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Bacterial Species-Specific Activity of a Fluoroquinolone against Two Closely Related Pasteurellaceae with Similar MICs: Differential In Vitro Inoculum Effects and In Vivo Efficacies
Author(s) -
Guillaume Lhermie,
Farid El Garch,
PierreLouis Toutain,
Aude Ferran,
Alain Bousquetmélou
Publication year - 2015
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0141441
Subject(s) - pasteurella multocida , microbiology and biotechnology , biology , pasteurellaceae , in vivo , in vitro , bacteria , antimicrobial , antibiotics , pasteurellosis , biochemistry , genetics , haemophilus influenzae
We investigated the antimicrobial activity of a fluoroquinolone against two genetically close bacterial species belonging to the Pasteurellaceae family. Time-kill experiments were used to measure the in vitro activity of marbofloxacin against two strains of Mannheimia haemolytica and Pasteurella multocida with similar MICs. We observed that marbofloxacin was equally potent against 10 5 CFU/mL inocula M . haemolytica and P . multocida . However, an inoculum effect was observed with P . multocida , meaning that marbofloxacin activity was decreased against a 10 8 CFU/mL inoculum, whereas no inoculum effect was observed with M . haemolytica . Marbofloxacin activity was also tested in a lung infection model with immunocompromised mice intratracheally infected with 10 9 CFU of each bacteria. At the same dose, the clinical and bacteriological outcomes were much better for mice infected with M . haemolytica than for those infected with P . multocida . Moreover, bacteriological eradication was obtained with a lower marbofloxacin dose for mice infected with M . haemolytica . Our results suggest that the differential in vivo marbofloxacin efficacy observed with the two bacterial species of similar MIC could be explained by a differential inoculum effect. Consequently, MICs determined on 10 5 CFU inocula were not predictive of the differences in antibiotic efficacies against high bacterial inocula of closely related bacterial strains. These results could stimulate further investigations on bacterial species-specific antibiotic doses in a clinical setting.

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