Bacterial Species-Specific Activity of a Fluoroquinolone against Two Closely Related Pasteurellaceae with Similar MICs: Differential In Vitro Inoculum Effects and In Vivo Efficacies.
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.
Vétoquinol, Lure, France.
Guillaume
G
Lhermie
Vétoquinol, Lure, France.
Farid
F
El Garch
INRA, UMR1331 TOXALIM, Toulouse, France; Université de Toulouse, INPT, ENVT, EIP, UPS, Toulouse, France.
Pierre-Louis
PL
Toutain
INRA, UMR1331 TOXALIM, Toulouse, France; Université de Toulouse, INPT, ENVT, EIP, UPS, Toulouse, France.
Aude A
AA
Ferran
INRA, UMR1331 TOXALIM, Toulouse, France; Université de Toulouse, INPT, ENVT, EIP, UPS, Toulouse, France.
Alain
A
Bousquet-Mélou
D000818:Animals; D000900:Anti-Bacterial Agents; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial / Q000235:genetics; D024841:Fluoroquinolones / Q000008:administration & dosage*; D006801:Humans; D016978:Mannheimia haemolytica / Q000187:drug effects* / Q000472:pathogenicity; D051379:Mice; D016979:Pasteurella multocida / Q000187:drug effects* / Q000472:pathogenicity; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000382:microbiology; D013045:Species Specificity
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; C080260:marbofloxacin