The pharmacokinetics and pharmacodynamics of vancomycin in clinical practice: evidence and uncertainties

Vancomycin has been used extensively since the late 1950s. Despite the introduction of several new valuable anti-Gram-positive antibiotics during recent years and the waning susceptibility of staphylococci to vancomycin, it remains the gold standard for the treatment of bacteraemia caused by methici...

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Bibliographic Details
Published in:Journal of antimicrobial chemotherapy 2013-04, Vol.68 (4), p.743-748
Main Authors: Vandecasteele, S J, De Vriese, A S, Tacconelli, E
Format: Article
Language:English
Subjects:
Adaptations
Anti-Bacterial Agents - administration & dosage
Anti-Bacterial Agents - pharmacokinetics
Antibiotics
Bacteremia
Biofilms
Clinical medicine
Data processing
Dose-response effects
Drug dosages
Drug resistance
Drug-Related Side Effects and Adverse Reactions - epidemiology
Gram-positive bacteria
Humans
Infusions, Intravenous
Inoculum
Microbial Sensitivity Tests
Minimum inhibitory concentration
Pharmacodynamics
Pharmacokinetics
Renal function
Staphylococcal Infections - drug therapy
Staphylococcus infections
Toxicity
Vancomycin
Vancomycin - administration & dosage
Vancomycin - pharmacokinetics
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Summary:Vancomycin has been used extensively since the late 1950s. Despite the introduction of several new valuable anti-Gram-positive antibiotics during recent years and the waning susceptibility of staphylococci to vancomycin, it remains the gold standard for the treatment of bacteraemia caused by methicillin-resistant staphylococci. Vancomycin has clear dose-response and dose-toxicity correlations. It is widely accepted that these correlations are best predicted by the AUC/MIC model, with target levels of >400 being the clinical cut-off. The experimental base of this model is less robust than frequently believed, and several important issues in vancomycin resistance, such as biofilm resistance and the inoculum effect, are not included. Based on this model, current dosing guidelines propose intermittent dosing of vancomycin with target trough levels of 15-20 mg/L. Dose adaptations according to renal function have been proposed but are not yet validated. Clinical data also support the use of continuous infusion with target plateau levels of 20-25 mg/L, with similar efficacy at the cost of lower nephrotoxicity. Despite decades of intense clinical use and numerous studies and publications, the optimal dosing strategy for vancomycin reconciling the high needs of the dose-response relationship with the serious drawbacks of the dose-toxicity relationship remains to be established.
ISSN:0305-7453
1460-2091
DOI:10.1093/jac/dks495