marta Rodríguez‐Créixems1,2,3, MD Patricia Muñoz1,2,3, MD Pablo Martín‐Rabadán 1, MDEmilia Cercenado1,2,3, Pharm DMaría Guembe1, PharmDEmilio Bouza1,2,3, MD

16:48 ‐ 17:00 Bacteraemia and surgical site infections (Platinum Suite 3/4)

Monday, April 02, 2012

1 Clinical Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Marañón, Department of Medicine. Facultad de Medicina. Universidad Complutense, Madrid, Spain2 CIBER de Enfermedades Respiratorias (CIBERES CD06/06/0058), Palma de Mallorca, Spain. 3 Red Española para la investigación en Patología Infecciosa (REIPI), RD06/0008/1025

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Evolution of CR‐BSI 479,710 admissions (mean, 59,964 admissions/year)

Significant BSI: 14,713 (30.67 episodes/1,000 ad) 1,208 episodes (8.2%) CR‐BSI

‐ 1.9 to 3.6 episodes/1,000 ad (mean, 2.5 ep/ ad)

10.918

1.11.193 1.177 1.207

2003 2004 2005 2006 2007 2008 2009 2010

CR-BSI/1000 Ad (p=0.598)

Results

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Evolution of incidence rate ratio of the CR‐BSI/1000 admissions in adult ICUs compared with the remaining hospital units

2003 2004 2005 2006 2007 2008 2009 2010Adult ICUs 1 0.749 0.743 0.9 0'001 0.652 0.877 0.548Other units 1 0'001 0.907 0.692 0.925 0'001 1.337 0'001

Incide

nce Ra

te Ratio

Adult ICUs Other units

Linear trend Linear trend

p=0.992

p=0.007

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EtiologyEtiology

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Etiologic shift

A shift in the etiologic spectrum of CRBSI may be in

progress, with a gradual decrease in Gram-positive

CRBSI and significant increases in Gram-negative

and Candida infections

Rodríguez-Créixems M. ECCMID 2012

Evolution and aetiologic shift of catheter‐related bloodstream

infections. Should the microbiology department be a watchtower for a

whole institution?

M. Rodríguez‐Creixems*, M. Guembe, P. Muñoz, P. Martín‐Rabadán, E.

Cercenado, E. Bouza (Madrid, ES)

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1,255 microorganisms from 1,208 ep CR‐BSI 48 polymicrobial (4%).

3. Evolution of etiology

Gram +67%

Gram ‐17%

Fungi16%

0% CR‐BSI

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Evolution of CRBSI etiology: Gram +ves

03 04 05 06 07 08 09 10Gram positive 1 0.693 0.81 0.674 0.768 0.839 1.208 0.751#REF! 1#REF! 1

Gram +(831 ep): 25% reduction (95% CI, 1‐44%; p=0.04)

S. aureus from 0.82 to 0.33 /1000 adm (9%/annual decrease; p=0.006)

Enterococcus spp. from 0.09 to 0.22 /1000 adm (19% annual increase; p=0.001).

CNS stable

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03 04 05 06 07 08 09 10Gram negative 1 0.797 1.899 2.211 1.814 2.036 2.821 1.554

Evolution of CRBSI etiology: Gram ‐ves

Gram ‐ (209 episodes): 8.9% increase (95% CI, 2.6‐15.7%; p=0.005)

Klebsiella spp., Enterobacter spp., Escherichia coli, Serratiaspp., and a miscellany of other bacteria in decreasing order

Pseudomonas aeruginosa: 14% annual increase(p=0.090)

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03 04 05 06 07 08 09 10Fungi 1 0.774 0.698 1.556 1.99 2.114 1.982 1.722

Evolution of CRBSI etiology

C. albicans: 24% annual increase (95% CI, 11‐38%; p<0.001)

The rest stable

Fungus: 14% increase (95% CI, 6‐21%; p<0.001)

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Gram negatives

17% of all CR-BSI

GN-CRBSI were more common in non

immunosuppressed, underlying neurologic conditions,

previous antimicrobial therapy, non–subclavian

insertion site, and rapid blood cultures growing (< 8

hours).Eworo A. ECCMID 2012

Case‐control analysis of Gram‐negative catheter‐related bloodstream

infection in a tertiary care medical centre

A. Eworo, P. Muñoz*, M. Rodríguez‐Creixems, A. Fernandez‐Cruz, E.

Reigadas, E. Bouza (Madrid, ES)

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Diagnostic techniques aftercatheter withdrawalDiagnostic techniques aftercatheter withdrawal

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Roll-plate technique (Maki)Roll-plate technique (Maki)

Semiquantitativetechnique

>14 u.f.c./plate

Fina Liñares photographsFina Liñares photographs

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Positivity : 102 ufc

Dx.- Sonication (Sherertz 1990)

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Vortex 1 min1 ml destill. water

Positivity 103 ufc

DX: Quantitative Vortex technique (Brun-Buisson, 1987)

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Methods for catheter tip culture

Bouza E. C.I.D. 2005

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DX: Long-term tunneled catheters

Prospective study, 149 tunneled catheters

Colonized (26.2%). Causing CRBSI 11 (7.4%)

Guembe M, Bouza E. J.Clin.Microbiol. 2012

Roll-plate method (95%)

Sonication (44%)

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DX: Long-term tunneled catheters

Gram stain of the tip in the prediction of

Colonization or CRBSI

Guembe M, Bouza E. J.Clin.Microbiol. 2012

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DX: Gram stain

Impression smear

Randomized trial, Gram stain

Before or after rolling ?

