Evaluation of a Bayesian Method for Predicting Vancomycin Dosing

The purpose of this study is to evaluate the performance of a vancomycin dosing program in predicting dosages necessary to achieve desired serum vancomycin concentrations in a relatively large patient population. With the completion of initial performance evaluation, revised pharmacokinetic parameter estimates derived in the initial evaluation are used to reevaluate program performance. The program uses population estimates of vancomycin's volume of distribution (Vd) and clearance (Cl) to initially predict dosing, then individualizes those estimates by a Bayesian algorithm (iterations) which uses dosing and the resulting serum vancomycin concentration data. Use of the Bayesian forecaster with one iteration significantly increases the calculated Cl value as compared with population estimates; two and three iterations significantly increase both Vd and Cl when compared with population estimates. Absolute values of the predicted minus observed peak serum vancomycin concentrations (accuracy) are 17.7 ± 14.0, 6.1 ± 3.6, and 3.4 ± 2.1 mg/L for dosing using population estimates, Bayesian with one iteration, and Bayesian with two iterations, respectively. Similarly, accuracy of predictions for trough concentrations is 13.8 ± 12.4, 3.5 ± 3.2, and 3.2 ± 2.6 mg/L for each method, respectively. Bias of dosing predictions in achieving desired peak and trough serum vancomycin concentrations is also significantly reduced by using the Bayesian algorithm. Use of the mean Vd and Cl values from three iterations as the starting parameters in a new group of 12 patients significantly improves program performance when compared with use of initial population parameters. Time of sampling for peak serum concentrations has no effect on program performance. In patients with impaired renal function, use of population estimates resulted in less accurate dosing prediction, but this less accurate performance was not observed with use of the Bayesian forecaster. These data demonstrate the accuracy and lack of bias in individualized dosing predictions using the Bayesian dosing method and the ability of revised pharmacokinetic parameter estimates to improve performance.

[1]  William J. Jusko,et al.  Berichten , 2005, Pharmaceutisch weekblad.

[2]  G. Archer,et al.  Staphylococcus epidermidis causing prosthetic valve endocarditis: microbiologic and clinical observations as guides to therapy. , 1983, Annals of internal medicine.

[3]  T. J. Breen,et al.  Biostatistical Analysis (2nd ed.). , 1986 .

[4]  D. Brater.  Pocket manual of drug use in clinical medicine , 1989 .

[5]  D. Brater,et al.  Bayesian and Least‐Squares Methods for Vancomycin Dosing , 1987, The American journal of the medical sciences.

[6]  J. Silva,et al.  Treatment of antibiotic-associated enterocolitis with vancomycin. , 1981, Reviews of infectious diseases.

[7]  W. Keane,et al.  Pharmacokinetics of vancomycin in patients with various degrees of renal function , 1984, Antimicrobial Agents and Chemotherapy.

[8]  J. Garrelts,et al.  Accuracy of Bayesian, Sawchuk-Zaske, and nomogram dosing methods for vancomycin. , 1987, Clinical pharmacy.

[9]  D. T. Rock,et al.  Comparison of steady-state pharmacokinetics of two dosage regimens of vancomycin in normal volunteers , 1987, Antimicrobial Agents and Chemotherapy.

[10]  B. Farber,et al.  Retrospective study of the toxicity of preparations of vancomycin from 1974 to 1981 , 1983, Antimicrobial Agents and Chemotherapy.

[11]  J. Jui,et al.  Community-acquired methicillin-resistant Staphylococcus aureus endocarditis in the Detroit Medical Center. , 1982, Annals of internal medicine.

[12]  D J Greenblatt,et al.  Vancomycin therapy in patients with impaired renal function: a nomogram for dosage. , 1981, Annals of internal medicine.

[13]  J. Rotschafer,et al.  Vancomycin pharmacokinetics in patients with various degrees of renal function , 1988, Antimicrobial Agents and Chemotherapy.

[14]  W. Bennett,et al.  Vancomycin pharmacokinetics, renal handling, and nonrenal clearances in normal human subjects , 1988, Clinical pharmacology and therapeutics.

[15]  C. A. Wood,et al.  Vancomycin enhancement of experimental tobramycin nephrotoxicity , 1986, Antimicrobial Agents and Chemotherapy.

[16]  T. Sorrell,et al.  Vancomycin therapy for methicillin-resistant Staphylococcus aureus. , 1982, Annals of internal medicine.

[17]  P J Huber,et al.  A Bayesian feedback method of aminoglycoside dosing , 1985, Clinical pharmacology and therapeutics.

[18]  R. Cipolle,et al.  Kinetic model for gentamicin dosing with the use of individual patient parameters , 1977, Clinical pharmacology and therapeutics.

[19]  R. Wise.  The Vancomycin Symposium: Summary and Comments , 1981 .

[20]  G. Matzke,et al.  Clinical Pharmacokinetics of Vancomycin , 1986, Clinical pharmacokinetics.

[21]  J. Rotschafer,et al.  Pharmacokinetics of vancomycin: observations in 28 patients and dosage recommendations , 1982, Antimicrobial Agents and Chemotherapy.

[22]  B. Cunha,et al.  Clinical usefulness of vancomycin. , 1983, Clinical pharmacy.

[23]  K. Lake,et al.  A Simplified Dosing Method for Initiating Vancomycin Therapy , 1985, Pharmacotherapy.

[24]  M. Rybak,et al.  Individualized Adjustment of Vancomycin Dosage: Comparison with Two Dosage Nomograms , 1986, Drug intelligence & clinical pharmacy.