In vitro activity of antimicrobial combinations against clinical isolates of susceptible and resistant Mycobacterium tuberculosis.

SETTING

University of Texas Medical Branch, Clinical Microbiology Laboratory.

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.