Comparative effectiveness of combinations of amikacin with penicillin G and amikacin with carbenicillin in gram-negative septicemia: double-blind clinical trial.

Preliminary results are presented for an ongoing, double-blind, clinical trial, in which the efficacy of amikacin plus penicillin G (Amik-Pen) and amikacin plus carbenicillin (Amik-Carb) is compared in treatment of severe gram-negative infections superimposed on serious underlying disease. All clinical isolates were sensitive to amikacin in vitro (minimal inhibitory concentration, less than 12 mug/ml). Results in 50 patients with cancer and documented gram-negative infection, 29 of which involved septicemia, were analyzed. In the Amik-Pen group, 40% of 15 cases of septicemia responded favorable to therapy, as compared with 86% of 14 cases of septicemia in the Amik-Carb group; this difference is statistically significant (P less than 0.02). When all patients were considered together, the outcome appeared more favorable (1) in infections caused by pathogens sensitive to both antibiotics used then in those caused by organisms sensitive to amikacin only (83% vs. 43%); (2) when the combined antibiotics demonstrated synergy in virto against the offending pathogen than when the combination was nonsynergistic (83% vs. 38%); and (3) when the peak serum antimicrobial dilution titer was larger than or equal to 1:8 than when titers were lower. The results of this study suggest that routine use of an antibiotic combination that has demonstrable in vitro synergy against the offending pathogen should be considered for the treatment of proven or suspected severe infections due to gram-negative bacilli.