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The in vitro activities of isepamicin against 117 Mycobacteria abscessus, 48 Mycobacterium fortuitum, and 20 Mycobacterium chelonae isolates were evaluated by a microdilution test. Isepamicin MIC 90 s were <16 g/ml for the three species. Isepamicin was as active as amikacin and kanamycin and more active than tobramycin, capreomycin, gentamicin, and streptomycin.Rapidly growing mycobacteria (RGM) can cause a wide spectrum of disseminated or localized diseases, especially pulmonary, skin, or soft tissue infections (6). Mycobacterium abscessus, Mycobacterium chelonae, and Mycobacterium fortuitum are the three major pathogenic RGM species. The management of RGM remains very difficult, especially for the problems associated with infection caused by M. abscessus (12).Aminoglycoside agents have the potential to be extremely active against RGM (1,5,15). Amikacin has shown excellent activities against RGM in several studies and currently is the most widely used aminoglycoside in the treatment of RGM (1,5,15,18). Amikacin and isepamicin, an aminoglycoside used in Asia, were developed by introducing the (S)-4-amino-2-hydroxybutyryl and (S)-3-amino-2-hydroxypropionyl side chains into the 1-amino groups of kanamycin and gentamicin, respectively (8). Isepamicin has shown excellent activities against a wide range of bacteria (4). The cyclic peptide capreomycin is sometimes considered an aminoglycoside because of its actions on bacterial ribosomes (7). This study compared the activities of isepamicin with those of five other aminoglycosides (amikacin, gentamicin, kanamycin, tobramycin, and streptomycin) and capreomycin against RGM.RGM isolates were collected between November 2005 and July 2006 and identified by the conventional biochemical methods (10). Some of these (136 isolates) were confirmed by PCR restriction enzyme analysis of the 65-kDa hsp gene (13). Totals of 117 M. abscessus, 48 M. fortuitum, and 20 M. chelonae nonduplicate clinical isolates were collected. Of them, 71 (61%), 12 (25%), and 7 (35%), respectively, were recovered from patients with probable RGM infections (in which cases identical RGM species were recovered from three or more specimens from the same patient).Broth microdilution MIC testing was performed according to CLSI guidelines (11,(16)(17)(18). The isolates were subcultured on Trypticase soy agar plates with 5% sheep blood (BBL Microbiology Systems) and incubated at 30°C for 72 h. Bacteria on the agar plates were collected and adjusted to a final inoculum (5 ϫ 10 5 CFU/ml) in cation-supplemented MuellerHinton broth (Difco, Detroit, MI). Serial double dilutions of the tested antimicrobial agents were prepared with the same broth, and the concentrations in the wells ranged from 0.25 to 128 g/ml. The inoculated trays were incubated at 30°C, and MICs were recorded after 3 to 5 days.RGM isolates with amikacin MICs of Ն64 g/ml are interpreted as resistant to amikacin and those with amikacin MICs of Յ16 g/ml as susceptible to amikacin according to the CLSI cutoff criteria (11). No interpretive criteria ha...