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Journal of Clinical Microbiology, January 2001, p. 183-190, Vol. 39, No. 1
0095-1137/01/$04.00+0   DOI: 10.1128/JCM.39.1.183-190.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Contemporary Assessment of Antimicrobial Susceptibility Testing Methods for Polymyxin B and Colistin: Review of Available Interpretative Criteria and Quality Control Guidelines

Ana C. Gales,1,2 Adriana O. Reis,2 and Ronald N. Jones1,*

Department of Pathology, University of Iowa College of Medicine, Iowa City, Iowa 52242,1 and Disciplina de Doenças Infecciosas e Parasitàrias, Universidade Federal de São Paulo, São Paulo, Brazil2

Received 29 June 2000/Returned for modification 4 September 2000/Accepted 16 October 2000

The emergence of infections caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter spp. has necessitated the search for alternative parenteral agents such as the polymyxins. The National Committee for Clinical Laboratory Standards (NCCLS) documents do not currently provide interpretative criteria for the testing of the polymyxins, colistin and polymyxin B. Therefore, an evaluation of the antimicrobial activity of colistin and polymyxin B was initiated using 200 bloodstream infection pathogens collected through the SENTRY Antimicrobial Surveillance Program. All susceptibility tests were performed according to the NCCLS recommendations. Polymyxin B and colistin displayed a nearly identical spectrum of activity, exhibiting excellent potency against P. aeruginosa (MIC90, 2 µg/ml) and Acinetobacter sp. (MIC90, 2 µg/ml). In contrast, they showed limited activity against some other nonfermentative bacilli such as Burkholderia cepacia (MIC90, >= 128 µg/ml). Excellent correlation was achieved between broth microdilution and agar dilution tests (r = 0.96 to 0.98); 94.3% of the results were ±1 log2 dilution between the methods used for both compounds. At a resistance breakpoint of >= 4 µg/ml for both agents, unacceptable false-susceptible or very major errors were noted for colistin (5%) and polymyxin B (6%). Modified zone criteria for colistin (<= 11 and >= 14 mm) and polymyxin B (<= 10 and >= 14 mm) were suggested, but some degree of error persisted (>= 3.5%). It is recommended that all susceptible disk diffusion results be confirmed by MIC tests using the preferred reference NCCLS method. The quality control (QC) ranges listed in the product package insert require an adjusted range by approximately 3 mm for both NCCLS gram-negative quality control strains. This evaluation of in vitro susceptibility test methods for the polymyxin class drugs confirmed continued serious testing error with the disk diffusion method, the possible need for breakpoint adjustments, and the recalculation of disk diffusion QC ranges. Clinical laboratories should exclusively use MIC methods to assist the therapeutic application of colistin or polymyxin B until disk diffusion test modifications are sanctioned and published by the NCCLS.

* Corresponding author. Present address: 345 Beaver Kreek Centre, Suite A, North Liberty, IA 52317. Phone: (319) 665-3370. Fax: (319) 665-3371.

Journal of Clinical Microbiology, January 2001, p. 183-190, Vol. 39, No. 1
0095-1137/01/$04.00+0   DOI: 10.1128/JCM.39.1.183-190.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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