Author, year of publication, reference Study design/location Drugs Duration of treatment Number of cases versus comparators Clinical response (%) Mycological response (%) or (EFA)∧ Overall (clinical + mycological) response (%) Mortality (%) Larsen et al., 1990 [177 ] RCT/USA Flu (400 mg) versus AmB (0.7 mg/kg) for 1 week then three-times weekly + 5FC (150 mg/kg) 10 weeks 14 versus 6 63 75 43 versus 100 19 versus 0 (
) Saag et al., 1992 [74 ] RCT (2 : 1)/USA Flu (200 mg) versus AmB (0.4 mg/kg) 10 weeks 131 versus 63 60 versus 67 43 versus 46 (10 weeks) 44 versus 40 15 versus 8 (2 weeks) 14 versus 18 De Gans et al., 1992 [178 ] RCT (non-blinded)/The Netherlands Itra (400 mg) versus AmB (0.3 mg/kg) + 5FC (150 mg/kg) 6 weeks 12 versus 10 NR NR 42 versus 100 0 Coker et al., 1993 [179 ] OS/Multicentre (Europe) LAMB (4 mg/kg/d) 2 weeks 23 74 66.7 NR 0 Menichetti et al., 1996 [180 ] Cohort/Italy Flu (800–1000 mg/d) 3 weeks 14 54.5 (10 weeks) NR 67.1 18.2
van Der Horst et al., 1997 [76 ] RCT/USA AmB (0.7 mg/kg) + 5FC (100 mg/kg) versus AmB (0.7 mg/kg) 2 weeks 202 versus 179 78 versus 83 60 versus 51 (2 weeks) NR Overall 5.5 (2 weeks); 3.9 (10 weeks)
Leenders et al., 1997 [181 ] RCT/The Netherlands L-AmB (4 mg/kg) versus Amb (0.7 mg/kg) 3 weeks 15 versus 13 87 versus 83 (10 weeks) 73 versus 38 (3 weeks) Overall 10.7 Mayanja-Kizza et al., 1998 [182 ] RCT/Uganda Flu (200 mg/d) + 5FC (150 mg/kg/d) versus Flu (200 mg/d) 8 weeks 30 versus 28 NR NR 32 versus 12 60 versus 84 (2 weeks); 68 versus 88 (6 months) Brouwer et al., 2004 [183 ] RCT/Thailand AmB (0.7 mg/kg) + FC (100 mg/kg) versus AmB (0.7 mg/kg) versus AmB (0.7 mg/kg) + Flu (400 mg) + FC (100 mg/kg) versus AmB (0.7 mg/kg) + Flu (400 mg) 2 weeks 15 versus 16 versus 16 versus 16 NR −0.54 versus –0.31 versus –0.38 versus –0.39∧ 64 (10 weeks) Overall 14.6 (2 weeks); 21.9 (10 weeks) Schaars et al., 2006 [85 ] Retrospective chart review/South Africa Flu (200 mg/d) year 1991–2000 Flu (400 mg/d) 2001 77 versus 128 NR NR NR 23.4 versus 26.6 Bicanic et al., 2007 [184 ] POT/South Africa AmB (1 mg/kg) versus Flu 400 mg 10 weeks 49 versus 5 67 versus 25* −0.48 versus –0.02∧ 38 versus 0† Overall mortality 17 (2 weeks); 37 (10 weeks) Bicanic et al., 2008 [185 ] RCT/South Africa AmB (1 mg/kg) + 5FC (100 mg) versus AmB (0.7 mg/kg) + 5FC (100 mg) 2 weeks 34 versus 30 74 versus 79* −0.56 versus –0.45∧ 60† 3 versus 9 (2 weeks); 21 versus 26 (10 weeks). Overall mortality 24 (10 weeks) and no differences between groups Longley et al., 2008 [186 ] Cohort/Uganda Flu (800 mg) versus Flu (1200 mg) then 400 mg 2 weeks + 8 weeks 30 versus 30 NR −0.07 versus –0.18∧ 40 versus 52* 37 versus 22 (2 weeks) 60 versus 48 (10 weeks) Dammert