Amphotericin B lipid complex: treatment of invasive fungal infections in patients refractory to or intolerant of amphotericin B deoxycholate

Figures & data

Table 1 Demographic characteristics of all patients registered in the Collaborative Exchange of Antifungal Research (CLEAR) database (N = 3514)

Characteristic	Value
Age, median (range), years	46 (<1–97)
Sex
Male	2039 (58)
Female	1466 (42)
Unknown	9 (<1)
Reason for starting therapy with ABLC
Refractory to prior antifungals	1411 (40)
Underlying renal disease and prior antifungal	84 (2)
Underlying renal disease and no prior antifungal	945 (27)
Intolerant of prior antifungals	573 (16)
No prior antifungal/no renal disease	431 (12)
First-line therapy with ABLCa	1376 (39)
Unknown	57 (2)
Other	13 (<1)
Underlying medical conditions and procedures
Hematologic disorders
Leukemia	1342 (38)
Lymphoma	285 (8)
Myelodysplastic syndrome	76 (2)
Aplastic anemia	53 (2)
Fanconi anemia	11 (<1)
Stem-cell transplantation
Allogeneic BMT	728 (21)
Autologous BMT	135 (4)
PSCT	171 (5)
Solid-organ transplantation	723 (21)
Solid tumor	344 (10)
Diabetes	261 (7)
AIDS	156 (4)
Renal disease	1111 (32)
Steroid therapy	524 (14.9)
Other	937 (27)

Note: Data are no. (%) of patients, except where noted. Patients may have had >1 primary underlying condition.

^a First-line therapy was defined as categories of no prior antifungal/no renal disease or underlying renal disease with no prior antifungal.

Abbreviations: ABLC, amphotericin B lipid complex; BMT, bone-marrow transplantation; GVHD, graft-versus-host disease; PSCT, peripheral stem-cell transplantation.

Adapted with permission from Pappas PG (ed). 2005. Amphotericin B lipid complex in the treatment of invasive fungal infections: results of the Collaborative Exchange of Antifungal Research (CLEAR), an industry-supported patient registry. Clin Infect Dis, 40(Suppl 6): S379–S83. Copyright © 2005. University of Chicago Press. All rights reserved.

Table 2 Clinical response to treatment with ABLC in patients with candidiasis, by prior treatment status

Type of infection	Refractory		Underlying renal disease		Intolerant of prior antifungal therapy	No prior antifungal therapy/no underlying renal disease	First-line therapy with ABLC^a	Second-line therapy with ABLC^b
	To all prior antifungal therapy	To prior azole	With prior antifungal therapy	With no prior antifungal therapy
C. albicans (n = 364)	93/139 (67)	67/104 (64)	7/12 (58)	65/115 (57)	28/50(56)	29/43(67)	94/158(60)	128/201(64)
Non-albicans Candida species (n = 375)	105/174 (60)	77/125 (62)	11/14 (79)	57/96 (59)	27/52 (52)	28/34 (82)	85/130 (65)	143/240 (60)
C. albicans + non-albicans Candida species (n = 90)	29/44 (66)	23/53 (66)	2/2 (100)	12/19 (63)	6/9 (67)	9/16 (56)	21/35 (60)	37/55 (67)
Multiple non-albicans Candida species (n = 25)	8/15 (53)	6/11 (55)	½ (50)	0/2 (0)	1/3 (33)	0/2 (0)	0/4 (0)	0/20 (50)
Total	235/372 (63)	173/293 (59)	21/30 (70)	134/232 (58)	62/114 (54)	66/95 (70)	200/327 (61)	318/516 (62)

Reproduced with permission from Ito JI, Hooshmand-Rad R. 2005. Treatment of Candida infections with amphotericin B lipid complex. Clin Infect Dis, 40(Suppl 6):S384–91. Copyright © 2005. University of Chicago Press. All rights reserved.

Abbreviation: ABLC, amphotericin B lipid complex.

Table 3 Clinical response to treatment with ABLC in patients with proven invasive aspergillosis by prior treatment status

Clinical response	Unknown (n = 11)	Second-line therapy with ABLC		Intolerant of prior antifungal therapy (n = 50)	First-line therapy with ABLC		Other (n = 2)	Total (n = 368)
		Refractory to prior antifungal therapy (n = 157)	Underlying renal disease/prior antifungal therapy (n = 9)		Underlying renal disease no prior antifungal therapy (n = 88)	No prior antifungal therapy/no renal disease (n = 51)
Cured	–	15 (10)	–	4 (8)	16 (18)	6 (12)	1 (50)	42 (11)
Improved	2 (18)	45 (29)	7 (78)	23 (46)	30 (34)	13 (26)	–	120 (33)
Stable	2 (18)	33 (21)	1 (11)	12 (24)	20 (23)	10 (20)	–	78 (21)
Deteriorated	7 (64)	64 (41)	1 (11)	11 (22)	22 (25)	22 (43)	1 (50)	128 (35)

Note: Data are no. (%) of patients.

From Chandrasekar and Ito (2005).

Abbreviation: ABLC, amphotericin B lipid complex.

