TY - JOUR
T1 - Pharmacokinetic/pharmacodynamic target attainment of ciprofloxacin in adult patients on general wards with adequate and impaired renal function
AU - de Vroom, Suzanne L.
AU - van Hest, Reinier M.
AU - van Daalen, Frederike V.
AU - Kuil, Sacha D.
AU - Mathôt, Ron A. A.
AU - Geerlings, Suzanne E.
AU - Jager, Nynke G. L.
PY - 2020/11
Y1 - 2020/11
N2 - Limited prospective data on pharmacokinetic/pharmacodynamic (PK/PD) target attainment of ciprofloxacin in patients with adequate and impaired renal function (eGFR <30 mL/min/1.73m2) are available in the literature. We aimed to investigate whether the PK/PD target (AUC/MIC ≥125) is attained in patients with adequate and impaired renal function receiving regular and reduced ciprofloxacin doses. This prospective observational cohort study included adult patients on general wards treated with ciprofloxacin. Three blood samples per patient were obtained for ciprofloxacin concentration measurement. Individual AUCs were calculated using a population PK model developed by non-linear mixed-effects modelling. Forty patients were included, of whom eight had impaired renal function and were treated with a guideline-recommended reduced dose. Using the clinical breakpoint MIC of the most isolated bacteria (Escherichia coli, 0.25 mg/L), AUC0–24/MIC ≥125 was attained in 13/32 (41%) patients with adequate renal function receiving regular doses and in 1/8 (13%) patients with impaired renal function receiving reduced doses. Median drug exposure (AUC0–24) for patients with impaired renal function was 19.0 [interquartile range (IQR) 14.2–23.3] mg/L•h, which was statistically significantly lower than that for patients with adequate renal function [29.3 (IQR 25.0–36.0) mg/L•h] (P < 0.01). AUC0–24/MIC ≥125 is not attained in the majority of adult patients on general wards for clinically relevant bacteria with MICs at or just below the clinical breakpoint. The risk of not attaining the target appears to be highest in patients with impaired renal function receiving guideline-recommended reduced doses, as drug exposure is significantly lower in these patients.
AB - Limited prospective data on pharmacokinetic/pharmacodynamic (PK/PD) target attainment of ciprofloxacin in patients with adequate and impaired renal function (eGFR <30 mL/min/1.73m2) are available in the literature. We aimed to investigate whether the PK/PD target (AUC/MIC ≥125) is attained in patients with adequate and impaired renal function receiving regular and reduced ciprofloxacin doses. This prospective observational cohort study included adult patients on general wards treated with ciprofloxacin. Three blood samples per patient were obtained for ciprofloxacin concentration measurement. Individual AUCs were calculated using a population PK model developed by non-linear mixed-effects modelling. Forty patients were included, of whom eight had impaired renal function and were treated with a guideline-recommended reduced dose. Using the clinical breakpoint MIC of the most isolated bacteria (Escherichia coli, 0.25 mg/L), AUC0–24/MIC ≥125 was attained in 13/32 (41%) patients with adequate renal function receiving regular doses and in 1/8 (13%) patients with impaired renal function receiving reduced doses. Median drug exposure (AUC0–24) for patients with impaired renal function was 19.0 [interquartile range (IQR) 14.2–23.3] mg/L•h, which was statistically significantly lower than that for patients with adequate renal function [29.3 (IQR 25.0–36.0) mg/L•h] (P < 0.01). AUC0–24/MIC ≥125 is not attained in the majority of adult patients on general wards for clinically relevant bacteria with MICs at or just below the clinical breakpoint. The risk of not attaining the target appears to be highest in patients with impaired renal function receiving guideline-recommended reduced doses, as drug exposure is significantly lower in these patients.
KW - Ciprofloxacin
KW - Dose reduction
KW - Impaired renal function
KW - Pharmacodynamics
KW - Pharmacokinetics
UR - http://www.scopus.com/inward/record.url?scp=85092095551&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ijantimicag.2020.106166
DO - https://doi.org/10.1016/j.ijantimicag.2020.106166
M3 - Article
C2 - 32941947
SN - 0924-8579
VL - 56
JO - International Journal of Antimicrobial Agents
JF - International Journal of Antimicrobial Agents
IS - 5
M1 - 106166
ER -