Diagnosis and Treatment of Extended-Spectrum and AmpC β-Lactamase

Abstract

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French

Objective:

To review the laboratory diagnosis of extended-spectrum β-lactamase (ESBL) and AmpC β-lactamase–producing bacteria and evaluate potential treatment options.

Data Sources:

A PubMed search, restricted to English-language articles, was conducted (1966–May 2007) using the search terms ESBL, AmpC, diagnosis, detection, carbapenem, ertapenem, fluoroquinolone, cephalosporin, cefepime, tigecycline, and colistin. Additional references were identified through review of bibliographies of identified articles.

Study Selection and Data Extraction:

All studies that evaluated laboratory methods for the detection of ESBLs and AmpC β-lactamases and/or the treatment of these organisms were reviewed. All articles that were deemed to be clinically pertinent were included and critically evaluated.

Data Synthesis:

Numerous laboratory techniques are available for the detection of ESBLs. In contrast, laboratory techniques for detection of AmpC β-lactamases are limited, particularly for plasmid-mediated AmpC β-lactamases. Routine microbiologic testing may not detect ESBLs or AmpC β-lactamases. Optimal antibiotic treatment options are derived from limited observational studies and case reports. Randomized clinical trials evaluating appropriate antibiotic treatment options are lacking. In vitro susceptibility does not always correlate with clinical outcomes. The use of imipenem was associated with the lowest incidence of mortality in patients with bacteremia due to ESBL-producing organisms.

Conclusions:

Laboratory detection of ESBLs for most organisms is possible with Clinical and Laboratory Standards Institute–recommended testing. However, these tests can be associated with both false negative and false positive results, particularly with organisms that harbor both ESBL- and plasmid-mediated AmpC β-lactamases. No established guidelines exist for the detection of AmpC β-lactamases. Imipenem and meropenem are superior to other antibiotics for the treatment of serious infections due to ESBL and AmpC β-lactamase–producing gram-negative bacteria. While in vitro data demonstrate that tigecycline, ertapenem, and colistin might be potential choices, clinical experience is lacking.

Keywords

antibacterial agents β-lactamase resistance Enterobacteriaceae microbial sensitivity tests

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References

Karas

Pillay

Muckart

Sturm

. Treatment failure due to extended spectrum beta-lactamase. J Antimicrob Chemother 1996;37:203–4.

Rice

Eckstein

DeVente

Shlaes

. Ceftazidime-resistant Klebsiella pneumoniae isolates recovered at the Cleveland Department of Veterans Affairs Medical Center. Clin Infect Dis 1996;23:118–24.

Paterson

Bonomo

. Extended-spectrum beta-lactamases: a clinical update. Clin Microbiol Rev 2005;18:657–86.

Babic

Hujer

Bonomo

. What's new in antibiotic resistance? Focus on beta-lactamases. Drug Resist Updat 2006;9:142–56.

Pai

Kang

Byeon

. Epidemiology and clinical features of bloodstream infections caused by AmpC-type–beta-lactamase-producing Klebsiella pneumoniae. Antimicrob Agents Chemother 2004; 48: 3720–8.

Shah

Hasan

Ahmed

Hameed

. Extended-spectrum beta-lactamases (ESbLs): characterization, epidemiology and detection. Crit Rev Microbiol 2004;30:25–32.

National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2004, issued October 2004. Am J Infect Control 2004; 32: 470–85.

Goossens

Grabein

. Prevalence and antimicrobial susceptibility data for extended-spectrum beta-lactamase- and AmpC-producing Enterobacteriaceae from the MYSTIC Program in Europe and the United States (1997–2004). Diagn Microbiol Infect Dis 2005;53:257–64.

Woodford

Reddy

Fagan

. Wide geographic spread of diverse acquired AmpC beta-lactamases among Escherichia coli and Klebsiella spp. in the UK and Ireland. J Antimicrob Chemother 2007;59:102–5.

10.

Alvarez

Tran

Chow

Jacoby

. Epidemiology of conjugative plasmid-mediated AmpC beta-lactamases in the United States. Antimicrob Agents Chemother 2004;48:533–7.

