Table 1.

Summarized characteristics of the eligible studies in the meta-analysis

Author	Country	Study period	Patient characteristic	Study design (No. of subjects)	Timing of vancomycin trough level measurement	Duration of vancomycin therapy
Casapao et al. [65, 66]	Michigan, USA	2004–2012	Patients with MRSA IE infections treated with VAN for ≥3 days, and who had initial VAN trough levels evaluated	Retrospective cohort study (n = 128)	Initial	NA
Zelenitsky et al. [67]	Canada	2002–2007	Patients age ≥18 years treated with VAN for MRSA-associated septic shock	Retrospective study (n = 34)	Initial
Tadros et al. [68]	Canada	2011	Patients aged ≥18 years with MRSA pneumonia infections treated with VAN, and who had at least one initial VAN trough level measurement	Prospective surveillance study (n = 161)	Average	NA
Arshad et al. [69]	USA	2005–2007	Patients with MRSA bacteraemia treated with VAN, while patients with acute renal failure on admission, dialysis and those not at steady-state after third dose of VAN were excluded	Retrospective study (n = 104)	Initial and average	NA
Leu et al. [34]	Taiwan	2009–2011	Patients with MRSA infections (most infections were pneumonia, wound infection, or bacteremia) treated with VAN for ≥3 days, and who had at least one VAN trough concentration measurement	Non-randomized comparative study (n = 76)	Not stated	NA
Kullar et al. [17]	Michigan, USA	2005–2010	Adult patients with complicated MRSAB infections treated with VAN for ≥72 h	Retrospective quasi-experimental study (n = 200)	Initial	Median durations of VAN were 13 and 8.5 days for patients with trough levels <15 and ≥15 mg/L, respectively
Rojas et al. [38]	Spain	2005–2009	Adult patients with MRSA bloodstream infections treated with VAN, and who had at least one VAN trough concentration measurement	Retrospective cohort study (n = 104)	Average	Median duration of VAN was 14 days (range 8–19) and 42.3% of patients received VAN for >14 days
Wunderink et al. [70]	USA	2004–2010	Patients aged ≥18 years with MRSA nosocomial pneumonia who had an expected survival of ≥72 h	Multicenter prospective study, since there was no randomization with respect to VAN trough levels (n = 333)	Average (Median)	NA
Bosso et al. [71]	South Carolina, USA	2008–2010	Patients aged ≥18 years with MRSA infections treated with VAN for ≥72 h, and who had at least one VAN trough concentration measured 2–4 days into therapy	Multicenter prospective observational study (n = 288)	Initial single trough level measured 2–4 days into therapy; in case of multiple measurements, the average trough level was calculated	Average length of VAN therapy was 9 days (median 7.5)
Chan et al. [72]	USA	2003–2007	Patients aged ≥17 years with MRSA VAP treated with ≥4 days of VAN therapy	Retrospective study (n = 72)	Initial single trough level measured after ≥3 doses of VAN therapy in patients with normal renal function or after a minimum of 5 estimated VAN half lives in patients with renal insufficiency or requiring hemodialysis	Mean durations of VAN were 10.8 days (range 7–23) and 11.6 days (range 7–42 days) for patients with trough levels <15 and ≥15 mg/L, respectively
Choi et al. [13]	Korea	2002–2010	Patients aged ≥15 years with MRSAB who received VAN for >48 h, and who had at least one VAN trough level measurement within 3–7 days into VAN therapy	Retrospective cohort study (n = 73)	Not stated	NA
Chung et al. [36]	Korea	2005–2007	Patients aged ≥18 years in the ICU who had MRSA pneumonia infection treated with VAN for ≥72 h	Prospective study (n = 68)	Initial trough level measured immediately before the next dose after 3–5 doses of VAN therapy	Mean durations of VAN were 15.5 and 12.8 days for patients with trough levels <15 and ≥15 mg/L, respectively
Clemens et al. [37]	USA	2008–2009	Patients aged ≥18 years with MRSAB who received VAN ≥24 h, and who had a documented steady-state VAN trough concentration measurement	Retrospective cohort study (n = 94)	Initial single trough level measured immediately before a scheduled dose after ≥24 h of completing VAN therapy	Average duration of VAN was 14.8 days (range 4–56)
Honda et al. [73]	USA	2005–2007	Patients aged ≥18 years with MRSAB who received VAN as initial therapy, and who had a documented steady-state VAN trough concentration measurement	Prospective cohort study (n=151)	Initial trough level measured before the 4th dose of VAN	NA
Kullar et al. [33]	USA	2005–2010	Adult patients with MRSAB infection who received VAN as initial therapy for ≥72 h	Retrospective cohort study (n = 280)	Initial trough level measured immediately before the 4th dose of VAN	NA
Hermsen et al. [35]	USA	2005–2007	Patients aged ≥19 years with MRSA pneumonia, endocarditis, or osteomyelitis treated with VAN for ≥5 days, and who had at least one VAN trough concentration measurement	Retrospective cohort study (n = 55)	Average	Median durations of VAN were 12 days (P25–P75: 8–18) and 11 days (P25–P75: 7–16) for patients with trough levels <15 and ≥15 mg/L, respectively
Jeffres et al. [31]	USA	1999–2005	All hospitalized patients with MRSA HCAP treated with VAN for ≥72 h	Retrospective cohort study (n =  = 94)	Initial trough level measured immediately after the 3rd dose of VAN	NA
Hidayat et al. [30]	California, USA	2004–2005	Patients aged ≥18 years infected with any type of nosocomial MRSA treated with VAN for ≥72 h	Prospective cohort study (n = 95)	Initial and average	Mean durations of VAN were 11.5 days (range 6.5–13.5) and 12 days (range 7–17) for patients with trough levels <15 and ≥15 mg/L, respectively

MRSA IE MRSA infective endocarditis, VAN vancomycin, NA not available, MRSAB MRSA bacteremia, VAP ventilator associated pneumonia, ICU intensive care unit, P25 25th percentile, P75 75th percentile, HCAP health care-associated pneumonia