Mississippi Mud No More: Cost-Effectiveness of Pharmacokinetic Dosage Adjustment of Vancomycin to Prevent Nephrotoxicity

William Darko, Pharm.D., Joseph J. Medicis, Pharm.D., Adrienne Smith, Pharm.D., Roy Guharoy, Pharm.D., David F. Lehmann, M.D., Pharm.D.

Disclosures

Pharmacotherapy. 2003;23(5) 

In This Article

Discussion

Our results show that significant cost savings are possible through implementation of targeted monitoring in selected subgroups. For patients receiving concomitant nephrotoxins, the data demonstrate that this strategy is not only cost-effective but that dominance exists, since both improvement in quality of care (reduction in nephrotoxicity) and cost savings occur. In the intensive care patients, both the mean cost and the sensitivity analysis demonstrate that pharmacokinetic monitoring and dosage adjustment are a more cost-effective strategy. However, in the oncology patients, the upper extreme of costs for the sensitivity analysis failed to demonstrate the same robustness.

This study is not without limitations. First, since scant data relate to the efficacy of monitoring vancomycin serum levels, we did not include a measure of efficacy in our analysis. We assumed that there would be no significant difference in mortality between the study and control groups; however, we presumed a change in morbidity related to renal dysfunction.

Second, approaches to monitoring vary from institution to institution; some clinicians obtain both peak and trough vancomycin serum concentrations, some obtain trough concentrations only, and others do no monitoring. Our objective was centered on an analysis of pharmacokinetics for monitoring. Hence, in the absence of two serum concentrations (vs trough only) we would be unable to apply patient-specific pharmacokinetic parameters. Therefore, we conducted our study as if one trough level was the equivalent of obtaining no levels.

Third, the trough concentration chosen was 10 mg/L; even though clinically used ranges vary widely, we used the 10-mg/L concentration because this number was referenced more frequently in published nephrotoxicity studies.

These data were the best available, and we believe that our sensitivity analysis addressed any significant variance that may have occurred. The frequency of nephrotoxicity derived from the literature may not be solely attributable to vancomycin. Regardless of the exact cause of renal impairment, the patients involved are clearly at higher risk of developing impaired renal function. Therefore, maintaining nontoxic (targeted) vancomycin trough concentrations seems prudent for these patient subpopulations.

In a study of pharmacokinetic monitoring and dosage adjustment of vancomycin in 70 immunocompromised patients with hematologic malignancies,[18] 50% of the patients received pharmacokinetic monitoring and dosage adjustment and the other half did not. The rates of nephrotoxicity were 13% and 33.3% for the pharmacokinetically adjusted and control groups, respectively. The authors concluded that pharmacokinetic monitoring with resultant dosage adjustment in this high-risk population was cost-effective. Although the sensitivity analysis in their study did exceed the cost of treating a nephrotoxicity episode by $2017.00, the mean costs were far less than the cost of treating a nephrotoxic event. These findings are reproduced in our analysis. To our knowledge, no other study has performed a cost-effectiveness or cost-benefit analysis of pharmacokinetic monitoring and dosage adjustment for intravenous vancomycin therapy to prevent nephrotoxicity.

Another study reported that in critically ill patients, individualized pharmacokinetic analysis of potentially nephrotoxic antibiotics is essential to maintain therapeutic, nontoxic levels of vancomycin serum concentration.[19] Our study showed that in critically ill patients it is cost-effective to monitor and adjust for those with high and low probability of developing nephrotoxicity. Other studies have suggested that because this patient population may be at high risk of developing nephrotoxicity due to variability in pharmacokinetics, monitoring and adjustment of potentially nephrotoxic antibiotics are essential.[20,21,22,23]

Evidence strongly supports increased risk of nephrotoxicity from vancomycin in patients receiving concurrent nephrotoxic drugs such as aminoglycosides.[20,21,22,23,24] Therefore, monitoring vancomycin serum concentrations to prevent toxic levels and possible subsequent nephrotoxicity is necessary.[25,26] Our study demonstrated a cost savings of $5564.10 with pharmacokinetic monitoring and dosage adjustment in this patient group. A cost savings of $12,428.57 was realized for patients at higher risk of developing nephrotoxicity. When all patients were analyzed collectively, the mean cost of preventing a nephrotoxic episode was $13,933.17 higher than the cost of treating nephrotoxicity at our institution. We believe that this analysis is generalizable to the germane questions regarding assignment of clinical pharmacist resources in an environment where such valuable resources are limited.

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