Sensitizing multi drug resistant Staphylococcus aureus isolated from surgical site infections to antimicrobials by efflux pump inhibitors.

Baiomy Amr A,Abbas Hisham A,Shaker Ghada H

doi:10.4314/ahs.v20i4.16

Abstract

Staphylococcus aureus is a common hospital acquired infections pathogen. Multidrug-resistant Methicillin-resistant Staphylococcus aureus represents a major problem in Egyptian hospitals. The over-expression of efflux pumps is a main cause of multidrug resistance. The discovery of efflux pump inhibitors may help fight multidrug resistance by sensitizing bacteria to antibiotics. This study aimed to investigate the role of efflux pumps in multidrug resistance. Twenty multidrug resistant S. aureus isolates were selected. Efflux pumps were screened by ethidium bromide agar cartwheel method and polymerase chain reaction. The efflux pump inhibition by seven agents was tested by ethidium bromide agar cartwheel method and the effect on sensitivity to selected antimicrobials was investigated by broth microdilution method. Seventy percent of isolates showed strong efflux activity, while 30% showed intermediate activity. The efflux genes mdeA, norB, norC, norA and sepA were found to play the major role in efflux, while genes mepA, smr and qacA/B had a minor role. Verapamil and metformin showed significant efflux inhibition and increased the sensitivity to tested antimicrobials, while vildagliptin, atorvastatin, domperidone, mebeverine and nifuroxazide showed no effect. Efflux pumps are involved in multidrug resistance in Staphylococcus aureus. Efflux pump inhibitors could increase the sensitivity to antimicrobials.

Highlights

Surgical site infections (SSIs) are those infections that affect either the skin or the underlying soft tissues at the surgical site with a primarily closed incision that occurs within 30 days post-surgery 1.In Gram-positive bacteria, efflux pumps fall into four unrelated families; small multi-drug resistance (SMR), major facilitator superfamily (MFS), adenosine triphosphate (ATP) binding cassette (ABC) and multi-drug and toxic extrusion (MATE)[6].Resistance of Staphylococcus aureus (S. aureus) to antimicrobial agents can take place by intrinsic or acquired resistance[2]
The objective of this study was the detection of efflux pump as a mechanism of resistance to antimicrobials in some (MDR) S. aureus isolates in addition to screening
Domperidone, atorvastatin, nifuroxazide, sulfamethoxazole-trimethoprim, ampicillin-sulbactam and mebeverine were obtained from Egyptian Pharmaceutical Industries Company (EPICO), Egypt, while vildagliptin and metformin were obtained from National Pharmaceutical Company (NAPCO), Egypt

Summary

Introduction

Surgical site infections (SSIs) are those infections that affect either the skin or the underlying soft tissues at the surgical site with a primarily closed incision that occurs within 30 days post-surgery 1.In Gram-positive bacteria, efflux pumps fall into four unrelated families; small multi-drug resistance (SMR), major facilitator superfamily (MFS), adenosine triphosphate (ATP) binding cassette (ABC) and multi-drug and toxic extrusion (MATE)[6].Resistance of Staphylococcus aureus (S. aureus) to antimicrobial agents can take place by intrinsic or acquired resistance[2]. Multidrug-resistant Methicillin-resistant Staphylococcus aureus represents a major problem in Egyptian hospitals. The discovery of efflux pump inhibitors may help fight multidrug resistance by sensitizing bacteria to antibiotics. Methods: Twenty multidrug resistant S. aureus isolates were selected. The efflux pump inhibition by seven agents was tested by ethidium bromide agar cartwheel method and the effect on sensitivity to selected antimicrobials was investigated by broth microdilution method. Verapamil and metformin showed significant efflux inhibition and increased the sensitivity to tested antimicrobials, while vildagliptin, atorvastatin, domperidone, mebeverine and nifuroxazide showed no effect. Conclusion: Efflux pumps are involved in multidrug resistance in Staphylococcus aureus. Efflux pump inhibitors could increase the sensitivity to antimicrobials. Sensitizing multi drug resistant Staphylococcus aureus isolated from surgical site infections to antimicrobials by efflux pump inhibitors.

Objectives

Methods

Results