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INFECTIOUS DISEASES

Diagnosis and Treatment of Extended-Spectrum and AmpC ß-Lactamase-Producing Organisms

Assistant Clinical Professor, Department of Clinical Pharmacy, School of Pharmacy, University of California at San Francisco, San Francisco, CA

B Joseph Guglielmo, PharmD

Professor and Chair, Department of Clinical Pharmacy, School of Pharmacy, University of California at San Francisco

Reprints: Dr. Yang, Department of Clinical Pharmacy, UCSF School of Pharmacy, 521 Parnassus Ave., Room C-152, San Francisco, CA 94143, fax 415/476-6632, yangk{at}pharmacy.ucsf.edu

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

Key Words: antibacterial agents, ß-lactamase, resistance, Enterobacteriaceae, microbial sensitivity tests

Published Online, July 31, 2007. www.theannals.com, DOI 10.1345/aph.1K213

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