Multiple combination bactericidal antibiotic testing for patients with cystic fibrosis infected with multiresistant strains of Pseudomonas aeruginosa

We developed a rapid in vitro antibiotic susceptibility test to screen doub le- and triple-antibiotic combinations for bactericidal activity against 75 multiresistant Pseudomonas aeruginosa isolates referred from 44 cystic fib rosis (CF) patients. When used alone, the most effective intravenous antibi otic, meropenem, was bactericidal against only 44% of the isolates. High-do se tobramycin (200 mug/ml; concentrations achievable by aerosol administrat ion) was bactericidal against 72% of isolates. Adding a second antibiotic s ignificantly improved bactericidal activity. The most effective double-anti biotic combinations contained high-dose tobramycin plus meropenem, piperaci llin/tazobactam, or ciprofloxacin, and were bactericidal against 88 to 94% of the isolates. Excluding high-dose tobramycin, the most effective intrave nous double-antibiotic combinations contained meropenem plus ciprofloxacin, tobramycin (4 mug/ml), or cefipime, and were bactericidal against 85%, 71% , and 70% of isolates, respectively. Adding a third antibiotic did not sign ificantly improve inhibition in vitro. We conclude that double-antibiotic c ombinations containing meropenem or high-dose tobramycin show the best bact ericidal activity in vitro against multiresistant strains of P. aeruginosa. Addition of a third antibiotic to these double-antibiotic combinations may be unnecessary.