Ruptures d'approvisionnement en médicaments anti-infectieux: causes et conséquences

International audienceAnti-infective drugs stock-outs are increasingly frequent, and this is unlikely to change. There are numerous causes for this, mostly related to parameters difficult to control: i) 60 to 80% of raw material or components are produced outside of Europe (compared to 20% 30 years ago), with subsequent loss of independence for their procurement; ii) the economic crisis drives the pharmaceutical companies to stop producing drugs of limited profitability (even among important drugs); iii) the enforcement of regulatory requirements and quality control procedures result in an increasing number of drugs being blocked during production. The therapeutic class most affected by drug stock-outs is that of anti-infective drugs, especially injectable ones, and many therapeutic dead ends have recently occurred. We provide an update on this issue, and suggest 2 major actions for improvement: i) to implement a group dedicated to anticipating drug stock-outs within the anti-infective committee in each health care center, with the objectives of organizing and coordinating the response whenever a drug stock-out is deemed at risk (i.e., contingency plans, substitution, communication to prescribers); ii) a national reflection lead by scientific societies, in collaboration with government agencies, upstream of the most problematic drug stock-outs, to elaborate and disseminate consensus guidelines for the management of these stock-outs

Enfuvirtide dans le traitement de l'infection à VIH (experience du service d'infectiologie du CHU de Nantes)

LYON1-BU Santé (693882101) / SudocRENNES1-BU Santé (352382103) / SudocSudocFranceF

Évaluation des pratiques professionnelles de prise en charge par les inhibiteurs de pompe à protons des hémorragies digestives hautes d'origine ulcéreuse au CHU de Rennes

L'évaluation des Pratiques Professionnelles vise à intégrer dans la pratique quotidienne une démarche d'amélioration continue de la qualité des soins. Dans ce cadre, nous avons mis en place une évaluation portant sur la qualité de la prise en charge des hémorragies digestives hautes d'origine ulcéreuse dans le service de gastro-entérologie du CHU de Rennes. Celle-ci a été menée sous forme d'audit et a ciblé l'évaluation du bon usage des IPP dans la prise en charge des ulcères gastro-duodénaux hémorragiques et des syndromes de Mallory-Weiss avant et après protocolisation. Au total, 60 patients ont été inclus, 28 du 1er au 30 juin2010 et 32 du 1er au 30 juin 2011. La comparaison des résultats de l'audit avant et après mise en place du protocole a permis de mettre en évidence les pratiques à améliorer : prescription des IPP après l'endoscopie pour les patients admis par le service des Urgences, indication du score de Forrest dans les comptes-rendus d'endoscopie, respect de la durée de perfusion des IPP hautes doses pour le traitement des lésions ulcéreuses à haut risque, réalisation d'un bolus d'IPP avant la perfusion continue, ne pas prescrire d'IPP hautes doses pour les lésions à faible risque, prescription des IPP dans les courriers de sortie en précisant la posologie et la durée de traitement. Le respect partiel des recommandations s'explique en partie par le fait que les prescripteurs ne se sont pas totalement appropriés le protocole, il reste donc à travailler sur les modalités de diffusion des recommandations de pratique clinique et sur la formation continue du personnel, notamment les internes. Une seconde évaluation des pratiques devra être réalisée afin de vérifier si les axes d'améliorations qui vont être mis en place auront un impact positif.NANTES-BU Médecine pharmacie (441092101) / SudocSudocFranceF

Pertinence des prescriptions des antibiotiques à dispensation contrôlée au CHU de Rennes (carbapénèmes (ertapénème et doripénème) en 2009-2010)

Depuis plus d'une décennie, la consommation d'antibiotiques en France reste supérieure à la moyenne européenne, avec pour risque principal un mésusage pouvant être à l'origine de l'émergence de bactéries multi-résistantes et par là même de situations en impasse thérapeutique. Au CHU de Rennes, des actions de bon usage des antibiotiques ont été entreprises par la Commission des Anti-Infectieux depuis de nombreuses années. En 2010, suite au constat d'une augmentation de la consommation des antibiotiques de la classe des carbapénèmes, il a été décidé de procéder à un audit sur la pertinence de prescription de deux carbapénèmes dans le cadre d'une Evaluation des Pratiques Professionnelle. Nous avons mené une étude rétrospective sur 127 dossiers de patients qui avaient reçu de l'ertapénème ou du doripénème au cours des années 2009 et 2010. Les résultats de cette étude réprospective concluent à un respect des recommandations dans la majorité des cas. Les indications des prescriptions ont été évaluées conformes au référentiel local à 75% et 95% respectivement pour l'ertapénème et le doripénème. Les critères de pertinence non conformes ont été justifiés par un expert. L'augmentation de consommation de ces antibiotiques ne semble donc pas provenir d'un mésusage sur notre établissement. Les efforts doivent néanmoins être poursuivis pour maintenir ce niveau de qualité et la mise en place de réunions pluri-disciplinaires au cours desquelles les prescriptions seraient analysées prospectivement peut constituer une piste pour l'amélioration continue de la prise en charge des patients.For over a decade, antibiotic use in France remains above the European average, with the main risk misuse can cause the emergence of multi-resistant bacteria and thus dead-end situation therapy. At University Hospital of Rennes, actions appropriate use of antibiotics have been undertaken by the Commission anti-infectives for many years. In 2010, following the finding of an increased consumption of antibiotics in the carbapenem class, it was decided to conduct an audit on the appropriateness of prescribing two carbapenems as part of an evaluation of professional practices. We conducted a retrospective study of 127 cases of patients who received ertapenem and doripenem in the years 2009 and 2010. The results of this retrospective study to conclude that the recommendations in most cases. 75% of ertapenem's and 95% of doripenem's indications for the prescriptions were found to be in keeping with the local standars. The indications that were not in compliance with the local standars were justified by an expert. THe increased consumption of these antibiotics does not seem to come from a misuse of our institution. Efforts need to be continued to maintain that level of quality and implementation of multidisciplinary meetings in which the prescriptions were analyzed prospectively may be an avenue for continuous improvement of care for patients.LYON1-BU Santé (693882101) / SudocRENNES1-BU Santé (352382103) / SudocSudocFranceF

