TABLE 2.

Characteristics, study quality, and safety results of randomized controlled trials of definitive therapy for invasive antifungal infection included in the analysis

Treatment and author, yr (reference)	Patients						Study quality				Regimen	Duration (days)	No. of patients	% of patients with:
	Pathogena	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
Pachl et al., 2006 (55)	Y	61.1	66	6	NAb	NA	NA	NA	Yes	Yes	Ambisome, 3 mg/kg/day, or Abelcet,c 5 mg/kg/day	10.5	69	NA	NA	4
											Ambisome or Abelcet plus Mycograbd	10.0	68	NA	NA	3
Bowden et al., 2002 (8)	M	46	50	32	70	47	NA	NA	Yes	Yes	Amphotericin B colloidal dispersion, 6.0 mg/kg/day	13.0	88	23	NA	NA
											Amphotericin B, 1-1.5 mg/kg/day	14.5	86	23	NA	NA
Cornely et al., 2007 (13)	M	50.7	62	73	93	20	NA	NA	Yes	Yes	Ambisome, 3 mg/kg/day for 14 days and then 3 mg/kg/day	15	115	20	NA	16
											Ambisome, 10 mg/kg/day for 14 days and then 3 mg/kg/day	14	111	32	NA	14
Ellis et al., 1998 (21)	M	48.4	72	84	77	20	NA	NA	No	No	Ambisome, 1 mg/kg/day	18	41	0	0	0
											Ambisome, 4 mg/kg/day	19	46	2	2	0
Leenders et al., 1998 (42)	Y, M	50.2	24	91	77	15	Adequate	Adequate	No	Yes	Ambisome, 5 mg/kg/day	13	52	6	2	17
											Amphotericin B, 1 mg/kg/day	14	54	13	0	15
Fleming et al., 2001 (26)	E, Y, M	58	NA	87	100	NA	Adequate	NA	No	Yes	Amphotericin B lipid complex, 3-5 mg/kg/day	10	43	21	NA	37
											Ambisome, 3-5 mg/kg/day	15	39	21	NA	56
Nucci et al., 1999 (54)	E, Y, M	18.1	75	82	74	10	NA	NA	No	No	Amphotericin B, 1-1.5 mg/kg/day in 5% dextrose	NA	33	0	0	0
											Amphotericin B, 1-1.5 mg/kg/day in intralipid	NA	28	0	0	0
Verweij et al., 1994 (79)	Y, M	41.7	61	100	100	NA	NA	NA	No	Yes	Amphotericin B, 0.5-1 mg/kg/day	10	14	0	0	0
											Amphotericin B, 0.5-1 mg/kg/day, + flucytosine	10	14	0	0	0
Azoles vs amphotericin
Abele-Horn et al., 1996 (1)	Y	59	71	0	NA	NA	Adequate	NA	No	Yes	Fluconazole, 200 mg/day	14.9	36	NA	NA	25
											Amphotericin B, 1-1.5 mg/kg/every 2 days, + flucytosine	15.4	36	NA	NA	19
Anaissie et al., 1996 (3)	Y	60.1	62	25	18*	18*	Adequate	Adequate	No	Yes	Fluconazole, 400 mg/day	9	80	1	1	3
											Amphotericin B, 0.67 mg/kg/day (25-50 mg/day)	9	80	4	0	4
Kullberg et al., 2005 (38)	Y	53.5	58	0	NA	NA	Adequate	Adequate	No	Yes	Voriconazole, 400 mg/day	15	272	15	NA	23
											Amphotericin B, 0.7-1 mg/kg/day for 4 days, and then fluconazole, 400 mg/day	15	131	7	NA	24
Kujath et al., 1993 (37)	Y	54	53	0	NA	NA	NA	NA	No	Yes	Fluconazole, 300 mg/day	NA	20	0	0	0
											Amphotericin B, 0.5 mg/kg/day, + flucytosine	NA	20	0	0	0
Rex et al., 1994 (64)	Y	59	51	0	0	0	NA	Adequate	No	No	Fluconazole, 400 mg/day	18	103	2	NA	14
											Amphotericin B, 0.5-0.6 mg/kg/day	17	103	3	NA	10
Rex et al., 2003 (65)	Y	56	51	0	NA	2	NA	Adequate	Yes	No	Fluconazole, 800 mg/day, + placebo	16.7	107	5	5	9
											Fluconazole, 800 mg/day, + amphotericin B, 0.6-0.7 mg/kg/day	15	112	6	5	8
van't Wout et al., 1991 (77)	Y, M	41.5	50	100	85	NA	NA	NA	No	Yes	Itraconazole, 400 mg/day	20	20	5	0	40
											Amphotericin B, 0.6 mg/kg/day or 0.3 mg/kg/day, + flucytosine	13	20	10	0	55
Herbrecht et al., 2002 (31)	M	49.5	68	45	43	34	NA	NA	No	Yes	Voriconazole, 400 mg/day	77	194	NA	NA	4
											Amphotericin B, 1-1.5 mg/kg/day	10	185	NA	NA	2
Echinocandins vs amphotericin
Kuse et al., 2007 (39)	Y	55.3	61	12	8	6	Adequate	Adequate	Yes	Yes	Micafungin, 100 mg/day	15	264	5	3	3
											Ambisome, 3 mg/kg/day	15	267	9	1	1
Mora-Duarte et al., 2002 (52)	Y	55.5	56	11	13	3	Adequate	Adequate	Yes	Yes	Caspofungin, 50 mg/day	12.1	114	3	NA	8
											Amphotericin B, 0.6-1.0 mg/kg/day	11.7	125	23	NA	15
Echinocandins vs azoles, Reboli et al., 2007 (63)	Y	58.1	51	3	NA	5	NA	NA	Yes	Yes	Anidulafungin, 100 mg/day	15.9	131	8	1	2
											Fluconazole, 400 mg/day	14.4	125	13	2	7
Echinocandins
Krause et al., 2004 (36)	Y	55	43	13	NA	NA	NA	NA	No	Yes	Anidulafungin, 50 mg/day	NA	40	NA	NA	3
											Anidulafungin, 75 mg/day	NA	40	NA	NA	0
											Anidulafungin, 100 mg/day	NA	40	NA	NA	5
Pappas et al., 2007 (57)	Y	55.9	58	9	NA	7	NA	NA	Yes	Yes	Micafungin, 100 mg/day	14	200	3	NA	NA
											Micafungin, 150 mg/day	14	202	3	NA	NA
											Caspofungin, 50 mg/day	14	193	4	NA	NA
Betts et al., 2009 (5)	Y	56.9	56	7	NA	5	Adequate	Adequate	Yes	Yes	Caspofungin, 50 mg/day	14.5	104	2	0	7
											Caspofungin, 150 mg/day	14.2	100	2	0	2

^aY, yeast; M, mold; E, empirical.

^bNA, not available due to not being reported in the published literature.

^cAbelcet is a lipid-amphotericin B complex.

^dMycograb is a recombinant antibody against fungal heat shock protein 90.