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Journal of Clinical Microbiology, May 1998, p. 1361-1365, Vol. 36, No. 5
0095-1137/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Effects of Following National Committee for Clinical Laboratory Standards and Deutsche Industrie Norm-Medizinische Mikrobiologie Guidelines, Country of Isolate Origin, and Site of Infection on Susceptibility of Escherichia coli to Amoxicillin-Clavulanate (Augmentin)

I. Simpson,1,* J. Durodie,1,dagger S. Knott,1,Dagger B. Shea,1 J. Wilson,1,§ and K. Machka2

Microbiology Research, SmithKline Beecham, Betchworth, Surrey RH3 7AJ, United Kingdom1 and SmithKline Beecham Pharma, Munich 80804, Germany2

Received 17 June 1997/Returned for modification 26 November 1997/Accepted 30 December 1997

Amoxicillin-clavulanate (Augmentin), as a combination of two active agents, poses extra challenges over single agents in establishing clinically relevant breakpoints for in vitro susceptibility tests. Hence, reported differences in amoxicillin-clavulanate percent susceptibilities among Escherichia coli isolates may reflect localized resistance problems and/or methodological differences in susceptibility testing and breakpoint criteria. The objectives of the present study were to determine the effects of (i) methodology, e.g., those of the National Committee for Clinical Laboratory Standards (NCCLS) and the Deutsche Industrie Norm-Medizinische Mikrobiologie (DIN), (ii) country of origin (Spain, France, and Germany), and (iii) site of infection (urinary tract, intra-abdominal sepsis, or other site[s]) upon the incidence of susceptibility to amoxicillin-clavulanate in 185 clinical isolates of E. coli. Cefuroxime and cefotaxime were included for comparison. The use of NCCLS methodology resulted in different distribution of amoxicillin-clavulanate MICs than that obtained with the DIN methodology, a difference highlighted by the 10% more strains found to be within the 8- to 32-µg/ml MIC range. This difference reflects the differing amounts of clavulanic acid present. NCCLS and DIN methodologies also produce different MIC distributions for cefotaxime but not for cefuroxime. Implementation of NCCLS and DIN breakpoints produced markedly different incidences of strains that were found to be susceptible, intermediate or resistant to amoxicillin-clavulanate. A total of 86.5% strains were found to be susceptible to amoxicillin-clavulanate by the NCCLS methodology, whereas only 43.8% were found to be susceptible by the DIN methodology. Similarly, 4.3% of the strains were found to be resistant by NCCLS guidelines compared to 21.1% by the DIN guidelines. The use of DIN breakpoints resulted in a fivefold-higher incidence of strains categorized as resistant to cefuroxime. There were no marked differences due to country of origin upon the MIC distributions for amoxicillin-clavulanate, cefuroxime, or cefotaxime, as determined with the NCCLS guidelines. Isolates from urinary tract and intra-abdominal infections were generally more resistant to amoxicillin-clavulanate than were isolates from other sites of infection.


* Corresponding author. Present address: MEWS Biomedical Ltd., The Mews, 26, St. Peter's Street, Caxton, Cambridgeshire, CB3 8PJ United Kingdom. Phone: (44 1954) 719972. Fax: (44 1954) 719972. E-mail: 106650,1652{at}compuserve.com.

dagger Present address: Redhill, Surrey RH1 6HE, United Kingdom.

Dagger Present address: Wells Medical Ltd., Royal Tunbridge Wells, Kent TN4 0JB, United Kingdom.

§ Present address: Hawthorns, Meadowside, Great Bookham, Surrey KT23 3LG, United Kingdom.


Journal of Clinical Microbiology, May 1998, p. 1361-1365, Vol. 36, No. 5
0095-1137/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.



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