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Table 2 Effect size of outcome measures of eligible studies

From: The safety and efficacy of high versus low vancomycin trough levels in the treatment of patients with infections caused by methicillin-resistant Staphylococcus aureus: a meta-analysis

Authors Concomitant nephrotoxic agent Outcome definition Comparable outcome High trough group, n (%) Low trough group, n (%) p valuea Crude OR (95% CI) Adjusted OR (95% CI)
Casapao et al. [65, 66] NA Mortality: 30-day all-cause mortality   n = 61 n = 67    
Mortality 12 (19.7) 14 (20.9) 0.962 0.93 (0.39–2.20) NA
Clinical success: (1) resolution of bacteremia in ≤7 days of VAN therapy; (2) resolution of signs and symptoms; (3) required no change of antibiotics; and, (4) non-recurrence of BSI or survived for at least 30 days   n = 34 n = 75    
Clinical success 15 (44.1) 30 (40) 0.846 1.18 (0.52–2.69) NA
Zelenitsky et al. [67] NA Mortality: 30-day all-cause mortality from the date of the first positive blood culture   n = 17 n = 18    
Mortality 5 (29.4) 13 (72.2) 0.028 0.16 (0.04–0.69) NA
Tadros et al. [68] NA Mortality: 30-day all-cause mortality   n = 41 n = 56    
Mortality 10 (24.4) 11 (19.6) 0.756 1.32 (0.50–3.48) NA
Arshad et al. [69] NA Mortality: Death within 30 days   n = 49 n = 55    
Mortality 7 (14.3) 3 (5.5) 0.185 2.89 (0.70–11.86) NA
Nephrotoxicity: Increase in SCr of 0.5 mg/dL or ≥50 % increase from initiation of VAN to 3 days for at least 2 consecutive measurements Nephrotoxicity 13 (26.5) 5 (9.1) 0.037 3.61 (1.18–11.03)  
Clinical success: (1) survived for at least 30 days; (2) without recurrence of MRSA infection at least 30 days; and/or, (3) negative blood culture
at least 6 days
Clinical success 40 (81.6) 48 (87.3) 0.601 0.65 (0.22–1.90)  
Leu et al. [34] Not stated Nephrotoxicity: Increase in SCr of 0.5 mg/d3L or decrease in CrCl >50 % from baseline   n = 45 n = 31    
Nephrotoxicity 10 (22.2) 5 (16.1) 0.717 1.49 (0.45–4.87) NA
Clinical cure: All signs and symptoms of infection were resolved after discontinuation of VAN Clinical cure 11 (24.4) 12 (38.7) 0.282 0.51 (0.19–1.38) NA
Kullar et al. [17] Aminoglycoside, colistin, acyclovir Mortality: 30-day all-cause mortality   n = 100 n = 100    
Mortality 13 (13.0) 8 (8.0) 0.356 1.72 (0.68–4.35) NA
Nephrotoxicity: increase in SCr concentrations of 0.5 mg/dL or ≥50% increase from baseline for at least 2–3 consecutive measurements Nephrotoxicity 18 (18.0) 15 (15.0) 0.703 1.24 (0.59–2.63) NA
Clinical success: (1) Survived for at least 30 days; (2) resolution of signs and symptoms of MRSAB at the end of VAN therapy; or, (3) eradication of MRSAB after at least 7 days of VAN therapy Clinical success 60 (60.0) 45 (45.0) 0.047 1.83 (1.05–3.21) NA
Rojas et al. [38] Not stated Mortality: overall mortality   n = 24 n = 61    
Mortality 8 (33.3) 22 (36.1) 0.988 0.89 (0.33–2.40) NA
Wunderink et al. [70] Not stated Nephrotoxicity: increase in SCr of 0.5 mg/dL if normal at baseline or 50% increase in SCr if abnormal at baseline   n = 118 n = 215    
Nephrotoxicity 26 (22.0) 24 (11.2) 0.013 2.25 (1.22–4.13) NA
Bosso et al. [71] Aminoglycoside, cyclosporine A, tacrolimus, nonsteroidal inflammatory agents, COX-2 inhibitors, ACEIs, ARB Nephrotoxicity: increase in SCr of 0.5 mg/dL or increase ≥50% in SCr from baseline for two consecutive measurements   n = 142 n = 146    n = 280
Nephrotoxicity 41 (28.9) 14 (9.6) <0.001 3.83 (1.98–7.40) 3.64 (1.75–7.59)b
Chan et al. [72] Not stated Mortality: all cause mortality at hospital discharge   n = 33 n = 39    
Mortality 5 (15.2) 6 (15.4) 0.763 0.98 (0.27–3.57) NA
Clinical cure: improvement in and resolution of signs and symptoms of VAP, and eradication of MRSA from subsequent BAL or sputum culture after completing ≥7 days of VAN therapy together with CPIS <6 at day 7 of therapy Clinical cure 24 (72.7) 27 (69.2) 0.948 1.19 (0.43–3.30) NA
Choi et al. [13] NA Nephrotoxicity: increase in SCr of 0.5 mg/dL or increase ≥50 % in SCr from baseline   n = 19 n = 37    
Nephrotoxicity 2 (10.5) 3 (8.1) 1.000 1.33 (0.20–8.75) NA
Chung et al. [36] Not stated Mortality: overall ICU mortality   n = 16 n = 38    
ICU mortality 7 (43.8) 17 (44.7) 0.816 0.96 (0.30–3.12) NA
