In vitro activity of antimicrobial combinations against clinical isolates of susceptible and resistant Mycobacterium tuberculosis
Objective: To evaluate in vitro the activity of rifabutin plus each of four other antimicrobial agents: isoniazid, amoxicillin/clavulanate, sparfloxacin and clarithromycin, against five susceptible (S-MTB) and five multidrug-resistant (MDR-TB) clinical isolates of Mycobacterium tuberculosis.
Design: The antimicrobial activity of each two-drug combination was assessed by macrodilution checkerboard technique using Bactec 460 and classified as synergistic, additive, or antagonistic, using the fractional inhibitory concentration index.
Results: For S-MTB, rifabutin + amoxicillin/clavulanate, rifabutin + isoniazid, rifabutin + sparfloxacin and rifabutin + clarithromycin acted synergistically against four, three, one and one isolate, respectively; clarithromycin + rifabutin was additive for one isolate. None of the combinations were antagonistic against S-MTB. For MDR-TB, rifabutin + amoxicillin/clavulanate, rifabutin + isoniazid, rifabutin + sparfloxacin and rifabutin + clarithromycin acted synergistically against one, one, one and two isolates, respectively, and additively against two, one, one and two isolates, respectively. Rifabutin + amoxicillin/clavulanate, rifabutin + isoniazid, and rifabutin + clarithromycin were antagonistic against one, two and two MDR-TB isolates, respectively.
Conclusion: Certain drug combinations acted synergistically against MDR-TB; however, the clinical predictive value of these in vitro experiments is unknown.
Document Type: Regular Paper
Affiliations: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA
Publication date: 1998-08-01
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