Development of gemifloxacin in vitro susceptibility test methods for gonococci including quality control guidelines

Gemifloxacin (formerly SE-265805 or LB20304a) is a new fluoronapthyridone w ith documented activity against Gram-positive and -negative organisms. The activity of gemifloxacin was rested against 150 Neisseria gonorrhoeae strai ns, using reference agar dilution, standardized disk diffusion, and Etest ( AB BIODISK, Solna, Sweden) methods. Gemifloxacin was very potent against ci profloxacin (CIPRO)-susceptible strains (MIC90, 0.008 mu g/ml) but was sign ificantly less active against the CIPRO-resistant gonococci (MIC90, 0.12 mu g/ml). Etest and reference agar dilution MIC results showed excellent corr elation (r = 0.96), and 98.7% MICs were within +/- one log, dilution. Agar dilution MICs were also compared to zone diameters obtained using gemifloxa cin 5-mu g disks; and complete intermethod categorical agreement (100%) was achieved applying breakpoints proposed as follows: less than or equal to 0 .25 mu g/ml (zone, greater than or equal to 25 mm) for susceptible and grea ter than or equal to 1 mu g/ml (zone, greater than or equal to 21 mm) for r esistant. Gemifloxacin MIC and disk diffusion test quality control (QC) ran ges were established for N. gonorrhoeae ATCC 49226. Data were collected fro m greater than or equal to seven laboratories, three GC agar medium lots fo r both agar MICs and disk methods, and two lots each of the 5- and 10-mu g disks. The proposed MIC QC range was 0.002 to 0.016 mu g/ml and the calcula ted mm zone ranges (median +/- 0.5 x average mm range) for both disks were similar, but contained only 88.1 to 91.9% of participant results. To achiev e the acceptable greater than or equal to 95% of all study results within r ange, a 43 to 51 mm limits (5-mu g disks) were necessary. The excellent bro ad-spectrum activity and a low reported adverse effects profile of gemiflox acin shows a potential for treatment of fluoroquinolone-resistant gonorrhea . (C) 2000 Elsevier Science Inc. All rights reserved.