Download PDF
Semin Respir Crit Care Med 2003; 24(1): 079-088
DOI: 10.1055/s-2003-37919
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Extended-Spectrum Beta-Lactamases

Jan E. Patterson
  • Departments of Medicine (Infectious Diseases) and Pathology, University of Texas Health Science Center at San Antonio, San Antonio, Texas
Further Information

Publication History

Publication Date:
14 March 2003 (online)

   Permissions and Reprints

ABSTRACT

Extended-spectrum beta-lactamases, most commonly found in Klebsiella pneumoniae and Escherichia coli, have increased markedly in the past decade, particularly in the intensive care unit setting. The problem has been significant in the United States but is even more prevalent in parts of Latin America and Asia. These plasmid-mediated beta-lactamases confer resistance to broad-spectrum beta-lactam antibiotics, including third- and fourth-generation cephalosporins, aztreonam, and extended-spectrum penicillins. Other resistances, such as aminoglycoside resistance and trimethoprim/sulfamethoxazole resistance, are often cotransferred on the same plasmid. Fluoroquinolone resistance is often associated, resulting in an organism that is resistant to most of the usual antimicrobial options. Although carbapenems are currently considered the drugs of choice for these pathogens, widespread use of these agents may lead to other resistance problems. Due to limited therapeutic options, prevention and control measures are important. Traditional infection control measures, such as contact precautions, are recommended to prevent spread in intensive care units. In addition, because this type of antimicrobial resistance appears to be particularly influenced by antibiotic utilization, antibiotic control measures may also be a very important intervention in limiting the spread of extended-spectrum beta-lactamases.

KEYWORDS

Extended-spectrum beta-lactamases - gram-negative resistance - Klebsiella pneumoniae

