The Involvement of Drug Efflux System in Amikacin Resistance of Multiple Drug Resistant Acintobacter baumannii Isolates in Isfahan, Iran

Abstract

Background: Due to the extensive usage of antibiotics in recent decades, the emergence of multiple drug-resistant (MDR) strains has dramatically increased. In the present study, we studied the distribution and involvement of drug efflux system in conferring resistance to amikacin in MDR isolates of Acinetobacter baumannii isolated from hospitalized patients. Methods: In this cross-sectional study 80 MDR A. baumannii were isolates isolated from hospitalized patients in Alzahra hospital, Isfahan, Iran. A. baumannii isolates were identified by standard microbiologic procedure and were confirmed by specific PCR primers. Minimum inhibitory concentration (MIC) was determined by agar dilution method according to CLSI guidelines. Carbonyl cyanide 3-chlorophenylhy­drazon (CCCP) was used as an efflux pump inhibitor for amikacin susceptibility. The presence of efflux genes was detected by PCR method. Results: Antibiotic susceptibility results showed that 39 of isolates had MIC ≥32 µg/mL and were amikacin-resistant. Totally, 41 isolates which had an amikacin MIC ≥2 μg/mL were tested for reduction of MIC in presence of 25 μg/mL efflux pumps inhibitor. After the treatment, 25 (61%) isolates had ≥2 fold and 15 (36.6%) isolates had 4 fold reduction in amikacin MIC. The results of PCR-amplifications indicated that the presence rate of AdeA, AdeB, AdeC, AbeM and AdeS genes were 100%, 96.3%, 95%, 98.8%, and 95%, respectively. Conclusion: In summary, significant involvement of drug efflux system in conferring resistance to amikacin along with high distribution of efflux genes suggests an alternative therapy using antibiotics in combination with efflux inhibitors in the fight against MDR isolates of A. baumannii.

Keywords

• Acinetobacter baumannii
• AdeABC genes
• Amikacin
• Efflux pumps
• MDR