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

BACKGROUND: Ceftriaxone is widely used to treat community-acquired CNS bacterial infections. French guidelines for meningitis in adults promote 75-100 mg/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 ≥4 g or ≥75 mg/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 31 month period. Median dosage and duration of ceftriaxone were 96.4 mg/kg/day (7 g/day) and 8 days, 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.

Implementing a clinical pharmacy survey of adverse drug events in a French emergency department.

BACKGROUND: The prevalence of adverse drug events (ADEs) occurring in the ambulatory setting is high, requiring the development of a coherent and comprehensive patient-safety policy framework. Former experiences demonstrated that emergency department (ED) surveillance can help characterise the burden of outpatient ADEs. We developed a clinical pharmacy programme called the clinical pharmacy survey of adverse drug events (CPSA) to support interventions and research projects in the area of ADE prevention and management. OBJECTIVE: To design a survey to identify and describe ADEs in patients visiting the medical ED of our tertiary care hospital. We report the results of the first 2 years of CPSA implementation and an assessment of its performance. SETTING: The medical ED of a French 3,000-bed tertiary care hospital. METHOD: Between January 2008 and December 2009, adult patients visiting our medical ED were included during randomised time slots. Data were collected by pharmacy students. ADEs were documented by a trained physician pharmacist team using the chart review method. MAIN OUTCOME MEASURE: The primary outcome was the number of patients visiting our ED with an ADE. The CPSA attributes were assessed on the basis of the Centers for Disease Control and Prevention's 2001 updated guidelines for evaluating public health surveillance systems. RESULTS: Of the 1,035 included patients, 201 experienced an ADE at the ED visit (19.4 %; 95 % confidence interval 15.8-23.0 %). Forty-seven ADEs (23.4 %) were unrelated to the patient's chief complaint. An ADE was the leading cause of 154 in the 1,035 admissions (14.9 %). The assessment of our method on the basis of the Centers for Disease Control and Prevention guidelines showed good performances in terms of data quality, stability, flexibility, timeliness, and acceptability, but not in terms of simplicity and representativeness. The profile of patients with an ADE at admission and detected ADEs did not significantly differ between years 2008 and 2009. CONCLUSION: Our experience demonstrates that clinical pharmacists can successfully implement a survey process of ADEs in an ED over time. Our method seems basic enough to suit most health care facilities with pharmacy students.

R57K polymorphism in the human immunodeficiency virus type 1 protease as predictor of early virological failure in a cohort of antiretroviral-naive patients treated mostly with a nelfinavir-containing regimen.

In 243 antiretroviral-naive human immunodeficiency-infected patients starting a first-line-protease inhibitor (mainly nelfinavir)-containing therapy, the presence of the polymorphism R57K in the protease at the inception of therapy was independently associated with a higher rate of virological failure.