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ESBL Jasmin Fauteux March 29 th 2012. PLC Intake 66 yo female with dysuria and pelvic pain Just returned from visit to Pakistan VS Normal Physical exam:

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Presentation on theme: "ESBL Jasmin Fauteux March 29 th 2012. PLC Intake 66 yo female with dysuria and pelvic pain Just returned from visit to Pakistan VS Normal Physical exam:"— Presentation transcript:

1 ESBL Jasmin Fauteux March 29 th 2012

2 PLC Intake 66 yo female with dysuria and pelvic pain Just returned from visit to Pakistan VS Normal Physical exam: Mild right CVA tenderness Seen 2d ago and given Cipro for UTI

3 UA: WBC-21-30 Nitrites +


5 E. Coli > 8 x 10 6 AmpicillinR CeftriaxoneR Pip/tazoS CiproR NitrofurantoinS TMP/SMXS Disposition?

6 Goals Definition Microbiology Incidence Risk factors Morbidity Management Prevention

7 A new problem? 1940s: First β-lactamase in E. coli 1980s: Introduction of Cefotaxime in Europe 1984: First reported case of ESBL in France and Germany 1988: First case in US

8 Definitions Beta-lactams – Beta-lactam ring that inhibits cell wall synthesis – Penicillins, cephalosporins, carbapenems and monobactams Beta-lactamase – Bacterial enzymes that open the beta-lactam ring, inactivating the antibiotic – Currently over 600 β-lactamases

9 Extended spectrum β-lactamase Activity against oxyimino-cephalosporins (3 rd generation) and monobactams but not the cephamycins Inhibition by beta-lactam inhibitors AmpC – Resitant to cephamycins and beta-lactam inhibitors Carbapenemase – Resistant to carbapenems

10 Extended spectrum β-lactamase Heterogeneous group Testing of various oxyimino-β-lactams required

11 Which bugs? All Gram-negative bacterias – Klebsiella species – E. coli – Pseudomonas – Acinetobacter – Burkholderia – Citrobacter – Enterobacter – Morganella – Proteus – Salmonella – Serratia – Shigella


13 Detection 2010 CLSI – New MIC criterias – Correlates with clinical outcome

14 CLSI Sensitivity ESBLCefotaximeCeftriaxoneCefpodoximeCeftazidimeCefepime Se99,2% 98,3%65,3%11,9% Sp40,7%41,5%44,9%55,9%99,2% AmpCCefotaximeCeftriaxoneCefpodoximeCeftazidimeCefepime Se100% 84,6%7,7% Sp34,6%41%32,1%39,7%100%

15 Any gram-negative bacteria Resistance to a single 3 rd generation cephalosporin

16 Klebsiella E. Coli 12,8% 4,7% 26,6% 13,9% 35,5% 26,3% 45,5% 25,9% 33,8% 32,4% 54,9% 12,9%

17 Canada ESBLAmp CCarbapenem R E. Coli4,4%*2,6% K. Pneumoniae1,3% Pseudomonas7,2%5,6% CANWARD 2008 *CANWARD 2007-2009

18 Calgary E. coli Molecular Epidemiology over an 11-Year Period (2000 to 2010) of Extended-Spectrum -Lactamase-Producing Escherichia coli Causing Bacteremia in a Centralized Canadian Region, Peirano et al, Journal of Clinical microbiology

19 Calgary E. Coli 2008-2010 Antibiograms – Sensitivity to Ceftriaxone ACHPLCFMCRGH E. Coli93%87%90%87%

20 Calgary K. pneumoniae Molecular epidemiology of extended-spectrum-b-lactamase-producing Klebsiella pneumoniae over a 10 year period in Calgary, Canada, Peirano, G. Journal of Clinical Microbiology

