Synergistic Combinational Effect of Antibiotics on Multi Drug Resistant P. aeruginosa Clinical Isolate

Abstract

Pseudomonas aeruginosa is equipped with serious health problems that cause high morbidity and high mortality rates. Amongst them, the incidence rate of multidrug resistant (MDR) P. aeruginosa has been increasing worldwide. The treatment of MDR P. aeruginosa has particularly become more challenging due to its inherent and acquired resistance to many existing antibiotic drugs. There is a demand for effective therapies, but the development of new antibiotics is in the pipeline, since an alternative such as the phage therapy has not been promising, however, strategies like combination therapy are more effective as compared to others. In this study, we identified synergistic combinations that showed effective against MDR P. aeruginosa. A total 84 combinations of 20 commercially available FDA cleared antibiotics were made, which include 50 double and 34 triple combinations. Out of 84, 25 combinations have high synergism, lower antibiotic generation and high MIC value individually. Imipenem- Levofloxacin and Amoxicillin-Clavulanic acid-Ofloxacin were found to be the most effective combinations against MDR P. aeruginosa isolates. These combinations were validated by time kill kinetics, and efficacy of combinations were checked on other isolates, whereby, IMP-LVX showed bactericidal killing against 80%, and AMX-CLA-OFX showed 60% synergistic killing of other MDR P. aeruginosa clinical isolates.