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Background  The resistance of cephalosporins is significantly serious in veterinary clinic. In order to inhibit the bacterial resistance production, the mutant selection window (MSW) hypothesis with  Escherichia coli  ( E. coli ) ATCC 25922 exposed to cefquinome in an animal tissue-cage model was investigated.    Results  Localized infection with  E. coli  was established in piglets, and the infected animals were administrated intramuscularly with various doses and intervals of cefquinome to provide antibiotic concentrations below the MIC 99 , between the MIC 99  and the mutant prevention concentration (MPC), and above the MPC.  E. coli  lost susceptibility when drug concentrations fluctuated between the lower and upper boundaries of the window, which defined  in vitro  as the MIC 99  (0.06 μg/mL) and the MPC (0.16 μg/mL) respectively. For PK/PD parameters, there were no mutant selection enrichment when T>MIC 99  was ≤ 25% or T>MPC was ≥ 50% of administration interval. When T>MIC 99  was > 25% and T>MPC was <50% of administration interval, resistance selection was observed. When AUC 24 h /MIC 99  and AUC 24 h /MPC were considered, the mutant selection window extended from 32.84 h to 125.64 h and from 12.83 h to 49.09 h, respectively.    Conclusions  These findings demonstrate that the MSW exists  in vivo  for time-dependent antimicrobial agents, and its boundaries fit well with those determined  in vitro . Maintenance of antimicrobial concentrations above the MPC for > 50% of administration interval is a straightforward way to restrict the acquisition of resistance in this tissue cage model. This situation was achieved with daily intramuscular doses of 1 mg cefquinome/kg body weight.

In vivo evaluation of mutant selection window of cefquinome against Escherichia coliin piglet tissue-cage model