Why is vancomycin toxic

Article Information. Access through your institution. Add or change institution. Save Preferences. Privacy Policy Terms of Use. Access your subscriptions. Free access to newly published articles. Purchase access. Rent article Rent this article from DeepDyve. Access to free article PDF downloads. The development of acute kidney injury includes a variety of risk factors as reported in published literature, including concomitant nephrotoxins, advanced age, total daily doses exceeding 4 grams, and hypotension [ 26 , 27 ].

Similarly, Zasowski and colleagues reported a 3-tofold increase in nephrotoxicity when the AUC:MIC ratio exceeded , even after controlling for other risk factors [ 30 ]. In comparison, our study suggests that individuals with liver disease are likely to exceed these AUC:MIC ratio thresholds. Regardless of the metric being used trough or AUC:MIC , the prevalence of a supratherapeutic concentration in this patient population is of concern. The secondary clinical outcomes e.

The difference was not significant and was likely related to a type II error given the wide confidence interval and the low overall incidence of acute kidney injury in the studied cohort 5. Another concern regarding vancomycin therapy and supratherapeutic trough concentration is the incidence of ototoxicity [ 8 , 31 ]. Due to the retrospective nature of this study, this adverse drug reaction was not observed in this specific patient cohort. The higher rate of acute kidney injury, mortality, and length of stay in the MSLD group may not be attributed solely to vancomycin therapy and subsequent trough concentration.

The severity of illness particularly liver disease also influences the length of stay, acute kidney injury, and mortality rates. Furthermore, patients with liver dysfunction can have a concomitant occurrence of hepatorenal syndrome.

Hepatorenal syndrome is a reversible renal impairment that can occur in those with advanced liver cirrhosis or fulminant hepatic failure [ 32 ]. Although the occurrence of this pathology was not studied in this cohort, hepatorenal syndrome can influence the risk of nephrotoxicity when vancomycin is administered.

In addition, only eight patients in the study had a Child—Pugh score of greater than 9 Class C. The use of other nephrotoxic agents along with vancomycin can also have an added negative effect on renal function, and the current study did not take these medications into consideration. Further studies should account for these variables when clinically assessing the outcomes of vancomycin usage in patients with liver dysfunction.

There are some limitations to the study that should be considered. The influence of concomitant medications, particularly nephrotoxins, were not included in the analysis due to the lack of data availability. Diuretics are known to increase risk of acute kidney injury and are recommended by clinical practice guidelines for the management of ascites in advanced liver disease [ 33 , 34 ].

Their use is essential in patients with advanced liver disease. Nonetheless, the acknowledgement that diuretic use and other risk factors are often present in individuals with liver disease further strengthens the need to exercise prudence when managing vancomycin therapy in this patient population.

To control for confounding, outcomes were analyzed after adjusting for the study variables. By virtue of similar treatments undergone among patients with the same disease, the strategy used in this study may have also accounted for medication use; however, one cannot definitively exclude the possibility that concomitant therapies may have confounded the results.

It is also important to control for comorbidities such as diabetes and heart failure since they can alter kidney function. The Charlson comorbidity index, which was included in the analysis, includes both diabetes and heart failure. As with any retrospective cohort study, the potential for information bias associated with the extracted medical information from the electronic health records exists.

To minimize the risk of information bias, data were extracted electronically and then confirmed through manual review of the electronic health records. This study examined the influence of pharmacokinetic parameters in patients with MSLD.

While vancomycin half-life was prolonged, clearance decreased in this patient population, which led to an increase in supratherapeutic exposure. Although MSLD was associated with an increased risk of nephrotoxicity, the increased risk compared to individuals with NMLD was not statistically significant. Future studies are needed to determine if dosage adjustments improve patient outcomes and if patients with liver disease are at greater risk of vancomycin related toxicity.

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