Individualized Pharmacokinetic Monitoring Reduces AAN
Study Objective. To examine the impact of individualized pharmacokinetic monitoring (IPM) on the development of aminoglycoside-associated nephrotoxicity (AAN).
Design. Retrospective case-control study.
Setting. Two teaching hospitals.
Subjects. Two thousand four hundred five patients who received aminoglycosides.
Intervention. Aminoglycoside therapy dosed by either IPM or physicians' directions.
Measurements and Main Results. Patients receiving IPM were significantly less likely to develop AAN by both univariate (7.9% vs 13.2%, p=0.02) and multivariate methods (odds ratio 0.42, p=0.002). Female sex was protective against AAN. Age 50 years and above, high initial aminoglycoside trough, long duration of therapy, and concurrent piperacillin, clindamycin, or vancomycin increased risk of AAN. We estimated that IPM decreased AAN costs by $90,995/100 patients.
Conclusion. Individualized pharmacokinetic monitoring significantly decreased the frequency of AAN and its associated economic costs.

Nephrotoxicity is the primary toxicity associated with aminoglycoside therapy. Its reported frequency varies widely, primarily due to different definitions, but in most reviews it was 5-15%. It is believed that aminoglycoside-associated nephrotoxicity (AAN) is the result of aminoglycoside accumulation in the renal cortex. The polycationic aminoglycoside molecule binds to the anionic brush border of proximal tubular renal cortical cells, leading to cellular uptake of the agent. Intracellularly, the aminoglycoside interferes with normal phospholipid transport, but it is unclear if this process is responsible for cortical cell death.

Individualized pharmacokinetic monitoring (IPM) is used by clinicians in an attempt to optimize aminoglycoside pharmacodynamics. Patient-specific pharmacokinetic parameters are examined to design a dosage that provides specific peak (and target maximum concentration:minimum inhibitory concentration ratios) and trough concentrations to achieve maximum therapeutic effect, reduce development of resistance, and minimize toxicity. Although many studies reported that IPM enhances aminoglycoside efficacy, few examined its impact on AAN. Most that did reported less AAN in patients receiving IPM, whereas others failed to find significant benefit of IPM. Unfortunately, most of these studies lacked appropriate control groups and compared their results only with historical controls or reported rates of AAN in the general population.

Despite AAN's well-known multifactorial nature, these studies either did not account for this or were not designed to control for it. Much work to identify risk factors for AAN has been done in patients receiving traditional dosing every 8 hours and in those who received IPM; however, IPM itself was never included in analyses as a potential risk or protective factor. In addition, considering the substantial economic costs of AAN, IPM could have significant economic benefits by reducing the disorder's frequency. Only a few studies have examined these potential economic benefits, and all reported shorter hospital stays and significant cost savings.

The primary goal of this study was to examine the impact of IPM on the development of AAN by comparing the frequency of AAN in patients receiving IPM with that in patients not receiving IPM. A secondary goal was to examine the significance of IPM as a risk factor for AAN using multiple logistic regression. We also evaluated economic costs and benefits associated with IPM compared with traditional dosing, and determined the significance of other potential risk factors for the development of AAN using both univariate and multivariate statistical procedures.