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Ceftriaxone dosing ...
Ceftriaxone dosing based on the predicted probability of augmented renal clearance in critically ill patients with pneumonia
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- Dreesen, Erwin (författare)
- Uppsala universitet,Institutionen för farmaci,Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Clin Pharmacol & Pharmacotherapy Unit, Leuven, Belgium,Pharmacometr Res Grp
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- Gijsen, Matthias (författare)
- Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Clin Pharmacol & Pharmacotherapy Unit, Leuven, Belgium.;Univ Hosp Leuven, Dept Pharm, Leuven, Belgium.
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- Elkayal, Omar (författare)
- Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Clin Pharmacol & Pharmacotherapy Unit, Leuven, Belgium.
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- Annaert, Pieter (författare)
- Katholieke Univ Leuven, Drug Delivery & Disposit, Dept Pharmaceut & Pharmacol Sci, Leuven, Belgium.;BioNotus, Niel, Belgium.
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- Debaveye, Yves (författare)
- Univ Hosp Leuven, Intens Care Unit, Leuven, Belgium.;Katholieke Univ Leuven, Dept Cellular & Mol Med, Lab Intens Care Med, Leuven, Belgium.
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- Wauters, Joost (författare)
- Univ Hosp Leuven, Med Intens Care Unit, Leuven, Belgium.;Katholieke Univ Leuven, Lab Clin Infect & Inflammatory Disorders, Dept Microbiol Immunol & Transplantat, Leuven, Belgium.
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- Karlsson, Mats O. (författare)
- Uppsala universitet,Institutionen för farmaci,Pharmacometr Res Grp
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- Spriet, Isabel (författare)
- Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Clin Pharmacol & Pharmacotherapy Unit, Leuven, Belgium.;Univ Hosp Leuven, Dept Pharm, Leuven, Belgium.
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(creator_code:org_t)
- 2022-07-11
- 2022
- Engelska.
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press. - 0305-7453 .- 1460-2091. ; 77:9, s. 2479-2488
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Objectives: PTA 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 (P-ARC,P-d+1; www.arcpredictor.com). Patients and methods: Thirty-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. Results: A 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 P-ARC,P-d+1 determined on the previous day. A high P-ARC,P-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 P-ARC,P-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% P-ARC,P-d+1 cut-off, respectively, was predicted to result in 81% PTA compared with 47% PTA under population-level once-daily 2 g dosing. Conclusions: Critically ill patients with CAP with a high P-ARC,P-d+1 may benefit from twice-daily 2 g ceftriaxone dosing for achieving adequate exposure on the next day.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
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