High-Dosage Cefazolin Achieves Sufficient Cerebrospinal Diffusion To Treat an External Ventricular Drainage-Related Staphylococcus aureus Ventriculitis

Abstract

A patient received continuous infusion of cefazolin 10 g then 8 g daily for an external ventricular drainage-related methicillin-susceptible Staphylococcus aureus (MSSA) ventriculitis. Median free concentrations in the cerebrospinal fluid were 11.9 and 6.1 mg/liter after 10- and 8-g doses, respectively. Free concentrations in the cerebrospinal fluid were always above the MIC usually displayed by methicillin-susceptible Staphylococcus aureus (MSSA) isolates. These results support the use of high-dose cefazolin to achieve sufficient meningeal concentrations.

Pharmacokinetic Evaluation of Cefazolin in the Cerebrospinal Fluid of Critically Ill Patients

“…Conversely, significant CSF accumulation and neurotoxicity were reported by others after multiple doses [ 12 ]. More recently, potentially therapeutic concentrations of cefazolin in CSF samples have been reported in less well-defined or smaller populations, though some reports rely on the low MSSA minimum inhibitory concentration (MIC) of 0.5 mg/L, which is an important caveat [ 6 , 7 , 18 , 19 ]. Of interest, 1 report used serial therapeutic drug monitoring and continuous infusion cefazolin of 10 or 8 g daily to effectively treat MSSA ventriculitis [ 6 ].…”

“…More recently, potentially therapeutic concentrations of cefazolin in CSF samples have been reported in less well-defined or smaller populations, though some reports rely on the low MSSA minimum inhibitory concentration (MIC) of 0.5 mg/L, which is an important caveat [ 6 , 7 , 18 , 19 ]. Of interest, 1 report used serial therapeutic drug monitoring and continuous infusion cefazolin of 10 or 8 g daily to effectively treat MSSA ventriculitis [ 6 ]. This case report found a median CSF concentration of 12 mg/L with a CSF:plasma ratio of 12% during a 10-g/d continuous infusion and a median CSF concentration of 6.1 mg/L with a CSF:plasma ratio of 10% during an 8-g/d continuous infusion.…”

“…Animal and limited human reports indicate that there may be CNS penetration of cefazolin at therapeutically used doses [ 12 , 14 ]. Further, a recent case report and case series suggested that continuous infusion of cefazolin can achieve therapeutic CSF concentrations resulting in bacterial eradication with the aid of therapeutic drug monitoring (TDM) [ 6 , 7 ]. If cefazolin adequately penetrates into the CSF and clinical trials confirm safety and efficacy for targeted susceptible central nervous system infections, clinicians would be presented with another treatment option.…”

Re: 'Cefazolin versus anti-staphylococcal penicillins for the treatment of patients with Staphylococcus aureus bacteremia' by Weis et al.

“…Frame and colleagues reported that cefazolin achieved higher concentrations in human brain tissue than did nafcillin [4]. In a patient with MSSA ventriculitis being treated with continuous intravenous infusions of high-dose cefazolin at 10 g and then 8 g daily, Gregoire et al [5] reported CSF cefazolin concentrations of 11.9 mg/L and 6.1 mg/L respectively.…”

Antistaphylococcal Penicillin vs Cefazolin for the Treatment of Methicillin-SusceptibleStaphylococcus aureusSpinal Epidural Abscesses

“…Another critical consideration for cefazolin is the supposed weak meningeal diffusion and lack of central nervous system (CNS) penetration [ 9 ]. On the contrary, a recent study showed that meningeal diffusion appeared sufficient with high-dose cefazolin [ 10 ]. Similarly, findings from 1 retrospective study suggested that patients who received cefazolin had a lower risk of mortality and a similar risk of recurrent infection than those who received ASPs [ 11 ].…”