11.

Moland

Black

Ourada

Reisbig

Hanson

Thomson

. Occurrence of newer beta-lactamases in Klebsiella pneumoniae isolates from 24 U.S. hospitals. Antimicrob Agents Chemother 2002;46:3837–42.

12.

Jacoby

Munoz-Price

. The new beta-lactamases. N Engl J Med 2005;352:380–91.

13.

Bush

Jacoby

Medeiros

. A functional classification scheme for beta-lactamases and its correlation with molecular structure. Antimicrob Agents Chemother 1995;39:1211–33.

14.

Bradford

. Extended-spectrum beta-lactamases in the 21st century: characterization, epidemiology, and detection of this important resistance threat. Clin Microbiol Rev 2001;14:933–51.

15.

Sanders

. Chromosomal cephalosporinases responsible for multiple resistance to newer beta-lactam antibiotics. Annu Rev Microbiol 1987;41:573–93.

16.

Sanders

Jr. . Type I beta-lactamases of gram-negative bacteria: interactions with beta-lactam antibiotics. J Infect Dis 1986;154:792–800.

17.

Nouda

Harabe

Sumita

Okuda

Fukasawa

. Beta-lactamase stability and inhibitory activity of meropenem combined with a potent antibacterial activity. Chemotherapy 1992;38:218–24.

18.

Ehrhardt

Sanders

Romero

Leser

. Sequencing and analysis of four new Enterobacter ampD alleles. Antimicrob Agents Chemother 1996;40:1953–6.

19.

Performance standards for antimicrobial susceptibility testing; 16th Informational Supplement. M100-S16. Wayne, PA: Clinical and Laboratory Standards Institute, 2006.

20.

Samaha-Kfoury

Araj

. Recent developments in beta lactamases and extended spectrum beta lactamases. BMJ 2003;327:1209–13.

21.

Miro

del Cuerpo

Navarro

Sabate

Mirelis

Prats

. Emergence of clinical Escherichia coli isolates with decreased susceptibility to ceftazidime and synergic effect with co-amoxiclav due to SHV-1 hyperproduction. J Antimicrob Chemother 1998;42:535–8.

22.

Rice

Carias

Hujer

. High-level expression of chromosomally encoded SHV-1 beta-lactamase and an outer membrane protein change confer resistance to ceftazidime and piperacillin–tazobactam in a clinical isolate of Klebsiella pneumoniae. Antimicrob Agents Chemother 2000; 44: 362–7.

23.

Balko

Karlowsky

Palatnick

Zhanel

Hoban

. Characterization of the inoculum effect with Haemophilus influenzae and beta-lactams. Diagn Microbiol Infect Dis 1999;33:47–58.

24.

Queenan

Foleno

Gownley

Wira

Bush

. Effects of inoculum and beta-lactamase activity in AmpC- and extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae clinical isolates tested by using NCCLS ESBL methodology. J Clin Microbiol 2004;42:269–75.

25.

Craig

Bhavnani

Ambrose

. The inoculum effect: fact or artifact? Diagn Microbiol Infect Dis 2004;50:229–30.

26.

Doi

Paterson

. Detection of plasmid-mediated class C beta-lactamases. Int J Infect Dis 2007;11:191–7.

27.

Bell

Chitsaz

Turnidge

Barton

Walters

Jones

. Prevalence and significance of a negative extended-spectrum β-lactamase (ESBL) confirmation test after a positive ESBL screening test among Escherichia coli and Klebsiella pneumoniae: results from the SENTRY Asia–Pacific surveillance program. J Clin Microbiol 2007;45:1478–82. Epub 7 March 2007.

28.

Livermore

Brown

. Detection of beta-lactamase–mediated resistance. J Antimicrob Chemother 2001;48(suppl 1):S59–64.

29.

Endimiani

Luzzaro

Perilli

. Bacteremia due to Klebsiella pneumoniae isolates producing the TEM-52 extended-spectrum beta-lactamase: treatment outcome of patients receiving imipenem or ciprofloxacin. Clin Infect Dis 2004;38:243–51.

30.

