As we mentioned above, the cutoff value for the effectiveness and safety of VCM is still under discussion, and it is important to clarify the optimal target value. In the clinical setting, dosage regimens based on the trough level is still used because it is a conventional method. A meta-analysis of AKI incidence indicated significantly higher incidence rates for trough concentrations ≥15 μg/mL compared to those for concentrations < 15 μg/mL. These results indicate a clear relationship between AKI incidence and increased trough concentrations. evaluated the risk of AKI at cutoff values of 10, 15, 20, and 25 μg/mL, and reported that the risk of AKI increased as the trough level increased. reported incidence rates for AKI of 21% for trough VCM concentrations of 10–15 μg/mL, 20% for 15–20 μg/mL, and 33% for ≥20 μg/mL.
One of the adverse events associated with VCM use is acute kidney injury (AKI). Thus, a reanalysis of the relationship between trough concentrations and effectiveness is needed. However, because AUC values increase as trough concentrations rise, it is unclear why or how this result was reached. They reported that no significant differences in mortality and treatment success rate between trough concentrations of ≥15 and < 15 μg/mL. performed a meta-analysis to clarify the relationship between trough concentrations and effectiveness. Furthermore, in cases of serious infections such as bacteraemia, infective endocarditis, osteomyelitis, meningitis, and hospital-acquired and healthcare-associated pneumonia caused by MRSA, trough concentrations of 15–20 μg/mL are recommended to further improve patient outcomes. On the other hand, in real-world clinical situations, trough concentrations are used as alternate indicators of AUC values, and in practice, target trough concentrations between 10 and 20 μg/mL are recommended to achieve an AUC/MIC ratio of ≥400 at MIC values of 0.5 and 1 μg/mL. Therefore, the target AUC/MIC value, which is an indicator of effectiveness in MRSA infection therapy, is still controversial. reported that the target AUC/MIC could not be calculated that related to the effectiveness and safety of VCM. The practice guidelines for TDM of VCM recommended an AUC/MIC ratio of ≥400 to predict the clinical efficacy of VCM against MRSA (MIC ≤1 μg/mL). However, its use requires therapeutic drug monitoring (TDM) to ensure its therapeutic effectiveness and avoid nephrotoxicity.Ī recent meta-analysis revealed that compared to low area under the curve/minimum inhibitor concentration ratios (AUC/MIC), high AUC/MIC ratios were associated with significantly lower mortality and treatment failure rates. Vancomycin (VCM) is a broad-spectrum antibiotic that acts against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), and is used for the treatment of several infections. Furthermore, compared to trough-guided monitoring, AUC-guided monitoring showed potential for decreasing nephrotoxicity.
We identified VCM trough concentrations and AUC values that correlated with effectiveness and safety. The incidence of AKI tended to be lower in AUC-guided monitoring than in trough-guided monitoring (OR 0.54, 95% CI 0.28–1.01) however, it was not significant in the analysis of mortality. Our meta-analysis of differences in monitoring strategies included four studies. The safety analysis revealed that high AUC value (cut-off 600 ± 15%) significantly increased the risk of AKI (OR 2.10, 95% CI 1.13–3.89). Analysis of the target area under the curve/minimum inhibitory concentration ratios (AUC/MIC) showed significantly lower treatment failure rates for high AUC/MIC (cut-off 400 ± 15%) (OR 0.28, 95% CI 0.18–0.45). The incidence of acute kidney injury (AKI) increased with increased trough concentrations and was significantly higher for trough concentrations ≥20 μg/mL compared to those at 15–20 μg/mL (OR 2.39, 95% CI 1.78–3.20). ResultsĪdult patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia with VCM trough concentrations ≥15 μg/mL had significantly lower treatment failure rates (OR 0.63, 95% CI 0.47–0.85). We calculated odds ratios (ORs) and 95% confidence intervals (CIs). We conducted our analysis using the MEDLINE, Web of Sciences, and Cochrane Register of Controlled Trials electronic databases searched on August 9, 2020. This systematic review and meta-analysis explored the relationship between vancomycin (VCM) monitoring strategies and VCM effectiveness and safety.