The pharmacokinetic/pharmacodynamic rationale for administering vancomycin via continuous infusion

Vancomycin is administered via intermittent infusion (II) almost exclusively in the United States, whereas continuous infusion (CI) dosing methods are used regularly in many European countries. The purpose of this literature analysis is to review current evidence regarding the advantages and disadvantages of CI vancomycin in relation to II, based on the pharmacokinetic and pharmacodynamic aspects of dosing and monitoring therapy, and to identify current practices of CI vancomycin dosing.

Medline, Cochrane and GoogleScholar databases were searched using vancomycin as a MeSH term, along with continuous and infusion in all fields, which identified 136 citations. A second search added the terms intermittent and survey, producing nine additional articles. All articles that reported an assessment of CI or II vancomycin administration in adult patients, based on clinical, pharmacokinetic, cost or monitoring considerations, were identified. A total of 43 publications were determined to be suitable for final analysis and possible inclusion in the report.

A meta-analysis of six studies concluded that CI vancomycin was associated with a lower relative risk of kidney injury than II therapy, although other studies reported equivocal findings. The results of several clinical studies suggest that CI vancomycin produces clinical outcomes that are comparable to II. Current vancomycin consensus guidelines promote aggressive dosing to achieve trough levels of 10-15 or 15-20 mg/L, but also include recommendations to target a daily area under the curve (AUC24 ) to minimum inhibitory concentration (MIC) ratio of at least 400. Because vancomycin is a non-concentration-dependent antibiotic, it might be more prudent to monitor steady-state serum concentrations (Css ) during a CI rather than trough concentrations during II, due to the questionable correlation between measured trough concentration and AUC. From a pharmacokinetic/pharmacodynamic perspective, vancomycin dosing and monitoring practices associated with CI offer potentially greater reliability than II. A major disadvantage of CI involves the possibility of having to intravenously co-administer another drug that might not be compatible with vancomycin.

Continuous infusion vancomycin therapy offers the advantage of Css monitoring, thus avoiding the variabilities associated with the timing of trough levels. Current CI practices include a loading dose of 15-20 mg/kg followed by an infusion of 10-40 mg/kg/day based on the patient's renal function, with a target Css of about 20-30 mg/L. An alternative approach to weight-based (mg/kg) CI dosing is to calculate the dose from an estimation of the patient's vancomycin clearance (in L/h), derived from creatinine clearance (CrCl) via the equation (CrCl∙0·041) + 0·22. The daily dose is then determined by multiplying vancomycin clearance (in L/h) by the desired AUC24 . A new CI vancomycin dosing chart includes clearance-based dosing recommendations for Css values ranging from 17·5 to 27·5 mg/L or AUC24 values ranging from 420 to 660 mg h/L. Although sufficient data already exist to support the use of CI vancomycin as a reasonable therapeutic alternative to II, there is still much to learn about administering the drug in this fashion.