Estudio farmacocinético de una pauta alternativa de dalbavancina para el tratamiento de infecciones osteoarticulares

Abstract

Diferentes regímenes terapéuticos con dalbavancina se han propuesto para tratamientos prolongados de las infecciones osteoarticulares, pero no se ha definido una pauta estandarizada. Basándonos en un estudio previo (Dunne et al. Antimicrob Agents Chemother. 2015), que mostraba concentraciones óseas adecuadas 14 días después de administrar 1 g de dalbavancina intravenosa, decidimos utilizar 1 g/14d como tratamiento estándar. El objetivo del estudio fue evaluar su concentración plasmática máxima (Cmax) y mínima (Cmin) en pacientes con infección osteoarticular tratados con 1g / 14d. Se realizó un estudio retrospectivo entre marzo/2018 y diciembre/2020 en el que se incluyeron pacientes con infecciones osteoarticulares que recibieron un régimen de 1g/14d. La Cmax se midió después de la 1ª y la 3ª dosis y la Cmin antes de la 2ª y la 3ª dosis. Las concentraciones séricas se analizaron mediante un método de cromatografía líquida acoplada a espectrometría de masas (LC/MS/MS), previamente validado en nuestro laboratorio. También se evaluó el impacto de la rifampicina en las concentraciones de dalbavancina Como principales conclusiones, las concentraciones de dalbavancina fueron homogéneas, lo que sugiere una baja variabilidad interindividual. El régimen propuesto de 1g/14d fue clínicamente eficaz y bien tolerado. La rifampicina concomitante no influyó en las concentraciones séricas de dalbavancina.

Title: Pharmacokinetic study of an alternative regimen of dalbavancin for the treatment of osteoarticular infections Background: Different therapeutic regimens have been proposed for long-term treatment of osteoarticular infections with dalbavancin, but a standardized regimen has not been defined. According to a previous study (Dunne et al. Antimicrob Agents Chemother. 2015) showing adequate bone concentrations 14 days after 1g, we decided to use 1g/14d as standard of care. The aim of the study was to evaluate its maximum (Cmax) and minimum (Cmin) plasma concentration in patients with osteoarticular infections treated with 1g/14d. Methods: A retrospective study was carried out between March/2018 and December/2020 in which patients with osteoarticular infections who received a regimen of 1g/14d were included. Cmax was measured after the 1st and 3th doses and Cmin before 2nd and 3th doses. Serum concentractions were analyzed by using a liquid chromatography method coupled to mass spectrometry (LC/MS/MS), previously validated in our laboratory. The impact of rifampin on dalbavancin concentrations was also evaluated. Results: 11 patients were included with a median age of 75 years, 8 were men. One had osteomyelitis, 6 had a chronic prosthetic infection, and 4 had an acute prosthetic infection. The most frequent microorganism isolated was S. epidermidis (6 of 11, 55%). The surgical technique used was replacement in 1 stage (5 out of 10, 50%), followed by DAIR (debridement with implant retention, in 3 out of 10, 30%) and replacement in 2 stages with spacer (2 out of 10, 20%). Mean Cmax was 228.1 and 234.4 mg/L on day 1 and 28, respectively. Mean Cmin was 20.4 and 27.5 mg/L on day 14 and 28, respectively. No diferences were observed when rifampin was added. All patients were cure, with a median follow up of 6.9 (4.8-20.2) months. No adverse effects were documented. Conclusions: Dalbavancin concentrations were homogeneous suggesting low interindividual variability. The proposed regimen of 1gr/14d was effective and welltolerated. Concomitant rifampin did not influence on serum concentrations of dalbavancin