Effects of Parenterally Administered Ciprofloxacin in a Murine Model of Pulmonary Pseudomonas aeruginosa Infection Mimicking Ventilator-Associated Pneumonia

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Abstract
Background and Methods: We compared the bacteriological, pharmacological and histopathological effects of parenterally administered ciprofloxacin (CPFX) to those of imipenem/cilastatin (IMP/CS) and cefozopran (CZOP) in a murine model of mucoid Pseudomonas aeruginosa pneumonia mimicking ventilator-associated pneumonia. Results: The minimum inhibitory concentrations (MICs) of CPFX, IMP and CZOP were 1.0, 1.0 and 4.0 mg/l, respectively. Treatment with CPFX resulted in a significant decrease in the number of viable bacteria [control, IMP/CS, CZOP and CPFX (mean ± SEM): 5.02 ± 0.20, 4.96 ± 0.38, 5.44 ± 0.13 and 3.27 ± 0.02 log10 colony-forming units lung, respectively]. Histopathological examination revealed that inflammatory changes in the CPFX-treated group were less marked than in other groups. Of the drugs analyzed, the pharmacokinetic parameters of area under the time-concentration curve (AUC)/MIC, AUC exceeding MIC and the time that lung concentrations of drug remained above the MIC were highest for CPFX. Conclusion: Our results suggest that parenterally administered ciprofloxacin is effective in ventilator-associated P. aeruginosa pneumonia.