ABSTRACT:
This study aimed to investigate the possible synergistic effects of three Non-steroidal anti-inflammatory drugs; piroxicam, ketoprofen, diclofenac sodium in addition to sodium ascorbate with ciprofloxacin, cefoperazone, tobramycin, amikacin and imipenem against established biofilms formed by five clinical isolates of Pseudomonas aeruginosa. The biofilm inhibiting effect of the antibiotics was investigated by determination of minimum regrowth concentration (MRC). Complete or partial synergism was found with 87% of the isolates. The highest synergistic effect was exerted by piroxicam with each of tobramycin and amikacin. Complete synergy was also observed for piroxicam with ciprofloxacin and cefoperazone, sodium ascorbate with cefoperazone, tobramycin, ciprofloxacin and amikacin, ketoprofen with tobramycin, imipenem and amikacin and diclofenac with each of tobramycin and amikacin. Partial synergy was found for imipenem with each of piroxicam, diclofenac and sodium ascorbate, cefoperazone with each of diclofenac sodium and ketoprofen. No synergy was observed with ketoprofen when combined with ciprofloxacin. Piroxicam was more synergistic than other tested agents, followed by sodium ascorbate, ketoprofen and diclofenac sodium. Piroxicam decreased the MRC of antibiotics by up to 128-1024 folds, sodium ascorbate by up to 4-256 folds, diclofenac sodium by up to 4-128 folds, while the MRCs were decreased by up to 2-128 folds in the presence of ketoprofen. Comparing the synergy of antibiotics when combined with the tested agents, the aminoglycosides amikacin and tobramycin were generally more potentiated than ciprofloxacin, cefoperazone and imipenem. With piroxicam, amikacin and tobramycin were more augmented than ciprofloxacin, cefoperazone and imipenem. Combined with sodium ascorbate, cefoperazone was more potentiated than amikacin, tobramycin, imipenem and ciprofloxacin. Higher synergistic effect of diclofenac sodium and ketoprofen was demonstrated with tobramycin and amikacin, while imipenem, cefoperazone and ciprofloxacin were less augmented. Our results suggest the use of antibiotics in combination with sodium ascorbate and NSAIDs to increase the efficacy of antibiotics against biofilm infections.