Summary
The resurgence of the use of and interest in vancomycin, in conjunction with the high degree of interpatient variability in its pharmacokinetic profile, has prompted the development of many and varied dosing methods. Several dosing nomograms have been proposed and evaluated, methods which are useful for initial dosing but do not allow for individualisation of dosage. Given these constraints, several investigators have attempted to apply conventional least-squares regression techniques and, more recently, Bayesian methodologies using either 1- or 2-compartment pharmacokinetic models.
Comparative information evaluating algorithmic methods demonstrates that those of Moellering and Lake offer the least biased and most precise predictions of vancomycin dosage. Patient individualisation using conventional least-squares methodology offers some improvement over nomogram-based methods, both in predictive performance and in dosage adjustment once serum concentration data are available. Overall, the latest data indicate that regimens which incorporate Bayesian principles tend to give better results than nomogram-based or conventional least-squares dosing methods for this drug.
Despite the advances in methods for dosing vancomycin, several questions remain to be answered. A lack of convincing evidence of a correlation between serum concentrations and therapeutic outcome has prompted debate over the need for serum concentration monitoring and, if it is needed, over which patient population would most benefit. Secondly, little comparative information is currently available as to the dosing of vancomycin in paediatric and neonatal patient populations. Several nomograms for initial dosing have been proposed, but only 2 have been subject to subsequent testing. Finally, information regarding cost-effectiveness and the quality of patient outcome is lacking from the current literature.
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References
Ackerman BH. Evaluation of three methods for determining initial vancomycin doses. DICP — Annals of Pharmacotherapy 23: 123–128, 1989
Ackerman BH, Olsen KM, Padilla CB. Errors in assuming a onecompartment model for vancomycin. Therapeutic Drug Monitoring 12: 304–305, 1990
Albrecht LM, Rybak MJ, Boike SC, Pancorbo S. Comparison of serum sampling methods for determining vancomycin dosage regimens. Therapeutic Drug Monitoring 10: 85–90, 1988
Alpert G, Campos JM, Harris MC, Preblud SR, Plotkin SA. Vancomycin dose in paediatrics reconsidered. American Journal of Diseases in Children 138: 20–22, 1984
Bailie GR, Neal D. Vancomycin ototoxicity and nephrotoxicity: a review. Medical Toxicology 3: 376–386, 1988
Birt JK, Chandler MHH. Using clinical data to determine vancomycin dosing parameters. Therapeutic Drug Monitoring 12: 206–209, 1990
Blouin RA, Bauer LA, Miller DD, Record KE, Griffen WO. Vancomycin pharmacokinetics in normal and morbidly obese subjects. Antimicrobial Agents and Chemotherapy 21: 575–580, 1982
Brown DL, Mauro LS. Vancomycin dosing chart for use in patients with renal impairment. American Journal of Kidney Disease 11: 15–19, 1988
Brummett RE, Fox KE. Vancomycin- and erythromycin-induced hearing loss in humans. Antimicrobial Agents and Chemotherapy 33: 791–796, 1989
Burton ME, Gentle DL, Vasko MR. Evaluation of a Bayesian method for predicting vancomycin dosing. DICP — Annals of Pharmacotherapy 23: 294–300, 1989
Burton ME, Vasko MR, Brater DC. Comparison of drug dosing methods. Clinical Pharmacokinetics 10: 1–37, 1985
Cimino MA, Rotstein C, Slaughter RL, Emrich LJ. Relationship of serum antibiotic concentrations to nephrotoxicity in cancer patients receiving concurrent aminoglycoside and vancomycin therapy. American Journal of Medicine 83: 1091–1097, 1987
Cunha BA, Quintiliani R, Deglin JM, Izard MW, Nightingale CH. Pharmacokinetics of vancomycin in anuria. Reviews of Infectious Disease 3 (Suppl.): S269–S272, 1981
Dutton AAC, Elmes PC. Vancomycin: report on treatment of patients with severe staphylococcal infections. British Medical Journal 1: 1144–1149, 1959
