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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 +

4

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

12

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

28

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

48

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!

53 Bibliography (1/4) Mandell, Douglas, and Bennett, Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 7th ed., 2010 Munoz-Price, Jacoby, “Extended spectrum beta lactamase”, Up to Date Online, Jan 20 th 2012, http://www.uptodate.com/contents/extended- spectrum-beta-lactamases?source=search_result&search=esbl&selectedTitle=1~39 Pitout JD, “Infections with extended-spectrum beta-lactamase-producing enterobacteriaceae: changing epidemiology and drug treatment choices”, Drugs. 2010 Feb 12;70(3):313-3 Fraimow HS, Tsigrelis C, “Antimicrobial resistance in the intensive care unit: mechanisms, epidemiology, and management of specific resistant pathogens”, Crit Care Clin. 2011 Jan;27(1):163-205Crit Care Clin. Dhillon R, Clark J, “ESBLs: A Clear and Present Danger?”, Crit Care Res Pract. 2012;2012:625170. Epub 2011 Jun 6.Crit Care Res Pract. Jacoby, Munoz-Price, “The new beta-lactamase”, N Engl J Med. 2005 Jan 27;352(4):380-91 Calgary Laboratory Services, “Antibiograms 2008-2010” Peirano G, “Molecular epidemiology of extended-spectrum-b-lactamase-producing Klebsiella pneumoniae over a 10 year period in Calgary, Canada”, J Antimicrob Chemother, Advanced Access published Feb 14th 2012 Zhanel et al., “Prevalence of Antimicrobial-Resistant Pathogens in Canadian Hospitals: Results of the Canadian Ward Surveillance Study (CANWARD 2008) ”, ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Nov. 2010, p. 4684–4693 Peirano et al, “Molecular Epidemiology over an 11-Year Period (2000 to 2010) of Extended-Spectrum -Lactamase-Producing Escherichia coli Causing Bacteremia in a Centralized Canadian Region``, J. Clin. Microbiol. 2012, 50(2):294. Pitout et al, “Molecular Characteristics of Extended-Spectrum--Lactamase- Producing Escherichia coli Isolates Causing Bacteremia in the Calgary Health Region from 2000 to 2007: Emergence of Clone ST131 as a Cause of Community-Acquired Infections“, Antimicrob. Agents Chemother. 2009, 53(7):2846. Bertrand et al, “Antimicrobial Susceptibility Among Gram-Negative Isolates Collected From Intensive Care Units in North America, Europe, the Asia-Pacific Rim, Latin America, the Middle East, and Africa Between 2004 and 2009 as Part of the Tigecycline Evaluation and Surveillance Trial“, Clinical Therapeutics, /Volume 34, Number 1, 2012 Baquero et al, “In Vitro Susceptibilities of Aerobic and Facultatively Anaerobic Gram-Negative Bacilli Isolated from Patients with Intra- Abdominal Infections Worldwide: 2005 Results from Study for Monitoring Antimicrobial Resistance Trends (SMART) “, SURGICAL INFECTIONS, Volume 10, Number 2, 2009 Polsfuss et al., “Comparison of European Committee on Antimicrobial Susceptibility Testing (EUCAST) and CLSI screening parameters for the detection of extended-spectrum β-lactamase production in clinical Enterobacteriaceae isolates “, J Antimicrob Chemother. 2012 Jan;67(1):159- 66. Epub 2011 Oct 3.J Antimicrob Chemother. Rodriguez-Bano et al., “Impact of changes in CLSI and EUCAST breakpoints for susceptibility in bloodstream infections due to extended- spectrum β-lactamase-producing Escherichia coli.“, Clin Microbiol Infect. 2011 Sep 13. doi: 10.1111/j.1469-0691.2011.03673 Matsumara et al., “Cefotaxime for the detection of extended-spectrum β-lactamase or plasmid-mediated AmpC β-lactamase and clinical characteristics of cefotaxime-non-susceptible Escherichia coli and Klebsiella pneumoniae bacteraemia.“, Eur J Clin Microbiol Infect Dis. 2011 Dec 31. [Epub ahead of print] Eur J Clin Microbiol Infect Dis.