Clinical success: resolution of baseline signs and symptoms of MRSA pneumonia in conjunction with improvement in or lack of progression of chest radiographic abnormalities Clinical success 8 (50.0) 15 (39.5) 0.680 1.53 (0.47–4.97) NA
Clemend et al. [37] Not stated Mortality: 30-day all-cause mortality   n = 68 n = 26    
Mortality 7 (10.3) 4 (15.4) 0.490 0.63 (0.17–2.37) 0.18 (0.03–1.12)c
Clinical success: (1) survived for at least 30 days; (2) eradication of MRSAB within 10 days from the initiation of VAN therapy; or, (3) absence of MRSAB for at least 30 days after discontinuation of therapy Clinical success 50 (73.5) 21 (80.8) 0.467 0.66 (0.22–2.02) 1.10 (0.26–4.76)c
Honda et al. [73] Not stated Mortality: any death within 28 days of initial hospital stay; or, if there were no readmission data >28 days after diagnosis of MRSAB available, SSDI was used to verify mortality   n = 64 n = 87    
Mortality 13 (20.3) 14 (16.1) 0.650 1.33 (0.58–3.06) NA
Kullar et al. [33] Aminoglycosides Nephrotoxicity: increase in SCr of 0.5 mg/dL or ≥50 % increase in SCr from baseline for 2 consecutive measurements   n = 77 n = 141    
Nephrotoxicity 10 (13.0) 23 (16.3) 0.648 0.77 (0.34–1.71) NA
Clinical success: surviving for at least 30 days, resolution of signs and symptoms of infection at the end of therapy, or absence of MRSAB for at least 7 days of VAN therapy   n = 86 n = 160    
Clinical success 52 (60.5) 62 (38.8) 0.002 2.42 (1.41–4.13) NA
Hermsen et al. [35] NSAIDs, aminoglycosides (n = 12), amphotericin B (n = 55), cisplatin, pentamidine, ribavirin, ACE inhibitors, angiotensin receptor blockers, and diuretics Nephrotoxicity: increase in SCr of 0.5 mg/dL or increase ≥50 % in SCr from baseline for at least 2 consecutive measurements   n = 16 n = 39    
Nephrotoxicity      
Definition 1 or 2 5 (31.3) 4 (10.3) 0.103 3.98 (0.91–17.46) 3.27 (0.70–15.25)d
Definition 3 4 (25.0) 5(12.8) 0.422 2.27 (0.52–9.86) NA
Mortality: in-hospital mortality Mortality 3 (18.8) 2 (5.1) 0.141 4.27 (0.64–28.47) NA
Clinical success: resolution of signs and symptoms of infection and no additional use of antibiotics or eradication of MRSA, defined as negative culture result at the end of VAN therapy Clinical success 4 (25.0) 21 (53.8) 0.098 0.29 (0.08–1.04) NA
Jeffres et al. [31] IV contrast dye (n = 24), loop diuretic (n = 49), amphotericin B (n = 5), aminoglycoside (n = 8), ACE-I or ARB (n = 19), cyclosporine or tacrolimus (n = 9), vasopressor (n = 14) Nephrotoxicity: increase in SCr of 0.5 mg/dL or increase in SCr ≥50 % from baseline for two consecutive measurements   n = 49 n = 45    
Nephrotoxicity 27 (55.1) 13 (28.9) 0.018 3.02 (1.28–7.11) 2.82 (1.02–7.74)e
Hidayat et al. [30] Amphotericin B, tobramycin, and tacrolimus (n = 27) Nephrotoxicity: Increase in SCr of 0.5 mg/dL or increase ≥50 % in SCr from baseline for 2 consecutive measurements   n = 63 n = 32    
Nephrotoxicity 11 (17.5) 0 (0) 0.014 NA NA
  1. OR odds ratio, 95% CI 95% confidence interval, VAN vancomycin, BSI bloodstream infections, S Cr serum creatinine, CrCl creatinine clearance, MRSAB MRSA bacteremia, ACEIs angiotensin converting enzyme inhibitors, ARB angiotensin receptor blocking agents, VAP ventilator-associated pneumonia, BAL bronchoalveolar lavage, CPIS clinical pulmonary infection score, NA not available, ICU intensive care unit, SSDI social security death index, NSAIDs nonsteroidal anti-inflammatory drugs
  2. aFisher’s exact test or Yates’ continuity correction test
  3. bAnalysis adjusted for covariates, including age, race, gender, hypotension, receipt of other nephrotoxic agents, length of vancomycin therapy, vancomycin dose per kg of body weight, ICU stay, and comorbidities
  4. cAnalysis adjusted for covariates, including age, source of bacteremia, duration of bacteremia ≥72 h, ICU care, received effective antibiotic within 24 h of positive blood culture, renal insufficiency (SCr ≥ 1.3 mg/dL), and vancomycin MIC
  5. dAnalysis adjusted for APACHE II score
  6. eAnalysis adjusted for covariates, including IV contrast dye, BUN:SCr ratio > 20, loop diuretic, aminoglycoside, duration of vancomycin ≥14 day, APACHE II score (1-point increments), and vasopressor administration