REFERENCES

  • 1 Shah P W, Stille W. Escherichia coli and Klebsiella pneumoniae strains more susceptible to cefoxitin than to third-generation cephalosporins [letter].  J Antimicrob Chemother . 1983;  11 597-598
    PubMedSearch in Google Scholar
  • 2 Jarlier V, Nicolas M H, Fournier G, Philippon A. Extended broad-spectrum beta-lactamases confering transferable resistance to newer beta-lactam agents in Enterobacteriaceae: hospital prevalence and susceptibility pattern.  Rev Infect Dis . 1988;  10 867-878
    PubMedSearch in Google Scholar
  • 3 Jacoby G A, Medeiros A A, O'Brien T F, Pinto M E, Jiang H. Broad-spectrum, transmissible beta-lactamases.  N Engl J Med . 1988;  319 723-724
    PubMedSearch in Google Scholar
  • 4 Quinn J P, Miyashiro D, Sahm D, Flamm R, Bush K. Novel plasmid-mediated beta-lactamase (TEM-10) conferring selective resistance to ceftazidime and aztreonam in clinical isolates of Klebsiella pneumoniae Antimicrob Agents Chemother .  1989;  33 1451-1456
    PubMedSearch in Google Scholar
  • 5 Diekema D J, Pfaller M A, Jones R N, the SENTRY Patricipants Group (Americas). Survey of bloodstream infections due to gram-negative bacilli: frequency of occurrence and antimicrobial susceptibility of isolates collected in the United States, Canada, and Latin America for the SENTRY Antimicrobial Surveillance Program, 1997.  Clin Infect Dis . 1999;  29 595-607
    CrossrefPubMedSearch in Google Scholar
  • 6 Bell J M, Turnidge J D, Gales A C, Pfaller M A, Jones R N. Prevalence of extended-spectrum beta-lactamase-producing clinical isolates in the Asia-Pacific region and South Africa: regional results from SENTRY Antimicrobial Surveillance Program (1998-99).  Diagn Microbiol Infect Dis . 2002;  42 (suppl 1) 193-198
    CrossrefPubMedSearch in Google Scholar
  • 7 Philippon A, Arlet G, Lagrange P H. Origin and impact of plasmid-mediated extended-spectrum beta-lactamases.  Eur J Clin Microbiol Infect Dis . 1994;  13 17-29
    PubMedSearch in Google Scholar
  • 8 Phillippon A, Labia R, Jacoby G. Extended-spectrum beta-lactamases.  Antimicrob Agents Chemother . 1989;  33 1131-1136
    PubMedSearch in Google Scholar
  • 9 Jacoby G A, Medeiros A A. More extended-spectrum beta-lactamases.  Antimicrob Agents Chemother . 1991;  35 1697-1704
    PubMedSearch in Google Scholar
  • 10 Pagani L, Micliavacca R, Pallecchi L. Emerging extended-spectrum beta-lactamases in Proteus mirabilis J Clin Microbiol .  2002;  40 1549-1552
    PubMedSearch in Google Scholar
  • 11 Medeiros A A. Evolution and dissemination of beta-lactamases accelerated by generations of beta-lactam antibiotics.  Clin Infect Dis . 1997;  24 (suppl 1) 19-45
    CrossrefPubMedSearch in Google Scholar
  • 12 Jacoby G A. Development of resistance in gram-negative pathogens: extended-spectrum beta-lactamases. In: Emerging Pathogens in Infectious Disease: A Hospital Practice Special Report February 1999. Minneapolis, Minn: McGraw-Hill 1999: 14-19
    Search in Google Scholar
  • 13 Jacoby G, Bush K. Amino acid sequences for TEM, SHV and OXA extended-spectrum and inhibitor resistant beta-lactamases.  Available at: http://www.lahey.org/studies/webt. htm. Accessed September 22 2002
    Search in Google Scholar
  • 14 Jacoby G A. Extended-spectrum beta-lactamases and other enzymes providing resistance to oxyimino-beta-lactams.  Infect Dis Clin N Amer . 1997;  11 875-887
    PubMedSearch in Google Scholar
  • 15 Guzman-Blanco M, Casellas J M, Sader H S. Bacterial resistance to antimicrobial agents in Latin America.  Infect Dis Clin N Amer . 2000;  14 67-81
    PubMedSearch in Google Scholar
  • 16 Katsanis G P, Spargo J, Ferraro M J, Sutton L, Jacoby G A. Detection of Klebsiella pneumoniae and Escherichia coli strains producing extended-spectrum beta-lactamases.  J Clin Microbiol . 1994;  32 691-696
    PubMedSearch in Google Scholar
  • 17 National Committee on Clinical Laboratory Standards. Performance Standards for Antimicrobial Susceptibility Testing; Eighth International Supplement. NCCLS Document M 100-58, 1998
  • 18 Thomson K S. Controversies about extended-spectrum and AmpC beta-lactamases.  Emerging Infect Dis . 2001;  7 333-336
    PubMedSearch in Google Scholar
  • 19 Sanders C C, Barry A L, Washington J A. Detection of extended-spectrum beta-lactamase-producing members of the family Enterobacteriaceae with the VITEK ESBL test.  J Clin Microbiol. 34 2997-3001
