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Antimicrobial Agents and Chemotherapy, December 2002, p. 3829-3836, Vol. 46, No. 12
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.12.3829-3836.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Mechanisms of Decreased Susceptibility to Cefpodoxime in Escherichia coli

Antonio Oliver,1,2* Linda M. Weigel,2 J. Kamile Rasheed,2 John E. McGowan Jr.,3 Patti Raney,2 and Fred C. Tenover2

Department of Microbiology, Ramon y Cajal Hospital, Madrid, Spain,1 Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention,2 Rollins School of Public Health, Emory University, Atlanta, Georgia3

Received 24 April 2002/ Returned for modification 15 July 2002/ Accepted 21 August 2002

Cefpodoxime is one of five antimicrobial agents recommended by the National Committee for Clinical Laboratory Standards for screening isolates of Klebsiella spp. and Escherichia coli for extended-spectrum ß-lactamase (ESBL) production. In a prior study, we noted that among 131 E. coli isolates for which the MIC of at least one extended-spectrum cephalosporin (ESC) or aztreonam was >=2 µg/ml (suggesting the presence of ESBL production), there were 59 isolates (45.0%) for which the MIC of cefpodoxime was 2 to 4 µg/ml (i.e., a positive ESBL screening test), but the MICs of ceftazidime, cefotaxime, and ceftriaxone were <=1 µg/ml (below the ESBL screening breakpoint). Thus, the results appeared to be false-positive ESBL screening tests. These 59 isolates were divided into five phenotypic groups based on the susceptibility patterns of the organisms to a variety of ß-lactam agents and further characterized. The first group (32 isolates) all produced a TEM-1 ß-lactamase, and changes in the major outer membrane proteins were detected in representative strains. The second group (18 isolates) lacked blaTEM but showed a number of porin changes; some also showed a modest elevation in production of the AmpC chromosomal ß-lactamase. In the third phenotypic group (seven isolates) all expressed an OXA-30 ß-lactamase. Some also harbored altered porins. The two remaining phenotypes each had a distinct pattern of porin changes with or without ß-lactamase production. These data indicate that several factors are associated with decreased susceptibility to cefpodoxime in E. coli, but none of the mechanisms are related to ESBL production. Current screening methods produced false-positive ESBL results for these isolates. Such isolates should not be classified as containing ESBLs, nor should interpretations of ESCs or aztreonam susceptibility be changed to resistant on test reports for these isolates.

* Corresponding author. Present address: Servicio de Microbiologia, Hospital Son Dureta, 07014, Palma de Mallorca, Spain. Phone: 34 971 175185. Fax: 34 971 175185. E-mail: aoliver{at}hsd.es.

Antimicrobial Agents and Chemotherapy, December 2002, p. 3829-3836, Vol. 46, No. 12
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.12.3829-3836.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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