et al., 2008 [187 ] Cohort/Perù AmB (0.7 mg/kg/d) 2-3 weeks 47 NR 25 (2 weeks) 68 (10 weeks) 70 (10 weeks) 13 (2 weeks) 22 (10 weeks) Pappas et al., 2009 [188 ] RCT/USA and Thailand AmB (0.7 mg/kg) versus AmB (0.7 mg/kg) + Flu (400 mg) versus AmB (0.7 mg/kg) + Flu (800 mg) 2 weeks 46 versus 48 versus 41 42.5 versus 28.3 versus 52.3 NR 71.4 versus 84.2 versus 83.3 (10 weeks) 22 versus 17 versus 18.4 (10 weeks) Hamill et al., 2010 [189 ] RCT/USA and Canada LamB (3 mg/kg/d) versus LamB (6 mg/kg/d) versus AmB (0.7 mg/kg/d) 2 weeks (11–21 days) 86 versus 94 versus 87 65.8 versus 75.3 versus 65.8 (2 weeks) 70.5 versus 72.9 versus 81.5 (10 weeks) 58.3 versus 48 versus 47.5 (2 weeks) 60 versus 70.7 versus 78.7 67.5 versus 73.7 versus 75.5 (10 weeks) 14 versus 9.6 versus 11.5 (10 weeks) Overall mortality at 10 weeks 11.6% Lightowler et al., 2010 [190 ] Cohort/South Africa AmB (0.7 mg/kg/d) versus Flu (400 mg/d) 2 weeks 148 versus 28 NR NR Fluconazole associated with 5.1 RR of death at 28 days Overall 28 (2 weeks); 32.3 (10 weeks) Falci et al., 2010 [191 ] Pilot/Brazil AmB (0.7 mg/kg/d) continuous infusion (24-h) + FC (100 mg/k/d) 2 weeks 12 NR −0.37∧ 80 10 (2 weeks); 10 (10 weeks) Nussbaum et al., 2010 [192 ] RCT/Malawi Flu (1200 mg/d) versus Flu (1200 mg/d) + FC (100 mg/kg/d) 2 weeks 20 versus 21 NR −0.11 versus −0.28∧ NR 10 versus 37 (2 weeks); 43 versus 58 (10 weeks) Overall 48.8 Jadhav et al., 2010 [193 ] RCT/India LamB (1 mg/kg) versus LamB (3 mg/kg) 3 weeks 11 versus 15 NR NR 36.6 versus 54 Overall 27 (10 weeks) Loyse et al., 2012 [194 ] RCT/South Africa AmB (0.7–1 mg/kg) + 5FC (100 mg/d) versus AmB (0.7–1 mg/kg/d) + Flu (800 mg/d) versus AmB (0.7–1 mg/kg) + Flu (1200 mg/d) versus AmB (0.7–1 mg/kg) + Vor (600 mg/d) 2 weeks 21 versus 22 versus 24 versus 14 NR −0.41 versus −0.38 versus −0.41 versus −0.44∧ NR Overall 12 (2 weeks); 29 (10 weeks) (no statistically significant differences among groups) Muzoora et al., 2012 [195 ] Cohort/Uganda Flu (1200 mg/d) + AmB (1 mg/kg/d) 2 weeks 30 NR −0.31 (2 weeks)∧ NR 23 (2 weeks); 28 (10 weeks) Jarvis et al., 2012 [196 ] RCT/South Africa AmB (1 mg/kg/d) + 5FC (100 mg/kg/d) versus AmB (1 mg/kg/d) + 5FC (100 mg/kg/d) + IFNγ (100 μ g) 2 doses versus AmB (1 mg/kg/d) + 5FC (100 mg/kg/d) + IFNγ (100 μ g) 6 doses 2 weeks 31 versus 29 versus 30 NR −0.49 versus 0.64 versus −0.64∧ NR 32 versus 33 versus 27 (10 weeks) Overall 14 (2 weeks) 27 (10 weeks) Jackson et al., 2012 [197 ] RCT/Malawi Flu (1200 mg/d) + AmB (1 mg/kg/d) versus Flu (1200 mg/d) + 5FC (100 mg/kg/d) + AmB (1 mg/kg/d for 7 days) 2 weeks 20 versus 20 NR −0.38 versus −0.50∧ NR No statistically significant differences at 2 and 10 weeks between the arms