Pharmacokinetics of Continuous-Infusion Meropenem for the Treatment of Serratia marcescens Ventriculitis in a Pediatric Patient

Neither guidelines nor best practices for the treatment of external ventricular drain (EVD) and ventriculoperitoneal shunt infections exist. An antimicrobial regimen with a broad spectrum of activity and adequate cerebrospinal fluid (CSF) penetration is vital in the management of both EVD and ventriculoperitoneal infections. In this case report, we describe the pharmacokinetics of continuous-infusion meropenem for a 2-year-old girl with Serratia marcescens ventriculitis. A right frontal EVD was placed for the management of a posterior fossa mass with hydrocephalus and intraventricular hemorrhage. On hospital day 6, CSF specimens were cultured, which identified a pan-sensitive Serratia marcescens with an initial cefotaxime minimum inhibitory concentration of 1g/ml or less. The patient was treated with cefotaxime monotherapy from hospital days 6 to 17, during which her CSF cultures and Gram's stain remained positive. On hospital day 26, Serratia marcescens was noted to be resistant to cefotaxime (minimum inhibitory concentration>16g/ml), and the antimicrobial regimen was ultimately changed to meropenem and amikacin. Meropenem was dosed at 40mg/kg/dose intravenously every 6hours, infused over 30minutes, during which, simultaneous serum and CSF meropenem levels were measured. Meropenem serum and CSF levels were measured at 2 and 4hours from the end of the infusion with the intent to perform a pharmacokinetic/pharmacodynamic analysis. The resulting serum meropenem levels were 12g/ml at 2hours and undetectable at 4hours, with CSF levels of 1 and 0.5g/ml at 2 and 4hours, respectively. On hospital day 27, the meropenem regimen was changed to a continuous infusion of 200mg/kg/day, with repeat serum and CSF meropenem levels measured on hospital day 33. The serum and CSF levels were noted to be 13 and 0.5g/ml, respectively. The serum level of 13g/ml corresponds to an estimated meropenem clearance from the serum of 10.2ml/kg/minute. Repeat meropenem levels from the serum and CSF on hospital day 37 were 15 and 0.5g/ml, respectively. After instituting the continuous-infusion meropenem regimen, only three positive CSF Gram's stains were noted, with the CSF cultures remaining negative. The continuous-infusion dosing regimen allowed for 100% probability of target attainment in the serum and CSF and a successful clinical outcome.