Efflux pump inhibition versus quorum sensing inhibition in hospital acquired multidrug resistant Pseudomonas aeruginosa isolates in Mansoura University Hospitals

Abstract

It is necessary to search for alternative strategies such as quorum sensing inhibitors (QSIs) and efflux pump inhibitors (EPIs) for treatment of multidrug resistant (MDR) Pseudomonas aeruginosa infections. Objectives: 1-Assessing and comparing the anti-biofilm activities of the EPI: carbonyl cyanide m-chlorophenylhydrazone (CCCP) and the QSI: baicalein against MDR strong biofilm forming P. aeruginosa isolates. 2-Assessing the presence of mexB and mexY genes encoding the MexAB-OprM and the MexXY-OprM efflux pumps, respectively in MDR P. aeruginosa isolates. Methodology: Wound samples were collected, cultured and antimicrobial susceptibility was done to select MDR P. aeruginosa and MDR ciprofloxacin resistant P. aeruginosa isolates (MDR CIP-R P. aeruginosa). The effects of CCCP and baicalein on the minimum inhibitory concentration (MIC) of ciprofloxacin were assessed. Biofilm eradication assay was done to compare the effects of CCCP and baicalein on preexisting premature and mature biofilms of MDR CIP-R P. aeruginosa isolates. The mexB and mexY genes were detected by PCR in isolated MDR P. aeruginosa. Results: Seventy one P. aeruginosa isolates were MDR and 53 of them were also resistant to ciprofloxacin (MDR CIP-R ). The sub-MIC concentrations of CCCP and baicalein resulted in ciprofloxacin MIC decrease factor (MDF) of ≥ 4 in 62.2%, and 52.8% MDR CIP-R P. aeruginosa isolates, respectively. The biofilm eradication assay indicated that ciprofloxacin combined with either CCCP or baicalein was more effective in eradicating both premature and mature biofilms than either drug alone. However, baicalein alone was superior to CCCP alone in eradicating both premature and mature biofilms. The mexB and mexY genes were detected in 100% and 93% MDR P. aeruginosa isolates, respectively. Conclusion: The use of anti-biofilm agents as EPIs and QSIs with antibiotics could be an effective strategy for treating MDR P. aeruginosa infections.