21 Calgary Klebsiella 2008-2010 Antibiograms – Sensitivity to Ceftriaxone ACHPLCFMCRGH Klebsiella species95%94%97%98%

22 Calgary P. aeruginosa 2008-2010 Antibiograms ACHPLCFMCRGH Ceftazidime93%94%87%96% Meropenem-94%91%90%

23 Risk Factors

24 Colonization is the main risk factor

25 Carrier -24-33% still colonized at 6mo -10-12% still colonized at 3+ years

26 Prior antibiotic use CONSISTENTLY increases your risk

27 All antibiotics 3 rd generation cephalosporins – Restriction of use caused reduction in ESBL infection


29 88% of healthy travelers returning from India were colonized with ESBL E.coli

30 Klebsiella E. Coli 12,8% 4,7% 26,6% 13,9% 35,5% 26,3% 45,5% 25,9% 33,8% 32,4% 54,9% 12,9%

31 - Hospital stay and contact - Health care workers contact - Long term care

32 Instrumentation Central or arterial line Urinary catheter Mechanical ventilation G/J-tube Hemodialysis

33 Severity of illness Comorbidities Low birth weight (NICU)

34 Who cares?

35 Hospital cost and length of stay roughly double

36 -OR for mortality = 2,35 -Adjusted for sepsis severity and with appropriate initial therapy = 1,37

37 Inappropriate therapy increases mortality by 2-10 fold

38 Back to our patient…

39 Management High bacterial inoculum Uncomplicated UTI

40 Everything but uncomplicated UTI Carbapenems – Need to speak to ID – Ertapenem 1g IV q 24hrs – In patient vs outpatient

41 Serious bacterial infections Treatment Even with In Vitro susceptibility, we should not use: – 3 rd generation cephalosporins – 4 th generation cephalosporins* – Cephamycins – Pip/tazo – Fluoroquinolones – Aminoglycosides * Might change with 2010 CLSI, potential future therapy

42 What if… Speak to ID -Amikacin -Tigecycline -Colistin

43 Uncomplicated UTI If sensitive -Nitrofurantoin - 5 days -Fosfomycin* - 3g PO once -Fluroquinolones – May be considered *Not available in Canada

44 Prevention Isolation of ESBL Responsible antibiotic use Avoiding unnecessary procedures

45 Contact Isolation Reduces incidence of ESBL by 55% In Calgary: - no isolation - no screening

46 Antibiotic stewardship Use of narrower spectrum antibiotics – Avoiding cephalosporins and fluroquinolones Minimizing days of therapy

