International Prospective Study of Klebsiella pneumoniae Bacteremia: Implications of Extended-Spectrum β-Lactamase Production in Nosocomial Infections

  1. David L. Paterson, MBBS, FRACP;
  2. Wen-Chien Ko, MD;
  3. Anne Von Gottberg, MBChB;
  4. Sunita Mohapatra, MD;
  5. Jose Maria Casellas, MBBS;
  6. Herman Goossens, MD;
  7. Lutfiye Mulazimoglu, MD;
  8. Gordon Trenholme, MD;
  9. Keith P. Klugman, MBChB;
  10. Robert A. Bonomo, MD;
  11. Louis B. Rice, MD;
  12. Marilyn M. Wagener, MPH;
  13. Joseph G. McCormack, MD, FRACP; and
  14. Victor L. Yu, MD
  1. From Veterans Affairs Medical Center, Pittsburgh, Pennsylvania; University of Queensland, Mater Adults Hospital, Brisbane, Queensland, Australia; Department of Medicine, National Cheng Kung University Medical College, Tainan, Taiwan; South African Institute of Medical Research, Johannesburg, South Africa; Rush Presbyterian St. Luke's Medical Center, Chicago, Illinois; Sanatorio San Lucas, Buenos Aires, Argentina; University Hospital, Antwerp, Belgium; Marmara University, Istanbul, Turkey; and Veterans Affairs Medical Center, Cleveland, Ohio.

    Abstract

    Background: Commonly encountered nosocomially acquired gram-negative bacteria, especially Klebsiella pneumoniae, produce extended-spectrum β-lactamases (ESBLs) as an antibiotic resistance mechanism.

    Objective: To determine whether microbiology laboratories should report the presence of ESBLs and to establish the infection-control implications of ESBL-producing organisms.

    Design: Prospective observational study.

    Setting: 12 hospitals in South Africa, Taiwan, Australia, Argentina, the United States, Belgium, and Turkey.

    Patients: 440 patients with 455 consecutive episodes of K. pneumoniae bacteremia between 1 January 1996 and 31 December 1997; of these, 253 episodes were nosocomially acquired.

    Measurements: The K. pneumoniae isolates were examined for the presence of ESBLs. Pulsed-field gel electrophoresis was used to analyze the molecular epidemiology of nosocomial bacteremia with ESBL-producing K. pneumoniae.

    Results: Overall, 30.8% (78 of 253) episodes of nosocomial bacteremia and 43.5% (30 of 69) episodes acquired in intensive care units were due to ESBL-producing organisms. After adjustment for potentially confounding variables, previous administration of β-lactam antibiotics containing an oxyimino group (cefuroxime, cefotaxime, ceftriaxone, ceftazidime, or aztreonam) was associated with bacteremia due to ESBL-producing strains (risk ratio, 3.9 [95% CI, 1.1 to 13.8]). In 7 of 10 hospitals with more than 1 ESBL-producing isolate, multiple strains with the same genotypic pattern were observed, indicating patient-to-patient spread of the organism.

    Conclusions: Production of ESBLs by Klebsiella pneumoniae is a widespread nosocomial problem. Appropriate infection control and antibiotic management strategies are needed to stem the spread of this emerging form of resistance.

    Article and Author Information

    • Acknowledgments: The authors thank the staff and patients of the following hospitals for their participation: Pittsburgh Veterans Affairs Medical Center, Pittsburgh, and Rush Presbyterian St. Luke's Medical Center, Chicago, Illinois; National Cheng Kung University Medical College, Tainan, Taiwan; Royal Brisbane Hospital, Mater Adults Hospital, and Greenslopes Private Hospital, Brisbane, Queensland, Australia; Hillbrow Hospital and Chris Hani Baragwanath Hospital, Johannesburg, South Africa; Marmara University Hospital, Istanbul, Turkey; University Hospital, Antwerp, Belgium; and San Lucas Hospital and Comunidad Olivos Hospital, Buenos Aires, Argentina.

    • Grant Support: By the Cottrell Fellowship of the Royal Australasian College of Physicians, Wyeth-Ayerst Pharmaceuticals, and Merck and Company.

