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

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Abstract

Amphotericin B lipid complex (ABLC) was introduced in the late 1990s as a less toxic alternative to amphotericin B (AmB) deoxycholate. ABLC is a safe and effective broad-spectrum drug in the treatment of invasive fungal infections in patients with infection refractory to AmB deoxycholate or in patients intolerant of the same formulation. The drug has not been rigorously evaluated for primary therapy. Recent availability of several newer potent and safe drugs has sharply curtailed the use of potentially nephrotoxic ABLC. However, AmB lipid complex is likely to continue to play a limited albeit significant clinical role in view of the narrow spectrum of activity and significant drug-drug interactions of the newer drugs and emergence of drug-resistant fungi.

Most cited references 49

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Epidemiology and outcome of zygomycosis: a review of 929 reported cases.

M M Roden, T. E. Zaoutis, W L Buchanan … (2005)

Zygomycosis is an increasingly emerging life-threatening infection. There is no single comprehensive literature review that describes the epidemiology and outcome of this disease. We reviewed reports of zygomycosis in the English-language literature since 1885 and analyzed 929 eligible cases. We included in the database only those cases for which the underlying condition, the pattern of infection, the surgical and antifungal treatments, and survival were described. The mean age of patients was 38.8 years; 65% were male. The prevalence and overall mortality were 36% and 44%, respectively, for diabetes; 19% and 35%, respectively, for no underlying condition; and 17% and 66%, respectively, for malignancy. The most common types of infection were sinus (39%), pulmonary (24%), and cutaneous (19%). Dissemination developed in 23% of cases. Mortality varied with the site of infection: 96% of patients with disseminated disease died, 85% with gastrointestinal infection died, and 76% with pulmonary infection died. The majority of patients with malignancy (92 [60%] of 154) had pulmonary disease, whereas the majority of patients with diabetes (222 [66%] of 337) had sinus disease. Rhinocerebral disease was seen more frequently in patients with diabetes (145 [33%] of 337), compared with patients with malignancy (6 [4%] of 154). Hematogenous dissemination to skin was rare; however, 78 (44%) of 176 cutaneous infections were complicated by deep extension or dissemination. Survival was 3% (8 of 241 patients) for cases that were not treated, 61% (324 of 532) for cases treated with amphotericin B deoxycholate, 57% (51 of 90) for cases treated with surgery alone, and 70% (328 of 470) for cases treated with antifungal therapy and surgery. By multivariate analysis, infection due to Cunninghamella species and disseminated disease were independently associated with increased rates of death (odds ratios, 2.78 and 11.2, respectively). Outcome from zygomycosis varies as a function of the underlying condition, site of infection, and use of antifungal therapy.

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The epidemiology of sepsis in the United States from 1979 through 2000.

Greg Martin, David Mannino, Stephanie Eaton … (2003)

Sepsis represents a substantial health care burden, and there is limited epidemiologic information about the demography of sepsis or about the temporal changes in its incidence and outcome. We investigated the epidemiology of sepsis in the United States, with specific examination of race and sex, causative organisms, the disposition of patients, and the incidence and outcome. We analyzed the occurrence of sepsis from 1979 through 2000 using a nationally representative sample of all nonfederal acute care hospitals in the United States. Data on new cases were obtained from hospital discharge records coded according to the International Classification of Diseases, Ninth Revision, Clinical Modification. Review of discharge data on approximately 750 million hospitalizations in the United States over the 22-year period identified 10,319,418 cases of sepsis. Sepsis was more common among men than among women (mean annual relative risk, 1.28 [95 percent confidence interval, 1.24 to 1.32]) and among nonwhite persons than among white persons (mean annual relative risk, 1.90 [95 percent confidence interval, 1.81 to 2.00]). Between 1979 and 2000, there was an annualized increase in the incidence of sepsis of 8.7 percent, from about 164,000 cases (82.7 per 100,000 population) to nearly 660,000 cases (240.4 per 100,000 population). The rate of sepsis due to fungal organisms increased by 207 percent, with gram-positive bacteria becoming the predominant pathogens after 1987. The total in-hospital mortality rate fell from 27.8 percent during the period from 1979 through 1984 to 17.9 percent during the period from 1995 through 2000, yet the total number of deaths continued to increase. Mortality was highest among black men. Organ failure contributed cumulatively to mortality, with temporal improvements in survival among patients with fewer than three failing organs. The average length of the hospital stay decreased, and the rate of discharge to nonacute care medical facilities increased. The incidence of sepsis and the number of sepsis-related deaths are increasing, although the overall mortality rate among patients with sepsis is declining. There are also disparities among races and between men and women in the incidence of sepsis. Gram-positive bacteria and fungal organisms are increasingly common causes of sepsis. Copyright 2003 Massachusetts Medical Society

