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The Effects of Combining β-lactam Antibiotics and Mefloquine in Multi-Drug Resistant <i>Pseudomonas aeruginosa</i>

Pseudomonas aeruginosa, a notorious opportunistic pathogen, is a leading cause of hospital-acquired infections. The newest generation of β-lactam antibiotics, the carbapenems, are often used to treat multi-drug resistant (MDR) P. aeruginosa infections. Treatment of P. aeruginosa has become increasingly difficult due to its remarkable ability to resist antibiotics through various intrinsic and acquired mechanisms. Physicians rely on a limited group of antibiotics to treat these infections, but many P. aeruginosa isolates are evolving to become resistant to all available antibiotics, including carbapenems. The multifaceted mechanisms underlying P. aeruginosa antibiotic resistance include β -lactamases, efflux pumps, altered membrane porins, and antibiotic binding site mutations of the penicillin binding proteins. There is an urgent need for continued research to better understand the resistance mechanisms used by P. aeruginosa, in order to develop novel therapeutic strategies. The purpose of this project was to investigate the effect of β-lactam antibiotics used in combination with the known efflux pump inhibitor mefloquine, on the growth of MDR P. aeruginosa. The effect of the combination of mefloquine andβ-lactams was investigated in vitro using the checkerboard method. In vitro assays showed that mefloquine when combined with certain β-lactam antibiotics produced no significant additional inhibition than the β-lactams antibiotics alone on MDR P. aeruginosa. Mefloquine, in combination with various β-lactams, did not restore clinically relevant sensitivity, even in those isolates where resistance is thought to be mediated by efflux pumps.

Identiferoai:union.ndltd.org:BGMYU2/oai:scholarsarchive.byu.edu:etd-11553
Date09 August 2024
CreatorsMaas, Kayla C.
PublisherBYU ScholarsArchive
Source SetsBrigham Young University
Detected LanguageEnglish
Typetext
Formatapplication/pdf
SourceTheses and Dissertations
Rightshttps://lib.byu.edu/about/copyright/

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