Multiple combination bactericidal antibiotic testing for patients with cystic fibrosis infected with Burkholderia cepacia

Most Burkholderia cepacia strains are resistant to many, or all, of the ant ibacterial agents commonly used in cystic fibrosis (CF), and selection of a ppropriate antibiotics for treatment of pulmonary exacerbations is therefor e difficult. We developed a technique for rapid in vitro testing of multipl e antibiotic combinations for B. cepacia isolates. For each of 119 multi-dr ug-resistant isolates of B. cepacia our multiple combination bactericidal t est (MCBT) studied the bactericidal activity of 10 to 15 antimicrobial agen ts using 225 +/- 97 single, double, and triple antibiotic combinations. Of the 119 isolates, 50% were resistant to all angle antibiotics tested, 8% we re resistant to all two-drug antibiotic combinations, but all were inhibite d by at least one bactericidal triple-drug combination. When used alone, me ropenem, ceftazidime and high-dose tobramycin (200 mu g/ml) were bactericid al against only 47, 15, and 14% of in vitro isolates, respectively. Using a double antibiotic combination improved bactericidal activity; meropenem-mi nocycline, meropenem-amikacin, and meropenem-ceftazidime combinations were bactericidal against 76, 73, and 73% of isolates, respectively. However, 47 % of isolates demonstrated antagonism (growth of an organism when a second antibiotic was added to a bactericidal single antibiotic). Triple antibioti c combinations that contained tobramycin, meropenem, and an additional anti biotic were most effective, and were bactericidal against 81 to 93% of isol ates. We conclude that triple-antibiotic combinations are more likely than double and single antibiotic combinations to be bactericidal against B. cep acia in vitro. MCBT testing is a useful technique to help clinicians decide on appropriate nonantagonistic combination antibiotic therapy for patients with. CF infected with B. cepacia.