Edwards DJ, Pancorbo S. Routine monitoring of serum vancomycin concentrations: waiting for proof of its value. Clinical Pharmacy 6: 652–654, 1987
Eli Lilly and Company. Vancomycin package insert, Indianapolis, Indiana, 1986
Farber BF, Moellering RC. Retrospective study of the toxicity of preparations of vancomycin from 1974 to 1981. Antimicrobial Agents and Chemotherapy 23: 138–141, 1983
Fitzsimmons WE, Postelnick MJ. Rational use of vancomycin serum concentrations. Update on Infectious Disease 2: 1–18, 1988
Garrelts JC, Godley PJ, Horton MW, Karboski JA. Accuracy of Bayesian, Sawchuk-Zaske, and nomogram dosing methods for vancomycin. Clinical Pharmacy 6: 795–799, 1987
Geraci JE, Heilman FR, Nichols DR, Wellman WE, Ross GT. Some laboratory and clinical experiences with new antibiotic, vancomycin. In Antibiotics Annual 1956-1957, pp. 90–106, Medical Encyclopedia Inc, New York, 1957
Gross JR, Kaplan SL, Kramer WG, Mason EO. Vancomycin pharmacokinetics in premature infants. Paediatric Pharmacology 5: 17–22, 1985
Healy DP, Polk RE, Garson ML, Rock DT, Comstock TJ. Comparison of steady-state pharmacokinetics of two dosage regimens of vancomycin in normal volunteers. Antimicrobial Agents and Chemotherapy 31: 393–397, 1987
Healy DP, Sahai JV, Fuller SH, Polk RE. Vancomycin-induced histamine release and ‘red man syndrome’: comparison of 1- and 2-hour infusions. Antimicrobial Agents and Chemotherapy 34: 550–554, 1990
Henry K, Steinberg I, Crossley KB. Vancomycin-induced neutropenia during the treatment of osteomyelitis in an outpatient. Drug Intelligence and Clinical Pharmacy 20: 783–785, 1986
Hurst AK, Yoshinaga MA, Mitani GH, Foo KA, Jelliffe RW, et al. Application of a Bayesian method to monitor and adjust vancomycin dosage regimens. Antimicrobial Agents and Chemotherapy 34: 1165–1171, 1990
Ingerman MJ, Santoro J. Vancomycin: a new old agent. Infectious Disease Clinics of North America 3: 641–651, 1989
James A, Koren G, Milliken J, Soldin S, Prober C. Vancomycin pharmacokinetics and dose recommendations for preterm infants. Antimicrobial Agents and Chemotherapy 31: 52–54, 1987
Kildoo CW, Lin LM, Gabriel MH, Folli HL, Modanlu HD. Vancomycin pharmacokinetics in infants: relationship to postconceptional age and serum creatinine. Developmental Pharmacology and Therapeutics 14: 77–83, 1990
Koo KB, Bachman RL, Chow AW. Vancomycin-induced neutropenia. Drug Intelligence and Clinical Pharmacy 20: 780–782, 1986
Krogstad DJ, Moellering RC, Greenblatt DJ. Single-dose kinetics of intravenous vancomycin. Journal of Clinical Pharmacology 20: 197–201, 1980
Lake KD, Peterson CD. A simplified dosing method for initiating vancomycin therapy. Pharmacotherapy 5: 340–344, 1985
Lake KD, Peterson CD. Evaluation of a method for initiating vancomycin therapy: experience in 205 patients. Pharmacotherapy 8: 284–286, 1988
Leonard MB, Koren G, Stevenson DK, Prober CG. Vancomycin pharmacokinetics in very low birth weight neonates. Paediatric Infectious Disease Journal 8: 282–286, 1989
Levine DP, Cushing RD, Jui J, Brown WJ. Community-acquired methicillin-resistance: Staphylococcus aureus endocarditis in the Detroit Medical Center. Annals of Internal Medicine 97: 330–338, 1982
Lisby-Sutch SM, Nahata MC. Dosage guidelines for the use of vancomycin based on its pharmacokinetics in infants. European Journal of Clinical Pharmacology 35: 637–642, 1988
Louria DB, Kaminski T, Buchman J. Vancomycin in severe staphylococcal infections. Archives of Internal Medicine 107: 225–240, 1961
Matzke GR, Kovarik JM, Rybak MJ, Boike SC. Evaluation of the vancomycin clearances creatinine-clearance relationship for predicting vancomycin dosage. Clinical Pharmacy 4: 311–315, 1985
Matzke GR, McGory RW, Halstenson CE, Keane WF. Pharmacokinetics of vancomycin in patients with various degrees of renal function. Antimicrobial Agents and Chemotherapy 25: 433–437, 1984
Matzke GR, Zhanel GG, Guay DRP. Clinical pharmacokinetics of vancomycin. Clinical Pharmacokinetics 11: 257–282, 1986
McCormack JP, Lynd LD, Pfeifer NM. Vancomycin cost containment through a therapeutic and pharmacokinetic drug monitoring service. Canadian Journal of Hospital Pharmacy 42: 3–9, 1989
