L’administration sous-cutanée de la téicoplanine permet-elle d’atteindre les objectifs thérapeutiques de téicoplaninémie résiduelle ? Évaluation rétrospective multicentrique au cours des infections ostéo-articulaires staphylococciques

Context: Subcutaneous administration of antibiotic therapy is routinely practiced by 95% of infectious disease specialists, despite this practice is usually off label. Teicoplanin may constitute an acceptable alternative in the treatment of staphylococcal bone and joint infection. It could be theoretically used by subcutaneous route, and then allow to reduce the length of hospitalization and avoid long-term venous central catheter. Nevertheless, this administration route has not been well evaluated yet. Our objective was to assess the trough concentration of teicoplanin obtained during subcutaneous administration in staphylococcal bone and joint infection (target trough concentration ≥ 15 mg/L), and to describe its efficacy and tolerance. Methods: All patients receiving teicoplanin by subcutaneous route for a staphylococcal bone and joint infection (excepting diabetic foot infection) between 2002 and 2015 were included in a retrospective multicentric cohort study in three French hospital centers (Chambery, Lyon, and Strasbourg). Results: Forty episodes of bone and joint infections were assessed, including 34 orthopedic device-related infections (85%) and 21 chronic infections (53%). The median age was 75 years (IQR, 62-84). The median glomerular filtration rate (GFR) was 68 ml/min/m2 (IQR, 56-91). Twenty-four isolates were methicillin-resistant (58%), including 13 Staphylococcus aureus and 11 coagulase negative Staphylococci, with a MIC for teicoplanin of 0.5 mg/L (IQR, 0.38-0.81) and 0.75 mg/L (IQR, 0.5-1), respectively. The median duration of treatment by teicoplanin was 46 days (IQR, 29-79), primarily in combination with rifampin (n = 23) or a fluoroquinolone (n = 16). Sixteen patients (40%) received a loading dose by intravenous route before switching to subcutaneous route. A median loading dose of 9.4 mg/kg/12 h (IQR, 6.1-13.1) was used in 35 patients (88%) (16 by IV route, 18 by SC route, 1 by IM route). The maintenance dose was 7.3 mg/kg/injection (IQR, 5.3-12.1). A 3 injections per week scheme of 15 mg/kg/injection (IQR, 10.3-15.9) was conducted in 13 (33%) patients. A trough concentration ≥ 15 mg/L was reached in 34 patients (85%) in a median delay of 4 days (IQR, 3-6). The trough concentrations during the first 20 days were not significantly different between the IV and SC (p = 0.462) routes. Trough concentrations reached by subcutaneous route were significantly higher if the loading dose was ≥ 9 mg/kg/injection (p 15 mg/L) et d’en décrire l’efficacité et la tolérance. Matériels et Méthodes : Étude rétrospective multicentrique (2002-2015) incluant tout patient traité par téicoplanine en SC pour une IOA à staphylocoque (infections de pied diabétique exclues) dans 3 centres : Strasbourg, Lyon et Chambéry. Résultats : Quarante épisodes d’IOA ont été inclus, dont 34 sur matériel (85%) et 21 chroniques (53%). L’âge médian était 75 ans (IQR, 62-84). Le débit de filtration glomérulaire (DFG) médian était de 68 mL/min/m2 (IQR, 56-91). Vingt-quatre souches étaient méti-R (58%), dont 13 Staphylococcus aureus (S.A) et 11 Staphylocoques à Coagulase Négative (SCN), avec des Concentrations Minimales Inhibitrices (CMI) respectives pour la téicoplanine de 0.5 mg/L (IQR, 0.38-0.81) et 0.75 mg/L (IQR, 0.5-1). La durée médiane du traitement par téicoplanine était de 46 jours (IQR, 29-79), principalement en association avec la rifampicine (n=23) ou une fluoroquinolone (n=16). Seize patients (40%) ont été traités par téicoplanine par voie intraveineuse (IV) avant le relais par voie SC. Une dose de charge (DDC) de 9.4 mg/kg/12h (IQR, 6.1-13.1) a été utilisée chez 35 patients (88%) (16 par voie IV, 18 en SC, 1 en IM). La dose d’entretien était de 7.3 mg/kg/injection (IQR, 5.3-12.1). Un relais en 3 injections par semaine de 15 mg/kg (IQR, 10.3-15.9) a été effectué chez 13 (33%) patients. Un TR ≥ 15 mg/L a été atteint chez 34 patients (85%) dans un délai médian de 4 jours (IQR, 3-6). Les TR mesurés durant les 20 premiers jours n’étaient pas significativement différents entre les voies IV et SC (p=0.462). Les TR atteints par voie SC étaient significativement plus élevés si la DDC était ≥ 9mg/kg/injection (p<10-3). On dénombrait 15 échecs (38%) dont 8 cas où le germe était différent de celui ciblé initialement. Neuf effets indésirables ont été rapportés chez 6 patients (15%), principalement d’ordre hématologique (n=3) et cutanéomuqueux (n=2). Conclusion : Chez nos patients, l’utilisation de la téicoplanine par voie SC a permis d’obtenir un TR ≥ 15 mg/L. Cette cible a été atteinte d’autant plus rapidement que la DDC était ≥ 9 mg/kg/injection. Le recours à la voie SC a permis de faciliter l’antibiothérapie parentérale des IOA staphylococciques. Son efficacité clinique et sa tolérance ont semblé correctes, mais ces résultats doivent être validés sur des études prospectives plus larges

Severe Thrombocytopenia after Zika Virus Infection, Guadeloupe, 2016.

International audienceSevere thrombocytopenia during or after the course of Zika virus infection has been rarely reported. We report 7 cases of severe thrombocytopenia and hemorrhagic signs and symptoms in Guadeloupe after infection with this virus. Clinical course and laboratory findings strongly suggest a causal link between Zika virus infection and immune-mediated thrombocytopenia

Increased risk of severe COVID-19 in hospitalized patients with SARS-CoV-2 Alpha variant infection: a multicentre matched cohort study

International audienceBackground: The impact of the variant of concern (VOC) Alpha on the severity of COVID-19 has been debated. We report our analysis in France.Methods: We conducted an exposed/unexposed cohort study with retrospective data collection, comparing patients infected by VOC Alpha to contemporaneous patients infected by historical lineages. Participants were matched on age (± 2.5 years), sex and region of hospitalization. The primary endpoint was the proportion of hospitalized participants with severe COVID-19, defined as a WHO-scale > 5 or by the need of a non-rebreather mask, occurring up to day 29 after admission. We used a logistic regression model stratified on each matched pair and accounting for factors known to be associated with the severity of the disease.Results: We included 650 pairs of patients hospitalized between Jan 1, 2021, and Feb 28, 2021, in 47 hospitals. Median age was 70 years and 61.3% of participants were male. The proportion of participants with comorbidities was high in both groups (85.0% vs 90%, p = 0.004). Infection by VOC Alpha was associated with a higher odds of severe COVID-19 (41.7% vs 38.5%-aOR = 1.33 95% CI [1.03-1.72]).Conclusion: Infection by the VOC Alpha was associated with a higher odds of severe COVID-19