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

Abstract:

Background

The relative distribution of cefazolin into the cerebrospinal fluid (CSF) remains debated. Determining the distribution of cefazolin to the CSF in non-infected adults may allow for further treatment applications of cefazolin. This prospective pharmacokinetic study aimed to determine the pharmacokinetic parameters of cefazolin in serum and CSF from external ventricular drains (EVD) in neurologically injured adults.

Methods

Blood and CSF was collected, using a biologic waste protocol, for cefazolin quantification and trapezoidal rule based pharmacokinetic analysis in a total of 15 critically ill adults receiving 2000mg IV every 8 hours or the renal dose equivalent for EVD prophylaxis.

Results

A median of 3 blood (range 2-4) and 3 CSF (range 2-5) samples were collected in each patient. The most common admitting diagnosis was subarachnoid hemorrhage (66.7%). Median calculated cefazolin CSF Cmax and Cmin (IQR) were 2.97mg/L (1.76-8.56) and 1.59mg/L (0.77-2.17), respectively. Median (IQR) CSF to serum area under-the-curve ratio was 6.7% (3.7%-10.6%), with time matched estimates providing a similar estimate (8.4%). Of those receiving cefazolin every 8 hours, the median and minimum directly measured CSF cefazolin concentration 4 hours or greater following administration were 1.87 and 0.78 mg/L, respectively.

Conclusion

Cefazolin dosed for EVD prophylaxis achieved CSF concentrations suggesting viability as a therapeutic option for patients with meningitis or ventriculitis due to susceptible bacteria such as methicillin-susceptible Staphylococcus aureus. Further clinical trials are required to confirm a role in therapy for cefazolin. Population-based pharmacokinetic-pharmacodynamic modeling may suggest an optimal cefazolin regimen for the treatment of central nervous system infections.