Blindness amphotericin

Amphotericin colloidal dispersion has been compared with amphotericin deoxycholate in a prospective, randomized, double-blind study in the empirical treatment of fever and neutropenia in 213 patients (25). Patients were stratified by age and concomitant use of ciclosporin or tacrolimus and then randomized to receive ABCD (4 mg/kg/day) or amphotericin deoxycholate (0.8 mg/ kg/day) for 14 days. Renal dysfunction was less likely to develop and occurred later with ABCD than with amphotericin deoxycholate. Likewise, the absolute and percentage fall in the serum potassium concentration from baseline to the end of therapy was greater with amphotericin deoxycholate than ABCD. However, probable or possible infusion-related hypoxia and chills were more common with ABCD than amphotericin deoxycholate. There was a therapeutic response in 50% of the patients who received ABCD and 43% of those who received amphotericin deoxycholate. Thus, ABCD was of comparable efficacy and less nephrotoxic than amphotericin deoxycholate, but infusion-related events were more common with ABCD. 

The results of a randomized, double-blind, multicenter comparison of liposomal amphotericin (3.0 mg/kg/ day) with conventional amphotericin deoxycholate (0.6 mg/kg/day) for empirical antifungal therapy in patients with persistent fever and neutropenia have been reported (47). The mean duration of therapy was 10.8 days for liposomal amphotericin (343 patients) and 10.3 days for amphotericin deoxycholate (344 patients). While the composite rates of successful treatment were similar (50% for liposomal amphotericin and 49% for amphotericin deoxycholate), significantly fewer of the patients who received the liposomal preparation had... 

In a prospective double-blind study of more than 600 patients, 0.6 mg/kg of DAMB was compared with 3.0 mg/kg of L-Amb, a dose relation at the lower limit of equivalent doses determined in an animal model (117). At these dosages, in a large prospective double-blind study, there was a doubling of serum creatinine concentration in 19% of neutropenic patients receiving empirical therapy with L-AmB and 34% receiving conventional amphotericin (47). 

Liposomal amphotericin (3 mg/kg/day) has been compared with conventional amphotericin (0.7 mg/kg/day) for induction therapy of moderate to severe disseminated histoplasmosis in a randomized, double-blind, multicenter trial in 81 patients with AIDS (119). The duration of induction was 2 weeks, to be followed by 10 weeks of itraconazole in the case of a response. Clinical success was achieved in 14 of 22 patients treated with conventional amphotericin compared with 45 of 51 patients who received liposomal amphotericin (difference, 24% 95% Cl = 1%, 52%). Culture conversion rates were similar. Three patients treated with conventional amphotericin and one treated with liposomal amphotericin died during induction. Infusion-related adverse effects were more common with conventional amphotericin (63%) than with liposomal amphotericin (25%). Nephrotoxicity occurred in 37% of patients treated with conventional amphotericin and 9% of patients treated with liposomal amphotericin. The results of this study suggest that liposomal amphotericin is less toxic than conventional amphotericin and is associated with improved survival. 

White MH, Bowden RA, Sandler ES, Graham ML, Noskin GA, Wingard JR, Goldman M, van Burik JA, McCabe A, Lin JS, Gurwith M, MUler CB. Randomized, double-blind clinical trial of amphotericin B coUoidal dispersion vs. amphotericin B in the empirical treatment of fever and neutropenia. Clin Infect Dis 1998 27(2) 296-302. 

Arathoon EG, Gotuzzo E, Noriega LM, Berman RS, DiNubile MJ, Sable CA. Randomized, double-blind, multicenter study of caspofungin versus amphotericin B for treatment of oropharyngeal and esophageal candidiases. Antimicrob Agents Chemother 2002 46(2) 45I-7. 

Kelsey SM, Goldman JM, McCann S, Newland AC, Scarffe JH, Oppenheim BA, Mufti GJ. Liposomal amphotericin (AmBisome) in the prophylaxis of fungal infections in neutropenic patients a randomised, double-blind, placebo-controlled study. Bone Marrow Transplant 1999 23(2) 163-8. 

Bowden R, Chandrasekar P, White MH, Li X, Pietrehi L, Gurwith M, van Bnrik JA, Laverdiere M, Safrin S, Wingard JR. A donble-blind, randomized, controhed trial of amphotericin B colloidal dispersion versns amphotericin B for treatment of invasive aspergillosis in immnnocom-promised patients. Chn Infect Dis 2002 35(4) 359-66. 

Arning M, Dresen B, Aul C, Schneider W. Influence of infusion time on the acute toxicity of amphotericin B results of a randomized double-blind study. Recent Results Cancer Res 1991 121 347-52. 

Ellis ME, al-Hokail A A, Clink HM, Padmos MA, Ernst P, Spence DG, Tharpe WN, Hillier VF. Double-blind randomized study of the effect of infusion rates on toxicity of amphotericin B. Antimicrob Agents Chemother 1992 36(l) 172-9. 

Sable CA, Villanueva A, Arathon E, Gotuzzo E, Turcato G, Uip D, Noriega L, Rivera C, Rojas E, Taylor V, Berman R, Calandra GB, Chodakewitz J. A randomized, double-blind, multicenter trial of MK-991 (L-743,872) vs. amphotericin B (AMB) in the treatment of Candida esophagitis in admts. Abstracts of the 37th Interscience Comerence on Antimicrobial Agents and Chemotherapy, 1997 LB-33. 

In vitro studies and experiments in animals have given conflicting results relating to potential antagonism between the effects of fluconazole and amphotericin on Candida species (71). However, large, randomized, double-blind comparisons of fluconazole with and without amphotericin for 5 days in non-neutropenic patients with... 

Bullock WE, Luke RG, Nuttall CE, Bhathena D. Can mannitol reduce amphotericin B nephrotlxicity Double-blind study and description of a new vascular lesion In kidneys. Antimicrob Agents Chemother 1976 10 555-63. 

Wingard JR, White MEI, Anaissie E, et al. A randomized, double-blind comparative trial evaluating the safety of liposomal amphotericin B versus amphotericin B lipid complex in the empirical treatment of febrile neutropenia. EAmph/ABEC Collaborative Study Group. Clin Infect Dis 2000 31 1155-63. 

Villanueva A, ArathoonEG, GotuzzoE, etal. A randomized double-blind study of caspofungin versus amphotericin for the treatment of candidal esophagitis. Clin Infect Dis 2001 33 1529-1535. 

Rex JH, Pappas PG, Karchmer AW, et al. A randomized and blinded multi center trial of high-dose fluconazole plus placebo versus fluconazole plus amphotericin B as therapy for candidemia and its consequences in nonneutropenic subjects. Clin Infect Dis 2003 36 1221-1228. 

Despite early enthusiasm, more recent studies have yielded more equivocal information. In a randomized, double blind study, Wingard et al [146] have compared the safety of two Upid formulations of amphotericin B in febrile neutropenic patients. Subjects were randomized to receive amphotericin B lipid complex (ABLC) at a dose of 5 mg/kg/d (n=78), liposomal amphotericin B (L-Amph) at a dose of 3 mg/kg/ d (n=85), or L-Amph at a dose of 5 mg/kg/d (n=81). They found that the incidence of nephrotoxicity (doubhng of the base-... 

Tollemar, J. et al, 1993. Randomized double-blind smdy of liposomal amphotericin B (Ambisome) prophylaxis of invasive fungal infections in bone marrow transplant recipients. Bone Marrow Transplant, 12(6), 577-582. 

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