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Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis.

Raoul Herbrecht, David W. Denning, Thomas Patterson … (2002)

Voriconazole is a broad-spectrum triazole that is active against aspergillus species. We conducted a randomized trial to compare voriconazole with amphotericin B for primary therapy of invasive aspergillosis. In this randomized, unblinded trial, patients received either intravenous voriconazole (two doses of 6 mg per kilogram of body weight on day 1, then 4 mg per kilogram twice daily for at least seven days) followed by 200 mg orally twice daily or intravenous amphotericin B deoxycholate (1 to 1.5 mg per kilogram per day). Other licensed antifungal treatments were allowed if the initial therapy failed or if the patient had an intolerance to the first drug used. A complete or partial response was considered to be a successful outcome. A total of 144 patients in the voriconazole group and 133 patients in the amphotericin B group with definite or probable aspergillosis received at least one dose of treatment. In most of the patients, the underlying condition was allogeneic hematopoietic-cell transplantation, acute leukemia, or other hematologic diseases. At week 12, there were successful outcomes in 52.8 percent of the patients in the voriconazole group (complete responses in 20.8 percent and partial responses in 31.9 percent) and 31.6 percent of those in the amphotericin B group (complete responses in 16.5 percent and partial responses in 15.0 percent; absolute difference, 21.2 percentage points; 95 percent confidence interval, 10.4 to 32.9). The survival rate at 12 weeks was 70.8 percent in the voriconazole group and 57.9 percent in the amphotericin B group (hazard ratio, 0.59; 95 percent confidence interval, 0.40 to 0.88). Voriconazole-treated patients had significantly fewer severe drug-related adverse events, but transient visual disturbances were common with voriconazole (occurring in 44.8 percent of patients). In patients with invasive aspergillosis, initial therapy with voriconazole led to better responses and improved survival and resulted in fewer severe side effects than the standard approach of initial therapy with amphotericin B. Copyright 2002 Massachusetts Medical Society

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Author and article information

Journal

Journal ID (nlm-ta): Ther Clin Risk Manag

Journal ID (publisher-id): Therapeutics and Clinical Risk Management

Title: Therapeutics and Clinical Risk Management

Publisher: Dove Medical Press

ISSN (Print): 1176-6336

ISSN (Electronic): 1178-203X

Publication date (Print): December 2008

Publication date (Electronic): December 2008

Volume: 4

Issue: 6

Pages: 1285-1294

Affiliations

Division of Infectious Diseases, Department of Internal Medicine, Wayne State University, Karmanos Cancer Institute, Detroit, MI, USA

Author notes

Correspondence: PH Chandrasekar, Harper University Hospital, 3990 John R, Detroit, MI 48201, USA, Tel +1 313 795 9649, Fax +1 313 993 0302, Email pchandrasekar@ 123456med.wayne.edu

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Publisher ID: tcrm-4-1285

PMC ID: 2643109

PubMed ID: 19337435

SO-VID: d304173c-c8ca-41d8-aab3-2ab9c1968c64

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

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Abstract

Most cited references 49

Epidemiology and outcome of zygomycosis: a review of 929 reported cases.

The epidemiology of sepsis in the United States from 1979 through 2000.

Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis.

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