    PubMed
  • 20 Jacoby G A, Han P. Detection of extended-spectrum beta-lactamases in clinical isolates of Klebsiella pneumoniae and Escherichia coli J Clin Microbiol .  1996;  34 908-911
    PubMedSearch in Google Scholar
  • 21 Centers for Disease Control and Prevention. Laboratory capacity to detect antimicrobial resistance, 1998.  Morb Mortal Wkly Rep . 2000;  48 1167-1171
    PubMedSearch in Google Scholar
  • 22 Fridkin S K, Gaynes R P. Antimicrobial resistance in intensive care units.  Clinics in Chest Medicine . 1999;  20 303-316
    CrossrefPubMedSearch in Google Scholar
  • 23 NNIS ICU Surveillance Report.  Available at: http://www. cdc.gov ncidod/hip/NNIS/AR Surv1198.pdf. Accessed September 22 2002
    Search in Google Scholar
  • 24 Paterson D L, Ko W C, Gottberg A V. 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 2206-2212
    CrossrefPubMedSearch in Google Scholar
  • 25 Winokur P L, Canton R, Casellas J M, Legakis N. Variations in the prevalence of strains expressing an extended-spectrum beta-lactamase phenotype and characterization of isolates from Europe, the Americas, and the Western Pacific region.  Clin Infect Dis . 2001;  32 (suppl 2) 94-103
    PubMedSearch in Google Scholar
  • 26 Lucet J C, Chevret S, Decre D. Outbreak of multiply resistant enterobacteriaceae in an intensive care unit: epidemiology and risk factors for acquisition.  Clin Infect Dis . 1996;  22 430-436
    PubMedSearch in Google Scholar
  • 27 De Champs C, Rouby D, Guelon D. A case-control study of an outbreak of infections caused by Klebsiella pneumoniae strains producing CTX-1 (TEM-3) beta-lactamase.  J Hosp Infect . 1991;  18 5-13
    PubMedSearch in Google Scholar
  • 28 Schiappa D A, Hayden M J, Matushek M G. Ceftazidime-resistant Klebsiella pneumoniae and Escherchia coli bloodstream infection: a case-control and molecular epidemiologic investigation.  J Infect Dis . 1996;  174 529-536
    PubMedSearch in Google Scholar
  • 29 Pena C, Pujol M, Ardanuy C. Epidemiology and successful control of a large outbreak due to Klebsiella pneumoniae producing extended-spectrum beta-lactamases.  Antimicrob Agents Chemother . 1998;  42 53-58
    PubMedSearch in Google Scholar
  • 30 Piroth L, Aube H, Doise J M, Vincent-Martin M. Spread of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae: are beta-lactamase inhibitors of therapeutic value?.  Clin Infect Dis . 1998;  27 76-80
    CrossrefPubMedSearch in Google Scholar
  • 31 Rice L B, Willey S H, Papanicolaou G B. Outbreak of ceftazidime resistance caused by extended-spectrum beta-lactamases at a Massachusetts chronic-care facility.  Antimicrob Agents Chemother . 1990;  34 2193-2199
    PubMedSearch in Google Scholar
  • 32 Lautenbach E, Patel J B, Bilker W B, Edelstein P H, Fishman N O. Extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae: risk factors for infection and impact of resistance on outcomes.  Clin Infect Dis . 2001;  32 1162-1171
    CrossrefPubMedSearch in Google Scholar
  • 33 Sader H S, Pfaller M A, Jones R N. Prevalence of important pathogens and the antimicrobial activity of parenteral drugs at numerous medical centers in the United States, II: Study of the intra- and interlaboratory dissemination of extended-spectrum beta-lactamase-producing Enterobacteriaceae Diagn Microbiol Infect Dis .  1994;  20 203-208
    PubMedSearch in Google Scholar
  • 34 Gazouli M, Kaufmann M E, Tzelepi E, Dimopoulou H, Paniara O, Tzouvelekis L S. Study of an outbreak of cefoxitin-resistant Klebsiella pneumoniae in a general hospital.  J Clin Microbiol . 1997;  35 508-510
    PubMedSearch in Google Scholar
  • 35 Horii T, Arakawa Y, Ohta M, Ichiyama S, Wacharotayankun R, Kato N. Plasmid-mediated ampC-type beta-lactamase isolated from Klebsiella pneumoniae confers resistance to broad-spectrum beta-lactams, including moxalactam.  Antimicrob Agents Chemother . 1993;  37 984-990
    PubMedSearch in Google Scholar
  • 36 Martinez-Martinez L, Hernandes-Alles S, Alberti S, Tomas J M, Benedi V J, Jacoby G A. In vivo selection of porin-deficient mutants of Klebsiella pneumoniae with increased resistance to cefoxitin and expanded-spectrum cephalosporins.  Antimicrob Agents Chemother . 1996;  40 342-348
    PubMedSearch in Google Scholar
