ADDITION OF RIFAMPIN TO TICARCILLIN-TOBRAMYCIN COMBINATION FOR THE TREATMENT OF PSEUDOMONAS-AERUGINOSA INFECTIONS - ASSESSMENT IN A NEUTROPENIC MOUSE MODEL

  • 1 January 1984
    • journal article
    • research article
    • Vol. 103  (6) , 878-885
Abstract
The efficacy of ticarcillin (100 mg/kg), tobramycin (1 mg/kg) and rifampin (43 and 7.2 mg/kg) individually and in combination was assessed in neutropenic mice infected with a lethal dose for 90% of population of 1 of 4 P. aeruginosa isolates. The study end point was survival at 120 h after infection. Treatment with the triple combination, ticarcillin plus tobramycin plus rifampin (43 mg/kg), was significantly superior to the double combination of ticarcillin plus tobramycin (P < 0.01). Although treatment with rifampin (43 mg/kg) alone yielded results similar to treatment with the triple combination in mice infected with 3 of the 4 isolates, rifampin-resistant mutants (minimal inhibitory concentration > 1000 .mu.g/ml) of P. aeruginosa were frequently isolated from surviving mice (26% of mice sampled). In mice treated with the triple combination, rarely were rifampin-resistant mutants isolated (3% of mice sampled). Rifampin alone was active against P. aeruginosa isolates only when peak serum concentrations of rifampin exceeded the rifampin minimal bactericidal concentration of the infecting isolate. The addition of rifampin to a standard therapy of antipseudomonal penicillin plus aminoglycoside may be useful in the treatment of serious P. aeruginosa infection.