Pharmacokinetic/pharmacodynamic of ceftobiprole in patients on ECMO.

Due to its bacteriological spectrum and efficacy in skin and soft tissue infections, ceftobiprole may be of interest for extracorporeal membrane oxygenation (ECMO) cannula-related infection. Whether or not ceftobiprole pharmacokinetic is changed by ECMO is not known. We performed a retrospective monocentric cohort study of 35 patients with suspected ECMO-related cannula infections (28 on ECMO, 7 after ECMO removal), who received ceftobiprole as empiric treatment, and had ceftobiprole blood levels measured at trough, peak and CT50 (50% of the dosing interval). Ceftobiprole blood levels of the 28 patients on ECMO were compared to those of the seven patients without ECMO. We also explored factors associated with low ceftobiprole trough level. Among the 35 patients included, 29 had a confirmed cannula-related infection and 48 pathogens were isolated. Ceftobiprole minimum inhibitory concentration (MIC) was determined in 29 out of these 48, and 23 (79%) were susceptible to ceftobiprole. Ceftobiprole blood levels (at trough, peak and CT50) were similar in ECMO and non-ECMO patients. Moreover, in patients whose pathogens responsible for infection were susceptible to ceftobiprole, 94% had a ceftobiprole trough level above the MIC. Ceftobiprole blood levels were decreased in patients with acute renal failure requiring renal replacement therapy (RRT) and in patients with increased renal clearance (defined as a creatinine clearance >130 ml/min), independently of ECMO. No other factor was associated with modification of ceftobiprole PK/PD. Ceftobiprole PK/PD is not different in patients during ECMO or after its withdrawal. Factors associated with decreased ceftobiprole blood levels were patients requiring RRT and patients with increased renal clearance.