Titre
Isolation and in-vitro and in-vivo characterisation of a mutant of Pseudomonas aeruginosa PAO1 that exhibited a reduced postantibiotic effect in response to imipenem.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Majcherczyk, P.A.
Auteure/Auteur
Kunz, S.
Auteure/Auteur
Hattenberger, M.
Auteure/Auteur
Vaxelaire, J.
Auteure/Auteur
Zak, O.
Auteure/Auteur
O'Reilly, T.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
0305-7453
Statut éditorial
Publié
Date de publication
1994-10
Volume
34
Numéro
4
Première page
485
Dernière page/numéro d’article
505
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Résumé
The postantibiotic effect (PAE) is the persistent inhibition of bacterial growth after a brief exposure to an antibiotic. Most beta-lactams do not induce a PAE for Gram-negative bacteria, but PAEs have been reported for carbapenems and penems. This study investigated the effect of sequential doses of imipenem on the PAE for Pseudomonas aeruginosa and Escherichia coli cultures in a chemostat. The PAE for the bacterial population did not change even after six successive exposures to imipenem. Nevertheless, screening of colonies isolated after repeated drug exposure identified a single P. aeruginosa mutant whose imipenem PAE was shortened, although the MIC was unchanged. The PAEs for the parent and mutant were studied in vitro in batch culture by monitoring: (i) viable counts; (ii) electrical impedance of the culture medium; (iii) incorporation of radiolabelled N-acetyl-D-glucosamine and (iv) cell volume changes. PAEs for the parent and mutant were found to be significantly different by all in-vitro methods used. Moreover, the median cell volume in antibiotic-exposed cultures remained much smaller and less heterogeneous than in the control cultures, even though both cultures were growing at the same rate. The mutant was found to have a reduced expression of a 52 kDa outer membrane protein. These observations suggest that factors in addition to suppression of bacterial growth should be considered when studying the PAE. The PAEs of imipenem for the parent and mutant were studied in a thigh infection model in leucopenic mice. Similar PAEs were observed in vivo for both parent and mutant in one experiment and no PAEs for either organism were found in a second experiment. This study showed that although the PAE is a stable in-vitro phenomenon, the lack of correlation between the in-vitro and in-vivo results warrants caution in attributing clinical significance to the PAE of imipenem.
Sujets
PID Serval
serval:BIB_02175ED277C5
PMID
Date de création
2008-01-24T12:54:32.850Z
Date de création dans IRIS
2025-05-20T18:30:34Z