1. Int J Antimicrob Agents. 2016 Jan;47(1):77-83. doi:
10.1016/j.ijantimicag.2015.11.004. Epub 2015 Nov 26.

Increase of efflux-mediated resistance in Pseudomonas aeruginosa during
antibiotic treatment in patients suffering from nosocomial pneumonia.

Riou M(1), Avrain L(2), Carbonnelle S(1), El Garch F(3), Pirnay JP(4), De Vos
D(4), Plésiat P(5), Tulkens PM(1), Van Bambeke F(6).

Author information: 
(1)Pharmacologie cellulaire et moléculaire & Louvain Drug Research Institute,
Université catholique de Louvain, Brussels, Belgium. (2)Coris BioConcept,
Gembloux, Belgium. (3)Pharmacologie cellulaire et moléculaire & Louvain Drug
Research Institute, Université catholique de Louvain, Brussels, Belgium;
Laboratoire de microbiologie, CHU Dinant-Godinne UCL Namur, Yvoir, Belgium.
(4)Laboratory for Molecular and Cellular Technology, Queen Astrid Military
Hospital, Neder-over-Heembeek, Brussels, Belgium. (5)Laboratoire de
bactériologie, Faculté de médecine, Université de Franche-Comté, Besançon,
France. (6)Pharmacologie cellulaire et moléculaire & Louvain Drug Research
Institute, Université catholique de Louvain, Brussels, Belgium. Electronic
address: francoise.vanbambeke@uclouvain.be.

Increases in antibiotic minimum inhibitory concentrations (MICs) for Pseudomonas 
aeruginosa during treatment are commonly observed but their relationship to
efflux overexpression remains poorly documented. In this study, pairs of first
[at time of diagnosis (D0)] and last [during treatment (DL)] P. aeruginosa
isolates were obtained from patients treated for suspicion of nosocomial
pneumonia. Pair clonality was determined by repetitive extragenic palindromic
PCR. Overexpression of mexA and mexX was assessed by real-time PCR, and
expression of mexC and mexE was assessed by PCR. Antibiotics received by patients
before and during treatment were determined from clinical charts. For D0
isolates, 24% were from patients without antibiotics for 1 month and 64% were
negative for mexA/mexX overexpression and mexC/mexE expression. For DL isolates, 
approximately one-half of the patients had received piperacillin/tazobactam,
amikacin, meropenem and/or cefepime, and 17% had received ciprofloxacin (alone or
in combination); 38% did not show changes in expression of the four genes,
whereas 38% showed increased expression for one gene (mainly mexA or mexX), 19%
for two genes (mainly mexA and mexX) and 5% for three or four genes. Isolates
overexpressing mexA or mexX had median MICs above EUCAST clinical resistance
breakpoints for ciprofloxacin, cefepime and meropenem, or for ciprofloxacin,
amikacin, cefepime and meropenem, respectively. mexA or mexX overexpression was
statistically significantly associated with patients' exposure to ciprofloxacin
and meropenem or cefepime and meropenem, respectively. Overexpression of genes
encoding antibiotic transporters in P. aeruginosa during treatment is frequent
and is associated with increases in MICs above EUCAST clinical susceptibility
breakpoints.

Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All
rights reserved.

PMID: 26691019  [PubMed - in process]