Prospective monitoring of cefepime in intensive care unit adult patients.

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Serval ID
serval:BIB_AE78D4090BA8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Prospective monitoring of cefepime in intensive care unit adult patients.
Journal
Critical Care
Author(s)
Chapuis T.M., Giannoni E., Majcherczyk P.A., Chioléro R., Schaller M.D., Berger M.M., Bolay S., Décosterd L.A., Bugnon D., Moreillon P.
ISSN
1466-609X (Electronic)
ISSN-L
1364-8535
Publication state
Published
Issued date
2010
Volume
14
Number
2
Pages
R51
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
INTRODUCTION: Cefepime has been associated with a greater risk of mortality than other beta-lactams in patients treated for severe sepsis. Hypotheses for this failure include possible hidden side-effects (for example, neurological) or inappropriate pharmacokinetic/pharmacodynamic (PK/PD) parameters for bacteria with cefepime minimal inhibitory concentrations (MIC) at the highest limits of susceptibility (8 mg/l) or intermediate-resistance (16 mg/l) for pathogens such as Enterobacteriaceae, Pseudomonas aeruginosa and Staphylococcus aureus. We examined these issues in a prospective non-interventional study of 21 consecutive intensive care unit (ICU) adult patients treated with cefepime for nosocomial pneumonia.
METHODS: Patients (median age 55.1 years, range 21.8 to 81.2) received intravenous cefepime at 2 g every 12 hours for creatinine clearance (CLCr) >or= 50 ml/min, and 2 g every 24 hours or 36 hours for CLCr < 50 ml/minute. Cefepime plasma concentrations were determined at several time-points before and after drug administration by high-pressure liquid chromatography. PK/PD parameters were computed by standard non-compartmental analysis.
RESULTS: Seventeen first-doses and 11 steady states (that is, four to six days after the first dose) were measured. Plasma levels varied greatly between individuals, from two- to three-fold at peak-concentrations to up to 40-fold at trough-concentrations. Nineteen out of 21 (90%) patients had PK/PD parameters comparable to literature values. Twenty-one of 21 (100%) patients had appropriate duration of cefepime concentrations above the MIC (T>MIC >or= 50%) for the pathogens recovered in this study (MIC <or= 4 mg/l), but only 45 to 65% of them had appropriate coverage for potential pathogens with cefepime MIC >or= 8 mg/l. Moreover, 2/21 (10%) patients with renal impairment (CLCr < 30 ml/minute) demonstrated accumulation of cefepime in the plasma (trough concentrations of 20 to 30 mg/l) in spite of dosage adjustment. Both had symptoms compatible with non-convulsive epilepsy (confusion and muscle jerks) that were not attributed to cefepime-toxicity until plasma levels were disclosed to the caretakers and symptoms resolved promptly after drug arrest.
CONCLUSIONS: These empirical results confirm the suspected risks of hidden side-effects and inappropriate PK/PD parameters (for pathogens with upper-limit MICs) in a population of ICU adult patients. Moreover, it identifies a safety and efficacy window for cefepime doses of 2 g every 12 hours in patients with a CLCr >or= 50 ml/minute infected by pathogens with cefepime MICs <or= 4 mg/l. On the other hand, prompt monitoring of cefepime plasma levels should be considered in case of lower CLCr or greater MICs.
Keywords
Adult, Aged, Aged, 80 and over, Anti-Bacterial Agents/administration & dosage, Anti-Bacterial Agents/adverse effects, Anti-Bacterial Agents/pharmacology, Cephalosporins/administration & dosage, Cephalosporins/adverse effects, Cephalosporins/</QualifierName> <QualifierName MajorTopicYN="N">, Cross Infection, Europe, Female, Humans, Intensive Care Units, Male, Middle Aged, Monitoring, Physiologic/methods, Pneumonia/drug therapy, Prospective Studies, Young Adult
Pubmed
Web of science
Open Access
Yes
Create date
01/07/2010 14:39
Last modification date
20/08/2019 15:18
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