Table 4 Clinical response to treatment with ABLC, according to age, in evaluable patients with documented fungal infection (N = 255)

Clinical response	All (n = 255)	0–3 mo (n = 32)	4 mo–1 yr (n = 19)	2–11 yr (n = 87)	12–20 yr (n = 117)
Cured	74 (29.0)*	19 (59.4)	6 (31.6)	23 (26.4)	26 (22.2)
Improved	65 (25.5)	4 (12.5)	6 (31.6)	24 (27.6)	31 (26.5)
Stable	43 (16.9)	3 (9.4)	5 (26.3)	19 (21.8)	16 (13.7)
Deteriorated	73 (28.6)	6 (18.8)	2 (10.5)	21 (24.1)	44 (37.6)
Cured + improved	139 (54.5)	23 (71.9)	12 (63.2)	47 (54.0)	57 (48.7)
Cured + improved + stable	182 (71.4)	26 (81.3)	17 (89.5)	66 (75.9)	73 (62.4)

* (%)

Reproduced with permission from Wiley JM, Seibel NL, Walsh TJ. 2005. Efficacy and safety of amphotericin B lipid complex in 548 children and adolescents with invasive fungal infections. Pediatr Infect Dis J, 24:167–174. © Lippincott Williams & Wilkins.

Abbreviation: ABLC, amphotericin B lipid complex.

Table 5 Renal function in ABLC-treated patients with fungal infections

Patient group	End-of-therapy renal function parameter
	Baseline S-Cr level, median (range), Mg/dL	Change in CCr median (range), mL/min	p	Doubling of baseline S-Cr level No. (%) of patients	p	Increase in S-Cr level To ≥ 2.5 mg/dL No. (%) of patients	p	New dialysis No. (%) of patients	p
All patients (N = 3514)	1.4 (0.08−6)	−3 (−119 to 118)	–	468 (13)	–	412 (12)	–	92 (3)	–
Age group
<18 years (n−454)	0.7 (0.1−6)	0 (−105 to 108)	–	71 (16)	–	27 (6)	–	12 (3)	–
≥18 years (n = 3048)	1.6 (0.08−6)	−3 (−119 to 118)	0.008	396 (13)	0.110	385 (13)	<0.001	80 (3)	0.975
Status prior to start of ABLC therapya
Refractoryb (n = 1411)	1.2 (0.08−6)	−5 (−111 to 99)	0.033	220 (16)	0.282	157 (11)	0.397	25 (2)	0.209
Underlying renal disease, prior antifungal therapy (n = 84)	2 (0.3−6)	0.5 (−107 to 52)	<0.001	11 (13)	0.307	14 (17)	0.056	4 (5)	0.027
Underlying renal disease, no prior antifungal therapy (n = 945)	2 (0.15−6)	0 (−99 to 118)	<0.001	83 (9)	<0.0091	133 (14)	0.025	44 (5)	<0.001
Intolerancec (n = 573)	1.4 (0.2−6)	0 (−108 to 101)	<0.001	60 (11)	<0.001	54 (9)	0.855	14 (2)	0.072
No prior antifungal therapy/no renal disease (n = 431)	1 (0.1−6)	–10 (−117 to 101)	–	77 (18)	–	42 (10)	–	4 (1)	–
Prior treatment
No prior Amb (n = 2056)	1.3 (0.08−6)	−5 (−119 to 118)	<0.001	311 (15)	<0.001	230 (11)	0.290	50 (2)	0.408
Prior AmB (n = 1398)	1.6 (0.19−6)	0 (−117 to 101)	–	146 (10)	–	173 (12)	–	40 (3)	…

Note: Statistical analysis was performed by using the median scores test for continuous variables and χ² or Fisher’s exact test, as appropriate, for categorical variables.

Abbreviations: AmB, amphotericin B deoxycholate; C_Cr, predicted creatinine clearance; S-Cr, serum creatinine.

^a P values in this subsection compare each category with patients in the “no prior antifungal medication/no underlying renal disease” category.

^b 22% of these patients also had underlying renal disease.

^c Intolerance included infusion-related toxicity, increasing S-Cr level, or hepatotoxicity.

Reproduced from Alexander BD, Wingard JR. 2005. Study of renal safety in amphotericin B lipid complex-treated patients. Clin Infect Dis, 40(Suppl 6):S414–S21. Copyright © 2005. University of Chicago Press. All rights reserved.

Table 6 Amphotericin B – clinical indications

➢ Invasive aspergillosis Voriconazole intolerance/failure ? in combination therapy with an echinocandin ➢ Cryptococcosis Meningitis/Diffuse Pneumonia In combination with flucytosine (many centers may use amphotericin B deoxycholate) ➢Histoplasmosis, blastomycosis, coccidioidomycosis Severe infection ➢Zygomycosis Higher than usual dose (>5 mg/kg/d) ➢Fusariosis* ? in combination with voriconazole ➢Empiric therapy Suspected invasive mold disease

* Different species of fusarium vary in their susceptibility to amphotericin B and voriconazole, and most laboratories do not identify the pathogen to the species level.

ChandrasekarPHItoJI2005Amphotericin B lipid complex in the management of invasive aspergillosis in immunocompromised patientsClin Infect Dis40Suppl 6S392S40015809925

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