Original Research

The Safety and Efficacy of AUC/MIC-Guided vs Trough-Guided Vancomycin Monitoring Among Veterans

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Background: Vancomycin is a commonly used antibiotic for the treatment of methicillin-resistant Staphylococcus aureu s (MRSA), which requires therapeutic drug monitoring (TDM). Guidelines recommend targeting an individualized area under the curve/minimum inhibitory concentration (AUC/MIC) ratio of 400 to 600 mg × h/L to maximize efficacy and minimize the risk of acute kidney injury (AKI). Before these guidelines, the accepted method of vancomycin TDM was using trough levels alone. To our knowledge, no studies of veterans have compared the difference in AKI incidence and time in the therapeutic range between monitoring strategies.

Methods: This single-site, retrospective, quasi-experimen tal study was conducted at the Sioux Falls Veterans Affairs Health Care System. The primary endpoint was the difference in vancomycin-induced AKI incidence between the 2 groups.

Results: This study included 97 patients with 43 in the AUC/MIC group and 54 in the trough-guided group. The incidence of vancomycin-induced AKI was 2% in the AUC/MIC group and 4% in the trough group ( P = .10). The incidence of overall AKI for AUC/MIC-guided and trough-guided TDM was 23% and 15% ( P = .29), respectively.

Conclusions: We did not find a significant difference in the incidence of vancomycin-induced or overall AKI between AUC/MIC- and trough-guided TDM. However, this study did indicate that AUC/MIC-guided TDM of vancomycin may be more effective than trough-guided TDM regarding a quicker time to and higher overall time in the therapeutic range. These findings support the recommendation to transition to the use of AUC/MIC-guided TDM of vancomycin in the veteran population.


 

References

Vancomycin is a commonly used glycopeptide antibiotic used to treat infections caused by gram-positive organisms. Vancomycin is most often used as a parenteral agent for empiric or definitive treatment of methicillin-resistant Staphylococcus aureus (MRSA). It can also be used for the treatment of other susceptible Staphylococcus or Enterococcus species. Adverse effects of parenteral vancomycin include infusion-related reactions, ototoxicity, and nephrotoxicity.1 Higher vancomycin trough levels have been associated with an increased risk of nephrotoxicity.1-4 The major safety concern with vancomycin is acute kidney injury (AKI). Even mild AKI can prolong hospitalizations, increase the cost of health care, and increase morbidity.2

In March 2020, the American Society of Health-System Pharmacists, the Infectious Diseases Society of America (IDSA), the Pediatric Infectious Disease Society, and the Society of Infectious Diseases Pharmacists released a consensus statement and guidelines regarding the optimization of vancomycin dosing and monitoring for patients with suspected or definitive serious MRSA infections. Based on these guidelines, it is recommended to target an individualized area under the curve/minimum inhibitory concentration (AUC/MIC) ratio of 400 to 600 mg × h/L to maximize clinical efficacy and minimize the risk of AKI.2

Before March 2020, the vancomycin monitoring recommendation was to target trough levels of 10 to 20 mg/L. A goal trough of 15 to 20 mg/L was recommended for severe infections, including sepsis, endocarditis, hospital-acquired pneumonia, meningitis, and osteomyelitis, caused by MRSA. A goal trough of 10 to 15 mg/L was recommended for noninvasive infections, such as skin and soft tissue infections and urinary tract infections, caused by MRSA. Targeting these trough levels was thought to achieve an AUC/MIC ≥ 400 mg × h/L.5 Evidence has since shown that trough values may not be an optimal marker for AUC/MIC values.2

The updated vancomycin therapeutic drug monitoring (TDM) guidelines recommend that health systems transition to AUC/MIC-guided monitoring for suspected or confirmed infections caused by MRSA. There is not enough evidence to recommend AUC/MIC-guided monitoring in patients with noninvasive infections or infections caused by other microbes.2

AUC/MIC-guided monitoring can be achieved in 2 ways. The first method is collecting Cmax (peak level) and Cmin (trough level) serum concentrations, preferably during the same dosing interval. Ideally, Cmax should be drawn 1 to 2 hours after the vancomycin infusion and Cmin should be drawn at the end of the dosing interval. First-order pharmacokinetic equations are used to estimate the AUC/MIC with this method. Bayesian software pharmacokinetic modeling based on 1 or 2 vancomycin concentrations with 1 trough level also can be used for monitoring. Preferably, 2 levels would be obtained to estimate the AUC/MIC when using Bayesian modeling.2

The bactericidal activity of vancomycin was achieved with AUC/MIC ratios of ≥ 400 mg × h/L. AUC/MIC ratios of < 400 mg × h/L increase the incidence of resistant and intermediate strains of S aureus. AUC/MIC-guided monitoring assumes an MIC of 1 mg/L. When the MIC is > 1 mg/L, it is less likely that an AUC/MIC ≥ 400 mg × h/L is achievable. Regardless of the TDM method used, AUC/MIC ratios ≥ 400 mg × h/L are not achievable with conventional dosing methods if the vancomycin MIC is > 2 mg/L in patients with normal renal function. Alternative therapy is recommended to be used for these patients.2

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