Population pharmacokinetics of meropenem in critically ill children with different renal functions

Rapp, M.; Urien, Saı̈k; Foissac, Frantz; Béranger, Agathe; Bouazza, Naïm; Benaboud, Sihem; Bille, Emmanuelle; Zheng, Yi; Gana, Inès; Moulin, F.; Lesage, Fabrice; Renolleau, Sylvain; Tréluyer, Jean Marc; Hirt, Déborah; Oualha, Mehdi

doi:10.1007/s00228-019-02761-7

Cited by 39 publications

(54 citation statements)

References 43 publications

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“…Multiple recent studies investigated the population PK of meropenem in critically ill pediatric patients; others were reviewed previously. 21,80 One recent study included 40 critically ill children with a median (range) age of 16.8 months (1.4-187.2 months) and eGFR using the Schwartz formula of 151 mL/min/1.73 m 2 (19-440 mL/min/1.73 m 2 ). 80 The relationship between eGFR and total meropenem clearance was described by an empirical power model.…”

Section: Complexities Associated With Antibiotic Therapy In Patients mentioning

confidence: 99%

Key Challenges in Providing Effective Antibiotic Therapy for Critically Ill Patients with Bacterial Sepsis and Septic Shock

Landersdorfer

Nation

2021

Clin Pharma and Therapeutics

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Early initiation of effective antibiotic therapy is vitally important for saving the lives of critically ill patients with sepsis or septic shock. The susceptibility of the infecting pathogen and the ability of the selected dosage regimen to safely achieve the required antibiotic exposure need to be carefully considered to achieve a high probability of a successful outcome. Critically ill patients commonly experience substantial pathophysiological changes that impact the functions of various organs, including the kidneys. Many antibiotics are predominantly renally eliminated and thus renal function is a major determinant of the regimen needed to achieve the required antibiotic exposure. However, currently, there is a paucity of guidelines to inform antibiotic dosing in critically ill patients, including those with sepsis or septic shock. This paper briefly reviews methods that are commonly used in critically ill patients to provide a measure of renal function, and approaches that describe the relationship between the exposure to an antibiotic and its antibacterial effects. Two common conditions that very substantially complicate the use of antibiotics in critically ill patients with sepsis, unstable renal function, and augmented renal clearance, are considered in detail and their potential therapeutic implications are explored. Suggestions are provided on how treatment of bacterial infections in critically ill patients with sepsis might be improved. Of high potential are model-informed approaches that aim to individualize initial treatment regimens based on patient and bacterial characteristics, with refinement of regimens during treatment in response to monitoring antibiotic concentrations, responsive measures of renal function, and other important clinical data.

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Section: Complexities Associated With Antibiotic Therapy In Patients mentioning

confidence: 99%

Key Challenges in Providing Effective Antibiotic Therapy for Critically Ill Patients with Bacterial Sepsis and Septic Shock

Landersdorfer

Nation

2021

Clin Pharma and Therapeutics

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“…However, detailed non-compartmental data for the ECMO and CRRT groups are not available. 11 Cies et al assessed the PPK of meropenem in 9 critically ill children; CL and Vd for this population were 6.99 ± 2.5 mL/(min‧kg) and 0.78 ± 0.73 L/kg, respectively, although the analysis excluded children receiving ECMO or CRRT. 12 In general, PK parameters are influenced by the ECMO device that is used, the physicochemical properties of the drug and the pathological changes in patients.…”

Section: What Is K Nown and Objec Tivementioning

confidence: 99%

“…Rapp et al reported the population pharmacokinetics (PPK) of meropenem in 40 critically ill children, among whom 8 received ECMO and 11 CRRT; the two‐compartment model showed CL, central volume of distribution (V1) and peripheral volume of distribution (V2) of 6.82 L/h, 40.6 L, and 9.2 L, respectively. However, detailed non‐compartmental data for the ECMO and CRRT groups are not available 11 . Cies et al assessed the PPK of meropenem in 9 critically ill children; CL and Vd for this population were 6.99 ± 2.5 mL/(min‧kg) and 0.78 ± 0.73 L/kg, respectively, although the analysis excluded children receiving ECMO or CRRT 12 …”

Section: What Is Known and Objectivementioning

confidence: 99%

“…Moreover, little is known about the influence on the filtration efficacy of β‐lactam antibiotics after inflammatory mediators block the hemofiltration membrane during CRRT. Multiple studies have demonstrated that prolonged infusion of meropenem can improve its PK parameters, with some suggesting a 24‐h continuous infusion at MIC >4 mg/L 11 . However, a 24‐h continuous infusion needs the drug solution to be changed every 3 hours owing to the instability of meropenem under ambient conditions; this may impose a significant financial burden on families or hospitals in developing countries.…”

Section: What Is Known and Objectivementioning

confidence: 99%

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Pharmacokinetics of meropenem in children with sepsis undergoing extracorporeal life support: A prospective observational study

Wang

Chen

et al. 2021

J Clin Pharm Ther

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“… Model covariates—RRT, actual body weight, estimated glomerular filtration rate (Schwartz). Crandon Jl et al [ 137 ] Braune S et al [ 138 ] Rapp M et al [ 139 ] Micafungin Adult ICU. N = 11 patients (242 plasma samples).…”

Section: Table A1mentioning

confidence: 99%

What Are the Current Approaches to Optimising Antimicrobial Dosing in the Intensive Care Unit?

et al. 2020

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Antimicrobial dosing in the intensive care unit (ICU) can be problematic due to various challenges including unique physiological changes observed in critically ill patients and the presence of pathogens with reduced susceptibility. These challenges result in reduced likelihood of standard antimicrobial dosing regimens achieving target exposures associated with optimal patient outcomes. Therefore, the aim of this review is to explore the various methods for optimisation of antimicrobial dosing in ICU patients. Dosing nomograms developed from pharmacokinetic/statistical models and therapeutic drug monitoring are commonly used. However, recent advances in mathematical and statistical modelling have resulted in the development of novel dosing software that utilise Bayesian forecasting and/or artificial intelligence. These programs utilise therapeutic drug monitoring results to further personalise antimicrobial therapy based on each patient’s clinical characteristics. Studies quantifying the clinical and cost benefits associated with dosing software are required before widespread use as a point-of-care system can be justified.

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Population pharmacokinetics of meropenem in critically ill children with different renal functions

Cited by 39 publications

References 43 publications

Key Challenges in Providing Effective Antibiotic Therapy for Critically Ill Patients with Bacterial Sepsis and Septic Shock

Key Challenges in Providing Effective Antibiotic Therapy for Critically Ill Patients with Bacterial Sepsis and Septic Shock

Pharmacokinetics of meropenem in children with sepsis undergoing extracorporeal life support: A prospective observational study

What Are the Current Approaches to Optimising Antimicrobial Dosing in the Intensive Care Unit?

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