Dalbavancin plasma concentrations in 133 patients: a PK/PD observational study
Charles Hervochon, Benjamin Hennart, Anne‐Gaëlle Leroy, Stéphane Corvec, David Boutoille, Éric Senneville, Albert Sotto, Gabriella Illes, P. Chavanet, Vincent Dubée, Alexandre Bleibtreu, Marie-Charlotte De Carné, Jean‐Philippe Talarmin, Matthieu Revest, Bernard Castan, Ronan Bellouard, Éric Dailly, Delphine Allorge, Aurélien Dinh, Paul Le Turnier, Matthieu Gregoire, the Dalbavancin Pharmacokinetics (DALBAP) study group, Paul Le Turnier, David Boutoille, Benjamin Gaborit, Colin Deschanvres, R. Lecomte, Marie Chauveau, Anne-Gaëlle Leroy, Stéphane Corvec, Vincent Lavigne-Quilichini, Pascale Bémer, A. Guillouzouic, Jean‐François Huon, Dominique Navas, Matthieu Gregoire, Ronan Bellouard, Charles Hervochon, Éric Dailly, Denis Waast, Christophe Nich, S. Touchais, Vincent Crenn, Vincent Dubée, Florian Berteau, P. Chavanet, Françoise Goirand, Aurélien Dinh, Benjamin Hennart, Catherine Hoskovec, Damien Mondon, Gabriela Illes, Albert Sotto, Catherine Lechiche, Hélène Boclé, Jean-Philippe Lavigne, Bernard Castan, Alexandre Bleibtreu, Jean‐Philippe Talarmin, L. Khatchatourian, Marie-Sarah Fangous, Florence Le Gall, Matthieu Revest, Vincent Cattoir, Florian Lemaitre, Éric Senneville, Marie-Charlotte De Carné, A. Therby, Stéphanie Balavoine, Pauline Bargain, Marlène Amara, Catherine Palette, Philippe Boisrenoult
Abstract
OBJECTIVES: Limited pharmacokinetics data support dalbavancin long-term use in off-label indications and the optimal dosing regimen is debated. We aimed to describe dalbavancin concentrations in an observational retrospective multicentre study. METHODS: Patients from 13 French hospitals, treated with 1500 mg doses of dalbavancin and for whom therapeutic drug monitoring was performed from June 2018 to March 2021 were included. Dalbavancin plasma concentrations were described at peak and 1, 2, 3, 4, 6 and 8 weeks after the last 1500 mg dose. Concentrations in patients weighing more or less than 75 kg and with a GFR greater or less than 60 mL/min were compared. Microbiological data were collected and dalbavancin MIC was measured when possible. RESULTS: One hundred and thirty-three patients were included (69% treated for bone and joint infections, 16% for endocarditis). Thirty-five patients received a single dose of dalbavancin and 98 received several administrations. Two, 3 and 4 weeks after the last dose, median plasma concentrations were respectively 25.00, 14.80 and 9.24 mg/L for the first doses and 34.55, 22.60 and 19.20 mg/L for the second or subsequent doses. Weight and renal function had an impact on pharmacokinetics. Infection was documented in 105 patients (Staphylococcus spp. in 68% of cases). Staphylococcus aureus was isolated in 32.5% of cases (median MIC: 0.047 mg/L) and Staphylococcus epidermidis in 27% of cases (median MIC of 0.047 mg/L). CONCLUSIONS: Plasma concentrations of dalbavancin were consistent with those described in clinical trials and those sought during the industrial development of the molecule.