Document Detail


Pharmacokinetics of meropenem in critically ill patients with severe infections.
MedLine Citation:
PMID:  23318279     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
BACKGROUND: : Meropenem is an effective β-lactam antibiotic that is frequently used to treat serious infections in both intensive care unit (ICU) and febrile neutropenic hematology/oncology (Hem/Onc) patients. Studies suggest that to be effective, meropenem concentrations must be maintained above the inhibitory concentrations for the majority of a dosing interval. However, the pharmacokinetics (PK) of meropenem seem to differ in critically ill patients compared with healthy or less ill subjects used to select labeled dosing regimens.
OBJECTIVES: : This study was designed to investigate meropenem PK in critically ill patients and to see how often standard dosing regimens produced adequate plasma concentrations. A secondary objective was to investigate how achieved concentrations were related to outcomes (morbidity and mortality) in these patients.
METHODS: : Meropenem plasma concentrations over time were measured using a high pressure liquid chromatography assay in febrile Hem/Onc and ICU patients who were treated with standard meropenem dosing schedules. Outcomes such as fever control and survival were assessed in these patients and compared with individual meropenem PK data and with recommended target concentrations.
RESULTS: : A total of 25 subjects including 10 febrile Hem/Onc and 15 ICU patients with a variety of serious illnesses and baseline renal function were studied. Mean peak concentrations were less variable than were pre-dose concentrations. Post peak and trough concentrations were often below recommended minimum inhibitory concentrations. Both clearance and volumes of distribution were greater than reported in less ill subjects, only in part explained by increased renal clearance. Therefore, serum concentrations often did not exceed recommended concentration targets even for moderately sensitive organisms. Inadequate concentrations were especially common in the mostly ill, febrile neutropenic Hem/Onc subjects and seemed to explain at least some therapeutic failures. Conversely, drug accumulation occurred in ICU subjects with decreased renal function.
CONCLUSIONS: : Standard meropenem dosing regimens were inadequate in many critically ill febrile, neutropenic Hem/Onc, and septic ICU patients. These data suggest a role for meropenem concentration monitoring in such patients.
Authors:
Lutz Binder; Harald Schwörer; Sebastian Hoppe; Frank Streit; Silke Neumann; Annett Beckmann; Rolf Wachter; Michael Oellerich; Philip D Walson
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Therapeutic drug monitoring     Volume:  35     ISSN:  1536-3694     ISO Abbreviation:  Ther Drug Monit     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7909660     Medline TA:  Ther Drug Monit     Country:  United States    
Other Details:
Languages:  eng     Pagination:  63-70     Citation Subset:  IM    
Affiliation:
Departments of *Clinical Chemistry †Gastroenterology and Endocrinology ‡Orthopedics §Hematology and Oncology ¶Anesthesiology ‖Cardiology and Pneumology, Center for Internal Medicine, University Medical Center Göttingen, Göttingen, Germany.
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