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Antimicrobial Agents and Chemotherapy, January 2001, p. 217-222, Vol. 45, No. 1
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.1.217-222.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Activity of Moxifloxacin by Itself and in Combination with Ethambutol, Rifabutin, and Azithromycin In Vitro and In Vivo against Mycobacterium avium

Luiz E. Bermudez,1,* Clark B. Inderlied,2 Peter Kolonoski,1 Mary Petrofsky,1 Priscilla Aralar,2 Martin Wu,1 and Lowell S. Young1

Kuzell Institute for Arthritis and Infectious Diseases, California Pacific Medical Center Research Institute, San Francisco,1 and Children's Hospital of Los Angeles, University of Southern California, Los Angeles,2 California

Received 12 June 2000/Returned for modification 24 August 2000/Accepted 19 October 2000

Moxifloxacin activity against Mycobacterium avium complex (MAC) was evaluated in vitro against 25 strains. The MIC was determined to range from 0.125 to 2.0 µg/ml. In addition, U937 macrophage monolayers infected with MAC strain 101 (serovar 1) were treated with moxifloxacin (0.25 to 8 µg/ml) daily, and the number of intracellular bacteria was quantitated after 4 days. Moxifloxacin showed inhibitory activity at 0.5 µg/ml and higher. To assess the activity of moxifloxacin containing regimens in vivo, we infected C57BL bg+/bg+ mice with 3 × 107 MAC strain 101 bacteria intravenously. One week later treatment was begun with the following: (i) moxifloxacin (50 mg/kg/day or 100 mg/kg/day), ethambutol (100 mg/kg/day), or a combination of moxifloxacin and ethambutol; or (ii) moxifloxacin (100 mg/kg/day), azithromycin (200 mg/kg/day), or rifabutin (40 mg/kg/day) as oral monotherapy; or (iii) all permutations of two-drug therapy or all three drugs in combination. All groups contained at least 14 animals, and the control group received the drug vehicle. After 4 weeks, quantitative blood cultures were obtained and the number of bacteria in liver and spleen was quantitated. Moxifloxacin, ethambutol, and azithromycin were active as single agents in liver, spleen, and blood. Rifabutin showed inhibitory activity only in the blood. Two-drug combinations containing azithromycin were no more active than azithromycin alone. Similarly, the three-drug combination was not more active than azithromycin alone in the spleen. Rifabutin did not add to the activity of any other single agent or two-drug combination. Moxifloxacin at both concentrations in combination with ethambutol was significantly more active than each drug alone.

* Corresponding author. Mailing address: Kuzell Institute, 2200 Webster St., Suite 305, San Francisco, CA 94115.

Antimicrobial Agents and Chemotherapy, January 2001, p. 217-222, Vol. 45, No. 1
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.1.217-222.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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