Appropriateness of ciprofloxacin dosing based on a population pharmacokinetic model

Purpose: Over the past two decades, the minimum inhibitory concentrations (MICs) of ciprofloxacin have been steadily increasing for gram-negative bacteria. One major reason cited for this "MIC creep" is underdosing of ciprofloxacin due to a lack of understanding of its pharmacodynamic properties. The primary objective of this study was to evaluate the frequency of underdosing of ciprofloxacin in a tertiary acute care medical center based on a population pharmacokinetic model. Secondary objectives included evaluation of appropriateness of dosing based on renal function and approved product labeling.Methods: Seventy-six patients were included in this single-center, retrospective study. Data collection included demographic, laboratory, and microbiology data along with details on antibiotic administration. Patient-specific predicted 24-hour area under the curve/MIC (AUC ₂₄/MIC) values were estimated using a population pharmacokinetic model with a goal predicted AUC₂₄/MIC of at least 100 and a preferred target value of 250.Results: Only 8% of the subjects obtained a predicted AUC₂₄/MIC higher than 250, while 34% of the subjects achieved a predicted AUC₂₄/MIC of 100 or less. The majority of patients (79%) received a total daily intravenous-equivalent dose of 800 mg, whereas only 8% of subjects received an initial total daily intravenous-equivalent dose of 1,200 mg, which is the recommended dose for most severe infections. Overall 26% of subjects were prescribed an appropriate initial dose for their estimated renal function based on infection type and severity.Conclusion: Ciprofloxacin for acute infection treatment was frequently underdosed based on US Food and Drug Administration-approved labeling and estimated predicted AUC₂₄/MIC at a tertiary acute care medical center.