Benefits of therapeutic drug monitoring of vancomycin: a systematic review and meta-analysis

Abstract

Background and objective: The necessity of therapeutic drug monitoring (TDM) for vancomycin is controversial. The objective of the current review was to evaluate the available evidence for the necessity of TDM in patients given vancomycin to treat Gram-positive infections.

Methods: Medline, Embase, Web of Sciences, the Cochrane Library and two Chinese literature databases (CNKI, CBM) were searched. Randomized controlled studies and observational studies that compared the clinical outcomes of TDM groups vs. non-TDM groups were included. Two reviewers independently extracted the data. The primary outcome was clinical efficacy of therapy. Secondary outcomes included vancomycin associated nephrotoxicity, duration of vancomycin therapy, length of hospital stay, and mortality. Meta-analysis was performed using the Mantel-Haenszel fixed effect method (FEM). Odds ratios (ORs) or weighted mean differences (WMD) with 95% confidence intervals (95%CIs) were calculated for categorical and continuous outcomes, respectively.

Results: One randomized controlled trial (RCT) and five cohort studies were included in the meta-analysis. Compared with non-TDM groups, TDM groups had significantly higher rates of clinical efficacy (OR = 2.62, 95%CI 1.34-5.11 P = 0.005) and decreased rates of nephrotoxicity (OR = 0.25, 95%CI 0.13-0.48 P<0.0001). Subgroup analyses showed that TDM group had significantly higher rates of clinical efficacy in both cohort studies subgroup (OR = 3.04, 95%CI 1.34-6.90) and in Asian population subgroup (OR = 3.04, 95%CI 1.34-6.90). TDM group had significantly decreased rates of nephrotoxicity in all subgroup. There was no significant difference in duration of vancomycin therapy (WMD = -0.40, 95%CI -2.83-2.02 P = 0.74) or length of stay (WMD = -1.01, 95%CI -7.51-5.49 P = 0.76) between TDM and non-TDM groups. Subgroup analyses showed there were no differences in duration of vancomycin therapy. Only one study reported mortality rates.

Conclusions: Studies to date show that TDM significantly increases the rate of clinical efficacy and decreases the rate of nephrotoxicity in patients treated with vancomycin.

Figure 1. Flow chart depicting the selection process of studies included in the meta-analysis.

Figure 2. Odds ratios of clinical efficacy: TDM versus non-TDM.

Test of clinical efficacy for overall effect: Z = 2.82 P = 0.005; test of clinical efficacy in cohort studies for overall effect: Z = 2.65 P = 0.008; test of clinical efficacy in RCT for overall effect: Z = 1.12 P = 0.265.

Figure 3. Odds ratios of nephrotoxicity (subgroup analysis by design): TDM versus non-TDM.

Test of nephrotoxicity for overall effect: Z = 4.17 P<0.0001; test of nephrotoxicity in cohort studies for overall effect: Z = 3.31 P = 0.001; test of nephrotoxicity in RCT for overall effect: Z = 2.60 P = 0.009.

Figure 4. Odds ratios of nephrotoxicity (subgroup analysis by geographic location of patients): TDM versus non-TDM.

Test of nephrotoxicity for overall effect: Z = 4.17 P<0.0001; test of nephrotoxicity in Asian population subgroup for overall effect: Z = 2.30 P = 0.022; test of nephrotoxicity in non-Asian population subgroup for overall effect: Z = 3.56 P<0.0001.

Figure 5. Weight Mean Difference of Duration of vancomycin therapy (subgroup analysis by design): TDM versus non-TDM.

Test of duration of vancomycin therapy for overall effect: Z = 0.33 P = 0.74; test of duration of vancomycin therapy in cohort studies for overall effect: Z = 0.21 P = 0.83; test of duration of vancomycin therapy in RCT for overall effect: Z = 0.61 P = 0.54.

Figure 6. Weight Mean Difference of Duraton of vancomycin therapy (subgroup analysis by geographic location of patients): TDM versus non-TDM.

Test of duration of vancomycin therapy for overall effect: Z = 0.33 P = 0.74; test of duration of vancomycin therapy in Asian population subgroup for overall effect: Z = 0.31 P = 0.75; test of duration of vancomycin therapy in non-Asian population subgroup for overall effect: Z = 1.27 P = 0.21.

Figure 7. Weight Mean Difference of Length of stay: TDM versus non-TDM.

Test of nephrotoxicity for overall effect: Z = 0.30 P = 0.76.