Background and objectives Staphylococcus aureus is an opportunistic pathogen that causes wide range of nosocomial and community-acquired infections which have spread worldwide leading to an urgent need for developing effective anti-staphylococcal agents. Efflux is an important resistance mechanism that bacteria used to fight the antimicrobial action. This study aimed to investigate the efflux mechanism in S. aureus and assess diclofenac, domperidone, glyceryl trinitrate and metformin as potential efflux pump inhibitors that can be used in combination with antibiotics for treating topical infections caused by S. aureus. Materials and methods Efflux was detected qualitatively by the ethidium bromide Cart-Wheel method followed by investigating the presence of efflux genes by polymerase chain reaction. Twenty-six isolates were selected for further investigation of efflux by Cart-Wheel method in absence and presence of tested compounds followed by quantitative efflux assay. Furthermore, antibiotics minimum inhibitory concentrations in absence and presence of tested compounds were determined. The effects of tested drugs on expression levels of efflux genes norA, fexA and tetK were determined by quantitative real time-polymerase chain reaction. Results Efflux was found in 65.3% of isolates, the prevalence of norA, tetK, fexA and msrA genes were 91.7%, 77.8%, 27.8% and 6.9%. Efflux assay revealed that tested drugs had potential efflux inhibitory activities, reduced the antibiotic’s MICs and significantly decreased the relative expression of efflux genes. Conclusion Diclofenac sodium, domperidone and glyceryl trinitrate showed higher efflux inhibitory activities than verapamil and metformin. To our knowledge, this is the first report that shows that diclofenac sodium, glyceryl trinitrate and domperidone have efflux pump inhibitory activities against S. aureus.

This study aims to investigate the resistance profile of enterococci to commonly used antibiotics to provide correct treatment of urinary tract infections and to stop the continual emergence of highly resistant species of bacteria. Three hundred and twenty five (325) urine samples were collected from patients in Urinary Tract (UT) Department and Outpatient urinary tract clinic of Zagazig University Hospitals in Zagazig city, Sharkia, Egypt. One hundred and twenty seven enterococcal isolates (39.1%) were isolated from urine samples. Seventy (55.1%) of enterococcal isolates were Enterococcus faecalis and fifty seven (44.9%) of enterococcal isolates were Enterococcus faecium. All the isolates are identified and the sensitivity to a number of antibiotics was determined by disc diffusion method. Using standard breakpoint sensitivity values: the highest percentages of resistance of enterococcal isolates were found for penicillin G, rifampin, erythromycin, doxycycline, ampicillin, lincomycin and amoxicillin. The moderate percentages of resistance were found for ciprofloxacin, azithromycin, clarithromycin and spiramycin, gentamicin and clindamycin, whereas the lowest percentages of resistance were seen for and chloramphenicol, vancomycin, teicoplanin, sulphamethoxazole/trimethoprim and imipenem. These values are seemed to be higher than wide world values. This is probably due to the variation in the bacterial sensitivity pattern over time and between different geographical districts, misusing of antibiotics and not continuing the antibiotic therapy for sufficient period of time. In conclusion, this high resistance rate represents a dangerous alarm that necessitates the search for new therapeutic options.

Staphylococcus aureus is one of the most common human pathogens that causes wide range of nosocomial and community acquired infections as wound and burn infections, food poisoning, endocarditis, pneumonia, meningitis and bacteremia. Beside its pathogenicity, it exhibits different antibiotic resistance mechanisms that complicate its treatment. Efflux is one of the resistance mechanisms that is used by bacterial pathogens to extrude antimicrobials as antibiotics and biocides and thus counteract their actions. Therefore, there is an urgent need for searching for compounds that have an efflux-inhibitory activity among the existing phar¬maceuticals and the compounds that are isolated from natural sources or the synthesis of novel derivatives to be able to treat S. aureus infections. Several efflux pump inhibitors have been identified or synthesized over the past years. In this review, we present the different compounds that have been proven to have an efflux-inhibitory activity against S. aureus and the current progress in their development.