Tolerability of high-dose ceftriaxone in CNS infections: a prospective multicentre cohort study

被引：28

作者：

Le Turnier, Paul ^{[1
]}

Navas, Dominique ^{[2
,3
]}

Garot, Denis ^{[4
]}

Guimard, Thomas ^{[5
]}

Bernard, Louis ^{[6
]}

Tattevin, Pierre ^{[7
]}

Vandamme, Yves Marie ^{[8
]}

Hoff, Jerome ^{[9
]}

Chiffoleau, Anne ^{[10
]}

Dary, Martin ^{[11
]}

Leclair-Visonneau, Laurene ^{[12
]}

Gregoire, Matthieu ^{[2
,13
]}

Pere, Morgane ^{[14
]}

Boutoille, David ^{[1
,2
]}

Sebille, Veronique ^{[14
]}

Dailly, Eric ^{[2
,13
]}

Asseray, Nathalie ^{[1
]}

Dailly, Eric ^{[2
,13
]}

Navas, Dominique ^{[2
,3
]}

Sebille, Veronique ^{[14
]}

Abgueguen, Pierre

Asseray, Nathalie ^{[1
]}

Bernard, Louis ^{[6
]}

Boutoille, David ^{[1
,2
]}

Bretonniere, Cedric

Caillon, Jocelyne

Chiffoleau, Anne ^{[10
]}

Dailly, Eric ^{[2
,13
]}

Dary, Martin ^{[11
]}

Garot, Denis ^{[4
]}

Guimard, Thomas ^{[5
]}

Hoff, Jerome ^{[9
]}

Leclair-Visonneau, Laurene ^{[12
]}

Marguerite, Monique

Navas, Dominique ^{[2
,3
]}

Raffi, Francois

Sebille, Veronique ^{[14
]}

Tattevin, Pierre ^{[7
]}

Vandamme, Yves-Marie

Boutoille, David ^{[1
,2
]}

Chiffoleau, Anne ^{[10
]}

Dary, Martin ^{[11
]}

Navas, Dominique ^{[2
,3
]}

Abgueguen, Pierre

Crochette, Nicolas

Vandamme, Yves-Marie

Bakoumas, Kostas

Bieber, Elsa

Colin, Gwenael

机构：

[1] Nantes Univ Hosp, Dept Infect Dis, Nantes, France

[2] Univ Nantes, EA 3826, Nantes, France

[3] Nantes Univ Hosp, Dept Pharm, Nantes, France

[4] Tours Univ Hosp, Anaesthesia & Crit Care Dept, Intens Care Unit, Tours, France

[5] La Roche Sur Yon Hosp, Dept Infect Dis, La Roche Sur Yon, France

[6] Tours Univ Hosp, Dept Infect Dis, Tours, France

[7] Rennes Univ Hosp, Dept Infect Dis, Rennes, France

[8] Angers Univ Hosp, Dept Infect Dis, Angers, France

[9] St Nazaire Hosp, Anaesthesia & Crit Care Dept, Intens Care Unit, St Nazaire, France

[10] Nantes Univ Hosp, Pharmacovigilance, Res Board, Nantes, France

[11] Nantes Univ Hosp, Emergency Dept, Nantes, France

[12] Nantes Univ Hosp, Neurol & Neurophysiol Dept, Nantes, France

[13] Nantes Univ Hosp, Dept Clin Pharmacol, Nantes, France

[14] Nantes Univ Hosp, Biostat Unit, Res Board, Nantes, France

来源：

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY | 2019年 / 74卷 / 04期

关键词：

BETA-LACTAM ANTIBIOTICS; PERFORMANCE LIQUID-CHROMATOGRAPHY; ADVERSE DRUG-REACTIONS; HUMAN PLASMA; NEUROTOXICITY; MANAGEMENT; ADULTS;

D O I：

10.1093/jac/dky553

中图分类号：

R51 [传染病];

学科分类号：

100401 ;

摘要：

Background Ceftriaxone is widely used to treat community-acquired CNS bacterial infections. French guidelines for meningitis in adults promote 75-100mg/kg/day ceftriaxone without an upper limit for dosage, yet little is known about the pharmacology and tolerability of such regimens. Patients and methods A multicentre prospective cohort study was conducted in adult patients to assess the adverse drug reactions (ADRs) of high-dose ceftriaxone (i.e. daily dosage 4g or 75mg/kg) in CNS infections and to analyse their related factors. Drug causality was systematically assessed by an expert committee who reviewed the medical charts of all included patients. Results A total of 196 patients were enrolled over a 31month period. Median dosage and duration of ceftriaxone were 96.4mg/kg/day (7g/day) and 8days, respectively. Nineteen ceftriaxone-related ADRs (mainly neurological) occurred in 17 patients (8.7%), with only one case of treatment discontinuation (biliary pseudolithiasis). In univariate analysis, older age, male gender, renal impairment and high trough ceftriaxone plasma concentration were associated with ceftriaxone-related ADRs. Conclusions High-dose ceftriaxone for CNS infection administered as recommended by French guidelines in adults was well tolerated overall, suggesting these recommendations could be applied and generalized. In patients with advanced age or renal insufficiency, prescription should be done with caution and therapeutic drug monitoring could be useful.

引用

页码：1078 / 1085

页数：8

共 33 条

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