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Annals of Intensive Care
Published in: Annals of Intensive Care 1/2017

Open Access 01-12-2017 | Research

Systematic overdosing of oxa- and cloxacillin in severe infections treated in ICU: risk factors and side effects

Authors: Mathilde Neuville, Najoua El-Helali, Eric Magalhaes, Aguila Radjou, Roland Smonig, Jean-François Soubirou, Guillaume Voiriot, Alban Le Monnier, Stéphane Ruckly, Lila Bouadma, Romain Sonneville, Jean-François Timsit, Bruno Mourvillier

Published in: Annals of Intensive Care | Issue 1/2017

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Abstract

Background

Oxacillin and cloxacillin are the most frequently used penicillins for the treatment of severe methicillin-susceptible Staphylococcus aureus infections in intensive care units (ICUs), especially endocarditis. International recommendations do not suggest any adaptation of the dosage in case of renal impairment. We wanted to assess the risk factors for overdosing in ICU and the related observed side effects.

Methods

All patients with a therapeutic drug monitoring of oxa- or cloxacillin between 2008 and 2014 were included. The target range of trough concentration for total antibiotic activity was considered to be 20–50 mg/L. Data concerning the infection, the given treatment, the renal function, and the attributed side effects of overdosing were collected. A logistic regression model was used to compute the measured trough concentrations.

Results

Sixty-two patients were included in this study. We found a median trough plasma concentration of 134.3 mg/L (IQR 65.3–201 mg/L). Ten patients (16.1%) reached the target concentration; all other patients (83.9%) were overdosed. Eleven patients (17.7%) experienced neurological side effects attributed to a high antibiotic concentration, i.e. persistent coma and delirium. When adjusted on the dosage used, the risk of overdosing was significantly associated with a creatinine clearance <10 mL/min (with or without hemodialysis).

Conclusion

With the suggested dose of 12 g/day for cloxacillin treatment in case of endocarditis and severe infections occurring in ICU, 83.9% of patients are largely overdosed. Considering the observed side effects, doses should be accurately monitored and reduced, particularly when renal replacement therapy is needed.
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Metadata
Title
Systematic overdosing of oxa- and cloxacillin in severe infections treated in ICU: risk factors and side effects
Authors
Mathilde Neuville
Najoua El-Helali
Eric Magalhaes
Aguila Radjou
Roland Smonig
Jean-François Soubirou
Guillaume Voiriot
Alban Le Monnier
Stéphane Ruckly
Lila Bouadma
Romain Sonneville
Jean-François Timsit
Bruno Mourvillier
Publication date
01-12-2017
Publisher
Springer Paris
Published in
Annals of Intensive Care / Issue 1/2017
Electronic ISSN: 2110-5820
DOI
https://doi.org/10.1186/s13613-017-0255-8

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