A multicenter, prospective randomized trial was conducted to determine if the addition of
rifampin to a combination
therapy of an antipseudomonal
beta-lactam agent and
aminoglycoside improves the outcome of patients with Pseudomonas aeruginosa
bacteremia. The Zelen protocol for randomized-consent design was used. Consent was sought only from patients randomized to the
experimental therapy (
rifampin+). If the
experimental therapy was refused, the patient would then receive the standard combination
therapy (control); however, when outcome was evaluated, all patients randomized to the rifampin+ group, including those that declined
rifampin, were compared with the control group. One hundred twenty-one consecutive hospitalized patients with positive blood cultures for P. aeruginosa were enrolled. Entry was stratified for prior use of empiric antipseudomonal
antibiotics,
neutropenia, severity of illness, and presence of
pneumonia. Fifty-eight patients were randomized to receive
rifampin (600 mg orally every 8 h for the first 72 h and then every 12 h for a total of 10 days) plus a
beta-lactam agent plus an
aminoglycoside. Sixty-three received the standard
therapy of a
beta-lactam plus an
aminoglycoside agent (control). Bacteriologic cure occurred significantly more frequently in patients randomized to the rifampin+ regimen. Breakthrough or relapsing
bacteremias occurred in 2% of the three-
drug (
rifampin+) group, compared with 14% for the two-
drug (standard therapy) group. Despite this favorable trend in bacteriological response, no significant differences in survival were seen for the two treatment groups.
Rifamycin derivatives warrant further clinical study as antipseudomonal agents. The Zelen protocol appears well suited for comparative trials of
antimicrobial agents.