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. 2020 Jan 27;64(2):e01943-19.
doi: 10.1128/AAC.01943-19. Print 2020 Jan 27.

Rifabutin Is Active against Mycobacterium abscessus in Mice

Thomas Dick  1   2 , Sung Jae Shin  3 , Won-Jung Koh  4 , Véronique Dartois  1   2   5 , Martin Gengenbacher  6
Affiliations

Rifabutin Is Active against Mycobacterium abscessus in Mice

Thomas Dick et al. Antimicrob Agents Chemother. .

Abstract

There is no reliable cure for Mycobacterium abscessus lung disease. Rifampin is not used clinically due to poor in vitro potency. In contrast, we have shown that rifabutin, another approved rifamycin used to treat tuberculosis, is potent in vitro against M. abscessus Here, we report that rifabutin is as active as clarithromycin against M. abscessus K21 in NOD.CB17-Prkdcscid/NCrCrl mice. This suggests that rifabutin should be considered a repurposing candidate for patients with M. abscessus disease.

Keywords: NTM; animal model; mouse model; nontuberculous mycobacteria; rifamycin.

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Figures

FIG 1
FIG 1
Rifabutin kills M. abscessus in mice. (A) Kinetics of bacterial burden in lungs and spleen of M. abscessus K21-infected NOD.CB17-Prkdcscid/NCrCrl mice. The inoculum of 106 CFU was delivered intranasally. At designated time points, lungs and spleens of 4 animals were homogenized and plated on agar for CFU determination. (B) Schematic representation of the murine M. abscessus lung infection model used in this study. (C and D) Animals infected with M. abscessus K21 underwent drug treatment for 10 consecutive days. Drugs were administered once daily by oral gavage to groups of 6 mice per study group. At 11 days postinfection, organ homogenates were plated on agar to determine the bacterial load. Results were analyzed using one-way analysis of variance (ANOVA) multicomparison and Tukey’s posttest. *, P < 0.05; **, P < 0.01; ***, P < 0.001. MICs reducing growth of M. abscessus K21 by 90% over 3 days for clarithromycin (CLR), rifampin (RIF), and rifabutin (RFB) were 0.6 μM, 50 μM, and 2.4 μM, respectively. CFU kinetics was carried out twice, and the drug efficacy study was done three times. Representative data sets are shown.
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