This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2020. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2020. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http:// www.springer.com/series/8901.

Background: There are currently few data concerning the cerebrospinal fluid (CSF) penetration of Daptomycin in patients with health care-associated meningitis. This study aims 1) to better characterize the pharmacokinetics of Daptomycin in humans during a 7 days intravenous (IV) therapy course, and 2) to study the penetration of Daptomycin in the CSF after IV infusion at the dose of 10 mg/Kg. Results: In this prospective observational study we enrolled nine patients with an implanted external ventricular drainage (EVD) and a diagnosis of a Health Care-Associated Meningitis. Daptomycin was administered at 10 mg/kg for a maximum of 7 days. The pharmacokinetic of Daptomycin was studied using a two-compartment population/pharmacokinetic (POP/PK) model and by means of a non-linear mixed effects modeling approach. A large inter-individual variability in plasma AUC (Range: 574.7-1366.3 h mg/L), paralleled by high peak plasma concentration (Cmax) (all values>60 mg/L) was noted. The inter-individual variability of CSF-AUC although significant (range: 1.17-6.81 h mg/L) was narrower than previously reported and with a late occurrence of CSF-Cmax (range: 6.04-9.54 hrs). The terminal half-life between plasma and CSF was similar. tmax values in CSF did not show a high inter-individual variability, and the fluctuations of predicted CSF concentrations were minimal. The mean value for Daptomycin penetration obtained from our model was 0.45%. Conclusions Our POP/PK model was able to describe the pharmacokinetics of daptomycin in both plasma and CSF, showing that Daptomycin (up to 7 days at 10mg/Kg) has minimal penetration into CNS. Furthermore, the observed variability of AUC, tmax and predicted concentration in CSF was lower than what previously reported in the literature. Based on the present findings, it is unlikely that Daptomycin could reach CSF concentrations high enough to have clinical efficacy; this should be tested in future studies.

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This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2020. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2020. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http:// www.springer.com/series/8901.