Extended Spectrum Beta-lactamases in Gram-negative Sepsis

  • D. L. Paterson


Escherichia coli, Klebsiella pneumoniae, and other enteric Gram-negative bacilli are commonly associated with sepsis. Bacteremia caused by such organisms may arise from infections of the urinary tract, the gastrointestinal tract and peritoneal cavity, the lungs, and less commonly from central venous lines and wounds. In many hospitals, at least one third of E. coli strains and greater than 95% of K. pneumoniae strains are resistant to ampicillin. This resistance is usually mediated in E. coli by a plasmid mediated β-lactamase known as TEM-1 and in K. pneumoniae by a chro-mosomally encoded β-lactamase known as SHV-1 (TEM refers to Temoneira, a patient from Athens, Greece, from whom a urinary tract isolate of E. coli bearing the TEM-1 β-lactamase was first isolated in the 1960s. SHV refers to sulfhydryl variable, in reference to the interaction of SHV-1 with p-chloromercuribenzoate). Both TEM-1 and SHV-1 can mediate resistance to ampicillin and first generation cephalosporins, but not to the third generation cephalosporins.


Klebsiella Pneumoniae Antimicrob Agent Clavulanic Acid Generation Cephalosporin ESBL Production 
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  1. 1.
    Knothe H, Shah P, Krcmery V, Antal M, Mitsuhashi S (1983) Transferable resistance to cefotaxime, cefoxitin, cefamandole and cefuroxime in clinical isolates of Klebsiella pneumoniae and Serratia marcescens. Infection 11: 315–317PubMedCrossRefGoogle Scholar
  2. 2.
    Brun-Buisson C, Legrand P, Arlet G, Jarlier V, Paul G, Philippon A (1987) Transferable enzymatic resistance to third-generation cephalosporins during nosocomial outbreak of multiresistant Klebsiella pneumoniae. Lancet 2: 302–306PubMedCrossRefGoogle Scholar
  3. 3.
    Sirot D, Sirot J, Labia R, et al (1987) Transferable resistance to third-generation cephalosporins in clinical isolates of Klebsiella pneumoniae: identification of CTX-1, a novel betalactamase. J Antimicrob Chemother 20: 323–334PubMedCrossRefGoogle Scholar
  4. 4.
    Babini GS, Livermore DM (2000) Antimicrobial resistance amongst Klebsiella spp. collected from intensive care units in Southern and Western Europe in 1997–1998. J Antimicrob Chemother 45: 183–189PubMedCrossRefGoogle Scholar
  5. 5.
    Livermore DM, Yuan M (1996) Antibiotic resistance and production of extended-spectrum beta-lactamases amongst Klebsiella spp. from intensive care units in Europe. J Antimicrob Chemother 38: 409–424PubMedCrossRefGoogle Scholar
  6. 6.
    Hanberger H, Garcia-Rodriguez JA, Gobernado M, Goossens H, Nilsson LE, Struelens MJ (1999) Antibiotic susceptibility among aerobic Gram-negative bacilli in intensive care units in 5 European countries. JAMA 281: 67–71PubMedCrossRefGoogle Scholar
  7. 7.
    Fluit AC, Jones ME, Schmitz FJ, Acar J, Gupta R, Verhoef J (2000) Antimicrobial susceptibility and frequency of occurrence of clinical blood isolates in Europe from the SENTRY antimicrobial surveillance program, 1997 and 1998. Clin Infect Dis 30: 454–460PubMedCrossRefGoogle Scholar
  8. 8.
    Gunseren F, Mamikoglu L, Ozturk S, et al (1999). A surveillance study of antimicrobial resistance of gram-negative bacteria isolated from intensive care units in eight hospitals in Turkey. J Antimicrob Chemother 43: 373–378PubMedCrossRefGoogle Scholar
  9. 9.
    NNIS (1999) Semiannual Report. http://www.cdc.gov/ncidod/hip/NNIS/dec99sar.pdfGoogle Scholar
  10. 10.
