In Vitro Activities of Isepamicin, Other Aminoglycosides, and Capreomycin against Clinical Isolates of Rapidly Growing Mycobacteria in Taiwan

Abstract

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...

Clinical and Microbiological Differences between Mycobacterium abscessus and Mycobacterium massiliense Lung Diseases

“…The inoculated plates were placed into plastic bags, incubated at 35°C in ambient air, and read after 72 h. The MIC was defined as the lowest concentration of drug that inhibited visible growth. Susceptibility was evaluated according to CLSI breakpoint recommendations (8,37) and those proposed previously by Shen et al (24).…”

Rapidly growing mycobacteria in Singapore, 2006–2011

“…However, our analyses revealed that only 2 (18%) of 11 M. chelonae isolates were susceptible to tobramycin, whereas amikacin was active against 86% of them. The recent studies by FernandezRoblas et al [17] and Shen et al [18] also reported high susceptibility rates of M. chelonae to amikacin, although notably more than 80% of their isolates remained susceptible to tobramycin. The small number of M. chelonae isolates in our study precluded definitive conclusions; nonetheless, the observation that few isolates were tobramycin susceptible, coupled with the almost nonexistent use of this aminoglycoside in clinical practice locally, highlighted the need to review the value of routine testing of tobramycin activity against M. chelonae (and other RGM) species in our local setting.…”

High efficacy of clofazimine and its synergistic effect with amikacin against rapidly growing mycobacteria

“…Diseases caused by RGM are often difficult to treat and have a high rate of recurrence. This is especially true for infections caused by Mycobacterium abscessus, which are often intractable to antibiotic therapy [1]. Amikacin is the only drug recommended in the 2007 American Thoracic Society guidelines for treatment of RGM infections.…”

“…In addition, we found that the cyclic peptide capreomycin, which has been used to treat multidrug-resistant tuberculosis (MDR-TB), was effective against M. fortuitum but showed poor activity against M. abscessus and M. chelonae [1]. Other studies have indicated that clofazimine, dapsone and d-cycloserine are effective against MDR-TB, Mycobacterium kansasii, Mycobacterium avium complex (MAC) and Mycobacterium leprae [3][4][5][6].…”

“…However, treatment may still take more than 12 months [2]. Combination therapy that includes at least one effective aminoglycoside, such as amikacin, is strongly recommended for an effective treatment regimen [1]. New agents that exhibit good activity against RGM are urgently required.…”