  • 37 Martinez-Martinez L, Pascual A, Jacoby G A. Quinolone resistance from a transferable plasmid.  Lancet . 1998;  351 797-799
    CrossrefPubMedSearch in Google Scholar
  • 38 Jett B D, Ritchie D J, Reichley R, Bailey T C, Sahm D F. In vitro activities of various beta-lactam antimicrobial agents against clinical isolates of Escherichia coli and Klebsiella spp. resistant to oxyimino cephalosporins.  Antimicrob Agents Chemother . 1995;  39 1187-1190
    PubMedSearch in Google Scholar
  • 39 Rice L B, Carias L L, Bonomo R A, Shlaes D M. Molecular genetics of resistance to both ceftazidime and beta-lactam-beta-lactamase inhibitor combinations in Klebsiella pneumoniae and in vivo response to beta-lactam therapy.  J Infect Dis . 1996;  173 151-158
    PubMedSearch in Google Scholar
  • 40 Thauvin-Eliopoulos C, Tripodi M F, Moellering Jr C R, Eliopoulos G M. Efficacies of piperacillin-tazobactam and cefepime in rats with experimental intra-abdominal abscesses due to an extended-spectrum beta-lactamase-producing strain of Klebsiella pneumoniae Antimicrob Agents Chemother .  1997;  41 1053-1057
    PubMedSearch in Google Scholar
  • 41 Meyer K S, Urban C, Eagan J A, Berger B J, Rahal J J. Nosocomial outbreak of Klebsiella infection resistant to late-generation cephalosporins.  Ann Int Med . 1993;  119 353-358
    PubMedSearch in Google Scholar
  • 42 Naumovski L, Quinn J P, Miyashiro D. Outbreak of ceftazidime resistance due to a novel extended-spectrum beta-lactamase in isolates from cancer patients.  Antimicrob Agents Chemother . 1992;  36 1991-1996
    PubMedSearch in Google Scholar
  • 43 Karas J A, Pillay D G, Muckart D, Sturm A W. Treatment failure due to extended spectrum beta-lactamase.  J Antimicrob Chemother . 1996;  37 203-204
    PubMedSearch in Google Scholar
  • 44 Pornull K J, Rodrigo G, Dornbusch K. Production of a plasmid-mediated AmpC-like beta-lactamase by a Klebsiella pneumoniae septicaemia isolate.  J Antimicrob Chemother . 1994;  34 943-954
    PubMedSearch in Google Scholar
  • 45 Bradford P A, Urban C, Mariano N, Projan S J, Rahal J J, Bush K. Imipenem resistance in Klebsiella pneumoniae is associated with the combination of ACT-1, a plasmid-mediated AmpC beta-lactamase, and the loss of an outer membrane protein.  Antimicrob Agents Chemother . 1997;  41 563-569
    PubMedSearch in Google Scholar
  • 46 Pangon B, Bizet C, Bure A. In vivo selection of a cephamycin-resistant, porin-deficient mutant of Klebsiella pneumoniae producing a TEM-3 beta-lactamase.  J Infect Dis . 1989;  159 1005-1006
    PubMedSearch in Google Scholar
  • 47 Roussel-Delvallez M, Sirot D, Berrouane Y. Bactericidal effect of beta-lactams and amikacin alone or in association against Klebsiella pneumoniae producing extended spectrum beta-lactamase.  J Antimicrob Chemother . 1995;  36 241-246
    PubMedSearch in Google Scholar
  • 48 Paterson D K, Mulazimoglu L, Casellas M N. Epidemiology of ciprofloxacin resistance and its relationship to extended-spectrum beta-lactamase production in Klebsiella pneumoniae isolates causing bacteremia.  Clin Infect Dis . 2000;  30 473-478
    CrossrefPubMedSearch in Google Scholar
  • 49 Neu H C. Carbapenems: special properties contributing to their activity.  Am J Med . 1985;  78 (suppl 6A) 33-40
    PubMedSearch in Google Scholar
  • 50 Paterson D L, Ko W C, Mohapatra S. Klebsiella pneumoniae bacteremia: impact of extended spectrum beta-lactamase production in a global study of 216 patients (abstract J210). Presented at the 37th Interscience Congress on Antimicrobial Agents and Chemotherapy, September 28-October 1, 1997, Toronto, Canada. Washington DC: American Society of Microbiology
  • 51 Bingen E H, Desgardins P, Arlet G. Molecular epidemiology of plasmid spread among extended broad-spectrum beta-lactamase-producing Klebsiella pneumoniae isolates in a pediatric hospital.  J Clin Microbiol . 1993;  31 179-184
    PubMedSearch in Google Scholar
  • 52 Prodinger W M, Fille M, Bauerfeind A. Molecular epidemiology of Klebsiella pneumoniae producing SHV-5 beta-lactamase: parallel outbreaks due to multiple plasmid transfer.  J Clin Microbiol . 1996;  34 564-568
    PubMedSearch in Google Scholar
  • 53 Gori A, Espinasse F, Deplano A, Nonhoff C, Nicolas M H, Struelens M J. Comparison of pulsed-field gel electrophoresis and randomly amplified DNA polymorphism analysis for typing extended-spectrum-beta-lactamase-producing Klebsiella pneumoniae J Clin Microbiol .  1996;  334 2448-2453
