Role of efflux pump inhibitor in decreasing antibiotic cross-resistance of Pseudomonas aeruginosa in a burn hospital in Iran

Abstract

Introduction: Multidrug resistance in Pseudomonas aeruginosa may be due to efflux pump overexpression. This study phenotypically examined the role of efflux pump inhibitors in decreasing antibiotic cross-resistance between beta-lactams, fluoroquinolones, and aminoglycosides in P. aeruginosa isolates from burn patients in Iran. Methodology: A total of 91 phenotypically and genotypically confirmed P. aeruginosa samples were studied. Multidrug cross-resistance was determined using the disk diffusion method and minimum inhibitory concentration (MIC) test. The contribution of efflux pumps was determined by investigating MIC reduction assay to markers of beta-lactams, fluoroquinolones, and aminoglycosides in the absence and presence of an efflux pump inhibitor. All the isolates were also tested by polymerase chain reaction for the presence of mexA, mexC, and mexE efflux genes. Results: Of the isolates, 81 (89%) and 83 (91.2%) were multidrug resistant according to the disk diffusion and MIC method, respectively. Cross-resistance was observed in 67 (73.6%) and 68 (74.7%) of isolates according to the disk diffusion and MIC method, respectively. In the presence of the efflux pump inhibitor, twofold or higher MIC reduction to imipenem, cefepime, ciprofloxacin, and gentamicin was observed in 59, 65, 55, and 60 isolates, respectively. Except for two isolates that were negative for mexC, all isolates were positive for mexA, mexC, and mexE genes simultaneously. Conclusion: Efflux pumps could cause different levels of resistance based on their expression in clinical isolates. Early detection of different efflux pumps in P. aeruginosa could allow the use of other antibiotics and efflux pump inhibitors in combination with antibiotic therapy.

Multidrug resistant Pseudomonas aeruginosa in Iran: A systematic review and metaanalysis

“…Finally, 350 articles were retained for detailed full-text evaluation. According to quality assessment criteria and inclusion/exclusion criteria, a total of 23 articles with full text reporting the prevalence of MDR P. aeruginosa were recruited for the systematic review and meta-analysis[1112131415161718192021222324252627282930313233] [Table 1]. In total, 10 studies from Tehran, 3 studies from Isfahan, 3 studies from Ahvaz, 2 studies from Orumieh, 1 study from Zahedan, 1 study from Zanjan, 1 study from Tabriz, 1 study from Guilan, and 1 study from Hamedan were involved.…”

“…In total, 10 studies from Tehran, 3 studies from Isfahan, 3 studies from Ahvaz, 2 studies from Orumieh, 1 study from Zahedan, 1 study from Zanjan, 1 study from Tabriz, 1 study from Guilan, and 1 study from Hamedan were involved. [1112131415161718192021222324252627282930313233] Figure 2 shows the distribution of MDR P. aeruginosa in different parts of Iran. By using random-effect models, the pooled prevalence of MDR P. aeruginosa was estimated to be 58% (95% confidence interval [CI]; 0.54–0.61).…”

It’s Not Easy Being Green: A Narrative Review on the Microbiology, Virulence and Therapeutic Prospects of Multidrug-Resistant Pseudomonas aeruginosa

“…The modes of antibiotic resistance in P. aeruginosa may be classified into three categories, including (i) adaptive (i.e., biofilm formation, dormant forms), (ii) intrinsic (see Table 2), and (iii) acquired resistance mechanisms (mutation or acquisition of integrons, plasmids, prophages, and transposons by the means of HGT), resulting in a rich and diverse resistome [161]. The occurrence of mutations may lead to antibiotic uptake reduction, antibiotic target modifications, and over-expression of both efflux pumps system and antibiotic inactivating enzymes [162][163][164]. In essence-apart from the fluoroquinolones (who present with excellent oral bioavailability)-all of the present therapeutic alternatives for P. aeruginosa need to be administered parenterally [165].…”

Molecular characterization of resistance mechanisms in Pseudomonas aeruginosa isolates resistant to carbapenems

“…Louis, USA) at a concentration of 50 µg/mL [17][18]. The MIC of the imipenem/inhibitor was compared to the MIC of imipenem alone using paired T test with p < 0.01 was considered significant.…”