Single, double or triple? In terms of vancomycin dosing kinetics, it’s an important question. Pharmacokinetic teachings tell us to select the simplest model and fewest compartments necessary to describe the data adequately. Thus the single compartment model is frequently used in initial dosing of vancomycin. For the most part, vancomycin dosing teachings include solving patient cases using one compartment pk formulas such as the Sawchuck-Zaske.1
A two compartment model acknowledges the distribution of vancomycin from plasma into tissues.
Troughs as a surrogate for AUC 0-24/MIC is a debate for another post, but in the real world the practice is to follow trough.6-8
Population: This was a prospective analysis of the divided vancomycin loading protocol in consecutive patients weighing > 137% IBW (mean weight: 111 + 31 kg) and admitted to a single community hospital (Marin General Hospital). Patients were excluded if they had long-term paralysis, pregnant, receiving some other vancomycin protocol or had monitoring errors.
Intervention: Divided load protocol was dependent on the IBW, % over IBW and CrCl. Most patients received 1g IV q6 x 4 doses unless they were a) very tall or b) low CrCl.
Within 12 hours:
- Trough 10-20, n = 48 (89%); mean 14.5 + 3.2
Trough > 10, n = 51 (94%); including the above 48 patients, with the other 3 (6%) having troughs > 20 (20.5 – 22.5)
Within 24 hours: 31 patients had troughs drawn at 24 hours. 19 patients had dosing interval changes that moved the trough draw beyond 24 hours (unclear why, i.e. change in protocol, poor follow up, clinical event (AKI), etc.)
- Trough 10-20, n = 30/32 (97%); mean 15.0 + 3.1
“The biphasic, divided-load obese protocol described here achieved vancomycin trough concentrations in the range of 10-20 within the first 12 hours of treatment for 89% of patients weighing up to 245.2kg, and 97% of trough concentrations sampled during maintenance dosing for the patients were within target range.”
Small sample, although met its predefined power at 12 hours.
Then there is whether it should be taken to a three compartment model.
We’re still between a rock and a hard place when it comes to dosing vancomycin in obese patients. This new approach seems logical and in this limited study and appears to achieve the desired outcome, but not necessarily improved patient oriented outcomes. Clearly more evidence is needed to hash out how to dose vancomycin in obese patients, but this protocol could have a role in the future.
1. Winter ME. Basic Clinical Pharmacokinetics. 3rdedition. Edited by Mary Anne Koda-Kimble, Applied Therapeutics Inc. Vancouver, WA. Copyright 1996
2. Matzke GR et al. Pharmacokinetics of vancomycin in patients with various degrees of renal function. Antimicrob Agents Chemother 1984:25;433-7
3. 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. Nov 2009;29(11):1275–1279
4. Wesner AR, Brackbill ML, Coyle LL, Kidd RS. Prospective trial of a novel nomogram to achieve updated vancomycin trough concentrations. Interdiscip Perspect Infect Dis. 2013;2013:839456. doi:10.1155/2013/839456
5. Reynolds DC, Waite LH, Alexander DP, DeRyke CA. Performance of a vancomycin dosage regimen developed for obese patients. Am J Health Syst Pharm. 2012;69:944-950
6. Brown J, Brown K, Forrest A. Vancomycin AUC24/MIC ratio in patients with complicated bacteremia and infective endocarditis due to methicillin-resistant Staphylococcus aureus and its association with attributable mortality during hospitalization. Antimicrob Agents Chemother. 2012;56:634-638. doi:10.1128/AAC.05609-11
7. Lodise TP, Drusano GL, Butterfield JM, Scoville J, Gotfried M, Rodvold KA. Penetration of vancomycin into epithelial lining fluid in healthy volunteers. Antimicrob Agents Chemother. 2011;55:5507-5511
8. Skhirtladze K, Hutschala D, Fleck T, et al. Impaired target site penetration of vancomycin in diabetic patients following cardiac surgery. Antimicrob Agents Chemother. 2006;50: 1372-1375
9. Denetclaw TH, Yu MK, Moua M, Dowling TC, Steinke D. Performance of a divided-load intravenous vancomycin dosing strategy for obese patients. Ann Pharmacother 2015;49(8): 861-868