    Pfaller MA, Jones RN, Doern GV (1999) Multicenter evaluation of the antimicrobial activity for six broad-spectrum beta-lactams in Venezuela: comparison of data from 1997 and 1998 using the Etest method. Diagn Microbiol Infect Dis 35: 153–158PubMedCrossRefGoogle Scholar
  11. 11.
    Pfaller MA, Jones RN, Doern GV, Salazar JC (1999) Multicenter evaluation of antimicrobial resistance to six broad-spectrum beta-lactams in Colombia: comparison of data from 1997 and 1998 using the Etest method. Diagn Microbiol Infect Dis 35: 235–241PubMedCrossRefGoogle Scholar
  12. 12.
    Lewis MT, Biedenbach DJ, Jones RN (1999) In vitro evaluation of broad-spectrum beta-lactams tested in medical centers in Korea: role of fourth-generation cephalosporins. Diagn Microbiol Infect Dis 35: 317–323PubMedCrossRefGoogle Scholar
  13. 13.
    Lewis MT, Biedenbach DJ, Jones RN (1999) In vitro evaluation of cefepime and other broad-spectrum beta-lactams against bacteria from Indonesian medical centers. Diagn Microbiol Infect Dis 35: 285–290PubMedCrossRefGoogle Scholar
  14. 14.
    Lewis MT, Yamaguchi K, Biedenbach DJ, Jones RN (1999) In vitro evaluation of cefepime and other broad-spectrum beta-lactams in 22 medical centers in Japan: a phase II trial comparing two annual organism samples. Diagn Microbiol Infect Dis 35: 307–315PubMedCrossRefGoogle Scholar
  15. 15.
    Yamaguchi K, Mathai D, Biedenbach DJ, Lewis MT, Gales AC, Jones RN (1999) Evaluation of the in vitro activity of six broad-spectrum beta-lactam antimicrobial agents tested against over 2000 clinical isolates from 22 medical centers in Japan. Japan Antimicrobial Resistance Study Group. Diagn Microbial Infect Dis 34: 123–134Google Scholar
  16. 16.
    Asensio A, Oliver A, Gonzalez-Diego P, et al (2000) Outbreak of a multiresistant Klebsiella pneumoniae strain in an intensive care unit: antibiotic use as risk factor for colonization and infection. Clin Infect Dis 30: 55–60PubMedCrossRefGoogle Scholar
  17. 17.
    Schiappa DA, Hayden MK, Matushek MG, et al (1996) Ceftazidime-resistant Klebsiella pneumoniae and Escherichia coli bloodstream infection: a case-control and molecular epidemiologic investigation. J Infect Dis 174: 529–536PubMedCrossRefGoogle Scholar
  18. 18.
    Lautenbach E, Patel JB, Bilker WB, Edelstein PH, Fishman NO (2001) Extended-spectrum beta-lactamase producing Escherichia coli and Klebsiella pneumoniae: risk factors for infection and impact of resistance on outcome. Clin Infect Dis 32: 1162–1171PubMedCrossRefGoogle Scholar
  19. 19.
    Ariffin H, Navaratnam P, Mohamed M, et al (2000) Ceftazidime-resistant Klebsiella pneumoniae bloodstream infection in children with febrile neutropenia. Int J Infect Dis 4: 21–25PubMedCrossRefGoogle Scholar
  20. 20.
    Rice LB, Eckstein EC, DeVente J, Shlaes DM (1996) Ceftazidime-resistant Klebsiella pneumoniae isolates recovered at the Cleveland Department of Veterans Affairs Medical Center. Clin Infect Dis 23: 118–124PubMedCrossRefGoogle Scholar
  21. 21.
    Saurina G, Quale JM, Manikal VM, Oydna E, Landman D (2000) Antimicrobial resistance in Enterobacteriaceae in Brooklyn, NY: epidemiology and relation to antibiotic usage patterns. J Antimicrob Chemother 45: 895–898PubMedCrossRefGoogle Scholar
  22. 22.
    Pena C, Pujol M, Ricart A, et al (1997) Risk factors for faecal carriage of Klebsiella pneumoniae producing extended-spectrum beta-lactamase ( ESBL-KP) in the intensive care unit. J Hosp Infect 35: 9–16PubMedCrossRefGoogle Scholar
  23. 23.
