The activities of fluoroquinolones and a new macrolide against 30 clinical isolates of Mycobacterium tuberculosis were determined in vitro by agar diffusion. In order of relative potencies against M. tuberculosis, temafloxacin (MIC for 90% of isolates [MIC9J, 2.3 ,ug/ml) was at least as active as the reference quinolones ofloxacin (MIC90, 2.4 ,ug/ml) and ciprofloxacin (MIC90, 4.3 jig/ml). Less active were difloxacin (MIC90, 4.7 ,Ig/ml), pefloxacin (MIC90, 6.7 ,iglml), and enoxacin (MIC90, 8.3 ,ug/ml). The macrolide clarithromycin was more potent than erythromycin but less potent than the fluoroquinolones. Our results suggest that the newer fluoroquinolones and clarithromycin should be included with ciprofloxacin and ofloxacin in pharmacokinetic studies that may lead to trials in human subjects with mycobacterial infections.The fluoroquinolones, a new class of antimicrobial agents, are structurally related to nalidixic acid and have pharmacologic and microbiologic properties attractive for their use in treating many infectious diseases caused by gram-negative and gram-positive bacteria. Good in vitro potencies against Mycobacterium tuberculosis have been reported for the fluoroquinolones ciprofloxacin (2, 3, 5, 6) and ofloxacin (3, 11); less active are norfloxacin (3, 5) and amifloxacin (3). Clarithromycin activity has not been reported.In this report, we compare with reference antimicrobial agents the in vitro potencies against M. tuberculosis of fluoroquinolones, difloxacin, temafloxacin, enoxacin, pefloxacin, and a new macrolide, clarithromycin.Antimicrobial agents. The following reagent powders were synthesized and supplied by Abbott Laboratories, North Chicago, Ill.: difloxacin (activity, 850 jig/mg), temafloxacin (activity, 1,000 jig/mg), and pefloxacin (activity, 1,000 pLg/ mg); erythromycin (activity, 763 ,ug/mg) and clarithromycin (activity, 993 p.g/mg) (licensed from Taisho Pharmaceuticals)were also prepared and supplied by Abbott Laboratories. Other reagent powders were received as gifts from their manufacturers: ciprofloxacin (activity, 858 plg/mg; Miles Pharmaceuticals, West Haven, Conn.), ofloxacin (activity, 1,000 ,ug/mg; Ortho Pharmaceuticals, Raritan, N.J.), and enoxacin (activity, 1,000 ,ug/mg; Warner Lambert, Ann Arbor, Mich.). Stock solutions (1,000 ,ug/ml) were prepared according to manufacturer instructions. Subsequent dilutions in sterile distilled water were added to molten media used in assays for the MICs of drugs.Mycobacteria. A total of 30 clinical isolates of M. tuberculosis were recovered from sputum specimens of patients prior to treatment at the Veterans Administration Medical Center, Buffalo, N.Y. After isolation and identification, the microorganisms were stored at 4°C on Lowenstein-Jensen medium (Difco Laboratories, Detroit, Mich.). For antimicrobial susceptibility testing, an indirect method (12) was used. Briefly, the strains were subcultured in Dubos broth base enriched with Dubos medium albumin (Difco) and incubated * Corresponding author.for 7 days or until growth prod...