Combination antibiotics against Pseudomonas aeruginosa, representing common and rare cystic fibrosis strains from different Irish clinics

Objectives: To evaluate the effect of antibiotic combination therapy versus single therapy against cystic fibrosis strains of Pseudomonas aeruginosa identified as common and rare among patient groups in different Irish hospitals. Methods: This study compares the susceptibility profiles of P. aeruginosa isolates from different cystic fibrosis (CF) clinics in Ireland, collected from 2004-2005. Strains were recovered in small numbers and typed by pulsed-field gel electrophoresis. Five common clonal variants were identified in five different hospitals, described as 'common strains'. A number of 'rare strains ' associated with any single patient were also included in the study. Certain virulence factors were determined and in vitro assays such as minimum inhibitory concentrations (MIC) and biofilm inhibitory concentrations (BIC) were employed to assess potential synergistic effects of antipseudomonal antibiotic combination therapy. Results: There was no distinct virulence factors associated with clinical strains that were common in comparison to those that were rare. Antibiotic combination testing revealed the majority of combinations were similar to the activity of either antibiotic used as single agents. Tobramycin-ceftazidime was the most effective combination exhibiting synergistic interactions (FIC <= 0.5) against certain clinical isolates of P. aeruginosa. Conclusion: The efficacy of single antibiotics and synergistic interactions of antibiotic combinations were strain specific, irrespective of virulence characteristics of P. aeruginosa. Common clonal P. aeruginosa strains do not have distinct characteristics that possibly influence persistence in the chronic CF lung. Tobramycin-ceftazidime may be successful for controlling specific P. aeruginosa strains. Further studies on representative isolates are needed to support these results.