Experimental in vitro efficacy study on the interaction of epiroprim plus isoniazid against Mycobacterium...

Thirty Mycobacterium tuberculosis strains (8: INH(R)/INH(R), 12: INH(R)/RIF(S), 10: INH(S)/RIF(S)) were examined against MICs of epiroprim (EPM) and isoniazid (INH) separately or in association. EPM alone proved to be insufficiently active against the various mycobacterial isolates (MIC > or =256 microg/ml). The observed average sensitivity to the association of EPM plus INH was, in contrast, considerably increased, as reflected by reduced MICs and lower percentages of resistant strains. MICs ranged between 16 and 32 microg/ml EPM and 2 and 4 microg/ml INH for INH(R) strains. All INH(S) isolates were inhibited by a concentration of 0.125 microg/ml EPM and 0.06 microg/ml INH. The fractional inhibitory concentration indices indicated an additive activity on INH(R)/RIF(R) strains and a synergistic activity on INH(R)/RIF(S) and INH(S)/RIF(S) strains. The synergistic activity of this drug association needs to be confirmed in an animal model.