Moellering RC, Krogstad DJ, Greenblatt DJ. Vancomycin therapy in patients with impaired renal function: a nomogram for dosage. Annals of Internal Medicine 94: 343–346, 1981
Musa DM, Pauly DJ. Evaluation of a new vancomycin dosing method. Pharmacotherapy 7: 69–72, 1987
Naqvi SH, Keenan WJ, Reichley RM, Fortune KP. Vancomycin pharmacokinetics in small, seriously ill infants. American Journal of Diseases in Children 140: 107–110, 1986
Nielsen HE, Hansen HE, Korsager B, Skov PE. Renal excretion of vancomycin as kidney disease. Acta Medica Scandinavica 197: 261–264, 1975
Polk RE, Healy DP, Schwartz LB, Rock DT, Garson ML, et al. Vancomycin and the red-man syndrome: pharmacodynamics of histamine release. Journal of Infectious Disease 157: 502–507, 1988
Pryka RD, Rodvold KA, Garrison M, Rotschafer JC. Individualizing vancomycin dosage regimens: one- vs two-compartment Bayesian models. Therapeutic Drug Monitoring 11: 450–454, 1989
Reed MD, Kleigman RM, Weiner JS, Huang M, Yamashita TS, et al. The clinical pharmacology of vancomycin in seriously ill preterm infants. Paediatric Research 22: 360–363, 1987
Rodvold KA. Therapeutic considerations for infections caused by Staphylococcus epidermidis. Pharmacotherapy 8 (Suppl.): 14S–18S, 1988
Rodvold KA, Blum RA, Fischer JH, Zokufa HZ, Rotschafer JC, et al. Vancomycin pharmacokinetics in patients with various degrees of renal function. Antimicrobial Agents and Chemotherapy 32: 848–852, 1988
Rodvold KA, Pryka RD, Garrison M, Rotschafer JC. Evaluation of a two-compartment Bayesian forecasting program for predicting vancomycin concentrations. Therapeutic Drug Monitoring 11: 269–275, 1989
Rodvold KA, Zokufa H, Rotschafer JC. Routine monitoring of serum vancomycin concentrations: can waiting be justified? Clinical Pharmacy 6: 655–658, 1987
Rotschafer JC, Crossley K, Zaske DE, Mead K, Sawchuk RJ, et al. Pharmacokinetics of vancomycin: observations in 28 patients and dosage recommendations. Antimicrobial Agents and Chemotherapy 22: 391–394, 1982
Rybak MJ, Albrecht LM, Berman JR, Warbasse LH, Svensson CK. Vancomycin pharmacokinetics in burn patients and intravenous drug abusers. Antimicrobial Agents and Chemotherapy 34: 792–795, 1990b
Rybak MJ, Albrecht LM, Boike SC, Chandrasekar PH. Nephrotoxicity of vancomycin, alone and with an aminoglycoside. Journal of Antimicrobial Chemotherapy 25: 679–687, 1990a
Rybak MJ, Boike SC. Individual adjustment of vancomycin dosage: comparison with two dosage nomograms. Drug Intelligence and Clinical Pharmacy 20: 64–68, 1986
Sawchuk RJ, Zaske DE. Pharmacokinetics of dosing regimens which utilize multiple intravenous infusions: gentamicin in burn patients. Journal of Pharmacokinetics and Biopharmaceutics 4: 183–195, 1976
Schaad UB, McCracken GH, Nelson JD. Clinical pharmacology and efficacy of vancomycin in paediatric patients. Journal of Paediatrics 96: 119–126, 1980
Schaible DH, Rocci ML, Alpert GA, Campos JM, Paul MH, et al. Vancomycin pharmacokinetics in infants: relationships to indices of maturation. Paediatric Infectious Disease 5: 304–308, 1986
Sheagren JN. Staphylococcus aureus: the persistent pathogen. New England Journal of Medicine 310: 1368–1373, 1437-1442, 1984
Sorrell TC, Collignon PJ. A prospective study of adverse reactions associated with vancomycin therapy. Journal of Antimicrobial Chemotherapy 16: 235–241, 1985
Sorrell TC, Packham DR, Shanker S, Foldes M, Munro R. Vancomycin therapy for methicillin-resistant Staphylococcus aureus. Annals of Internal Medicine 97: 344–350, 1982
Uaamnuichai M, Day RB, Brater DC. Bayesian and least-squares methods for vancomycin dosing. American Journal of Medical Science 294: 100–104, 1987
Zokufa HZ, Rodvold KA, Blum RA, Riff LJ, Fischer JH, et al. Simulation of vancomycin peak and trough concentrations using five dosing methods in 37 patients. Pharmacotherapy 9: 10–16, 1989
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Pryka, R.D., Rodvold, K.A. & Erdman, S.M. An Updated Comparison of Drug Dosing Methods. Clin. Pharmacokinet. 20, 463–476 (1991). https://doi.org/10.2165/00003088-199120060-00003
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DOI: https://doi.org/10.2165/00003088-199120060-00003