title: High-dose continuous oxacillin infusion results in achievement of pharmacokinetics targets in critically ill patients with deep sternal wound infections following cardiac surgery.
abstract: Knowledge regarding antimicrobial therapy strategies in deep sternal wound infections (DSWI) following cardiac surgery is limited. Therefore, we aimed to determine the steady-state plasma and mediastinal concentrations of oxacillin administered by continuous infusion in critically ill patients with DSWI and to compare these concentrations with the susceptibility of staphylococci recovered. A continuous infusion of oxacillin (150 to 200 mg/kg of body weight/24 h) was administered after a loading dose (50 mg/kg). Plasma and mediastinal concentrations of total and unbound oxacillin were determined 4 h after the loading dose (H4) and then at day 1 (H24) and day 2 (H48). Twelve patients were included. Nine patients exhibited bacteremia, 5 were in septic shock, 8 were positive for Staphylococcus aureus, and 4 were positive for coagulase-negative staphylococci. The median MIC (first to third interquartile range) was 0.25 (0.24 to 0.41) mg/liter. Median plasma concentrations of total and unbound oxacillin at H4, H24, and H48 were, respectively, 64.4 (41.4 to 78.5) and 20.4 (12.4 to 30.4) mg/liter, 56.9 (31.4 to 80.6) and 21.7 (6.5 to 27.3) mg/liter, and 57.5 (32.2 to 85.1) and 20 (14.3 to 35.7) mg/liter. The median mediastinal concentrations of total and unbound oxacillin at H4, H24, and H48 were, respectively, 2.3 (0.7 to 25.9) and 0.9 (<0.5 to 15) mg/liter, 29.1 (19.7 to 38.2) and 12.6 (5.9 to 19.8) mg/liter, and 31.6 (14.9 to 42.9) and 17.1 (6.7 to 26.7) mg/liter. High-dose oxacillin delivered by continuous infusion is a valuable strategy to achieve our pharmacokinetic target (4× MIC) at the site of action at H24. But concerns remain in cases of higher MICs, emphasizing the need for clinicians to obtain the MICs for the bacteria and to monitor oxacillin concentrations, especially the unbound forms, at the target site.
authors: Service de Réanimation Chirurgicale, Pôle Anesthésie-SAMU, Urgences, Réanimations (ASUR), Hôpital Pontchaillou, Rennes, France INSERM U991, Hôpital Pontchaillou, Rennes, France Université Rennes 1, Faculté de Médecine, Rennes, France nicolas.nesseler@chu-rennes.fr.
authors: Nicolas
authors: N
authors: Nesseler
authors: Université Rennes 1, Faculté de Médecine, Rennes, France Service de Pharmacologie Biologique, Hôpital Pontchaillou, Rennes, France.
authors: Marie-Clémence
authors: MC
authors: Verdier
authors: Service de Réanimation Chirurgicale, Pôle Anesthésie-SAMU, Urgences, Réanimations (ASUR), Hôpital Pontchaillou, Rennes, France INSERM U991, Hôpital Pontchaillou, Rennes, France Université Rennes 1, Faculté de Médecine, Rennes, France.
authors: Yoann
authors: Y
authors: Launey
authors: Service de Réanimation Chirurgicale, Pôle Anesthésie-SAMU, Urgences, Réanimations (ASUR), Hôpital Pontchaillou, Rennes, France Université Rennes 1, Faculté de Médecine, Rennes, France.
authors: Alexandre
authors: A
authors: Malherbe
authors: Université Rennes 1, Faculté de Médecine, Rennes, France Service de Pharmacologie Biologique, Hôpital Pontchaillou, Rennes, France.
authors: Marine
authors: M
authors: Dermu
authors: Université Rennes 1, Faculté de Médecine, Rennes, France Laboratoire de Bactériologie-Virologie, Hôpital Pontchaillou, Rennes, France.
authors: Caroline
authors: C
authors: Piau
authors: Université Rennes 1, Faculté de Médecine, Rennes, France Service de Chirurgie Cardio-vasculaire et Thoracique, Hôpital Pontchaillou, Rennes, France.
authors: Erwan
authors: E
authors: Flécher
authors: Service de Biochimie, Hôpital Pontchaillou, Rennes, France.
authors: Olivier
authors: O
authors: Tribut
authors: Service de Réanimation Chirurgicale, Pôle Anesthésie-SAMU, Urgences, Réanimations (ASUR), Hôpital Pontchaillou, Rennes, France INSERM U991, Hôpital Pontchaillou, Rennes, France Université Rennes 1, Faculté de Médecine, Rennes, France.
authors: Yannick
authors: Y
authors: Mallédant
authors: Service de Réanimation Chirurgicale, Pôle Anesthésie-SAMU, Urgences, Réanimations (ASUR), Hôpital Pontchaillou, Rennes, France INSERM U991, Hôpital Pontchaillou, Rennes, France Université Rennes 1, Faculté de Médecine, Rennes, France.
authors: Philippe
authors: P
authors: Seguin
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D016638:Critical Illness; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous / Q000379:methods; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D010068:Oxacillin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D011446:Prospective Studies; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects; D014946:Wound Infection / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D010068:Oxacillin