vancomycin treatment: analysis of efficacy and safety

Abstract

Background: According to vancomycin properties and to assure rational use of antimicrobials vancomycin is ranged among reserved antimicrobials with restricted regimen of prescribing. Its useful spectrum is restricted to Gram-positive pathogens with particular activity against multiple resistant coagulase negative staphylococci and methicillin-resistant Staphylococcus aureus causing severe infectious diseases as septicemias, endocarditis, hospital pneumonia, skin and soft tissue infections, infections associated with venous catheters and diphteroidal infections in immunocompromised patients. In most cases vancomycin is prescribed to critically ill patients often with co-morbidity of renal disfunction or renal failure. In such cases excessive vancomycin retention in the body must be considered. In patients with vancomycin plasma levels exceeding 10 µmol/L (15 µg/mL) the risk of nephrotoxicity is increased. Optimal antibiotic therapy, tailored to the individual patient is the only way to maintain therapeutic vancomycin plasma levels. This approach is also of great importance to combat antimicrobial resistance.

Materials methods: and The aim of the study was to determine proper use of vancomycin in real hospital environment. In this retrospective analysis 26 patients treated with vancomycin in the Jesenice General Hospital in the years 2005 and 2006 were included. All clinical data were obtained from patient records. Vancomycin plasma levels were obtained from Hospital Department of Laboratory Diagnostics. Pharmacokinetic analysis of clinical and laboratory data was performed at the Department of Biopharmaceutics and Pharmacokinetics of Faculty of Pharmacy at University of Ljubljana applying population approach by nonlinear mixed effects modeling as implemented in the NONMEM® computer programme. Onecompartment model was used for the analysis. Influence of various biochemical and demographic parameters on clearance and distribution volume of vancomycin was in vestigated.

Results: Among the covariates tested significant effect of creatinine clearance calculated by the Cockroft-Gault equation on vancomycin clearance was determined. Plasma levels of vancomycin for a chosen dosing regimen can be predicted a priori in each patient on the basis of developed model and estimates of creatinine clearance.

Conclusions: Pharmacokinetic analysis enables the design of individual dosing regimen for patients with impaired renal function. With patient individualised dosing regimen of vancomycin, nephrotoxicity can be prevented and an increase in efficacy can be achieved. Moreover, reduced risk of antimicrobial resistance by the proper use of vancomycin is expected.