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Antimicrobial Agents and Chemotherapy, October 2000, p. 2848-2852, Vol. 44, No. 10
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

In Vitro Activities of the Ketolides Telithromycin (HMR 3647) and HMR 3004 Compared to Those of Clarithromycin against Slowly Growing Mycobacteria at pHs 6.8 and 7.4

Nalin Rastogi,1,* Khye Seng Goh,1 Mylene Berchel,1 and André Bryskier2,3

Unité de la Tuberculose et des Mycobactéries, Institut Pasteur, 97165 Pointe à Pitre Cedex, Guadeloupe,1 and Domaine Antibiothérapie, Hoechst-Marion-Roussel, 93230 Romainville,2 and Laboratoire de Microbiologie, Centre Hospitalier Dupouy, 95107 Argenteuil Cedex,3 France

Received 12 April 2000/Returned for modification 31 May 2000/Accepted 19 June 2000

The in vitro activities of HMR 3647 (telithromycin) and HMR 3004, two novel semisynthetic ketolides, were investigated and compared with that of the reference macrolide drug, clarithromycin, against 34 strains of slowly growing mycobacteria at pHs 6.8 and 7.4, as determined radiometrically. The MICs at pH 7.4 were about 1 to 2 dilutions lower than those observed at pH 6.8. In terms of the highest to the lowest activity, the three antibiotics could be classified as follows: clarithromycin > HMR 3004 > HMR 3647. Among the species tested, Mycobacterium bovis BCG, M. ulcerans, M. avium, and M. paratuberculosis were moderately susceptible to HMR 3004 and HMR 3647 (MICs at pH 7.4, <= 5.0 and <= 20.0 µg/ml, respectively, versus <= 1.25 µg/ml for clarithromycin), whereas M. tuberculosis, M. africanum, M. bovis, and M. simiae were resistant (MICs, >= 10.0 and >= 40.0 µg/ml, respectively, at pH 7.4). Although not more active than clarithromycin in vitro, the high level of intracellular accumulation of the two ketolides inside phagocytes warrants further screening in experimental animal models.

* Corresponding author. Mailing address: Unité de la Tuberculose et des Mycobactéries, Institut Pasteur, Morne Jolivière B.P. 484, 97165 Pointe à Pitre Cedex, Guadeloupe. Phone: 590-893-881. Fax: 590-893-880. E-mail: rastogi{at}ipagua.gp.

Antimicrobial Agents and Chemotherapy, October 2000, p. 2848-2852, Vol. 44, No. 10
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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