TABLE 1.
Characteristics, study quality, and safety results of randomized controlled trials of empirical therapy for invasive antifungal infection included in the analysis
| Treatment and author, yr (reference) | Patients |
Study quality |
Regimen | Treatment duration (days) | No. of patients | % of patients with: |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mean age (yr) | % male | % of patients with: |
Allocation generation | Allocation concealment | Double blinding | Intention to treat | Discontinuation due to adverse reaction | Discontinuation due to elevated serum transaminase level | Transaminase level elevation not requiring stopping of treatment | ||||||
| Neutropenia | Leukemia | Transplantation | |||||||||||||
| Amphotericin B formulations | |||||||||||||||
| EORTC | 39.3 | 61 | 100 | 75 | 0 | NAa | NA | No | No | Amphotericin B, 0.6 mg/kg of body weight/day | NA | 68 | 21 | 0 | 0 |
| International Antimicrobial Therapy Cooperative Group, 1989 (23) | |||||||||||||||
| No antifungal treatment | NA | 64 | 5 | 0 | 0 | ||||||||||
| Prentice et al., 1997 (62) | 21.4 | 59 | 98 | 59 | NA | NA | Adequate | No | Yes | Ambisome, 1 mg/kg/day | NA | 118 | NA | NA | 11 |
| Ambisome, 3 mg/kg/day | NA | 118 | NA | NA | 22 | ||||||||||
| Amphotericin B, 1 mg/kg/day | NA | 102 | NA | NA | 20 | ||||||||||
| Schoffski et al., 1998 (69) | 43.4 | 69 | 100 | 69 | NA | NA | NA | No | Yes | Amphotericin B, 0.75 mg/kg/day in 5% glucose | 11.3 | 24 | 0 | 0 | 21 |
| Amphotericin B, 0.75 mg/kg/day in 20% intralipid | 9.9 | 27 | 0 | 0 | 17 | ||||||||||
| Subira et al., 2004 (75) | 45.5 | 53 | 100 | 70 | 39 | NA | Adequate | No | Yes | Amphotericin B lipid complex, 1 mg/kg/day | 8 | 49 | 4 | 2 | 22 |
| Amphotericin B, 0.6 mg/kg/day | 6 | 56 | 20 | 0 | 25 | ||||||||||
| Walsh et al. 1999 (82) | 41.5 | 54 | 100 | 54 | 46 | Adequate | Adequate | Yes | Yes | Ambisome 3 mg/kg/day | 10.8 | 343 | 0 | 0 | 18 |
| Amphotericin B, 0.6 mg/kg/day | 10.3 | 344 | 0 | 0 | 20 | ||||||||||
| White et al., 1998 (87) | 36 | 62 | 100 | 27 | 69 | NA | Adequate | Yes | Yes | Amphotericin B colloidal dispersion, 4 mg/kg/day | 8 | 101 | 18 | NA | NA |
| Amphotericin B, 0.8 mg/kg/day | 7.5 | 95 | 21 | NA | NA | ||||||||||
| Wingard et al., 2000 (89) | 45 | 53 | 100 | 33 | 49 | NA | NA | Yes | Yes | Ambisome, 3 mg/kg/day | 8.6 | 85 | 13 | NA | 12 |
| Ambisome, 5 mg/kg/day | 8.3 | 81 | 12 | NA | 12 | ||||||||||
| Amphotericin B lipid complex, 5 mg/kg/day | 7.5 | 78 | 32 | NA | 12 | ||||||||||
| Azoles vs amphotericin B | |||||||||||||||
| Boogaerts et al., 2001 (6) | 48.3 | 60 | 100 | 63 | 38 | Adequate | NA | No | Yes | Itraconazole, 200 mg/day | 8.5 | 192 | 19 | 3 | 11 |
| Amphotericin B, 1 mg/kg/day | 7 | 192 | 38 | 0 | 8 | ||||||||||
| Ellis et al., 1995 (22) | 24.6 | 56 | 100 | 85 | 20 | NA | NA | Single | No | Fluconazole, 4 mg/kg/day (maximum, 400 mg/day) | NA | 16 | 0 | 0 | 6 |
| Amphotericin B, 0.5 mg/kg/day | NA | 25 | 0 | 0 | 4 | ||||||||||
| Malik et al., 1998 (46) | 33.5 | 65 | 100 | 59 | NA | NA | NA | No | Yes | Fluconazole, 400 mg/day | 7.9 | 52 | 0 | 0 | 10 |
| Amphotericin B, 0.5 mg/kg/day | 8.3 | 48 | 4 | 0 | 19 | ||||||||||
| Schuler et al., 2007 (70) | 52.5 | 69 | 100 | 73 | 42 | NA | NA | No | Yes | Itraconazole, 200 mg/day | NA | 81 | 22 | 0 | 9 |
| Amphotericin B, 0.7-1 mg/kg/day | NA | 81 | 57 | 0 | 7 | ||||||||||
| Silling et al., 1999 (72) | 46.1 | 58 | 100 | 85 | NA | NA | NA | No | Yes | Fluconazole, 5.7 mg/kg/day (maximum, 400 mg/day) | NA | 51 | 0 | 0 | NA |
| Amphotericin B, 0.75 mg/kg/day + flucytosine | NA | 47 | 0 | 0 | NA | ||||||||||
| Viscoli et al., 1996 (80) | 25.5 | 71 | 100 | 63 | 53 | Adequate | Adequate | No | Yes | Fluconazole, 6 mg/kg/day (maximum, 400 mg/day) | 13 | 56 | 0 | 0 | 18 |
| Amphotericin B, 0.8 mg/kg/day | 10 | 56 | 9 | 2 | 11 | ||||||||||
| Walsh et al., 1991 (85) | 26.5 | NA | 100 | 63 | NA | NA | NA | No | No | Ketoconazole, 800 mg/day | NA | 32 | 4 | 0 | 22 |
| Amphotericin B, 0.5 mg/kg/day | NA | 32 | 13 | 0 | 31 | ||||||||||
| Walsh et al., 2002 (84) | 45.6 | 54 | 100 | 52 | 50 | Adequate | NA | No | No | Fluconazole, 400 mg/day | 8 | 158 | 1 | 1 | 1 |
| Amphotericin B, 0.5 mg/kg/day | 10 | 159 | 7 | 1 | 1 | ||||||||||
| Winston et al., 2000 (90) | 47 | 49 | 100 | 50 | 38 | NA | NA | No | Yes | Voriconazole, 3 mg/kg every 12 h or 200 mg orally every 12 h after at least 3 days of intravenous therapy | 7 | 415 | 5 | NA | 18 |
| Ambisome, 3 mg/kg/day | 7 | 422 | 5 | NA | 23 | ||||||||||
| Echinocandins vs amphotericin B, Walsh et al., 2004 (86) | 50 | 56 | 100 | 74 | 7 | NA | NA | Yes | Yes | Caspofungin, 50 mg/day | 13.0 | 564 | 5 | NA | 9 |
| Ambisome, 3 mg/kg/day | 12.5 | 547 | 8 | NA | 12 | ||||||||||
a
NA, not available due to not being reported in the published literature.