The monitoring of vancomycin: a systematic review and meta-analyses of area under the concentration-time curve-guided dosing and trough-guided dosing

Abstract

Background: This systematic review and meta-analysis explored the relationship between vancomycin (VCM) monitoring strategies and VCM effectiveness and safety.

Methods: We conducted our analysis using the MEDLINE, Web of Sciences, and Cochrane Register of Controlled Trials electronic databases searched on August 9, 2020. We calculated odds ratios (ORs) and 95% confidence intervals (CIs).

Results: Adult 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). 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). 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 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). Our meta-analysis of differences in monitoring strategies included four studies. 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.

Conclusions: We identified VCM trough concentrations and AUC values that correlated with effectiveness and safety. Furthermore, compared to trough-guided monitoring, AUC-guided monitoring showed potential for decreasing nephrotoxicity.

Keywords: AUC; Meta-analysis; Nephrotoxicity; Trough; Vancomycin.

Fig. 1

Flow chart of the selection process for studies. a Studies of trough-guided monitoring strategy associated with effectiveness and safety of VCM treatment. b Studies of AUC-guided monitoring strategy associated with effectiveness and safety of VCM treatment. c Studies of AUC-guided monitoring vs. trough-guided monitoring strategy associated with effectiveness and safety of VCM treatment

Fig. 2

Methodological quality summary for each included study. The studies included in the evaluation of target trough concentration for a effectiveness and b safety. The studies included in the evaluation of c target AUC/MIC for effectiveness and d AUC for safety. e The studies included in the evaluation of effectiveness and safety associated with VCM monitoring strategy

Fig. 3

Forest plot of the treatment failure associated with VCM trough concentration. The vertical line indicates no significant difference between the groups compared. Diamond shapes and horizontal lines represent ORs and 95% CIs, respectively. Squares indicate point estimates, and the size of each square indicates the weight of each study included in this meta-analysis. a ≥10 μg/mL vs. < 10 μg/mL. b ≥15 μg/mL vs. < 15 μg/mL

Fig. 4

Forest plot of the risk of nephrotoxicity associated with VCM trough concentration. The vertical line indicates no significant difference between the groups compared. Diamond shapes and horizontal lines represent ORs and 95% CIs, respectively. Squares indicate point estimates, and the size of each square indicates the weight of each study included in this meta-analysis. a 10–15 μg/mL vs. < 10 μg/mL. b 15–20 μg/mL vs. 10–15 μg/mL. c > 20 μg/mL vs. 15–20 μg/mL

Fig. 5

Forest plot of treatment failure and risk of nephrotoxicity associated with VCM AUC/MIC ratio and AUC value. The vertical line indicates no significant difference between the groups compared Diamond shapes and horizontal lines represent ORs and 95% CIs, respectively. Squares indicate point estimates, and the size of each square indicates the weight of each study included in this meta-analysis. a The OR of treatment failure associated with AUC/MIC ratios restricted with 400 ± 15% (392.7–451). b The OR of risk of nephrotoxicity associated with AUC values restricted with 600 ± 15% (550–683)

Fig. 6

Forest plot of the effectiveness and risk of nephrotoxicity associated with VCM monitoring. The vertical line indicates no significant difference between the groups compared Diamond shapes and horizontal lines represent ORs and 95% CIs, respectively. Squares indicate point estimates, and the size of each square indicates the weight of each study included in this meta-analysis. a The OR of mortality associated with different monitoring strategies. b The OR of risk of nephrotoxicity associated with the difference in monitoring strategy