Comparison of the activity of antibiotic combinations in vitro with clinical outcome and resistance emergence in serious infection by Pseudomonas aeruginosa in non-neutropenic patients

Techniques for demonstrating synergy in vitro were compared in testing different beta-lactam-aminoglycoside combinations against 30 isolates of Pseudomonas aeruginosa. Poor concordance was noted among the results from chequerboard and 6 h and 24 h time-kill methods. Comparison of in-vitro synergy results with clinical outcome in 14 patients with pseudomonas infection showed that antagonism in the 24 h time-kill method was the most reliable prognostic indicator of clinical and bacteriological outcome. Although more than 70% of patients were cured clinically with cefsulodin or ticarcillin with tobramycin or amikacin, pseudomonas resistant to the beta-lactam emerged in 7 of 14 patients (50%); of those seven, three had poor clinical outcome. The rationale of adding aminoglycoside to beta-lactams against P. aeruginosa to prevent emergence of resistance needs closer examination.