The effect of non-antibiotic antimicrobials on the development of antibiotic resistant pseudomonas aeruginosa strains / Mostafa Arafa Mohamed Ali Tag Eldein ; Supervised Ossama Eltayeb , Aymen S. Yassin , Mona T. Kashef

Thesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Microbiology and Immunology

Antimicrobial resistance is a major public health concern undermining the effective treatment of many infections. Several studies have addressed the role of improper use of antibiotics in the spread of antimicrobial resistance. However, few studies have explored the effect of Non-antibiotic antimicrobials. In this work, the role of chlorhexidine, as an antiseptic, is studied in the selection of resistant Pseudomonads aeruginosa mutants and their cross resistance to different antibiotics. The mutation frequency after short exposure to sub-inhibitory concentrations of chlorhexidine was compared to the spontaneous mutation frequency, in standard P. aeruginosa PAO1 strain. Different stable mutants were generated, from the standard strain, either by serial passage in increasing concentrations of chlorhexidine or by single exposure to lethal concentration of chlorhexidine. The generated mutants were tested for cross-resistance to commonly used antibiotics by determination of their minimum inhibitory concentrations (MIC). The accompanied phenotypic changes in membrane permeability, outer membrane proteins profile and efflux function was evaluated. The effect of exposure to sub-lethal concentration of chlorhexidine on expression of some multidrug efflux pump genes was investigated in the parent strain. No significant change in the spontaneous mutation frequency was recorded by chlorhexidine exposure. Twelve stable mutants, with more than eightfold increase in chlorhexidine MIC, were generated. Some mutants had two- to four- fold increase in the MIC against Cefepime, Ceftazidime, Meropenem, Ciprofloxacin, and Amikacin compared to the parent strain. This was accompanied by decreased outer membrane permeability, changes in outer membrane proteins, indicated by protein loss or acquisition. Using efflux pump inhibitor, chlorhexidine resistance was reverted in most isolates. Exposure to sub-inhibitory concentrations of chlorhexidine induced the expression the multidrug efflux pump MexXY

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