Population pharmacokinetics and Monte Carlo dosing simulations of meropenem during the early phase of severe sepsis and septic shock in critically ill patients in intensive care units

Antimicrobial Agents and Chemotherapy
Sutep JaruratanasirikulMaseetoh Samaeng

Abstract

Pathophysiological changes during the early phase of severe sepsis and septic shock in critically ill patients, resulting in altered pharmacokinetic (PK) patterns for antibiotics, are important factors influencing therapeutic success. The aims of this study were (i) to reveal the population PK parameters and (ii) to assess the probability of target attainment (PTA) for meropenem. The PK studies were carried out following administration of 1 g of meropenem every 8 h during the first 24 h of severe sepsis and septic shock in nine patients, and a Monte Carlo simulation was performed to determine the PTA of achieving 40% exposure time during which the free plasma drug concentration remains above the MIC (fT>MIC) and 80% fT>MIC. The volume of distribution (V) and total clearance (CL) of meropenem in these patients were 23.7 liters and 7.82 liters/h, respectively. For pathogens with MICs of 4 μg/ml, the PTAs of 40% fT>MIC following administration of meropenem as a 1-h infusion of 1 g every 8 h and a 4-h infusion of 0.5 g every 8 h were 92.52% and 90.29%, respectively. For pathogens with MICs of 2 μg/ml in immunocompromised hosts, the PTAs of 80% fT>MIC following administration of 1-h and 4-h infusions of 2 g of meropenem every 8 h we...Continue Reading

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Citations

Feb 27, 2016·Expert Review of Anti-infective Therapy·J Nicholas O'DonnellMarc H Scheetz
Apr 7, 2016·European Journal of Clinical Pharmacology·Francesca MattioliAntonello Di Paolo
Apr 27, 2016·Médecine et maladies infectieuses·P LonguetUNKNOWN Groupe des référents en infectiologie d’Île-de-France (GRIF)
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Nov 5, 2016·International Journal of Antimicrobial Agents·Danny TsaiJason A Roberts
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Sep 6, 2020·The Journal of Antimicrobial Chemotherapy·Carla BastidaDolors Soy
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Aug 2, 2020·The Journal of Antimicrobial Chemotherapy·A ContejeanD Hirt
Jan 8, 2021·European Journal of Clinical Pharmacology·Rezvan HassanpourMohammad Sistanizad

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