A NEW ROLE OF METFORMIN AS AN EFFLUX PUMP INHIBITOR IN KLEBSIELLA PNEUMONIA

Abstract

Respiratory tract infections caused by Klebsiella pneumoniae are frequently associated with high mortality and morbidity rates. Treatment of these infections is usually difficult due to the emergence of multiple resistances to antibiotics. Multidrug efflux pumps are greatly involved in antibiotic resistance in Gram-negative bacteria including Klebsiella pneumoniae. In the current study, efflux activity was observed in 93.75% of Klebsiella pneumoniae clinical isolates by the qualitative acridine orange agar method. This finding was further confirmed genotypically by polymerase chain reaction that showed the presence of efflux genes AcrA, AcrB, TolC and mdtk in these isolates. The ability of metformin to inhibit efflux activity was compared with the reference efflux pump inhibitors verapamil and ascorbic acid. Metformin was more active than ascorbic acid and less active than verapamil. Up to our knowledge, this is the first report that shows that metformin has an efflux pump-inhibiting activity in Klebsiella pneumoniae.