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Are Standard Dosing Regimens of Ceftriaxone Adapted for Critically Ill Patients with Augmented Creatinine Clearance?

dc.rights.licenseopenen_US
dc.contributor.authorOLLIVIER, Julien
dc.contributor.authorCARRIÉ, Cédric
dc.contributor.authorD’HOUDAIN, Nicolas
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorDJABAROUTI, Sarah
dc.contributor.authorPETIT, Laurent
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorXUEREB, Fabien
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorLEGERON, Rachel
dc.contributor.authorBIAIS, Matthieu
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorBREILH, Dominique
dc.date.accessioned2020-11-16T12:42:26Z
dc.date.available2020-11-16T12:42:26Z
dc.date.issued2019-01
dc.identifier.issn0066-4804, 1098-6596en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/14028
dc.description.abstractEnABSTRACT The objective of the present study was to determine whether augmented renal clearance (ARC) impacts negatively on ceftriaxone pharmacokinetic (PK)/pharmacodynamic (PD) target attainment in critically ill patients. Over a 9-month period, all critically ill patients treated with ceftriaxone were eligible. During the first 3 days of antimicrobial therapy, every patient underwent 24-h creatinine clearance (CL CR ) measurements and therapeutic drug monitoring of unbound ceftriaxone. ARC was defined by a CL CR of ≥150 ml/min. Empirical underdosing was defined by a trough unbound ceftriaxone concentration under 2 mg/liter (percentage of the time that the concentration of the free fraction of drug remained greater than the MIC [ fT \textgreaterMIC ], 100%). Monte Carlo simulation (MCS) was performed to determine the probability of target attainment (PTA) of different dosing regimens for various MICs and three groups of CL CR (\textless150, 150 to 200, and \textgreater200 ml/min). Twenty-one patients were included. The rate of empirical ceftriaxone underdosing was 62% (39/63). A CL CR of ≥150 ml/min was associated with empirical target underdosing with an odds ratio (OR) of 8.8 (95% confidence interval [CI] = 2.5 to 30.7; P \textless 0.01). Ceftriaxone PK concentrations were best described by a two-compartment model. CL CR was associated with unbound ceftriaxone clearance ( P = 0.02). In the MCS, the proportion of patients who would have failed to achieve a 100% fT \textgreaterMIC was significantly higher in ARC patients for each dosage regimen (OR = 2.96; 95% CI = 2.74 to 3.19; P \textless 0.01). A dose of 2 g twice a day was best suited to achieve a 100% fT \textgreaterMIC . When targeting a 100% fT \textgreaterMIC for the less susceptible pathogens, patients with a CL CR of ≥150 ml/min remained at risk of empirical ceftriaxone underdosing. These data emphasize the need for therapeutic drug monitoring in ARC patients.
dc.language.isoENen_US
dc.subjectArticle CLINIQUE
dc.title.enAre Standard Dosing Regimens of Ceftriaxone Adapted for Critically Ill Patients with Augmented Creatinine Clearance?
dc.typeArticle de revueen_US
dc.identifier.doi10.1128/AAC.02134-18en_US
dc.subject.halSciences du Vivant [q-bio]/Médecine humaine et pathologieen_US
bordeaux.journalAntimicrobial Agents and Chemotherapyen_US
bordeaux.pagee02134–18en_US
bordeaux.volume63en_US
bordeaux.hal.laboratoriesBiologie des maladies cardiovasculaires - U1034en_US
bordeaux.issue3en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03007510
hal.version1
hal.date.transferred2020-11-16T12:42:31Z
hal.exporttrue
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