Diagnosis and treatment of extended-spectrum and AmpC beta-lactamase-producing organisms

Ann Pharmacother. 2007 Sep;41(9):1427-35. doi: 10.1345/aph.1K213. Epub 2007 Jul 31.

Abstract

Objective: To review the laboratory diagnosis of extended-spectrum beta-lactamase (ESBL) and AmpC beta-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 beta-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 beta-lactamases are limited, particularly for plasmid-mediated AmpC beta-lactamases. Routine microbiologic testing may not detect ESBLs or AmpC beta-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 beta-lactamases. No established guidelines exist for the detection of AmpC beta-lactamases. Imipenem and meropenem are superior to other antibiotics for the treatment of serious infections due to ESBL and AmpC beta-lactamase-producing gram-negative bacteria. While in vitro data demonstrate that tigecycline, ertapenem, and colistin might be potential choices, clinical experience is lacking.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Aged, 80 and over
  • Anti-Bacterial Agents / therapeutic use*
  • Bacterial Proteins / biosynthesis*
  • Ceftriaxone / therapeutic use
  • Drug Resistance, Multiple, Bacterial
  • Humans
  • Imipenem / therapeutic use
  • Klebsiella Infections / drug therapy
  • Klebsiella Infections / microbiology*
  • Klebsiella pneumoniae / drug effects
  • Klebsiella pneumoniae / enzymology*
  • Male
  • Meropenem
  • Microbial Sensitivity Tests
  • Pneumonia, Bacterial / drug therapy
  • Pneumonia, Bacterial / microbiology*
  • Thienamycins / therapeutic use
  • beta-Lactamases / biosynthesis*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Thienamycins
  • Imipenem
  • Ceftriaxone
  • AmpC beta-lactamases
  • beta-Lactamases
  • Meropenem