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Antimicrobial Agents and Chemotherapy, April 1999, p. 862-867, Vol. 43, No. 4
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Ampicillin-Sulbactam and Amoxicillin-Clavulanate Susceptibility Testing of Escherichia coli Isolates with Different beta -Lactam Resistance Phenotypes

Antonio Oliver, María Pérez-Vázquez, Manuel Martínez-Ferrer, Fernando Baquero, Luis de Rafael, and Rafael Cantón*

Servicio de Microbiología, Hospital Ramón y Cajal, 28034-Madrid, Spain

Received 18 August 1998/Returned for modification 3 December 1998/Accepted 3 February 1999

The activities of ampicillin-sulbactam and amoxicillin-clavulanate were studied with 100 selected clinical Escherichia coli isolates with different beta -lactam susceptibility phenotypes by standard agar dilution and disk diffusion techniques and with a commercial microdilution system (PASCO). A fixed ratio (2:1) and a fixed concentration (clavulanate, 2 and 4 µg/ml; sulbactam, 8 µg/ml) were used in the agar dilution technique. The resistance frequencies for amoxicillin-clavulanate with different techniques were as follows: fixed ratio agar dilution, 12%; fixed concentration 4-µg/ml agar dilution, 17%; fixed ratio microdilution, 9%; and disk diffusion, 9%. Marked discrepancies were found when these results were compared with those obtained with ampicillin-sulbactam (26 to 52% resistance), showing that susceptibility to amoxicillin-clavulanic acid cannot be predicted by testing the isolate against ampicillin-sulbactam. Interestingly, the discrimination between susceptible and intermediate isolates was better achieved with 4 µg of clavulanate per ml than with the fixed ratio. In contrast, amoxicillin susceptibility was not sufficiently restored when 2 µg of clavulanate per ml was used, particularly in moderate (mean beta -lactamase activity, 50.8 mU/mg of protein) and high-level (215 mU/mg) TEM-1 beta -lactamase producer isolates. Four micrograms of clavulanate per milliliter could be a reasonable alternative to the 2:1 fixed ratio, because most high-level beta -lactamase-hyperproducing isolates would be categorized as nonsusceptible, and low- and moderate-level beta -lactamase-producing isolates would be categorized as nonresistant. This approach cannot be applied to sulbactam, either with the fixed 2:1 ratio or with the 8-µg/ml fixed concentration, because many low-level beta -lactamase-producing isolates would be classified in the resistant category. These findings call for a review of breakpoints for beta -lactam-beta -lactamase inhibitor combinations.

* Corresponding author. Mailing address: Servicio de Microbiología, Hospital Ramón y Cajal, Carretera de Colmenar Km 9.1, 28034-Madrid, Spain. Phone: 34-913368330. Fax: 34-913368809. E-mail: rafael.canton{at}hrc.es.

Antimicrobial Agents and Chemotherapy, April 1999, p. 862-867, Vol. 43, No. 4
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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