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. 2015 Oct 27;10(10):e0141441.
doi: 10.1371/journal.pone.0141441. eCollection 2015.

Bacterial Species-Specific Activity of a Fluoroquinolone against Two Closely Related Pasteurellaceae with Similar MICs: Differential In Vitro Inoculum Effects and In Vivo Efficacies

Guillaume Lhermie  1 , Farid El Garch  1 , Pierre-Louis Toutain  2 , Aude A Ferran  2 , Alain Bousquet-Mélou  2
Affiliations

Bacterial Species-Specific Activity of a Fluoroquinolone against Two Closely Related Pasteurellaceae with Similar MICs: Differential In Vitro Inoculum Effects and In Vivo Efficacies

Guillaume Lhermie et al. PLoS One. .

Abstract

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 105 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 108 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 109 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 105 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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Conflict of interest statement

Competing Interests: Guillaume Lhermie and Farid El Garch have an affiliation to the commercial funder Vetoquinol. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Time-kill curves of low (105 CFU/mL) (A and B) and high (108 CFU/mL) (C and D) inocula of M. haemolytica (A and C) and for P. multocida (B and D) in the presence of marbofloxacin (concentrations shown in multiple of the MIC (MIC = 0.016μg/mL for P multocida and MIC = 0.03 μg/mL for M. haemolytica).
Fig 2
Fig 2. Bactericidal effect of marbofloxacin against low (A) and high (B) inocula of M. haemolytica (full symbols) and P. multocida (open symbols) isolates.
Fig 3
Fig 3. Mean bacterial counts in the lungs of mice infected with P. multocida (dark bars) or with M. haemolytica (white bars) after intraperitoneal administrations of different doses of marbofloxacin.
Different letters in superscript above bars indicate that values are statistically different.
See this image and copyright information in PMC

References

    1. Canton R, Morosini MI. Emergence and spread of antibiotic resistance following exposure to antibiotics. FEMS Microbiol Rev. 2011;35: 977–991. 10.1111/j.1574-6976.2011.00295.x - DOI - PubMed
    1. Drusano GL, Preston SL, Fowler C, Corrado M, Weisinger B, Kahn J. Relationship between fluoroquinolone area under the curve: minimum inhibitory concentration ratio and the probability of eradication of the infecting pathogen, in patients with nosocomial pneumonia. J Infect Dis. 2004;189: 1590–1597. . - PubMed
    1. Forrest A, Nix DE, Ballow CH, Goss TF, Birmingham MC, Schentag JJ. Pharmacodynamics of intravenous ciprofloxacin in seriously ill patients. Antimicrob Agents Chemother. 1993;37: 1073–1081. . - PMC - PubMed
    1. Gehring R, Riviere JE. Limitations of MIC as the sole criterion in antimicrobial drug dosage regimen design: the need for full characterization of antimicrobial pharmacodynamic profile especially for drug-resistant organisms. Vet J. 2013;198: 15–18. 10.1016/j.tvjl.2013.07.034 - DOI - PubMed
    1. CLSI. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard-Eighth Edition. Document M7-A8. 2009;29-2(ISBN 1-56238-689-1).

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