Impacts of dosing frequency of the combination rifampin-streptomycin on its bactericidal and sterilizing activities against Mycobacterium ulcerans in mice.

Abstract	Because of operational limitations, a significant proportion of the health centers at the peripheral level are able to provide treatment to Buruli ulcer patients with the combination rifampin (rifampicin)-streptomycin (RIF-STR) only five times weekly (5/7) instead of seven times weekly (7/7), as recommended. The objective of this experiment is to assess the impacts of various dosing frequencies of the combination on its bactericidal and sterilizing activities against Mycobacterium ulcerans in mice. The results demonstrate that the bactericidal activities did not differ significantly among five dosing frequencies of the combination, ranging from seven times to twice weekly, whereas the sterilizing activities differed widely. RIF-STR 7/7 was the only regimen that was able to sterilize the infection after 4 to 8 weeks of treatment; the sterilizing activities associated with reduced dosing frequencies were significantly diminished, and 8 weeks of 5/7 administration yielded a relapse rate greater than the generally accepted level of 5%. We recommend that the duration of treatment with 5/7 administration be prolonged beyond 8 weeks and that additional experiments with mice be carried out, with sufficient statistical power to compare the relapse rates of M. ulcerans infection between 8 weeks of 7/7 administration and 10 and 12 weeks of 5/7 administration of RIF-STR.
Authors	Baohong Ji, Aurélie Chauffour, Alexandra Aubry, Jérome Robert, Murad Ibrahim, Vincent Jarlier
Journal	Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 53 Issue 7 Pg. 2955-9 (Jul 2009) ISSN: 1098-6596 [Electronic] United States
PMID	19364857 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Anti-Bacterial Agents Rifampin Streptomycin
Topics	Animals Anti-Bacterial Agents (pharmacology, therapeutic use) Buruli Ulcer (drug therapy) Drug Therapy, Combination Female Mice Mice, Inbred BALB C Mycobacterium ulcerans (drug effects) Rifampin (pharmacology, therapeutic use) Streptomycin (pharmacology, therapeutic use) Treatment Outcome

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