Diagnosis and treatment of extended-spectrum and AmpC beta-lactamase-producing organisms.
OBJECTIVE
To review the laboratory diagnosis of extended-spectrum beta-lactamase (ESBL) and AmpC beta-lactamase-producing bacteria and evaluate potential treatment options.


METHODS
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.


METHODS
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.


RESULTS
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.
Department of Clinical Pharmacy, School of Pharmacy, University of California at San Francisco, San Francisco, CA 94143, USA. yangk@pharmacy.ucsf.edu
Katherine
K
Yang
B Joseph
BJ
Guglielmo
D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000096:biosynthesis*; D002443:Ceftriaxone / Q000627:therapeutic use; D024901:Drug Resistance, Multiple, Bacterial; D006801:Humans; D015378:Imipenem / Q000627:therapeutic use; D007710:Klebsiella Infections / Q000188:drug therapy / Q000382:microbiology*; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D018410:Pneumonia, Bacterial / Q000188:drug therapy / Q000382:microbiology*; D013845:Thienamycins / Q000627:therapeutic use; D001618:beta-Lactamases / Q000096:biosynthesis*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D013845:Thienamycins; D015378:Imipenem; D002443:Ceftriaxone; C048795:AmpC beta-lactamases; D001618:beta-Lactamases; D000077731:Meropenem