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Antimicrobial Agents and Chemotherapy, August 1998, p. 2070-2073, Vol. 42, No. 8
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

In Vitro Susceptibility of Mycobacterium ulcerans to Clarithromycin

F. Portaels,1,* H. Traore,1 K. De Ridder,1 and W. M. Meyers2

Department of Microbiology, Institute of Tropical Medicine, Antwerp, Belgium,1 and Armed Forces Institute of Pathology, Washington, D.C. 20306-60002

Received 9 March 1998/Returned for modification 13 April 1998/Accepted 1 June 1998

Buruli ulcer (BU), caused by Mycobacterium ulcerans, was recently recognized by the World Health Organization as an important emerging disease. While antimycobacterial therapy is often effective for the earliest nodular or ulcerative lesions, medical management of BU lesions in patients presenting for treatment is usually disappointing, leaving wide surgical excision the only alternative. Advanced ulcerated lesions of BU rarely respond to antimycobacterial agents; however, perioperative administration of such drugs may prevent relapses or disseminated infections. Clarithromycin possesses strong activity in vitro and in vivo against most nontuberculous mycobacteria. In this study we determined the antimycobacterial activity of this drug in vitro against 46 strains of M. ulcerans isolated from 11 countries. The MIC of clarithromycin was determined at pH 6.6 (on 7H11 agar) and at pH 7.4 (on Mueller-Hinton agar). The MICs ranged from 0.125 to 2 µg/ml at pH 6.6 and from <0.125 to 0.5 µg/ml at pH 7.4. For the majority of the strains, geographic origin did not play a significant role. Thirty-eight strains (83%) were inhibited by 0.5 µg/ml at pH 7.4. These MICs are below peak therapeutic concentrations of clarithromycin obtainable in blood. These results suggest that clarithromycin is a promising drug both for the treatment of early lesions of M. ulcerans and for the prevention of hematogenous dissemination of the etiologic agent during and after surgery. Studies should be initiated to evaluate the effects of clarithromycin in combination with ethambutol and rifampin on M. ulcerans both in vitro and in experimentally infected mice. Multidrug regimens containing clarithromycin may also help control the secondary bacterial infections sometimes seen in BU patients, most importantly osteomyelitis.

* Corresponding author. Mailing address: Institute of Tropical Medicine, Nationalestraat 155, B-2000 Antwerp, Belgium. Phone: 32 3 247 63 24. Fax: 32 3 247 63 33. E-mail: portaels{at}itg.be.

Antimicrobial Agents and Chemotherapy, August 1998, p. 2070-2073, Vol. 42, No. 8
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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