Vancomycin is typically given as an intermittent infusion adjusted for body weight and renal function. Some clinicians believe that a continuous infusion of vancomycin may simplify therapy and make serum vancomycin levels more consistent.
Goal Vancomycin Level (Plateau)
Because continuous infusion vancomycin is a rare clinical occurrence, there is a lack of data regarding the optimal “plateau” level (serum drug level during continuous infusion therapy). Current evidence suggests that the vancomycin AUC:MIC ratio is the most important pharmacodynamic parameter associated with treatment success.1 Given that current guidelines recommend an AUC:MIC ratio of at least 400, a plateau of 20-25 mcg/mL (20 mcg/mL * 24 hrs) would provide an AUC:MIC ratio > 400 for isolates with an MIC of 1-1.5 mcg/mL.
Clinical Evidence for Continuous Infusion Vancomycin
A 2001 French study compared intermittent vancomycin (IIV) to continuous infusion vancomycin (CIV) in patients with methicillin-resistant Staphylococcal infections (mostly bacteremia and pneumonia, and mostly Staphylococcus aureus).2 The study targeted a trough of 10-15 mcg/mL (for IIV) and a plateau of 20-25 mcg/mL (for CIV).
Unfortunately, the study was not blinded and was extremely underpowered (needed 320 patients – enrolled 119). Of note, the study had 50-72% of isolates with a vancomycin MIC of 2 mcg/mL, which current guidelines suggest would be inappropriate for vancomycin therapy.1
Not surprising given its 23% post-hoc power, there was no difference seen between IIV and CIV in microbiological outcomes, clinical outcomes, or nephrotoxicity. The authors conclude that the CIV group may have been more cost effective because fever levels were drawn; however, by protocol, the IIV protocol needed to have both a peak and trough level drawn, whereas the CIV group only needed a single plateau level. Because peak levels are typically not done in practice, the relevance of this finding is completely irrelevant.
What about an MIC of 2 mcg/mL?
The 2009 ASHP/IDSA/SIDP guidelines1 recommend against the use of vancomycin for the treatment of bacteria with a vancomycin MIC of 2 mcg/mL or more. The guidelines recommend alternative therapy because some data have demonstrated a higher incidence of treatment failure in isolates with an MIC ≥ 2 mcg/mL. Regarding a continuous vancomycin infusion, a plateau level of 33 mcg/mL would be required to maintain an AUC:MIC ratio > 400; however, the safety of such a high continuous level is unknown and untested.
Summary
- There is a theoretical benefit to continuous infusion vancomycin in that it may produce more predictable and consistent vancomycin drug levels. More consistent levels could potentially lead to better outcomes.
- If a continuous vancomycin infusion is used, a plateau level of 20-25 mcg/mL is reasonable to maintain an AUC:MIC ratio of > 400 (assuming an MIC of 1 to 1.5 mcg/mL).
- To date, only one underpowered French study has really examined whether continuous vancomycin is better than intermittent vancomycin. The study found no difference in either safety or efficacy endpoints.2
- Current guidelines do not encourage the use of continuous infusion vancomycin regimens because they are unlikely to substantially improve patient outcomes compared to intermittent dosing1
References
- Rybak MJ, Lomaestro BM, Rotschafer JC, et al. Therapeutic monitoring of vancomycin in adults summary of consensus recommendations from the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Pharmacotherapy. 2009;29(11):1275-9. PMID 19873687
- Wysocki M, Delatour F, Faurisson F, et al. Continuous versus intermittent infusion of vancomycin in severe Staphylococcal infections: prospective multicenter randomized study. Antimicrob Agents Chemother. 2001;45(9):2460-7. PMID 11502515
