Microbiological relevance and clinical potential of ampicillin-cloxacillin synergism

Recent demonstration "in vitro" that combinations of ampicillin and cloxacillin, using concentrations at which neither were previously effective, will kill certain resistant Gram negative bacteria, has important clinical potential. We therefore studied 50 ampicillin resistant Gram negative rods cultured from septicemic patients for synergism. 7 of 23 E. coli strains with a minimal bactericidal concentration (MBC) of 128 microgram/ml were killed by combinations containing 4-32 microgram/ml ampicillin and 16-32 microgram/ml cloxacillin. These same strains were also resistant to cephalothin. Synergism was also noted in 1/4 strains of Enterobacter, 1/3 strains of Serratia, 5/14 strains of Klebsiella and 1/6 strains of Pseudomonas. In separate experiments ampicillin (56 mg/kg) and cloxacillin (14 mg/kg) was administered intravenously over a period of thirty minutes. Peak serum levels measured simultaneously at the end of the infusion were 235 +/- 11 (SEM) microgram/ml for ampicillin and 85 +/- 7 microgram/ml for cloxacillin. Levels of ampicillin/cloxacillin measured one and two hours after the infusion were 117/32 and 43/8 microgram/ml. T 1/2 of ampicillin and cloxacillin were 0.8 and 0.5 h respectively. Since the serum concentrations of both antibiotics measured one hour after the infusion were greater that levels required for "in vitro" synergism, we suggest that combinations of ampicillin and cloxacillin would be of importance in the treatment of Gram negative septicemia, since such therapy would increase the bactericidal effect of the sera without increasing the risk of toxic side effects.