Kang

Kim

Park

. Bloodstream infections due to extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae: risk factors for mortality and treatment outcome, with special emphasis on antimicrobial therapy. Antimicrob Agents Chemother 2004;48:4574–81.

31.

Paterson

Von Gottberg

. Antibiotic therapy for Klebsiella pneumoniae bacteremia: implications of production of extended-spectrum beta-lactamases. Clin Infect Dis 2004;39:31–7.

32.

Wong-Beringer

. Therapeutic challenges associated with extended-spectrum, beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae. Pharmacotherapy 2001; 21: 583–92.

33.

Wong-Beringer

Hindler

Loeloff

. Molecular correlation for the treatment outcomes in bloodstream infections caused by Escherichia coli and Klebsiella pneumoniae with reduced susceptibility to ceftazidime. Clin Infect Dis 2002;34:135–46.

34.

Colodner

Samra

Keller

. First national surveillance of susceptibility of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella spp. to antimicrobials in Israel. Diagn Microbiol Infect Dis 2007;57:201–5.

35.

Raveh

Yinnon

Broide

Rudensky

. Susceptibilities of ESBL-producing Enterobacteriaceae to ertapenem, meropenem and piperacillin-tazobactam with and without clavulanic acid. Chemotherapy 2007;53:185–9. Epub 7 Mar 2007.

36.

Woodford

Dallow

Hill

. Ertapenem resistance among Klebsiella and Enterobacter submitted in the UK to a reference laboratory. Int J Antimicrob Agents 2007;29:456–9.

37.

Pillay

Adhikari

Sturm

. Piperacillin/tazobactam in the treatment of Klebsiella pneumoniae infections in neonates. Am J Perinatol 1998;15:47–51.

38.

Emery

Weymouth

. Detection and clinical significance of extended-spectrum beta-lactamases in a tertiary-care medical center. J Clin Microbiol 1997;35:2061–7.

39.

Paterson

Singh

Gayowski

Marino

. Fatal infection due to extended-spectrum beta-lactamase-producing Escherichia coli: implications for antibiotic choice for spontaneous bacterial peritonitis. Clin Infect Dis 1999;28:683–4.

40.

Pena

Pujol

Ardanuy

. Epidemiology and successful control of a large outbreak due to Klebsiella pneumoniae producing extended-spectrum beta-lactamases. Antimicrob Agents Chemother 1998;42:53–8.

41.

Paterson

Von Gottberg

. Outcome of cephalosporin treatment for serious infections due to apparently susceptible organisms producing extended-spectrum beta-lactamases: implications for the clinical microbiology laboratory. J Clin Microbiol 2001;39:2206–12.

42.

Crowley

. Extended-spectrum beta-lactamases in blood culture isolates of Klebsiella pneumoniae: seek and you may find! J Antimicrob Chemother 2001; 47: 728–9.

43.

Pfaller

Sader

Fritsche

Jones

. Antimicrobial activity of cefepime tested against ceftazidime-resistant gram-negative clinical strains from North American Hospitals: report from the SENTRY Antimicrobial Surveillance Program (1998–2004). Diagn Microbiol Infect Dis 2006;56:63–8.

44.

Zanetti

Bally

Greub

. Cefepime versus imipenem–cilastatin for treatment of nosocomial pneumonia in intensive care unit patients: a multicenter, evaluator-blind, prospective, randomized study. Antimicrob Agents Chemother 2003;47:3442–7.

45.

Song

Moland

Hanson

Lewis

Jorgensen

Thomson

. Failure of cefepime therapy in treatment of Klebsiella pneumoniae bacteremia. J Clin Microbiol 2005;43:4891–4.

46.

Ambrose

Bhavnani

Jones

. Pharmacokinetics-pharmacodynamics of cefepime and piperacillin-tazobactam against Escherichia coli and Klebsiella pneumoniae strains producing extended-spectrum beta-lactamases: report from the ARREST program. Antimicrob Agents Chemother 2003;47:1643–6.

47.

Lee

Kuti

Nicolau

. Cefepime pharmacodynamics in patients with extended spectrum beta-lactamase (ESBL) and non-ESBL infections. J Infect 2007;54:463–8. Epub 24 Oct 2006. DOI 10.1016/jinf.2006.09.004

48.

