Comparison of Efficacies of Oral Levofloxacin and Oral Ciprofloxacin in a Rabbit Model of a Staphylococcal Abscess

Abstract

Oral levofloxacin was compared to oral ciprofloxacin in aStaphylococcus aureus subcutaneous abscess model in rabbits. Rabbits were surgically prepared with subcutaneous wiffle balls (43 mm in diameter) and allowed to recover for 4 to 6 weeks. Rabbits were infected by direct injection into the capsule withS. aureus ATCC 29213 (5 × 105 CFU) and were allowed to remain infected for 8 days before the initiation of anti-infective treatment. Efficacy was determined by assessing the bacterial load within the capsule over a 10-day treatment period. In single-dose pharmacokinetic studies in infected rabbits, similar area under the concentration-time curve/MIC ratios were obtained in the plasma and abscess fluid for levofloxacin at 45 mg/kg of body weight and ciprofloxacin at 200 mg/kg of body weight. Similar efficacies were seen with levofloxacin at 45 mg/kg/day and ciprofloxacin 400 mg/kg/day by day 10. In this model, levofloxacin was significantly more efficacious than ciprofloxacin (P < 0.01).

Protection Afforded by Fluoroquinolones in Animal Models of Respiratory Infections with Bacillus anthracis, Yersinia pestis, and Francisella tularensis

“…Therefore, with respect to these two models, there appears to be concordance between ED 50 /ED 100 doses, fluoroquinolone concentrations and a desirable therapeutic effect. In addition, the serum concentrations and the derived kinetic parameters are consistent with the published literature [40, 47, 58, 59]. The noted limitation of these concentration data is the fact they were obtained in uninfected animals and involved single-dose administration.…”

“…Deziel et al [37] reported AUC/MIC ratios of approximately 200-300 were needed for effective therapy; however, outcome was highly dependent on the animal model used and frequency of dose administration. Finally, the C max /MIC and AUC/MIC ratios determined from data in the present study may have been even higher in infected animals with diminished hepatic and renal elimination receiving multiple-dose administration [58]. …”

Testing the mutant selection window in rabbits infected with methicillin-resistant Staphylococcus aureus exposed to vancomycin

“…During this recovery period, the rabbits were observed daily, and the Wiffle ball became walled off and filled with sterile fluid. 13 Approximately 3.0×10 10 cfu S. aureus ATCC 43300 culture was concentrated in 1 mL of 0.9% NaCl and injected into each pre-implanted plastic ball. Two days after infection, 0.5 mL of tissue-cage fluid was withdrawn from each plastic ball for a viable bacteria count.…”

Relationship between Cefquinome PK/PD Parameters and Emergence of Resistance of Staphylococcus aureus in Rabbit Tissue-Cage Infection Model

“…In addition, MIC- and MPC-related pharmacokinetic/pharmacodynamic (PK/PD) parameters play an important role in the application of the MSW hypothesis to elucidate the development of resistance ( Firsov et al, 2003 ). The tissue-cage model was usually used to study the PK/PD parameters because drug concentrations and the selective amplification of resistant bacteria can be directly measured at the infected site, and the in vivo model also simulates the dynamic relationship among the antimicrobial agents, organism, and pathogens ( Craig, 1993 ; Fernandez et al, 1999 ).…”