Effect of renal clearance and continuous renal replacement therapy on appropriateness of recommended meropenem dosing regimens in critically ill patients with susceptible life-threatening infections

Article Article scientifique Article Effect of renal clearance and continuous renal replacement therapy on appropriateness of recommended meropenem dosing regimens in critically ill patients with susceptible life-threatening infections eng 2018-12-01 author Burger Raphaël Internal Medicine Service, Department of Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland.,Infectious Diseases Service, Department of Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland. author Guidi Monia Clinical Pharmacology Service, Lausanne University Hospital (CHUV), Lausanne, Switzerland.,School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland. 762075 author Calpini Valérie School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland. 518159 author Lamoth Frédéric Infectious Diseases Service, Department of Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland.,Institute of Microbiology, Department of Laboratories, Lausanne University Hospital (CHUV), Lausanne, Switzerland. author Decosterd Laurent Clinical Pharmacology Service, Lausanne University Hospital (CHUV), Lausanne, Switzerland. author Robatel Corinne Clinical Pharmacology Service, Lausanne University Hospital (CHUV), Lausanne, Switzerland. author Buclin Thierry Clinical Pharmacology Service, Lausanne University Hospital (CHUV), Lausanne, Switzerland. author Csajka Chantal Clinical Pharmacology Service, Lausanne University Hospital (CHUV), Lausanne, Switzerland.,School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland. 657943 Section des sciences pharmaceutiques (FARMA) author Marchetti Oscar Infectious Diseases Service, Department of Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland.,Department of Medicine, Ensemble Hospitalier de la Côte, Morges, Switzerland. 3413-3422 10.1093/jac/dky370 30304491 0305-7453 Background: Meropenem plasma concentration above a pathogen's MIC over the whole dosing interval (100% ƒT>MIC) is a determinant of outcome in severe infections. Significant variability of meropenem pharmacokinetics is reported in ICU patients. Objectives: To characterize meropenem pharmacokinetics in variable CLCR or renal replacement therapy and assess the appropriateness of recommended regimens for MIC coverage. Methods: A pharmacokinetic analysis (NONMEM) was conducted with external model validation. Patient characteristics were tested on meropenem clearance estimates, differentiated according to the presence/absence of continuous renal replacement therapy (CRRT, CLCRRT or CLno-CRRT). Simulations evaluated the appropriateness of recommended dosing for achieving 100% fT>MIC in 90% of patients. Results: A total of 101 patients were studied: median 63 years (range 49-70), 56% male, SAPS II 38 (27-48). 32% had a CLCR >60 mL/min, 49% underwent CRRT and 32% presented severe sepsis or septic shock. A total of 127 pathogens were documented: 76% Gram-negatives, 24% Gram-positives (meropenem MIC90 2 mg/L, corresponding to EUCAST susceptibility breakpoint). Three hundred and eighty plasma and 129 filtrate-dialysate meropenem concentrations were analysed: two-compartment modelling best described the data. Predicted meropenem CLno-CRRT was 59% lower in impaired (CLCR 30 mL/min) compared to normal (CLCR 100 mL/min) renal function. Simulations showed that recommended regimens appropriately cover MIC90 in patients with CLCR <60 mL/min. Patients with CLCR of 60 to <90 mL/min need 6 g/day to achieve appropriate coverage. In patients with CLCR ≥90 mL/min, appropriate exposure is achieved with increased dose, frequency of administration and infusion duration, or continuous infusion. Conclusions: Recommended meropenem regimens are suboptimal in ICU patients with normal or augmented renal clearance. Modified dosing or infusion modalities achieve appropriate MIC coverage for optimized antibacterial efficacy in meropenem-susceptible life-threatening infections. Open Access - Licence nationale Oxford University Press Aged Anti-Bacterial Agents / administration & dosage Anti-Bacterial Agents / pharmacokinetics Bacterial Infections / drug therapy Computer Simulation Critical Illness Female Humans Male Meropenem / administration & dosage Meropenem / pharmacokinetics Metabolic Clearance Rate Middle Aged Plasma / chemistry Prospective Studies Renal Insufficiency / complications Renal Insufficiency / therapy Renal Replacement Therapy Dewey 615 31 Section des sciences pharmaceutiques 17 false 887 Pharmacie hospitalière et clinique The journal of antimicrobial chemotherapy 73 12 c8fc70c1-d69d-49da-b31e-7992cab82b04 Article (Published version) Public Article-scientifique-from-unpaywall.pdf 308647 application/pdf OA NATIONAL 2ec46c47148545ffd43d634272c4d6323ea0213e4bfe68ebfb29d90dbf3b7385 openAccess Faculté des sciences / Section des sciences pharmaceutiques

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Effect of renal clearance and continuous renal replacement therapy on appropriateness of recommended meropenem dosing regimens in critically ill patients with susceptible life-threatening infections	The journal of antimicrobial chemotherapy	2018	67	313
Caractérisation du profil pharmacocinétique du méropénème chez des patients de soins intensifs avec ou sans épuration extrarénale		2013	189	6

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Calpini, Valérie