Contemporary assessment of antimicrobial susceptibility testing methods for polymyxin B and colistin: Review of available interpretative criteria andquality control guidelines

The emergence of infections caused by multidrug-resistant Pseudomonas aerug inosa and Acinetobacter spp. has necessitated the search for alternative pa renteral agents such as the polymyxins. The National Committee for Clinical Laboratory Standards (NCCLS) documents do not currently provide interpreta tive criteria for the testing of the polymyxins, colistin and polymyxin B. Therefore, an evaluation of the antimicrobial activity of colistin and poly myxin B was initiated using 200 bloodstream infection pathogens collected t hrough the SENTRY Antimicrobial Surveillance Program. All susceptibility te sts were performed according to the NCCLS recommendations. Polymyxin B and colistin displayed a nearly identical spectrum of activity, exhibiting exce llent potency against P. aeruginosa (MIC90, 2 mug/ml) and Acinetobacter sp, (MIC90, 2 mug/ml). In contrast, they showed limited activity against some other nonfermentative bacilli such as Burkholderia cepacia (MIC90, greater than or equal to 128 mug/ml). Excellent correlation was achieved between br oth microdilution and agar dilution tests (r = 0.96 to 0.98); 94.3% of the results were +/-1 log(2) dilution between the methods used for both compoun ds. At a resistance breakpoint of greater than or equal to4 mug/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 (l ess than or equal to 11 and greater than or equal to 14 mm) and polymyxin B (less than or equal to 10 and greater than or equal to 14 mm) were suggest ed, but some degree of error persisted (greater than or equal to3.5%). It i s recommended that all susceptible disk diffusion results be confirmed by M IC tests using the preferred reference NCCLS method. The quality control (Q C) ranges listed in the product package insert require an adjusted range by approximately 3 mm for both NCCLS gram-negative quality control strains. T his evaluation of in vitro susceptibility test methods for the polymyxin cl ass drugs confirmed continued serious testing error with the disk diffusion method, the possible need for breakpoint adjustments, and the recalculatio n 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.