Multiple combination bactericidal testing (MCBT) for patients with multiresistant Pseudomonas aeruginosa undergoing lung transplantation

Background: Multiresistant Pseudomonas aeruginosa (PsA) is a common pathogen, and has been isolated in 54% (n 53) of patients with cystic fibrosis prior to lung transplantation (LTx) in this institute since 1989. Another 30% develop multiresistant profiles within one year of LTx. With increasing in vitro resistance suboptimal antibiotic therapy may occur resulting in prolonged morbidity and increased treatment costs. Aim: Determine the optimal bactericidal activity of combination antibiotic therapy for multiresistant PsA before and after LTx. Methods: Sputum isolates underwent MCBT with eight antibiotics singly and in combination. Overall 83 single, double and triple combinations were tested for each sample. These were evaluated for in vitro synergy, absence of synergy, or antagonism. Results: Nine patients (4 males, 17 isolates) were screened with MCBT. The most effective single antibiotic, meropenem, was bactericidal against 18% (n 3) of isolates. Adding a second antibiotic moderately improved bactericidal combinations. The most effective combinations contained meropenem plus either amikacin, tobramycin (10 g/mL) or ceftazidime, and were bactericidal against 41%, 35% and 29% of isolates, respectively. Adding a third antibiotic significantly improved bactericidal combinations in vitro. The most effective combinations contained meropenem, tobramycin (10 g/mL), and either ceftazidime, cefepime, or ciprofloxacin, and were bactericidal against 88%, 81% and 75% of isolates respectively. Subsequently, six of these nine patients (67%) have demonstrated clinical benefit from synergistic triple antibiotic therapy. Conclusions: Increased bactericidal combinations in vitro, and probably in vivo, occurs with the synergy of some triple antibiotic combinations for multiresistant PsA. MCBT testing may assist in more appropriate antibiotic therapy and reduce associated morbidity and antibiotic costs.