    • Potential Financial Conflicts of Interest:Consultancies: D.L. Paterson (Cubist Pharmaceuticals, AstraZeneca, Merck), K.P. Klugman (Abbott Laboratories, AstraZeneca, Bayer Corp., GlaxoSmithKline Pharmaceuticals), L.B. Rice (Elan, Wyeth, Merck, AstraZeneca, Bristol-Myers Squibb, Ortho-McNeil); Honoraria: D.L. Paterson (Wyeth, Merck, AstraZeneca, Pfizer, Gilead), H. Goossens (Merck), K.P. Klugman (Abbott Laboratories, AstraZeneca, Bayer Corp., GlaxoSmithKline Pharmaceuticals), L.B. Rice (Elan, Wyeth, Merck, Ortho-McNeil); Expert testimony: L.B. Rice (Wyeth); Grants received or pending: D.L. Paterson (Elan, Pharmacia, Merck, AstraZeneca, Dade Microscan, Pfizer, Ortho-McNeil, Bristol-Myers Squibb), H. Goossens (Merck), K.P. Klugman (Abbott Laboratories, Bayer Corp., Bristol-Myers Squibb Co., GlaxoSmithKline Pharmaceuticals), R.A. Bonomo (AstraZeneca, Wyeth Pharmaceuticals, Bristol-Myers Squibb), L.B. Rice (Ortho-McNeil, Elan, Wyeth).

    • Requests for Single Reprints: Victor L. Yu, MD, Infectious Disease Section, Veterans Affairs Medical Center, University Drive C, Pittsburgh, PA 15240; e-mail, vly+{at}pitt.edu.

    • Current Author Addresses: Dr. Paterson: Division of Infectious Diseases, University of Pittsburgh Medical Center, 3601 Fifth Avenue, Pittsburgh, PA 15213.

    • Dr. Ko: National Cheng Kung University Hospital, 138 Sheng Li Road, Tainan, Taiwan.

    • Dr. Von Gottberg: NHLS, Corner De Korte and Hospital Streets, Johannesburg 2000, Republic of South Africa.

    • Drs. Mohapatra and Trenholme: Section of Infection Diseases, Rush Presbyterian St. Luke's Medical Center, Chicago, Illinois.

    • Dr. Casellas: Centro de Estudias en Antimicrobianos, Triunvirato 2789, Buenos Aires, Argentina.

    • Dr. Goossens: Department of Microbiology, University Hospital, Antwerp, Belgium.

    • Dr. Mulazimoglu: Department of Microbiology, Marmara University, Istanbul, Turkey.

    • Dr. Klugman: Emory University, 1518 Clifton Road, Atlanta, GA 30322.

    • Drs. Bonomo and Rice: Louis Stokes Cleveland Veterans Affairs Medical Center, 10701 East Boulevard, Cleveland, OH 44106.

    • Ms. Wagener: University of Pittsburgh, Pittsburgh, PA 15240.

    • Dr. McCormack: University of Queensland Department of Medicine, Mater Adults Hospital, Brisbane, Queensland 4101, Australia.

    • Dr. Yu: Infectious Disease Section, Veterans Affairs Medical Center, University Drive C, Pittsburgh, PA 15240.

    • Author Contributions: Conception and design: D.L. Paterson, K.P. Klugman, J.G. McCormack, V.L. Yu.

    • Analysis and interpretation of the data: D.L. Paterson, A. Von Gottberg, K.P. Klugman, L.B. Rice, M.M. Wagener, V.L. Yu.

    • Drafting of the article: D.L. Paterson, A. Von Gottberg, J.G. McCormack, V.L. Yu.

    • Critical revision of the article for important intellectual content: D.L. Paterson, J.M. Casellas, K.P. Klugman, L.B. Rice, J.G. McCormack.

    • Final approval of the article: D.L. Paterson, A. Von Gottberg, H. Goossens, K.P. Klugman, L.B. Rice, M.M. Wagener, J.G. McCormack, V.L. Yu.

    • Provision of study materials or patients: W.-C. Ko, A. Von Gottberg, S. Mohapatra, H. Goossens, G. Trenholme, K.P. Klugman, V.L. Yu.

    • Statistical expertise: M.M. Wagener.

    • Obtaining of funding: V.L. Yu.

    • Administrative, technical, or logistic support: A. Von Gottberg, R.A. Bonomo.

    • Collection and assembly of data: D.L. Paterson, W.-C. Ko, A. Von Gottberg.

    Summary for Patients

    • Summaries for Patients:Worldwide Prevalence of Antibiotic Resistance in the Bacteria Klebsiella pneumoniae Ann Intern Med January 6, 2004 140:I-43
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    1. Ann Intern Med January 6, 2004 vol. 140 no. 1 26-32
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