The susceptibility to ciprofloxacin of 548 clinical isolates of rapidly growing mycobacteria belonging to eight subgroups or species was determined. The 170 isolates of Mycobacteriumfortuitum biovar. fortuitum were most susceptible; the MIC for 90% of the organisms was 0.125 ,Ig/ml. The other biovariants of M. fortuitum, M. smegmatis, and the M. chelonae-like organ'isms were less susceptible; the modal MIC was 0.5 ,ig/ml, and the MIC for 90% of organisms was 1.0 ,ug/ml. The two subspecies of M. chelonae were generally resistant, with only 8% of 206 isolates falling in the moderately susceptible category (MIC, 2 gig/ml) and only 2% falling in the susceptible category (MIC, sl ,ug/ml). MICs of ofloxacin averaged 1 to 2 dilutions higher than those of ciprofloxacin for all subgroups tested. Three patients with M. fortuitum cutaneous disease relapsed after an initial response to therapy with ciprofloxacin, and their isolate was shown to have acquired drug resistance.Mutational frequencies for M. fortuitum with ciprofloxacin were relatively high (10-5 to l0-7), and MICs for single-step mutants were similar to those for the clinically resistant strains. Thus, despite the excellent activity of ciprofloxacin against rapidly growing mycobacterial groups other than M. chelonae, single-drug therapy should be used with caution because of the risk of development of mutational resistance.The rapidly growing mycobacteria produce a wide spectrum of clinical diseases. The most common is a localized cutaneous infection that follows open trauma or a puncture wound (18). Optimal therapy for these infections appears to be surgical debridement and antimicrobial therapy based on susceptibility testing (3,17). Drugs that have proven effective in this setting include amikacin, doxycycline, sulfonamides, erythromycin, and cefoxitin (3,15,17).Recent studies have suggested that the newest class of antibiotics-the fluorinated quinolones-has good activity against the rapidly growing mycobacteria, especially Mycobacterium fortuitum and Mycobacterium smegmatis (2,5,12,13,16,21). However, none of these studies included large numbers of isolates, and there have been only three case reports of the clinical use of the newer quinolones as single agents (6, 19; L. W. Rumans and P. G. Anikerholz, Abstr. Annu. Meet. Am. Soc. Microbiol. 1989, U56, p. 164) and one study in which the drug was used in combination (20). We tested the susceptibilities to the quinolones of a large number of isolates of rapidly growing mycobacteria that had been identified to species and subspecies. We report the results of these studies, case studies of four patients with cutaneous infections due to M. fortuitum whose isolates were resistant to ciprofloxacin after drug therapy, and the mutational frequency of isolates of M. fortuitum to ciprofloxacin resistance.( Isolates of M. fortuitum biovar. peregrinum and the unnamed third biovariant complex were separated from isolates of M. fortuitum biovar. fortuitum on the basis of the resistance of M. fortuitum biovar. peregrinum ...