Lautenbach

Strom

Bilker

Patel

Edelstein

Fishman

. Epidemiological investigation of fluoroquinolone resistance in infections due to extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae. Clin Infect Dis 2001; 33: 1288–94.

49.

Spanu

Luzzaro

Perilli

Amicosante

Toniolo

Fadda

. Occurrence of extended-spectrum beta-lactamases in members of the family Enterobacteriaceae in Italy: implications for resistance to beta-lactams and other antimicrobial drugs. Antimicrob Agents Chemother 2002;46:196–202.

50.

Sekowska

Janicka

Klyszejko

Wojda

Wroblewski

Szymankiewicz

. Resistance of Klebsiella pneumoniae strains producing and not producing ESBL (extended-spectrum beta-lactamase) type enzymes to selected non–beta-lactam antibiotics. Med Sci Monit 2002;8: BR100–4.

51.

Sorlozano

Gutierrez

de Dios Luna

. High presence of extended-spectrum beta-lactamases and resistance to quinolones in clinical isolates of Escherichia coli. Microbiol Res 2006. Epub 27 Mar 2006. DOI 10.1016/j.micres.2006.02.003

52.

Kizirgil

Demirdag

Ozden

Bulut

Yakupogullari

Toraman

. In vitro activity of three different antimicrobial agents against ESBL producing Escherichia coli and Klebsiella pneumoniae blood isolates. Microbiol Res 2005;160:135–40.

53.

Paterson

Mulazimoglu

Casellas

. Epidemiology of ciprofloxacin resistance and its relationship to extended-spectrum beta-lactamase production in Klebsiella pneumoniae isolates causing bacteremia. Clin Infect Dis 2000;30:473–8.

54.

Hope

Warner

Potz

Fagan

James

Livermore

. Activity of tigecycline against ESBL-producing and AmpC-hyperproducing Enter-obacteriaceae from south-east England. J Antimicrob Chemother 2006;58:1312–4.

55.

Navon-Venezia

Leavitt

Carmeli

. High tigecycline resistance in multidrug-resistant Acinetobacter baumannii. J Antimicrob Chemother 2007; 59: 772–4.

56.

Peleg

Potoski

Rea

. Acinetobacter baumannii bloodstream infection while receiving tigecycline: a cautionary report. J Antimicrob Chemother 2007;59:128–31.

57.

Sader

Jones

Stilwell

Dowzicky

Fritsche

. Tigecycline activity tested against 26,474 bloodstream infection isolates: a collection from 6 continents. Diagn Microbiol Infect Dis 2005;52:181–6.

58.

Meagher

Ambrose

Grasela

Ellis-Grosse

. The pharmacokinetic and pharmacodynamic profile of tigecycline. Clin Infect Dis 2005;41(suppl 5):S333–40.

59.

Babinchak

Ellis-Grosse

Dartois

Rose

Loh

. The efficacy and safety of tigecycline for the treatment of complicated intra-abdominal infections: analysis of pooled clinical trial data. Clin Infect Dis 2005;41(suppl 5):S354–67.

60.

Ellis-Grosse

Babinchak

Dartois

Rose

Loh

. The efficacy and safety of tigecycline in the treatment of skin and skin-structure infections: results of 2 double-blind phase 3 comparison studies with vancomycin–aztreonam. Clin Infect Dis 2005;41(suppl 5):S341–53.

61.

Bishara

Livne

Ashkenazi

. Antibacterial susceptibility of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae and Escherichia coli. Isr Med Assoc J 2005; 7: 298–301.

62.

Nation

Turnidge

. Colistin: the re-emerging antibiotic for multidrug-resistant gram-negative bacterial infections. Lancet Infect Dis 2006;6:589–601.

Diagnosis and Treatment of Extended-Spectrum and AmpC β-Lactamase–Producing Organisms

Abstract

Objective:

Data Sources:

Study Selection and Data Extraction:

Data Synthesis:

Conclusions:

Keywords

Get full access to this article

References