In vitro activity of clarithromycin in combination with other antimicrobial agents against biofilm-forming Pseudomonas aeruginosa strains.

摘要

The aim of the study was to investigate the biofilm-production of 60 Pseudomonas aeruginosa strains isolated from clinical samples and to examine the effect of different antimicrobials and their combinations with clarithromycin on biofilm-formation. The minimal inhibitory concentrations (MICs), minimal biofilm inhibitory concentrations (MBICs), and antibiotic synergy by calculating the fractional inhibitory concentration (FIC) index were determined for the following antibiotics: ceftazidime, cefepime, piperacillin/tazobactam, imipenem, meropenem, levofloxacin, ciprofloxacin, gentamicin, amikacin, tobramycin, netilmicin and clarithromycin. A total of 14 (23.3%) isolates out of 60 isolates of P. aeruginosa were biofilm positive. Cefepime, imipenem and meropenem had the lowest MIC 90 values. Piperacillin/tazobactam and clarithromycin had the highest MIC 90 values. Imipenem, meropenem, piperacillin/tazobactam and clarithromycin had the lowest MBIC 90 values. For biofilm-forming P. aeruginosa strains 2-fold to 128-fold higher MBIC values than MIC values were obtained for ceftazidime, cefepime, imipenem, amikacin and netilmicin. The MBIC was 2-fold to 512-fold lower then the MIC values in the case of piperacillin/tazobactam, ciprofloxacin, levofloxacin and clarithromycin. Synergy was generally demonstrated for clarithromycin in combination with aminoglycosides, fluoroquinolones or ceftazidime. However, surprisingly it was found that combinations of clarithromycin with carbapenems or cefepime led to an antagonistic interaction: combination of clarithromycin with imipenem, meropenem or ertapenem showed antagonism in 37.5%, 50% and 62.5% of the strains tested whereas its combination with cefepime expressed antagonism in 75% of the strains, respectively. To the best of our knowledge no one has previously described this phenomenon so far.