LAUSR

Dear Editor, Antibiotic therapy is the mainstay of the treatment of severe infections. Antibiotics are administered as long as therapeutic drug concentrations are required, typically 5–10 days for most infections [1]. Due to changes in the pharmacokinetics of antibiotics in critically ill patients, and altered clearance of the drug [2], accumulation may occur, and antibiotic effects may persist after the administration has been stopped. It is unknown how long antibiotic concentrations remain detectable in the blood. We studied the plasma concentration of piperacillin until 48 h after treatment discontinuation in 20 critically ill patients. We evaluated whether the remaining concentration reached the target (piperacillin concentration above 20 mg/l) and how long piperacillin concentrations in the plasma were detectable. Details of the study are available in the supplemental appendix. Twenty patients were included, and full data sets from 18 patients were available for analysis. The median age of the patients was 62 years [interquartile range (IQR) 60–68]. Fourteen patients were treated for a respiratory infection, three patients for an abdominal infection, and in one patient the focus was unknown. The median Acute Physiology And Chronic Health Evaluation (APACHE) score was 27 (IQR 24–30). The median Sequential Organ Failure Assessment (SOFA) score was 9 (IQR 6–13) at the start of antibiotic treatment and 6 (IQR 5–7) at the time of antibiotic discontinuation. The median measured creatinine clearance (CrCl) was 77 ml/min (IQR 68–138). Two patients had a CrCl below 60 ml/min. The piperacillin concentrations after cessation of therapy are summarized in Table 1. No patients had a piperacillin concentration above 20 mg/l at 24 h or later. One patient had a concentration of 25.8 mg/l at 12 h. This patient had an average CrCl of 21 ml/min and received a reduced dose of 8 g over 24 h.