Assessment of combination therapy by time kill curve analysis and chequerboard assay for treatment of multi-drug resistant Pseudomonas aeruginosa isolates

Multidrug resistant Pseudomonas aeruginosa is a major nosocomial pathogen, and effective therapy presents a great clinical challenge. Combination therapy, employing pre-existing antibiotics, is an attractive approach for the treatment of such infections which may also curtail drug resistance. This study was undertaken with the objectives to assess the synergy of five different antimicrobial combinations (piperacillin-tazobactum with levofloxacin, cefoperazone-sulbactum with levofloxacin, piperacillin-tazobactum with amikacin, cefoperazone-sulbactum with amikacin and amikacin with levofloxacin for the treatment of Pseudomonas aeruginosa isolates with varied susceptibility profile by time kill curve assay and the chequerboard technique. In our study concordance between these two methods was noted in 71.7% isolates tested. Le-Pt combination demonstrated maximum synergy (72.7%), followed by Ak-Le (66.7%) and Ak-Cfs (60%) combination. Le-Cfs and Ak-Pt however, showed synergy in significantly lower number of isolates. However, at sub-MIC concentrations Ak-Pt combination was found to be most effective. Synergy between different drugs should be routinely monitored for exploring more feasible treatment options and to prevent the emergence of multi-drug resistant strains. Piperacillin- tazobactum emerged as a versatile drug whose potential should be explored with other drugs for combination treatment of P. aeruginosa isolates.