    D’Agata E, Venkataraman L, DeGirolami P, Weigel L, Samore M, Tenover F (1998) The molecular and clinical epidemiology of enterobacteriaceae-producing extended-spectrum betalactamase in a tertiary care hospital. J Infect 36: 279–285PubMedCrossRefGoogle Scholar
  24. 24.
    Wiener J, Quinn JP, Bradford PA, et al (1999) Multiple antibiotic-resistant Klebsiella and Escherichia coli in nursing homes. JAMA 281: 517–523PubMedCrossRefGoogle Scholar
  25. 25.
    Mangeney N, Niel P, Paul G, et al (2000) A 5-year epidemiological study of extended-spectrum beta-lactamase producing Klebsiella pneumoniae isolates in a medium-and long-stay neurological unit. J Appl Microbiol 88: 504–511PubMedCrossRefGoogle Scholar
  26. 26.
    Lucet JC, Chevret S, Decre D, et al (1996) Outbreak of multiply resistant Enterobacteriaceae in an intensive care unit: epidemiology and risk factors for acquisition. Clin Infect Dis 22: 430–436PubMedCrossRefGoogle Scholar
  27. 27.
    Green M, Barbadora K (1998) Recovery of ceftazidime-resistant Klebsiella pneumoniae from pediatric liver and intestinal transplant recipients. Pediatr Transplant 2: 224–230PubMedGoogle Scholar
  28. 28.
    Soulier A, Barbut F, Ollivier JM, Petit JC, Lienart A (1995) Decreased transmission of Enterobacteriaceae with extended-spectrum beta-lactamases in an intensive care unit by nursing reorganization. J Hosp Infect 31: 89–97PubMedCrossRefGoogle Scholar
  29. 29.
    Paterson DL, Mulazimoglu L, Casellas JM, et al (2000) Epidemiology of ciprofloxacin resistance and its relationship to extended-spectrum beta-lactamase production in Klebsiella pneumoniae isolates causing bacteremia. Clin Infect Dis 30: 473–478PubMedCrossRefGoogle Scholar
  30. 30.
    Brisse S, Milatovic D, Fluit AC, Verhoef J, Schmitz FJ (2000) Epidemiology of quinolone resistance of Klebsiella pneumoniae and Klebsiella oxytoca in Europe. Eur J Clin Microbiol Infect Dis 19: 64–68PubMedCrossRefGoogle Scholar
  31. 31.
    Martinez-Martinez L, Pascual A, Hernandez-Alles S, et al (1999) Roles of beta-lactamases and porins in activities of carbapenems and cephalosporins against Klebsiella pneumoniae. Antimicrob Agents Chemother 43: 1669–1673PubMedGoogle Scholar
  32. 32.
    Paterson DL, Ko WC, Von Gottberg A, et al (2001) 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 39: 2206–2212PubMedCrossRefGoogle Scholar
  33. 33.
    Medeiros AA, Crellin J (1997) Comparative susceptibility of clinical isolates producing extended spectrum beta-lactamases to ceftibuten: effect of large inocula. Pediatr Infect Dis 16 (3 Suppl): S49–S55Google Scholar
  34. 34.
    Rice LB, Yao JD, Klimm K, Eliopoulos GM, Moellering RC Jr (1991) Efficacy of different beta-lactams against an extended-spectrum beta-lactamase-producing Klebsiella pneumoniae strain in the rat intra-abdominal abscess model. Antimicrob Agents Chemother 35: 1243–1244PubMedCrossRefGoogle Scholar
  35. 35.
    Thauvin-Eliopoulos C, Tripodi MF, Moellering RC Jr, Eliopoulos GM (1997) 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 41: 1053–1057PubMedGoogle Scholar
  36. 36.
    Fantin B, Pangon B, Potel G, et al (1990) Activity of sulbactam in combination with ceftriaxone in vitro and in experimental endocarditis caused by Escherichia coli producing SHV-2-like beta-lactamase. Antimicrob Agents Chemother 34: 581–586PubMedCrossRefGoogle Scholar
  37. 37.