    PubMedSearch in Google Scholar
  • 54 Marchese A, Arlet G, Schito G C, Langrange P H, Philippon A. Detection of SHV-5 extended-spectrum beta-lactamase in Klebsiella pneumoniae strains isolated in Italy.  Eur J Clin Microbiol Infect Dis . 1996;  15 245-248
    CrossrefPubMedSearch in Google Scholar
  • 55 Branger C, Bruneau B, Lesimple A L. Epidemiological typing of extended-spectrum-beta-lactamase-producing Klebsiella pneumoniae isolates responsible for five outbreaks in a university hospital.  J Hosp Infect . 1997;  36 23-36
    CrossrefPubMedSearch in Google Scholar
  • 56 Gouby A, Neuwirth C, Bourg G. Epidemiological study by pulsed-field gel electrophoresis of an outbreak of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in a geriatric hospital.  J Clin Microbiol . 1994;  32 301-305
    PubMedSearch in Google Scholar
  • 57 Bauernfeind A, Rosenthal J E, Eberlein E, Holley M, Schweighart S. Spread of Klebsiella pneumoniae producing SHV-5 beta-lactamase among hospitalized patients.  Infection . 1993;  21 18-22
    CrossrefPubMedSearch in Google Scholar
  • 58 Nouvellon M, Pons J-L, Sirot D, Combe J-L, Lemeland J-F. Clonal outbreaks of extended-spectrum beta-lactamase-producing strains of Klebsiella pneumoniae demonstrated by antibiotic susceptibility testing, beta-lactamase typing, and multilocus enzyme electrophoresis.  J Clin Microbiol . 1994;  32 2625-2627
    PubMedSearch in Google Scholar
  • 59 French G L, Shannon K P, Simmons N. Hospital outbreak of Klebsiella pneumoniae resistant to broad-spectrum cephalosporins and beta-lactam-beta-lactamase inhibitor combinations by hyperproduction of SHV-5 beta-lactamase.  J Clin Microbiol . 1996;  34 358-363
    PubMedSearch in Google Scholar
  • 60 Monnet D L, Biddle J W, Edwards J R, the National Nosocomial Infections Surveillance System. Evidence of interhospital transmission of extended-spectrum beta-lactam-resistant Klebsiella pneumoniae in the United States, 1986 to 1993.  Infect Control Hosp Epidemiol . 1997;  18 492-498
    PubMedSearch in Google Scholar
  • 61 Arlet G, Rouveau M, Casin I, Bouvet P JM, Lagrange P H, Philippon A. Molecular epidemiology of Klebsiella pneumoniae strains that produce SHV-4 beta-lactamase and which were isolated in 14 French hospitals.  J Clin Microbiol . 1994;  32 2553-2558
    PubMedSearch in Google Scholar
  • 62 Garner J S, and the Hospital Infection Control Practices Advisory Committee. Guideline for isolation precautions in hospitals.  Am J Infect Control . 1996;  24 24-52
    CrossrefPubMedSearch in Google Scholar
  • 63 Rice L B, Eckstein E C, DeVente J, Shlaes D M. Ceftazidime-resistant Klebsiella pneumoniae isolates recovered at the Cleveland Department of Veterans Affairs Medical Center.  Clin Infect Dis . 1996;  223 118-124
    PubMedSearch in Google Scholar
  • 64 Bradford P A, Cherubin C E, Idemyor V, Rasmussen B A, Bush K. Multiply resistant Klebsiella pneumoniae strains from two Chicago hospitals: identification of the extended-spectrum TEM-12 and TEM-10 ceftazidime-hydrolyzing beta-lactamases in a single isolate.  Antimicrob Agents Chemother . 1994;  38 761-766
    PubMedSearch in Google Scholar
  • 65 Brun-Buisson C, Legrand P, Philippon A, Montravers F, Ansquer M, Duval J. Transferable enzymatic resistance to third-generation cephalosporins during nosocomial outbreak of multiresistant Klebsiella pneumoniae Lancet .  1987;  ii 302-306
    PubMedSearch in Google Scholar
  • 66 Patterson J E, Hardin T C, Kelly C, Garcia R C, Jorgensen J H. Association of antibiotic utilization measures and control of multiple drug resistance in extended-spectrum beta-lactamase-producing (ESBL) Klebsiella pneumoniae Infect Control Hosp Epid .  2000;  21 455-458
    PubMedSearch in Google Scholar
  • 67 Rahal J J, Urban C, Horn D. Class restriction of cephalosporin use to control total cephalosporin resistance in nosocomial Klebsiella J Amer Med Assoc .  1998;  280 1233-1237
    PubMedSearch in Google Scholar
  • 68 Decre D, Gachot B, Lucet J C, Arlet G, Bergogne-Berezin E, Regnier B. Clinical and bacteriologic epidemiology of extended-spectrum beta-lactamase-producing strains of Klebsiella pneumoniae in a medical intensive care unit.  Clin Infect Dis . 1998;  27 834-844
    PubMedSearch in Google Scholar