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.


METHODS
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.


METHODS
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.
Pujal
Meritxell
M
Pharmacy Service (UASP), Hospital Clínic de Barcelona, University of Barcelona, Villarroel, 170, 08036 Barcelona, Spain.
Soy
Dolors
D
Codina
Carles
C
Ribas
Josep
J
D000328:Adult; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D016470:Bacteremia / Q000097:blood / Q000188:drug therapy; D002555:Cerebrospinal Fluid / Q000382:microbiology; D002557:Cerebrospinal Fluid Shunts / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D005767:Gastrointestinal Diseases / Q000097:blood / Q000188:drug therapy / Q000382:microbiology; D006349:Heart Valve Diseases / Q000097:blood / Q000188:drug therapy; D006801:Humans; D006849:Hydrocephalus / Q000188:drug therapy / Q000601:surgery; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011014:Pneumonia / Q000097:blood / Q000188:drug therapy; D016459:Prosthesis-Related Infections / Q000097:blood / Q000188:drug therapy; D012189:Retrospective Studies; D013210:Staphylococcus / Q000187:drug effects / Q000302:isolation & purification; D014640:Vancomycin / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D014640:Vancomycin