Cryptococcosis in Australasia and the treatment of cryptococcal and other fungal infections with liposomal amphotericin B

2002 ◽  
Vol 49 (suppl_1) ◽  
pp. 57-61 ◽  
Author(s):  
Sharon C. A. Chen
Keyword(s):  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Fungal Infections ◽  
Randomized Study ◽  
Initial Therapy ◽  
Liposomal Amphotericin B ◽  
Lipid Complex ◽  
Reduced Toxicity ◽  
Main Barrier ◽  
Immunocompromised Hosts

Abstract Cryptococcus neoformans is an important fungal pathogen in both immunocompromised and immunocompetent hosts. The mean annual incidence during 1994–1997 was 6.6 cases per million people per year in Australia, and 2.2 cases per million people per year in New Zealand. C. neoformans var. neoformans caused 85% of 312 episodes (98% of episodes in immunocompromised hosts) and C. neoformans var. gattii caused 15% (44% in immunocompetent hosts). The AIDS-specific incidence declined significantly over the 3 years. Mortality from cryptococcosis remains substantial. In trials involving small numbers of AIDS patients, liposomal amphotericin B (AmBisome) was found to be active against C. neoformans, with mycological response rates of 67–85%; however, maintenance therapy with an oral antifungal agent is required indefinitely. In a randomized study of patients with cryptococcal meningitis, AmBisome (4 mg/kg/day) produced mycological eradication in 73% of patients compared with 38% with conventional amphotericin. AmBisome resulted in significantly earlier sterilization of cerebrospinal fluid than conventional amphotericin (7–14 days versus 21 days) and was less nephrotoxic. The benefit of this reduced toxicity is denied to many patients because of an enormous cost barrier. In a survey of the practices of clinical mycologists in Australia, 11 experts responded to a questionnaire survey regarding the use of available lipid preparations. Their indications for use as initial therapy were mucormycosis (7/10), renal failure (7/10), Fusarium infection (2/10) and aspergillosis (2/10). Cryptococcosis, candidosis and febrile neutropenia were rarely regarded as an indication; failed therapy with conventional amphotericin was an indication to use AmBisome for 8/11 respondents. The majority believed that AmBisome was equivalent to conventional amphotericin, with amphotericin B lipid complex and AmBisome equivalent to each other in terms of efficacy. The main barrier to replacement of conventional amphotericin with lipid preparations was seen as an issue of cost.

Voriconazole and Liposomal Amphotericin B (Ambisome) Effectively Prevent Mold Infections in Patients (pts) with Acute Myelogenous Leukemia (AML) Following Remission Induction Chemotherapy (RIC).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2773-2773 ◽  
Author(s):  
Gloria N. Mattiuzzi ◽  
Elihu H. Estey ◽  
Mike Hernandez ◽  
Maria E. Cabanillas ◽  
Francis Giles ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Fungal Infections ◽  
Antifungal Prophylaxis ◽  
Myelogenous Leukemia ◽  
High Rate ◽  
Liposomal Amphotericin B ◽  
Remission Induction ◽  
Drug Discontinuation ◽  
Lipid Complex

Abstract Invasive fungal infections (IFI) are a frequent cause of morbidity and death in pts with AML and high-risk myelodysplastic syndrome (HR-MDS). Because early diagnosis of IFI is difficult, antifungal prophylaxis (AFP) including mold-active agents has become an important strategy to reduce morbidity and mortality in this patient population and is routinely used at MDACC for AML and HR-MDS pts undergoing RIC. We retrospectively compared the efficacy and safety of 6 AFP regimens (Sept 97- July 04) among 659 evaluable pts with newly diagnosed AML and HR-MDS who received RIC and had been enrolled in our prospective AFP trials. See regimens listed in Table below. There were no significant differences among the 6 regimens with regard to key baseline characteristics (age, gender, diagnosis, cytogenetics, type of RIC, Zubrod PS, WBC count, non-fungal infection and protected environment) and median days of AFP. 37 pts (5.6%) developed IFI (yeast 3 %; mold 2.6%). No mold infections were observed among pts randomized to AMBI or VORI. With the exception of VORI, which was significantly more effective than IV ITRA (p =0.03), all comparisons of efficacy among the AFP regimens were not significant. Drug discontinuation was the highest with IV VORI (21%) and ABLC (18%). VORI was more toxic than IV ITRA, Caspo, and F+I (p=0.023, 0.001 and 0.031 respectively). VORI toxicity was reversible and consisted of visual and/or auditory hallucinations and elevation in serum bilirubin. There was a trend toward developing VORI toxicity if baseline bilirubin levels were elevated (OR=4.9; p=0.10). We conclude that the rate of IFI in AML and HR-MDS pts undergoing RIC given mold-active AFP is 5.6 %. VORI and AMBI effectively prevented mold infections. VORI was more effective that IV ITRA but was associated with a high rate of reversible drug-related adverse events. ABLC (n=131) AMBI (n=69) F+I (n=67) IV ITRA (n=225) CASPO (n=106) VORI (n=61) ABLC: Amphotericin B Lipid Complex: 2.5 mg/kg IV three times/week; AMBI: Liposomal Amphotericin B: 3 mg/kg IV three times/week; F+I: Fluconazole: 400 mg (tab)/d + Itraconazole: 200 mg (caps)/d; IV ITRA: IV itraconazole: 200 mg BID X 2 d, then 200 mg IV/d; CASPO: Caspofungin: 50 mg IV/d; VORI: Voriconazole: 400 mg IV BID x 2 d, then 300 mg IV BID. Median age, years (range) 65(21–87) 63(36–83) 57(19–84) 62(17–89) 65(22–82) 59(23–79) Zubrod ≤ 2 (%) 127(97) 69(100) 65(97) 214(95) 101(95) 61(100) Median days AFP (range) 17(3–32) 14(3–28) 16(3–44) 20(3–41) 21(3–38) 21(3–34) Breakthrough IFI (%) 7(5) 3(4) 3(5) 17(8) 7(7) 0     Yeast (%) 2(2) 3(4) 1(1) 11(5) 3(3) 0     Mold (%) 5(4) 0 2(3) 6(3) 4(4) 0 Drug-related AFP DC (%) 24(18) 10(14) 5(7) 23(10) 4(4) 13(21)