Bouza E. D.M.I.D. 2006

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DX: Gram stain

Bouza E. D.M.I.D. 2006

Author. Year

Study Sen % Spe% PPV% NPV%

Cooper1985NEJM

Cath tips 100 97 84 100

Collignon1987Arch I M

Cath tips 83 81 44 96

Aygun2006DMID

Cath tips 100 95 70 100

Bouza2006DMID

Before CAfter C

94.3%69.6%;

92.4%96.2%

80.6%86.7%;

98.0%/90.0%;

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Is all this valid for implantabledevices?Is all this valid for implantabledevices?

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DX: Implantable systemsDX: Implantable systems

Douard MC. C.I.D. 1999

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DX: Implantable systemsDX: Implantable systems

PunchPunch

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Reservoire

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Catheter tip

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Conservative Diagnostictechniques. Conservative Diagnostictechniques.

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High Positive Predictive ValueLow Negative Predictive Value

Dx: Clinical clues: Exit site infectionDx: Clinical clues: Exit site infection

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Are surveillance cultures useful and anticipative?Are surveillance cultures useful and anticipative?

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4/2/2012 51Bouza E. Crit.Care Med. 2005

Dx. Surveillance of superficial cultures

A prospective cohort study11 bed ICU for Major Heart Surgery130 patients, 561 catheters3,712 cultures taken

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Prediction of superficial cultures for CR-BSIPrediction of superficial cultures for CR-BSI

Sensitivity 100% (74.7-100)

Specificity 64.7% (60.5-68.6)

PPV 7.2% (4.2-11.8)

NPV 100% (98.7-100)

PLR 2.83 (2.83-2.83)

NLR 0 (0.10-0.10)

Accuracy 65.6% (65.5-65.7)

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Predictive Value of Superficial Cultures to Anticipate Tunneled Hemodialysis Catheter-Related Bloodstream Infections. “COCADI”

Department of Nephrology

Department of Clinical Microbiology and Infectious Diseases

Surveillance superficial cultures (skin and hubs)

Patients with an hemodialysis tunneled catheter

HIGH PREVALENCE OF CATHETER USE.

INCIDENCE CRBSI RATE: 0,35 EPISODES / 1,000 CATHETER DAYS.

HIGH PREVALENCE OF SKIN COLONIZATION (64.3%).

NONE OF UN-COLONIZED POPULATION DEVELOPED INFECTION (SENSITIVITY AND NPV 100%).

COLONIZED POPULATION PREVENTIVE MEASURES.

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Conservative diagnostic techniques?Conservative diagnostic techniques?

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DX: Comparative quantitative bacteremiaDX: Comparative quantitative bacteremia

≥ 3 timesSpecificity 100%

Sensitivity >80%

Mosca . Surgery 1987Mermel L. C.I.D. 2009

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DX: Differential time to positivityDX: Differential time to positivity

Blot. J.Clin.Microbiol. 1998Mermel L. CID. 2009

≥ 2 hoursFor all microorganisms?

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Raad I. Ann.Intern.Med. 2004

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DTP: In Intensive Care UnitsDTP: In Intensive Care Units

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DQC:LysisSuperficial DTP

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Superficial DQC DTTP

Sensitivity 78.6 71.4 96.4

Specificity 92.0 97.7 90.3

PPV 61.1 83.3 61.4

NPV 96.4 95.6 99.4

Accuracy 90.2 94.1 91.2

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IDSA Guidelines-2009: Blood culturesIDSA Guidelines-2009: Blood cultures

16It is not clear how many lumens of the catheter must be cultured to do differential blood cultures

Mermel L. C.I.D. 2009

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4/2/2012 62Guembe M. Bouza E. C.I.D. In press

Number of lumens to culture

How Many Lumens Should Be Cultured inthe Conservative Diagnosis of Catheter-Related Bloodstream Infections?

Multilumen catheters with confirmed CR-BSIBlood obtained by all lumensMissed episodes if blood had not been

cultured from 1 or 2 lumens

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4/2/2012 63Guembe M. Bouza E. C.I.D. 2011

Episodes diagnosed according to blood taken from different lumens

Double-Lumen (112)

Triple lumen (59)

Culturing 1 lumen

72.8% 62.7%

Culturing 2 lumens

100% 84.2%

Culturing 3lumens

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Is all of this valid for Candidemia?Is all of this valid for Candidemia?