47 Avoid unnecessary procedures


49 Carbapenem resistance

50 Pseudomonas: 3,3% A. Baumannii: 2,7% E. Coli & Klebsiella: 0,1% Mortality:40-60% Contact ID & contact isolation

51 Thanks to Dr. Michael Parkins Dr. Shawn Dowling

52 Thank you!

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55 Bibliography (3/4) Ben-Avi et al., “Influx of extended-spectrum beta-lactamase-producing enterobacteriaceae into the hospital.”, Clin Infect Dis. 2006 Apr 1;42(7):925-34. Epub 2006 Feb 27.Clin Infect Dis. Martins et al., “Endemic extended-spectrum beta-lactamase-producing Klebsiella pneumoniae at an intensive care unit: risk factors for colonization and infection.”, Microb Drug Resist. 2006 Spring;12(1):50-8.Microb Drug Resist. Skrlin et al., “Impact of ceftriaxone de-restriction on the occurrence of ESBL-positive bacterial strains and antibiotic consumption.”, J Chemother. 2011 Dec;23(6):341-4. Tumbarello et al., “Costs of bloodstream infections caused by Escherichia coli and influence of extended-spectrum-beta-lactamase production and inadequate initial antibiotic therapy.”, Antimicrob Agents Chemother. 2010 Oct;54(10):4085-91. Epub 2010 Jul 26. Marchaim et al., “National multicenter study of predictors and outcomes of bacteremia upon hospital admission caused by Enterobacteriaceae producing extended-spectrum beta-lactamases.”, Antimicrob Agents Chemother. 2010 Dec;54(12):5099-104. Epub 2010 Sep 13.Antimicrob Agents Chemother. Tumbarello et al., “Predictors of mortality in patients with bloodstream infections caused by extended-spectrum-beta-lactamase-producing Enterobacteriaceae: importance of inadequate initial antimicrobial treatment.”, Antimicrob Agents Chemother. 2007 Jun;51(6):1987-94. Epub 2007 Mar 26.Antimicrob Agents Chemother. Wouter et al., “Effects of confounders and intermediates on the association of bacteraemia caused by extended-spectrum b-lactamase-producing Enterobacteriaceae and patient outcome: a meta-analysis”, J Antimicrob Chemother. 2012 Mar 5. [Epub ahead of print]J Antimicrob Chemother. Schwaber et al., “Mortality and delay in effective therapy associated with extended-spectrum beta-lactamase production in Enterobacteriaceae bacteraemia: a systematic review and meta-analysis.”, J Antimicrob Chemother. 2007 Nov;60(5):913-20. Epub 2007 Sep 11.J Antimicrob Chemother. Rottier et al., “Effects of confounders and intermediates on the association of bacteraemia caused by extended-spectrum β-lactamase-producing Enterobacteriaceae and patient outcome: a meta-analysis.”, J Antimicrob Chemother. 2012 Mar 5. [Epub ahead of print]J Antimicrob Chemother. Park et al., “Clinical and Microbiologic Characteristics of Cephalosporin-Resistant Escherichia coli in Three Centers in the United States.”, Antimicrob Agents Chemother. 2012 Apr;56(4):1870-6. Epub 2012 Jan 30. Antimicrob Agents Chemother. Kanj et al., “Current Concepts in Antimicrobial Therapy Against Resistant Gram-Negative Organisms: Extended-Spectrum β-Lactamase–Producing Enterobacteriaceae, Carbapenem-Resistant Enterobacteriaceae, andMultidrug-Resistant Pseudomonas aeruginosa”, Mayo Clin Proc. 2011 Mar;86(3):250-9.Mayo Clin Proc. Garau J, “Other antimicrobials of interest in the era of extended-spectrum b-lactamases: fosfomycin, nitrofurantoin and tigecycline``, Clin Microbiol Infect. 2008 Jan;14 Suppl 1:198-202.Clin Microbiol Infect. Meier et al., “Extended-spectrum b-lactamase-producing Gram-negative pathogens in community-acquired urinary tract infections:an increasing challenge for antimicrobial therapy”, Infection. 2011 Aug;39(4):333-40. Epub 2011 Jun 25.

56 Bibliography (4/4) Éveillard et al., “Diffusion des entérobactéries productrices de β-lactamase à spectre élargi et évolution de leur incidence sur une période de 16 mois dans un centre hospitalier universitaire”, Pathol Biol (Paris). 2001 Sep;49(7):515-21. Lowe et al., “Disparity in infection control practices for multidrug-resistant Enterobacteriaceae.”, Am J Infect Control. 2012 Feb 21. [Epub ahead of print] Ofner-Agostini, “Infection control and antimicrobial restriction practices for antimicrobial-resistant organisms in Canadian tertiary care hospitals. Ofner-Agostini M, Varia M, Johnston L, Green K, Simor A, Amihod B, Bryce E, Henderson E, Stegenga J, Bergeron F; Canadian Nosocomial Infection Surveillance Program, Gravel D.”, Am J Infect Control. 2007 Nov;35(9):563-8. Thomas et al., “Radical reduction of cephalosporin use at a tertiary hospital after educational antibiotic intervention during an outbreak of extended-spectrum b-lactamase-producing Klebsiella pneumoniae”, J Antimicrob Chemother. 2011 May;66(5):1161-7. Epub 2011 Mar 4. Matasaje et al., “Carbapenem-resistant Gram-negative bacilli in Canada 2009–10: results from the Canadian Nosocomial Infection Surveillance Program (CNISP)”, J Antimicrob Chemother. 2012 Mar 7. [Epub ahead of print] Baldwin et al., “Carbapenem resistance in Canada”, Cordova er al., “[Clinical and epidemiological study of an outbreak of KPC-producing Klebsiella pneumoniae infection in Buenos Aires, Argentina.]”, Enferm Infecc Microbiol Clin. 2012 Feb 15. [Epub ahead of print]

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