Pharmacoeconomic Analysis of Amphotericin B Lipid Complex versus Liposomal Amphotericin B in the Treatment of Fungal Infections

2004 ◽  
Vol 22 (5) ◽  
pp. 301-310 ◽  
Author(s):  
Joseph L Kuti ◽  
Srividya Kotapati ◽  
Peter Williams ◽  
Blair Capitano ◽  
Charles H Nightingale ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Fungal Infections ◽  
Pharmacoeconomic Analysis ◽  
Liposomal Amphotericin B ◽  
Lipid Complex ◽  
Complex Versus ◽  
Amphotericin B Lipid Complex

Efficacy of Early Administration of Liposomal Amphotericin B in Patients with Septic Shock: A Nationwide Observational Study

2020 ◽  
Author(s):  
Masato Tashiro ◽  
Takahiro Takazono ◽  
Yuki Ota ◽  
Tomotaro Wakamura ◽  
Akinori Takahashi ◽  
...  
Keyword(s):  
Septic Shock ◽  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Fungal Infections ◽  
Survival Rates ◽  
Liposomal Amphotericin B ◽  
National Database ◽  
Shock Onset ◽  
Significant Difference ◽  
Nationwide Observational Study

Abstract To determine the most suitable time to initiate liposomal amphotericin B (L-AMB) treatment in patients with invasive fungal infections, patients with septic shock treated with L-AMB were identified from the Japanese Diagnosis Procedure Combination national database to determine their survival rates following septic shock onset, mortality during shock, and shock cessation period. We identified 141 patients administered L-AMB: 60 patients received treatment on the day of septic shock onset (early L-AMB group), whereas 81 patients received treatment after the onset (delayed L-AMB group). Survival rates after septic shock onset were higher in the early L-AMB group than in the delayed L-AMB group (4 weeks: 68.4% vs 57.9%, P=0.197; 6 weeks: 62.2% vs 44.5%, P=0.061; 12 weeks: 43.4% vs 35.0%, P=0.168, respectively). Mortality during septic shock was significantly lower in the early L-AMB group than in the delayed L-AMB group (13% vs 42%, P<0.001), with a significant difference confirmed after adjusting for confounding factors (odds ratio: 0.240, 95% confidence interval: 0.096-0.601, P=0.002). Septic shock cessation period was shorter in the early L-AMB group than in the delayed L-AMB group (7.0±7.0 days vs 16.5±15.4 days, P<0.001). L-AMB administration at septic shock onset could be associated with early shock cessation and decreased mortality.

Liposomal Amphotericin B for Visceral Leishmaniasis in a Kidney Allograft Patient

2002 ◽  
Vol 18 (4) ◽  
pp. 187-191 ◽  
Author(s):  
Marina Valente ◽  
Massimo Marroni ◽  
Claudio Sfara ◽  
Daniela Francisci ◽  
Lisa Malincarne ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Visceral Leishmaniasis ◽  
Transplant Recipient ◽  
Renal Transplant Recipient ◽  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Liposomal Amphotericin B ◽  
Blood Monocytes ◽  
Lipid Complex ◽  
First Case

Objective To report a case of visceral leishmaniasis treated with liposomal amphotericin B (LAB) after probable failure with amphotericin B lipid complex (ABLC). Case Summary A 62-year-old white renal transplant recipient was admitted for pyrexia, hepato-splenomegaly, and pancytopenia. Leishmania amastigotes were detected from bone marrow aspirate and in circulating blood monocytes and neutrophils. The patient, who weighed 56 kg, received ABLC at a starting dose of 200 mg/d (3.6 mg/kg of body weight per day) for 13 days, achieving a total dose of 2,600 mg (46 mg/kg) without clinical improvement. The patient was switched to 100 mg/d (1.8 mg/kg) of LAB for 10 days, after which a dose of 250 mg (4.5 mg/kg) was repeated on days 17,24,31, and 38. Twenty-four hours after the first dose of LAB, the patient showed an excellent clinical response. On the following days, there was a progressive increase in hemoglobin concentration and leukocyte and platelet counts. Three months later, the patient was asymptomatic. Discussion Although treatment with ABLC appears to be effective for the treatment of Indian patients with visceral leishmaniasis, experience with immunocompromised patients is limited. This is the first case of a renal transplant recipient in which ABLC was used to treat visceral leishmaniasis without remarkable efficacy, but with infusion-related adverse effects perhaps due to the use of higher doses. Conclusions A randomized comparative trial is needed to compare LAB with ABLC in the treatment of visceral leishmaniasis in patients who have received kidney allografts.

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