The objective of the thesis was to evaluate the active efflux as a mechanism of resistance to β-lactams in Pseudomonas aeruginosa isolated from European patients with cystic fibrosis. Our findings emphasize the increased prevalence of multidrug-resistant isolates. They also demonstrate that active efflux plays a major role in β-lactam resistance. In particular, active efflux confers high-level resistance to meropenem and avibactam (new β-lactamase inhibitor), when combined with alterations in OprD porins. Furthermore, natural mutations in the genes encoding MexAB-OprM efflux pump restore the activity of temocillin (considered as inactive against P. aeruginosa) against a non-negligible proportion of isolates. This work re-examines the concept that efflux confers only low-level resistance. In addition, it allows to better position the interest of antibiotics used in the context of cystic fibrosis.
Chalhoub, H. (2016). Impact of efflux mechanisms on susceptibility and resistance to beta-lactam antibiotics in Pseudomonas aeruginosa : beyond the usual concepts. https://hdl.handle.net/2078.5/38555