Are higher vancomycin doses needed in ventricle-external shunted patients?

OBJECTIVE

Hydrocephalus is usually resolved by diverting cerebrospinal fluid through a surgically implanted intra-ventricular catheter (shunt). The aim of this study was to characterize vancomycin pharmacokinetic (PK) parameters and optimal dosage in shunted patients under vancomycin treatment.

SETTING

Intensive Care and Neurosurgical Units. University Hospital.

METHODS

Retrospective data of vancomycin blood concentrations, demographics and biochemical parameters, from a Therapeutic Drug Monitoring (TDM) program, in ventricle-external shunted patients (Group A) and controls (Group B) were collected. In all subjects, several blood samples at steady state conditions were drawn. Individual PK parameters such as drug clearance (CL) and volume of distribution (V) were estimated by using an one-compartmental PK model and later, dosage regimens were individually adjusted by Bayesian analysis. The obtained CL and V mean +/- standard deviation were compared between both groups (A versus B). Vancomycin dosage regimens between both groups were also compared.

MAIN OUTCOME MEASURES

Patients demographics, clinical records, creatinine clearance by Cockcroft-Gault, vancomycin blood levels, vancomycin pK parameters and optimal initial IV vancomycin dosage.

RESULTS

Forty-five patients were included in the study: 15 patients in group A and 30 subjects in group B. Significant differences between CL(A) and CL(B) means were observed, while not between V(A) and V(B). In shunted patients, the required vancomycin daily dose to reach target concentrations was significantly higher than the dose needed in the control group (49.25 +/- 12.28 mg/kg/day vs. 31.74 +/- 6.70 mg/kg/day; P < 0.0005).

CONCLUSIONS

Greater vancomycin clearance was found in our shunted patients, thus they required higher vancomycin daily doses compared to the control group. Consequently, vancomycin TDM in shunted patients should be advisable in order to guarantee antibiotic blood concentrations within the recommended therapeutic range.