Outcomes analysis

In the analysis of the relationship between trough levels of VCM and its effectiveness and nephrotoxicity, the primary outcomes (effectiveness and nephrotoxicity) were defined according to each study’s definition. Definitions of the nephrotoxicity criteria in each study are indicated in Table S4.

Unlike trough levels, the included studies showed considerable variation in the AUC/MIC ratio and AUC value cutoff in the comparison of clinical failure and adverse effects. Considering the differences in methodological and technical measurements, rounding within 15% of the AUC was considered appropriate for the meta-analysis. Therefore, the cut-off value of AUC/MIC ratios of 340–460 was defined as 400, and AUC values of 510–690 were defined as 600. The analysis of the relationship between the AUC values of VCM and its effectiveness and nephrotoxicity, the primary outcomes (effectiveness and nephrotoxicity) were defined as follows: effectiveness was defined as a clinical response, treatment failure, mortality, or bacterial eradication, while nephrotoxicity was defined as according to the 2009 VCM consensus guideline (a serum creatinine (SCr) increase of ≥0.5 mg/dL or ≥ 50% of the baseline SCr for ≥2 consecutive measurements) or AKIN stage 1 (SCr increase of ≥0.3 mg/dL or ≥ 1.5 times the baseline SCr).

Our analysis of the differences in monitoring strategies defined effectiveness and safety as the primary outcome measures. Effectiveness was defined as mortality, while nephrotoxicity was defined according to the 2009 VCM consensus guideline or AKIN stage 1, as described above.