Meropenem prevents levofloxacin-induced resistance in penicillin-resistant pneumococci and acts synergistically with levofloxacin in experimental meningitis.

Détails

ID Serval
serval:BIB_7EBB828C3FD3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Meropenem prevents levofloxacin-induced resistance in penicillin-resistant pneumococci and acts synergistically with levofloxacin in experimental meningitis.
Périodique
European Journal of Clinical Microbiology and Infectious Diseases
Auteur(s)
Cottagnoud P., Cottagnoud M., Acosta F., Flatz L., Kühn F., Stucki A., Entenza J.
ISSN
0934-9723[print], 0934-9723[linking]
Statut éditorial
Publié
Date de publication
2003
Volume
22
Numéro
11
Pages
656-662
Langue
anglais
Résumé
The aim of the present study was to investigate the potential synergy between meropenem and levofloxacin in vitro and in experimental meningitis and to determine the effect of meropenem on levofloxacin-induced resistance in vitro. Meropenem increased the efficacy of levofloxacin against the penicillin-resistant pneumococcal strain KR4 in time-killing assays in vitro and acted synergistically against a second penicillin-resistant strain WB4. In the checkerboard, only an additive effect (FIC indices: 1.0) was observed for both strains. In cycling experiments in vitro, levofloxacin alone led to a 64-fold increase in the MIC for both strains after 12 cycles. Addition of meropenem in sub-MIC concentrations (0.25 x MIC) completely inhibited the selection of levofloxacin-resistant mutants in WB4 after 12 cycles. In KR4, the addition of meropenem led to just a twofold increase in the MIC for levofloxacin after 12 cycles. Mutations detected in the genes encoding for topoisomerase IV (parC) and gyrase (gyrA) confirmed the levofloxacin-induced resistance in both strains. Addition of meropenem was able to completely suppress levofloxacin-induced mutations in WB4 and led to only one mutation in parE in KR4. In experimental meningitis, meropenem, given in two doses (2 x 125 mg/kg), produced a good bactericidal activity (-0.45 Deltalog10 cfu/ml.h) comparable to one dose (1 x 10 mg/kg) of levofloxacin (-0.44 Deltalog10 cfu/ml.h) against the penicillin-resistant strain WB4. Meropenem combined with levofloxacin acted synergistically (-0.93 Deltalog10 cfu/ml.h), sterilizing the CSF of all rabbits.
Mots-clé
Animals, DNA, Bacterial/analysis, Disease Models, Animal, Dose-Response Relationship, Drug, Drug Resistance, Bacterial, Drug Synergism, Drug Therapy, Combination, Female, Male, Meningitis, Pneumococcal/drug therapy, Microbial Sensitivity Tests, Ofloxacin/pharmacology, Penicillin Resistance, Polymerase Chain Reaction/methods, Rabbits, Reference Values, Sensitivity and Specificity, Streptococcus pneumoniae/drug effects, Streptococcus pneumoniae/isolation & purification, Thienamycins/pharmacology
Pubmed
Web of science
Création de la notice
24/01/2008 14:45
Dernière modification de la notice
03/03/2018 18:42
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