Impact of efflux mechanisms on susceptibility and resistance to beta-lactam antibiotics in Pseudomonas aeruginosa : beyond the usual concepts

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.(BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 201