TY - JOUR
AU1 - Dreesen, Erwin
AU2 - Gijsen, Matthias
AU3 - Elkayal, Omar
AU4 - Annaert, Pieter
AU5 - Debaveye, Yves
AU6 - Wauters, Joost
AU7 - Karlsson, Mats O
AU8 - Spriet, Isabel
AB - ObjectivesPTA of protein-unbound ceftriaxone may be compromised in critically ill patients with community-acquired pneumonia (CAP) with augmented renal clearance (ARC). We aimed to determine an optimized ceftriaxone dosage regimen based on the probability of developing ARC on the next day (PARC,d+1; www.arcpredictor.com).Patients and methodsThirty-three patients enrolled in a prospective cohort study were admitted to the ICU with severe CAP and treated with ceftriaxone 2 g once daily. Patients contributed 259 total ceftriaxone concentrations, collected during 1 or 2 days (±7 samples/day). Unbound fractions of ceftriaxone were determined in all peak and trough samples (n = 76). Population pharmacokinetic modelling and simulation were performed using NONMEM7.4. Target attainment was defined as an unbound ceftriaxone concentration >4 mg/L throughout the dosing interval.ResultsA two-compartment population pharmacokinetic model described the data well. The maximal protein-bound ceftriaxone concentration decreased with lower serum albumin. Ceftriaxone clearance increased with body weight and PARC,d+1 determined on the previous day. A high PARC,d+1 was identified as a clinically relevant predictor for underexposure on the next day (area under the receiver operating characteristics curve 0.77). Body weight had a weak predictive value and was therefore considered clinically irrelevant. Serum albumin had no predictive value. An optimal PARC,d+1 threshold of 5.7% was identified (sensitivity 73%, specificity 69%). Stratified once- or twice-daily 2 g dosing when below or above the 5.7% PARC,d+1 cut-off, respectively, was predicted to result in 81% PTA compared with 47% PTA under population-level once-daily 2 g dosing.ConclusionsCritically ill patients with CAP with a high PARC,d+1 may benefit from twice-daily 2 g ceftriaxone dosing for achieving adequate exposure on the next day.
TI - Ceftriaxone dosing based on the predicted probability of augmented renal clearance in critically ill patients with pneumonia
JF - Journal of Antimicrobial Chemotherapy
DO - 10.1093/jac/dkac209
DA - 2022-07-11
UR - https://www.deepdyve.com/lp/oxford-university-press/ceftriaxone-dosing-based-on-the-predicted-probability-of-augmented-rXoK0KgmlC
SP - 2479
EP - 2488
VL - 77
IS - 9
DP - DeepDyve
ER -