Journal of Antimicrobial Chemotherapy (2002) 50, 140-142
© 2002 The British Society for Antimicrobial Chemotherapy
Correspondence |
In vitro activity of a novel des-fluoro(6) quinolone, garenoxacin (BMS-284756), against rapidly growing mycobacteria and Nocardia isolates
Department of Microbiology, Bristol-Myers Squibb Company, Wallingford, CT 06492, USA
Sir,
Rapidly growing mycobacteria (in particular, Mycobacterium fortuitum, Mycobacterium abscessus and Mycobacterium chelonae) and Norcardia are most often associated with cutaneous and pulmonary infections. Antimicrobial treatment of these pathogens is difficult because it is long-term (at least 2–3 months), and sometimes requires surgical intervention.1 Primary tuberculous therapies are generally ineffective against the rapidly growing mycobacteria, and drug susceptibility to the rapid growers is species dependent.
Garenoxacin (BMS-284756, T3811ME) is a new quinolone in clinical development, including treatment for respiratory infections, and skin and skin structure infections. It is more active than marketed quinolones against common Gram-positive bacteria, as well as some strains that are resistant to ciprofloxacin.2
In this study we compared the in vitro activity of garenoxacin with other traditional antibacterial agents against strains of Nocardia spp. and the rapidly growing mycobacteria, two-thirds of which were clinical isolates. MICs were determined by the microbroth dilution method recommended by the NCCLS, using cation-supplemented Mueller–Hinton broth (plus 0.2 U/mL thymidine phosphorylase when trimethoprim–sulfamethoxazole was tested).3 The final bacterial inoculum size was c. 105 cfu/mL. The MIC plates were incubated at 30°C (except for Norcadia spp., at 35°C) for 5 days (except for M. fortuitum, for 3 days). Staphylococcus aureus ATCC 29213 and Escherichia coli ATCC 25922 were included as quality control strains. The MIC was the lowest concentration of drug that yielded complete inhibition of growth, and for trimethoprim–sulfamethoxazole, 80% growth inhibition was the endpoint.
Garenoxacin’s activity against the rapid growing mycobacteria is species dependent. Garenoxacin is very active (MICs < 0.25 mg/L) against M. fortuitum and Mycobacterium smegmatis (Table 1). It is active (MICs < 4 mg/L) against some M. chelonae strains. However, garenoxacin is inactive against M. abscessus. This spectrum is similar to those reported for other quinolones (e.g. ciprofloxacin and ofloxacin) against rapidly growing mycobacteria.4 Although ciprofloxacin appears to be four-fold more active in vitro against some members of the rapidly growing mycobacterial species, the clinical dose of garenoxcin produces three times the drug exposure (AUC) compared with the standard dose of ciprofloxacin.5
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Against Nocardia, garenoxacin was active against Nocardia brasiliensis (MICs < 2 mg/L) and some strains of Nocardia asteroides (MIC50, 0.13 mg/L) (Table 1). Garenoxacin was more active (by
four-fold) than ciprofloxacin against Nocardia. Of the non-quinolone comparators tested, linezolid, imipenem and amikacin were the most frequently active against the rapidly growing mycobacteria (Table 1). Linezolid, amikacin and trimethoprim–sulfamethoxazole were the non-quinolone antimicrobial agents most often active against Norcardia spp.
In summary, garenoxacin is active against most rapidly growing mycobacterial species, with the exception of M. abscessus. Garenoxacin is active against the Nocardia isolates tested. These in vitro results indicate that garenoxacin may be useful in the treatment of infections caused by rapidly growing mycobacteria and Nocardia spp.
Footnotes
* Corresponding author. Tel: +1-203-677-6370;Fax: +1-203-677-7867; E-mail: fungtomj{at}bms.com 
References
1 . Brown, A., Wallace, R. J. & Onyi, G. (1996). Activities of the glycyclines N,N-dimethylglycylamido-minocycline and N,N-dimethylglycylamido-6-demethyl-6-deoxytetracycline against Norcardia spp. and tetracycline-resistant isolates of rapidly growing mycobacteria. Antimicrobial Agents and Chemotherapy 40, 874–8.[Abstract]
2 . Fung-Tomc, J. C., Minassian, B., Kolek, B., Huczko, E., Alesksunes, L., Stickle, T. et al. (2000). Antibacterial spectrum of a novel des-fluoro(6) quinolone, BMS-284756. Antimicrobial Agents and Chemotherapy 44, 3351–6.
3 . National Committee for Clinical Laboratory Standards. (2000). Susceptibility Testing of Mycobacteria, Nocardia, and Other Aerobic Actinomycetes—Second Edition: Tentative Standard M24-T2. NCCLS, Villanova, PA.
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Wallace, R. J., Jr, Bedsole, G., Sumter, G., Sanders, C. V., Steele, L. C., Brown, B. A. et al. (1990). Activities of ciprofloxacin and ofloxacin against rapidly growing mycobacteria with demonstration of acquired resistance following single-drug therapy. Antimicrobial Agents and Chemotherapy 34, 65–70.
5 . Gajjar, D. A., Russo, R., Bello, A., Christopher, L., Geraldes, M. & Grasela, D. (2001). Safety, tolerability and pharmacokinetics of intravenous BMS-284756 in healthy subjects. In Programs and Abstracts of the Forty-first Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, CA, 2001. Abstract 44, p. 8. American Society for Microbiology, Washington, DC.
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