| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
Guest Access | Sign In via User Name/Password
|
|
|
|||||||
Guest Access | Sign In via User Name/Password |
|||||||||
Electronic Letters to:
|
|
Electronic letters published:
![[Read eLetter]](/icons/misc/sectionDOWN.gif){kind=icon}
Limitations to vancomycin pharmacokinetic parameters determined retrospectively in assessing outcome
|
|
|||
|
Brian A. Potoski, Clinical Pharmacist University of Pittsburgh Medical Center, Jason M. Pogue
Send letter to journal:
potoskiba{at}upmc.edu Brian A. Potoski, et al.
|
We read with interest the study by Jeffres and colleagues (October 2006).(1) The authors have employed equations to calculate specific pharmacokinetic (PK) parameters that were unattainable due to retrospective data collection. The limitations of these parameters in the context of the study warrant discussion. Equations 2 and 4 determine vancomycin clearance and an elimination rate constant, respectively, and were derived from PK studies in patients not exclusively in ICU.(2,3) Antimicrobial PK parameters, however, may differ between ICU and non-ICU populations.(4) A study evaluating vancomycin PK in ICU patients observed both a high inter individual variability in peak and trough vancomycin serum concentrations and a decrease in vancomycin clearance at steady state without a concomitant decrease in creatinine clearance;(5) neither of which would be accounted for by the equations used by Jeffres.(1) Although the number of patients in ICU in the current study was not stated, the high percentage of patients requiring mechanical ventilation supports this perception. Given the above limitations, the use of these equations may have lead to poor and unreliable predicted and extrapolated values. Secondly, the authors state that equation 6 was used to predict a peak for subsequent trough extrapolation in those patients without serum vancomycin samples. This equation uses the pharmacokinetic parameter "volume of distribution" (Vd) in the denominator, yet the authors do not state how this was calculated. If it was calculated using equations 2 and 4 (Vd = Vancomycin Clearance / Ke), it should be noted that the equation for vancomycin clearance (equation 2) is different from the vancomycin clearance equation as part of the Area under the curve (AUC) calculation (equation 7). These differing clearance equations are taken from two separate PK studies.(3,6) This inconsistency may further contribute to unreliable predictions of AUC. Lastly, the vancomycin infusion time was omitted from the peak equation (equation 6). This is only relevant for infusion times greater than one hour, yet vancomycin doses to achieve trough levels of >15mcg/ml are typically greater than 1g and are infused over more than one hour. This omission may lead to an overestimation of predicted concentrations as drug elimination during infusion is not accounted for. In conclusion this study has several PK limitations not identified by the authors, yet collectively these may have significantly impacted study results and conclusions. (1) Jeffres MN, Isakow W, Doherty JA, et al. Predictors of mortality for methicillin-resistant Staphylococcus aureus health-care-associated- pneumonia: Specific evaluation of vancomycin pharmacokinetic indices. Chest 2006; 130:947-55. (2) Matzke GR, McGory RW, Halstenson CE, et al. Pharmacokinetics of vancomycin in patients with various degrees of renal function. Antimicrob Agents Chemother. 1984; 25:433-7. (3) Moellering RC Jr, Krogstad DJ, Greenblatt DJ. Vancomycin therapy in patients with impaired renal function: A nomogram for dosage. Ann Intern Med 1981;94:343-46. (4) Roberts JA, Lipman J. Antibacterial dosing in intensive care: pharmacokinetics, degree of disease and pharmacodynamics of sepsis. Clin Pharmacokinet 2006;45:755-73. (5) Polard E, LeBouquin V LeCorre P, et al. Non steady state and steady state PKS bayesian forecasting and vancomycin pharmacokinetics in ICU adult patients. Ther Drug Monit 1999; 21:395-403. (6) Rodvold, KA, Blum RA, Fischer JH, et al. Vancomycin pharmacokinetics in patients with various degrees of renal function. Antimicrob Agents Chemother. 1988;32:848-52. |
|||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
eLetters: