High-Dose Ceftriaxone for Bacterial Meningitis and Optimization of Administration Scheme Based on Nomogram.

High dosages of ceftriaxone are used to treat central nervous system (CNS) infections. Dosage adaptation according to the glomerular filtration rate is currently not recommended. Ceftriaxone pharmacokinetics (PK) was investigated by a population approach in patients enrolled in a French multicenter prospective cohort study who received high-dose ceftriaxone for CNS infection as recommended by French guidelines (75 to 100 mg/kg of body weight/day without an upper limit). Only those with suspected bacterial meningitis were included in the PK analysis. A population model was developed using Pmetrics. Based on this model, a dosing nomogram was developed, using the estimated glomerular filtration rate (eGFR) and total body weight as covariates to determine the optimal dosage allowing achievement of targeted plasma trough concentrations. Efficacy and toxicity endpoints were based on previous reports, as follows: total plasma ceftriaxone concentrations of ≥20 mg/liter in >90% of patients for efficacy and ≤100 mg/liter in >90% of patients for toxicity. Based on 153 included patients, a two-compartment model including eGFR and total body weight as covariates was developed. The median value of the unbound fraction was 7.57%, and the median value of the cerebral spinal fluid (CSF)/plasma ratio was 14.39%. A nomogram was developed according to a twice-daily regimen. High-dose ceftriaxone administration schemes, used to treat meningitis, should be adapted to the eGFR and weight, especially to avoid underdosing using current guidelines. (This study has been registered at ClinicalTrials.gov under identifier NCT01745679.).

Risk-benefit Assessment of Systematic Thoracoabdominal-pelvic Computed Tomography in Infective Endocarditis.

BACKGROUND: In the management of infective endocarditis (IE), the presence of extracardiac complications has an influence on both diagnosis and treatment. Current guidelines suggest that systematic thoracoabdominal-pelvic computed tomography (TAP-CT) may be helpful. Our objective was to describe how systematic TAP-CT affects the diagnosis and the management of IE. METHODS: In this multicenter cohort study, between January 2013 and July 2016 we included consecutive patients who had definite or possible IE according to the Duke modified criteria, validated by endocarditis teams. We analyzed whether the Duke classification and therapeutic management were modified regarding the presence or the absence of IE-related lesion on CT and investigated the tolerance of this examination. RESULTS: Of the 522 patients included in this study, 217 (41.6%) had 1 or more IE-related lesions. On the basis of CT results in asymptomatic patients, diagnostic classification was upgraded from possible endocarditis to definite endocarditis for only 4 cases (0.8%). The presence of IE-related lesions on CT did not modify the duration of antibiotic treatment (P = .55), nor the decision of surgical treatment (P = .39). Specific treatment of the lesion was necessary in 42 patients (8.0%), but only 9 of these lesions (1.9%) were asymptomatic and diagnosed only on the TAP-CT. Acute kidney injury (AKI) within 5 days of CT was observed in 78 patients (14.9%). CONCLUSIONS: The TAP-CT findings slightly affected diagnosis and treatment of IE in a very small proportion of asymptomatic patients. Furthermore, contrast media should be used with caution because of the high risk of AKI.

[Developing a terminology in the French language for clinical practice and research in drug safety]. / Iatrogénie médicamenteuse : contribution à l'uniformisation de la terminologie en langue française pour la pratique de soins et la recherche clinique.

While several attempts have been made to clarify the English terminology of drug-related iatrogeny, a consensus has still not been reached in the French language. We set up a multidisciplinary task force to propose a terminology that differs from the one used in pharmacovigilance and risk management. We prefer the term "adverse drug event" (ADE) over "adverse drug reaction", and recommend avoiding the term "adverse event", which is too general. We propose to classify ADEs as "direct drug effect" or "drug involvement in a multifactorial pathological condition", taking into account the close relationship commonly found between drug and non-drug etiologies of a pathology. The consistent association between the notions "error" and "preventability" is also questionable, and we suggest assessing the "ameliorability" of ADEs rather than their "preventability". "Misuse" (i.e., the non-respect by the patient of the drug label) must be distinguished from "off-label use or substance abuse".

Assessment of adverse drug event recognition by emergency physicians in a French teaching hospital.

OBJECTIVES: The frequency and the severity of drug-related visits in emergency department (ED) make the improvement of adverse drug event (ADE) recognition a crucial issue. As part of a research project aiming to improve the diagnosis and the management of ADEs in ED, the authors conducted a pilot study whose primary objective was to assess ADE recognition by emergency physicians. METHODS: The patients presenting to the ED were included at randomised time periods between 1 October 2007 and 31 March 2008 in this prospective cross-sectional study. The primary outcome was the frequency of ADEs that were attributed to a medication-related problem by the emergency physician. RESULTS: A total of 423 patients met the inclusion criteria, of which 95 experienced an ADE (22.5%; 95% CI 18.6% to 26.7%). Emergency physicians correctly attributed 33 of these cases (34.7%; 95% CI 25.3% to 45.2%) to a medication-related problem. Of the 28 cases in which the ADE was considered as a 'direct drug effect' (29.5%; 95% CI 20.6% to 39.7%), 16 were correctly identified by emergency physicians (57.1%; 95% CI 37.2% to 75.5%). Of the 67 cases in which the ADE was considered as a 'drug involvement in a multifactorial pathological condition' (70.5%; 95% CI 60.3% to 79.4%), 17 were correctly attributed (25.4%; 95% CI 15.5% to 37.5%). CONCLUSIONS: ADEs are frequent in EDs and are not well recognised by emergency physicians, especially when the drug is involved in a multifactorial pathological condition.

[Development of a tool for the identification of socially vulnerable hospital patients]. / Elaboration d'un outil de repérage des usagers en situation de vulnérabilité sociale consultant à l'hôpital.

OBJECTIVE: To develop and assess the metrological properties of a simple to use tool to identify socially vulnerable outpatients. METHODS: A multidisciplinary group of professionals selected five characteristics identifying social vulnerability, integrated in a self-reported questionnaire, from which 5 criteria identify the socially vulnerable outpatients consulting the hospital. The metrological performance of the tool was assessed on a sample of randomly selected outpatients admitted to the emergency department and the results referred to the independent assessment of two social workers. The sensitivity and specificity of the tool were determined and ROC curves drawn. RESULTS: 222 patients were included, aged from 15 to 93 Years (mean: 53 Years), 59% of whom were men. 78% filled out the questionnaire on their own, while 22% required help, usually for physical or material reasons and 87% answered the five questions without any difficulty. The kappa coefficient of agreement between the two social workers was estimated at 0.94 (CI: 0.89-0.98). The sensitivity of the self reported questionnaire was of 70% (CI: 64-76) and its specificity of 77% (CI: 71-82). The ROC curves showed that the modified tool had a sensitivity of 80% (Sp: 67%). With only 2 characteristics, this sensitivity was of 76% (Sp: 73%). CONCLUSION: This tool, which is based on the advice of various experts, is valid and presents acceptable metrological properties. Once some simplifications have been made, the questionnaire could be used in routine in any patient consulting the hospital because it is acceptable, simple to use and can be rapidly filled-in.