Synergism of trimethoprim combined with aminoglycosides in vitro and in serum of volunteers.

In vitro synergism of trimethoprim plus amikacin and trimethoprim plus sisomicin against 66 gram-negative bacilli was studied by microtiter checkerboard dilution. Synergism was defined as an FIC or FBC index equal to or less than 0.5. Fifty-two percent of strains were inhibited and 65% killed synergistically by the former combination, and 27% and 36% respectively by the latter combination (p less than 0.01). Serum bactericidal activity against 16 strains resistant to ampicillin and/or cephalothin was studied using serum from five volunteers one and six hours after intravenous administration of trimethoprim (160 mg), amikacin (250 mg) or the combination, and from six volunteers after administration of trimethoprim, tobramycin (1 mg/kg) or the combination. With trimethoprim and amikacin serum bactericidal titers greater than or equal to 1:8 were found more frequently with the combination (77 of 80 samples) than with either drug alone (trimethoprim 19 of 80 samples, amikacin 60 of 80 samples, p less than 0.01). Trimethoprim plus amikacin may be useful in the treatment of infections with gram-negative rods resistant to cephalothin and ampicillin.