Synergistic activities of clarithromycin and antituberculous drugs against multidrug-resistant Mycobacterium tuberculosis.

Abstract

The rise of multidrug-resistant Mycobacterium tuberculosis has complicated therapy for tuberculosis and led us to search for a potentially active combination of drugs against these strains. The susceptibilities of 12 strains of multidrug-resistant M. tuberculosis to standard antituberculous drugs (isoniazid, rifampin, ethambutol, and pyrazinamide), clarithromycin, and its metabolite, 14-hydroxyclarithromycin, were determined by use of the BACTEC radiometric method. All strains were resistant to at least two of the antituberculous drugs. Clarithromycin and 14-hydroxyclarithromycin MICs were in the range indicating resistance at > or = 8.0 micrograms/ml for all strains. Combination testing by the BACTEC method was performed with various concentrations of isoniazid, rifampin, and ethambutol, and with clarithromycin/14-hydroxyclarithromycin at fixed concentrations of 2.0/0.5 micrograms/ml, respectively. Addition of clarithromycin/14-hydroxyclarithromycin to these antituberculous drug mixtures resulted in a 4- to 32-fold reduction in MICs of isoniazid, rifampin, and ethambutol and made resistant strains susceptible. Fractional inhibitory concentrations ranged from 0.23 to 0.50 for all strains, suggesting a synergistic interaction between standard antituberculous drugs and clarithromycin/14-hydroxyclarithromycin. The ability of clarithromycin/14-hydroxyclarithromycin to enhance the activities of isoniazid, ethambutol, and rifampin in vitro suggests that this combination may be efficacious in the treatment of multidrug-resistant M. tuberculosis infections.

• Authors: S J Cavalieri, J R Biehle, W E Sanders Jr
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 39 Issue 7 Pg. 1542-5 (Jul 1995) ISSN: 0066-4804 [Print] United States
• PMID: 7492101 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antitubercular Agents
• 14-hydroxyclarithromycin
• Clarithromycin

Topics

• Antitubercular Agents (pharmacology)
• Clarithromycin (analogs & derivatives, pharmacology)
• Drug Synergism
• Drug Therapy, Combination
• Microbial Sensitivity Tests
• Mycobacterium tuberculosis (drug effects)
• Tuberculosis, Multidrug-Resistant (drug therapy)