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Median time to positivity in Candidemia blood cultures (hours)Median time to positivity in Candidemia blood cultures (hours)

0 20 40 60 80

C krusei

C. tropicalis

C. parapsilosis

C. albicans

C. glabrata

Bouza E. Unpublished information. 2012

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Diferential time to positivity

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Time to positivity< 30 hSensitive but non-specific> 30 h Rule out Catheter origin

Time to positivity and candidemia

Ben-Ami R. J.Clin.Microb. 2008

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108 episodes of candidemia in adults (84) and children (24)

Our study in Madrid

> 30 h > 30 h

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Is the species of Candida of any help?Is the species of Candida of any help?

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C. parapsilosis is more frequently associated to catheter infection and has a better prognosis

Candida parapsilosis

Anaissie E. Am.J.Med. 1998

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Our Experience in HGUGM. Madrid

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How to treat?How to treat?

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Systemic +

Lock therapy

Systemic +

Lock therapy

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GlycopeptidesLinezolid

++Ceftazidime/Cefepime

Aztreonam

Carbapenems/Pip-Tazo

Tx: Drugs for empirical therapyTx: Drugs for empirical therapy

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-Taurolidine

-Derivative of Tauronimide

-Antiseptic developed in the 60’s

-Active against Gram + and Gram –

-Antifungal activity

-Available as a 2% solution

-Non toxic. Metabolized to taurine+CO2+H2O

-Can be administered intraperitoneally and IV

-Taurolidine

-Derivative of Tauronimide

-Antiseptic developed in the 60’s

-Active against Gram + and Gram –

-Antifungal activity

-Available as a 2% solution

-Non toxic. Metabolized to taurine+CO2+H2O

-Can be administered intraperitoneally and IV

Treatment: TaurolidineTreatment: Taurolidine

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Technique2.3 mL

74% ethanol

20-24 h

Treatment: Antibiotic lock techniqueTreatment: Antibiotic lock technique

Dannenberg C. J.Ped.Hemat.Oncol.2003

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PreventionPrevention

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Pronovost P. N.Engl.J.Med. 2006

The tolerance 0

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4/2/2012 79Labeau SO. Crit.Care.Med. 2009

Knowledge of European nurses

¿What European ICU nurses know about preventive measures of CRI’s?

26 countries, 3405 questionnaires

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4/2/2012 80Ramritu P. Am.J.Infect. Control. 2008

Antibiotic coated catheters.

Non antibiotic coated catheteres vs Antibiotic coated cathetersIntensive Care Units

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4/2/2012 81Lorente L. C.I.D. 2008

Rifampin-Miconazole Coated catheters

ICU. Femoral catheters (184)

73 Rifa-Miconazole/115 standardYugular Catheters (241)

114 Rifa-Miconazole/127 standard

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4/2/2012 82Lorente L. C.I.D. 2008

8,6/1000

Femoral

4,93/1000

Yugular

Rifampin-Miconazole Coated catheters

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Ethanol lock prevencion

Academic, prospective, randomized, clinical trial

Intensive Care Unit post Major Heart Surgery

Prevention of CR-BSI, Tolerance

Pérez-Granda M. ECCMID 2012

Ethanol lock therapy in the prevention of catheter‐related bloodstream

infections after major heart surgery

M.J. Pérez, J.M. Barrio*, C. Rincón, J. Hortal, P. Martín‐Rabadán, S.

Pernia, E. Bouza (Madrid, ES)

Ethanol Locks

every 3 days

Conventional care

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Prospective randomized, clinical trial

Intensive Care Unit post Major Heart Surgery

Prevention of CR-BSI, Tolerance

Pérez-Granda M. ECCMID 2012

Ethanol Locks

every 3 days

Conventional care

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Non-significant reduction in CR-BSI

Cumbersome and some adverse eventsPérez-Granda M. ECCMID 2012

Ethanol Locks

every 3 days

100 cases

Conventional care

100 cases

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The future

Better definitions of CR-BSI. Genotypic identity

Better diagnostic techniques: Molecular biology

Better catheter materials

Better antibiotic treatments with catheter

preservation

Better prevention and zero tolerance to infection

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10Commandments10Commandments

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1.- ESCMID executive

2.- Award Committee

3.- Founding Members of the SEIMC

4.- My mentors

5.- My long term and short term colleagues

6.- The Spanish Microbiologists and ID clinicians

7.- The old members of my team

8.- The young members of my team

9.- My very generous friends

10.- My family and grandson

1.- ESCMID executive

2.- Award Committee

3.- Founding Members of the SEIMC

4.- My mentors

5.- My long term and short term colleagues

6.- The Spanish Microbiologists and ID clinicians

7.- The old members of my team

8.- The young members of my team

9.- My very generous friends

10.- My family and grandson

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The endThe end

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