Background
Systemic Escherichia coli infections cause early mortality of commercial broiler chickens. Although enrofloxacin has long been used in poultry, the in vivo pharmacokinetic/pharmacodynamic (PK/PD) relationship of enrofloxacin against E. coli is unclear. The present study aimed to establish an in vivo PK/PD model of enrofloxacin against E. coli in seven-day-old chicks and to ascertain whether the selection of target organ for PD determination is critical for parameter magnitude calculation in enrofloxacin PK/PD modeling.
Conclusions
The in vivo effectiveness of enrofloxacin against E. coli in different organs was not identical after administration of the same dosage. To describe the magnitude of PK/PD parameter exactly, bacterial loading reduction in different organs as PD endpoints should be evaluated and compared in PK/PD modeling. The selection of a target organ to evaluate PDs is critical for rational dosage recommendation.
Results
The in vivo effectiveness of enrofloxacin against E. coli in different organs varied, with the Emax ranging from - 4.4 to - 5.8 Log10 colony forming units (cfu)/mL or cfu/g. Both the surrogate AUC0-24/MIC of enrofloxacin or AUC0-24/MIC of the combination of enrofloxacin and ciprofloxacin correlated well with effectiveness in each organ. The AUC0-24/MIC ratio of the combination of enrofloxacin and ciprofloxacin producing bactericidal and elimination effects were 21.29 and 32.13 in blood; 41.68, and 58.52 in the liver; and 27.65 and 46.22 in the lung, respectively. Conclusions: The in vivo effectiveness of enrofloxacin against E. coli in different organs was not identical after administration of the same dosage. To describe the magnitude of PK/PD parameter exactly, bacterial loading reduction in different organs as PD endpoints should be evaluated and compared in PK/PD modeling. The selection of a target organ to evaluate PDs is critical for rational dosage recommendation.