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

Abstract

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.)

Oral Communication Abstracts

“…This study aimed at describing the cardiovascular complications related to the use of cannabis reported to the French monitoring system of psychoactive substance use disorders (SUDs) between 2011 and 2017. Indeed, a previous analysis for the period 2006-2010 identified a first signal of cannabis-related serious cardiovascular disorders in France which was since confirmed [1][2][3][4]. Evidence on the potential cardiovascular risks associated with cannabis use has grown in the 2010s.…”

“…Material and methods: The three following complementary data sources were analyzed for the years 2010 and 2016: (i) the national health insurance databases, which record reimbursed medications dispensed in community pharmacies, (ii) the national survey OSIAP, which records non-dispensed falsified prescriptions presented to community pharmacies [2], and (iii) the national survey OPPIDUM, which is conducted in drug users followed in specialized care centers [3]. In the national health insurance databases, we quantified the quantity of pregabalin obtained by doctor shopping (i.e., by overlapping prescriptions from multiple prescribers for the same medication) in 2010 and 2016 using a previously validated algorithm [4]. Results: Illegal obtaining of pregabalin increased in each data source.…”

“…CO-007 | Drug-induced skin ulcers: A combined disproportionality analysis using data from Medline and VigiBase® D. Duron 1 ; S. Blaise 2 ; J. L. Cracowski 1,3 ; M. Roustit 1,3 ; C. Khouri 1,3,4 1 Clinical Pharmacology Department, INSERM CIC1406, Grenoble Alpes University Hospital -Grenoble (France); 2 Vascular Medicine Department, Thorax and Vessels Division, Grenoble Alpes University Hospital -Grenoble (France); 3 INSERM UMR 1042 -HP2, Univ. Grenoble Alpes -Grenoble (France); 4 Pharmacovigilance Department, Grenoble Alpes University Hospital -Grenoble (France) Introduction: Skin ulcers are a common complaint causing pain, negatively affecting the individual's quality of life, provoking social discomfort, and representing a substantial economic burden to healthcare systems. While many etiologies and risk factors have been identified, little is known about drug-related skin ulcers.…”

“…Discussion/Conclusion: Accounting for multiple aspects of ICSRs has clear conceptual and empirical advantages over disproportionality analysis. CRPV -Limoges (France); 2 CRPV -Rennes (France); 3 CRPV -Lille (France); 4 CRPV Pitié Salpétrière -Paris (France); 5 CRPV -Montpellier (France); 6 CRPV Cochin -Paris (France); 7 CRPV -Besançon (France); 8 CRPV -Rouen (France); 9 CRPV -Amiens (France); 10 CRPV -Nantes (France); 11 CRPV -Brest (France); 12 CRPV -Caen (France); 13 CRPV -Lyon (France); 14 CRPV -Strasbourg (France); 15 CRPV -Toulouse (France); 16 Le réseau français des CRPV (France) Introduction: In 2007, the incidence of Adverse Drug Reaction (ADR)-related hospitalizations in France was 3.6% [1]. Vitamin-K-antagonists were the most common drugs associated with admissions.…”

“…Results: We included 229 cases. The median Kardaun's score was 4 (IQR [3][4][5]. The median age was 61 years (IQR 45-74) and the sex ratio was 1:1.…”