54 Bibliography (2/4) Rodriguez-Bano et al., “Community-Onset Bacteremia Due to Extended-Spectrum b-Lactamase–Producing Escherichia coli: Risk Factors and Prognosis “, Clin Infect Dis. 2010 Jan 1;50(1):40-8.Clin Infect Dis. Rodriguez-Bano et al., “Epidemiology and clinical features of community-acquired, healthcare-associated and nosocomial bloodstream infections in tertiary-care and community hospitals.”, Clin Microbiol Infect. 2010 Sep;16(9):1408-13.Clin Microbiol Infect. Sang-Oh et al., “Reduced Use of Third‐Generation Cephalosporins Decreases the Acquisition of Extended‐Spectrum Beta‐Lactamase– Producing Klebsiella pneumoniae”, Control and Hospital Epidemiology, Vol. 25, No. 10 (October 2004), pp. 832-837 Huang et al., “Risk factors of nosocomial infection with extended-spectrum beta-lactamase-producing bacteria in a neonatal intensive care unit in China.”, Infection. 2007 Oct;35(5):339-45. Epub 2007 Aug 25.Infection. Otéo et al., “Extended-spectrum b-lactamase producing Escherichia coli: changing epidemiology and clinical impact”, Infection. 2007 Oct;35(5):339-45. Epub 2007 Aug 25.Infection. Harris et al., “Risk factors for colonization with extended-spectrum beta-lactamase-producing bacteria and intensive care unit admission.”, Emerg Infect Dis. 2007 Aug;13(8):1144-9.Emerg Infect Dis. Kuster et al., “Risks factors for infections with extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae at a tertiary care university hospital in Switzerland.”, Infection. 2010 Feb;38(1):33-40. Epub 2010 Jan 27. Infection. Tangdén et al., “Foreign travel is a major risk factor for colonization with Escherichia coli producing CTX-M-type extended-spectrum beta-lactamases: a prospective study with Swedish volunteers.”, Antimicrob Agents Chemother. 2010 Sep;54(9):3564-8. Epub 2010 Jun 14. Antimicrob Agents Chemother. Leung et al., “Prevalence and predictors of MRSA, ESBL, and VRE colonization in the ambulatory IBD population.”, J Crohns Colitis. 2012 Jan 9. [Epub ahead of print]J Crohns Colitis. Paterson et al., “International prospective study of Klebsiella pneumoniae bacteremia: implications of extended-spectrum beta- lactamase production in nosocomial Infections.”, Ann Intern Med. 2004 Jan 6;140(1):26-32Ann Intern Med. Pena et al., ” Epidemiology and successful control of a large outbreak due to Klebsiella pneumoniae producing extended-spectrum beta- lactamases.”, Antimicrob Agents Chemother. 1998 Jan;42(1):53-8.Antimicrob Agents Chemother. Lucet et al., “Outbreak of multiply resistant enterobacteriaceae in an intensive care unit: epidemiology and risk factors for acquisition.”, Clin Infect Dis. 1996 Mar;22(3):430-6. Clin Infect Dis. Apisarthanarak et al., “Duration of Stool Colonization in Patients Infected with Extended-Spectrum b-Lactamase–Producing Escherichia coli and Klebsiella pneumoniae “, Clinical Infectious Diseases 2008; 46:1322–3 Tham et al., “Duration of colonization with extended-spectrum beta-lactamaseproducing Escherichia coli in patients with travellers ’ diarrhoea”, Scandinavian Journal of Infectious Diseases, 2012; Early Online, 1–5 Alsterlund et al., “Long-term carriage of extended-spectrum beta-lactamase-producing Escherichia coli”, Scandinavian Journal of Infectious Diseases, 2012; 44: 51–54 Freeman et al., “Bloodstream infection with extended-spectrum beta-lactamase-producing Enterobacteriaceae at a tertiary care hospital in New Zealand: risk factors and outcomes.”, Int J Infect Dis. 2012 Mar 6. [Epub ahead of print]

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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