Appropriateness of Ciprofloxacin Dosing Based on a Population Pharmacokinetic Model

Abstract

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 (AUC24/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.