Alemtuzumab as rescue therapy in a cohort of 16 aggressive multiple sclerosis patients previously treated by Mitoxantrone: an observational study.

International audienceOur study aimed to describe safety and neurological impact of alemtuzumab as last-line rescue therapy in aggressive multiple sclerosis (MS) patients, previously treated by Mitoxantrone (MITOX). Between June 2004 and October 2013, 13 patients received alemtuzumab at 20 mg/day and 3 at 12 mg/day for 5 days. EDSS, relapses, secondary progression were prospectively assessed 12 and 6 months before treatment, at baseline and every 3 months. Mean follow-up was 6.2 years [1–10]. Mean age at alemtuzumab start was 40 years [26–49] for 8 Secondary Progressive (SP) and 30 years [26–35] for 8 Relapsing-Remitting (RR) patients. MS duration was 13.7 (±3) and 8.3 (±4) years, respectively. During the 12 months before alemtuzumab, annual relapse rate was 0.75 and 3.14, respectively and the 16 patients accumulated 2–30 new gadolinium enhancing lesions. 4 patients (suboptimal responders) received alemtuzumab during MITOX and 12 patients 1–7.8 years after MITOX. Out of 8 SPMS, 2 were disease free up to last visit (4.7 and 8 years), 5 improved or stabilized but only transiently and 1 worsened. Out of 8 RRMS, 1 remained stable up to last visit (8.7 years) despite 1 relapse and active MRI at 18 months and 7 improved (1–4 point EDSS): 4 remained disease free up to last visit (12, 24, 38 months and 7 years), 2 were successfully retreated at 25 and 33 months and 1 worsened progressively 24 months after alemtuzumab. 2 patients developed Grave’s disease and 1 hypothyroidism. Alemtuzumab controls aggressive RRMS despite previous use of MITOX

Indications des antifongiques systémiques, spécialité par spécialité

National audienc

Tinzaparin, an alternative to subcutaneous unfractionated heparin, in patients with severe and end-stage renal impairment: a retrospective observational single-center study

International audienceBackground: Tinzaparin could be easier to manage than unfractionated heparin in patients with severe renal impairment. However, clinical and pharmacologic data regarding its use in such patients are lacking.Objectives: The aims of this study were to determine, in patients with estimated glomerular filtration rate (eGFR) of <30 mL.min⁻1, tinzaparin pharmacokinetics (PK) parameters using a population PK approach and bleeding and thrombotic complications.Methods: We performed a retrospective observational single-center study, including in-patients with eGFR of <30 mL.min⁻1 receiving prophylactic (4500 IU.d⁻1) or therapeutic (175 IU.kg⁻1.d⁻1) tinzaparin. Measured anti-Xa levels were analyzed using a nonlinear mixed-effects modeling approach. Individual predicted tinzaparin exposure markers at steady state were calculated for each patient and dosing regimen. The PK was also evaluated through Monte Carlo simulations based on the final covariate model parameter estimates.Results: Over a 22-month period, 802 tinzaparin treatment periods in 623 patients were analyzed: two-thirds received a prophylactic dose, 66% had an eGFR of <20 mL.min⁻1, and 25% were on renal replacement therapy. In patients for whom anti-Xa measurements were performed (n = 199; 746 values), PK parameters, profiles, and maximum plasma concentrations were comparable with those in patients without renal impairment or in healthy volunteers. In the whole population, major bleeding occurred in 2.4% and 3.5% of patients receiving prophylactic and therapeutic doses over a median 9- and 7-day treatment period, respectively. No patients had thrombotic complications.Conclusion: Tinzaparin PK parameters and profiles were not affected by renal impairment. This suggests that tinzaparin, at therapeutic or prophylactic dose, could be an alternative to unfractionated heparin in hospitalized patients with severe renal impairment