Table 2.
Effect size of outcome measures of eligible studies
| 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 |
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
aFisher’s exact test or Yates’ continuity correction test
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
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
dAnalysis adjusted for APACHE II score
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