Ampicillin-chloramphenicol interaction against enteric Gram-negative organisms.

Because two children with Salmonella osteomyelitis responded differently to a combination of ampicillin and chloramphenicol, we investigated the activity of each antibiotic and the combination against 21 enteric organisms including Salmonella sp. and other Gram-negative bacilli. Ampicillin was bactericidal against all 21 organisms (minimal bactericidal concentration (MBC) range, 0.25 to 16 micrograms/ml). Chloramphenicol was bactericidal against 5 (MBC range, 2 to 16 micrograms/ml) and bacteriostatic against 16 (MBC, greater than or equal to 64 micrograms/ml). Fractional lethal indices indicated that chloramphenicol and ampicillin were antagonistic (fractional lethal concentration, greater than 1.2) against all 16 bacteria for which chloramphenicol was bacteriostatic, and the ampicillin MBC increased from a mean of 2.2 micrograms/ml to 37.2 micrograms/ml. The two antibiotics were synergistic (fractional lethal concentration, less than 0.8) against the five organisms for which chloramphenicol was bactericidal, and the ampicillin MBC was lowered from a mean of 3.0 micrograms/ml to 0.4 micrograms/ml. Our data indicate that the combination of ampicillin and chloramphenicol can be synergistic or antagonistic against Gram-negative enteric bacteria depending on whether chloramphenicol is bactericidal or bacteriostatic against the specific organism.