Liposomal amphotericin B compared with amphotericin B deoxycholate in the treatment of documented and suspected neutropenia‐associated invasive fungal infections

Abstract

Summary. It has been suggested that a better outcome of neutropenia-associated invasive fungal infections can be achieved when high doses of lipid formulations of amphotericin B are used. We now report a randomized multicentre study comparing liposomal amphotericin B (AmBisome, 5 mg/kg/d) to amphotericin B deoxycholate (AmB, 1 mg/kg/ d) in the treatment of these infections. Of 106 possible patients, 66 were enrolled and analysed for efficacy: nine had documented fungaemia, 17 had other invasive mould infections and 40 had suspected pulmonary aspergillosis. After completion of the course medication, in the AmBisome group (n ¼ 32) 14 patients had achieved complete response, seven a partial response and 11 were failures as compared to 6, 13 and 15 patients (n ¼ 34) treated with AmB (P ¼ 0·09); P ¼ 0·03 for complete responders. A favourable trend for AmBisome was found at day 14, in patients with documented infections and in patients with pulmonary aspergillosis (P ¼ 0·05 and P ¼ 0·096 respectively). Mortality rates were lower in patients treated with AmBisome (adjusted for malignancy status, P ¼ 0·03). More patients on AmB had a >100% increase of their baseline serum creatinine (P < 0·001).The results indicate that, in neutropenic patients with documented or suspected invasive fungal infections AmBisome 5 mg/kg/d was superior to AmB 1 mg/kg/d with respect to efficacy and safety.

Pseudohyperphosphatemia associated with high-dose liposomal amphotericin B therapy

“…This lipid formulation has a favorable toxicity profile when compared to conventional amphotericin B deoxycholate [2][3][4] and has been approved for use at dosages ranging from 3 to 6 mg/kg/day for indications including empirical therapy of persistent febrile neutropenia, systemic aspergillus, candida, and cryptococcus infections, visceral leishmaniasis, and cryptococcal meningitis in HIV infected patients. The improved safety and tolerability of this formulation have allowed for the use of increasingly higher dosages for the treatment of refractory infections [5][6][7][8].…”

“…Exceeding a calcium-phosphate product of 5.64 (mmol/l) 2 can result in tissue deposition of calcium phosphate crystals and organ dysfunction. The precipitation of calcium phosphate can also result in symptomatic hypocalcemia, manifested by cardiac arrhythmias, hypotension, and tetany.…”

Adverse effects of antifungal therapies in invasive fungal infections: review and meta-analysis

“…In the meta-analysis, 11 randomized controlled trials reported fever in patients receiving study medications: fluconazole vs AmB [17-19, 26, 32], L-AmB vs AmB [25,28], ABCD vs AmB [27,30], and ABLC vs L-AmB [31,34], but a majority of these studies were too heterogeneous to be pooled. With the exclusion of the German study by Abele-Horn et al [17], which used a dose of fluconazole inconsistent with the four other studies, trials comparing fluconazole with AmB had the following patient inclusion criteria: Malik et al [26] and Winston et al [32] required neutropenia [absolute neutrophil count (ANC) <500 cells/ mm 3 ]; Viscoli et al [18], Malik et al [26], and Winston et al [32] included only patients with hematologic malignancies and defined "fever" as >38°C, whereas Anaissie et al [19] used a threshold of >38.3°C (101°F).…”

Mucormicose rinocerebral: apresentação de caso com sobrevida e revisão de literatura

“…Segundo Mileshkin et al, uma alternativa é a anfotericina B lipossomal, com menos toxicidade permitindo atingir doses mais elevadas 21 . Leenders et al 20 realizaram um estudo multicêntrico randomizado comparando a eficácia da anfotericina B lipossomal e a anfotericina B não lipossomal, e encontraram resultado superior naqueles pacientes tratados com a primeira delas.…”

“…Rios-Gonçalves et al 19 relatam sobrevida de dois casos com tratamento com anfotericina B seguido de tratamento cirúrgico. Outros autores recomendam anfotericina B lipossomal pois causa menos toxicidade permitindo uso de maiores doses, com melhores respostas ao tratamento 20 .…”