    Paterson DL, Singh N, Gayowski T, Marino IR (1999) Fatal infection due to extended-spectrum beta-lactamase-producing Escherichia coli: implications for antibiotic choice for spontaneous bacterial peritonitis. Clin Infect Dis 28: 683–684PubMedCrossRefGoogle Scholar
  38. 38.
    Siu LK, Lu PL, Hseuh PR, et al (1999) Bacteremia due to extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in a pediatric oncology ward: clinical features and identification of different plasmids carrying both SHV-5 and TEM-1 genes. J Clin Microbiol 37: 4020–4027PubMedGoogle Scholar
  39. 39.
    Pangon B, Bizet C, Bure A, et al (1989) In vivo selection of a cephamycin-resistant, porin deficient mutant of Klebsiella pneumoniae producing a TEM-3 beta-lactamase. J Infect Dis 159: 1005–1006PubMedCrossRefGoogle Scholar
  40. 40.
    Wong-Beringer A (2001) Therapeutic challenges associated with extended-spectrum, betalactamase-producing Escherichia coli and Klebsiella pneumoniae. Pharmacotherapy 21: 583592Google Scholar
  41. 41.
    Meyer KS, Urban C, Eagan JA, Berger BJ, Rahal JJ (1993) Nosocomial outbreak of Klebsiella pneumoniae resistant to late generation cephalosporins. Ann Intern Med 119: 353–358PubMedCrossRefGoogle Scholar
  42. 42.
    Rice LB, Willey SH, Papanicolaou GA, et al (1990) Outbreak of ceftazidime resistance caused by extended-spectrum beta-lactamases at a Massachusetts chronic-care facility. Antimicrob Agents Chemother 34: 2193–2199PubMedCrossRefGoogle Scholar
  43. 43.
    Szabo D, Filetoth Z, Szentandrassy J, et al (1999) Molecular epidemiology of a cluster of cases due to Klebsiella pneumoniae producing SHV-5 extended-spectrum beta-lactamase in the premature intensive care unit of a Hungarian hospital. J Clin Microbiol 37: 4167–4169PubMedGoogle Scholar
  44. 44.
    Rahal JJ, Urban C, Horn D (1998) Class restriction of cephalosporin use to control total cephalosporin resistance in nosocomial Klebsiella. JAMA 280: 1233–1237PubMedCrossRefGoogle Scholar
  45. 45.
    Piroth L, Aube H, Doise JM, Vincent-Martin M (1998) Spread of extended-spectrum betalactamase-producing Klebsiella pneumoniae: are beta-lactamase inhibitors of therapeutic value? Clin Infect Dis 27: 76–80PubMedCrossRefGoogle Scholar
  46. 46.
    Patterson JE, Hardin TC, Kelly CA, Garcia RC, Jorgensen JH (2000) Association of antibiotic utilization measures and control of multiple drug resistance in Klebsiella pneumoniae. Infect Control Hosp Epidemiol 21: 455–458PubMedCrossRefGoogle Scholar
  47. 47.
    Paterson DL, Singh N, Rihs JD, Squier C, Rihs BL, Muder RR (2001) Control of an outbreak of infection due to extended-spectrum beta-lactamase-producing Escherichia coli in a liver transplantation unit. Clin Infect Dis 33: 126–128PubMedCrossRefGoogle Scholar
  48. 48.
    Brun-Buisson C, Legrand P, Rauss A, et al (1989) Intestinal decontamination for control of nosocomial multiresistant Gram-negative bacilli. Ann Intern Med 110: 873–881PubMedCrossRefGoogle Scholar
  49. 49.
    De Champs CL, Guelon DP, Gamier RM, et al (1993) Selective digestive decontamination by erythromycin-base in a polyvalent intensive care unit. Intensive Care Med 19: 191–196PubMedCrossRefGoogle Scholar
  50. 50.
    Decre D, Gachot B, Lucet JC, et al (1998) Clinical and bacteriologic epidemiology of extended-spectrum beta-lactamase-producing strains of Klebsiella pneumoniae in a medical intensive care unit. Clin Infect Dis 27: 834–844PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media New York 2002

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  • D. L. Paterson

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