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Published on: August 30, 2018
Intrapulmonary concentrations of ceftobiprole high doses administered by continuous infusion in critically ill
Claire Roger1, Bernard Allaouchiche2,3,4, Daniel Quintão De Moraes5
1Division of Anesthesia and Critical Care, Pain and Emergency Medicine, UR-UM103 IMAGINE, Univ Montpellier, Nîmes University Hospital, Montpellier, France.
Background:
Optimal antimicrobial drug exposure in the lung is required for ensuring successful treatment of community-acquired pneumonia (CAP). Little is known about the intrapulmonary pharmacokinetics (PK) of ceftobiprole when administered by continuous infusion (CI).
Objective:
To determine the PK of high doses (3 g/day) CI of ceftobiprole in the plasma and epithelial lining fluid (ELF) in mechanically ventilated patients with CAP.
Methods:
Patients receiving a CI of ceftobiprole (2.5 g daily after a 0.5 g bolus loading dose) for the treatment of severe CAP were eligible. Plasma and ELF samples were collected over 3 days of therapy. Concentrations were analysed by HPLC-UV, and population PK modelling was conducted using Monolix™. Monte Carlo simulations were performed to estimate the probability of target attaining a free ELF concentration of 100% of time above MIC.
Results:
Twelve patients, 2 female, median (IQR) age 67 (58-71), were enrolled with 108 plasma and 12 ELF concentrations included in the population analysis. The median (min-max) lung penetration ratio was 30 (15-45) % after 3 doses of ceftobiprole. In the Monte Carlo simulations, higher doses given as CI (3 g/day) may be necessary for MICs up to 2 mg/L in patients with normal renal function. The final PK model using a 4 × MIC plasma target may help to approximate ELF target attainment.
Conclusions:
The use of high doses of ceftobiprole given by CI may be necessary to achieve PK/pharmacodynamic targets in ELF in critically ill patients with CAP and normal renal function, especially when less susceptible pathogen is suspected or identified.
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