Interferon-?? and Colony-Stimulating Factors as Adjuvant Therapy for Refractory Fungal Infections in Children

Abzug, Mark J.; Walsh, Thomas J.

doi:10.1097/01.inf.0000134314.65398.bf

Cited by 108 publications

(56 citation statements)

References 28 publications

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“…Cytokines that activated phagocytic activity, such as gamma interferon and granulocyte-macrophage colony-stimulating factor, increase the ability of phagocytes to kill agents of mucormycosis in vitro (44). A recent case report suggested a favorable outcome in a leukemic child with rhinocerebral mucormycosis following the addition of gamma interferon and granulocyte-macrophage colony-stimulating factor to the regimen (3). Further studies of cytokines that activate host phagocyte function are warranted for this disease.…”

Section: Other Adjunctive Therapiesmentioning

confidence: 99%

Novel Perspectives on Mucormycosis: Pathophysiology, Presentation, and Management

2005

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Mucormycosis is a life-threatening fungal infection that occurs in immunocompromised patients. These infections are becoming increasingly common, yet survival remains very poor. A greater understanding of the pathogenesis of the disease may lead to future therapies. For example, it is now clear that iron metabolism plays a central role in regulating mucormycosis infections and that deferoxamine predisposes patients to mucormycosis by inappropriately supplying the fungus with iron. These findings raise the possibility that iron chelator therapy may be useful to treat the infection as long as the chelator does not inappropriately supply the fungus with iron. Recent data support the concept that high-dose liposomal amphotericin is the preferred monotherapy for mucormycosis. However, several novel therapeutic strategies are available. These options include combination therapy using lipid-based amphotericin with an echinocandin or with an azole (largely itraconazole or posaconazole) or with all three. The underlying principles of therapy for this disease remain rapid diagnosis, reversal of underlying predisposition, and urgent surgical debridement

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Section: Other Adjunctive Therapiesmentioning

confidence: 99%

Novel Perspectives on Mucormycosis: Pathophysiology, Presentation, and Management

2005

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“…Additionally, high oxygen pressure inhibits the germination of fungal spores and growth of mycelia in vitro (Robb 1966). Similarly, case reports have described survival of patients with mucormycosis treated with adjunct recombinant granulocyte colony-stimulating factor and granulocyte macrophage colonystimulating factor or with recombinant interferon-g in conjunction with lipid formulations of AmB (Gonzalez et al 1997;Kullberg and Anaissie 1998;Ma et al 2001;Mastroianni 2004;Abzug and Walsh 2004). Granulocyte colony -stimulating factor-mobilized granulocyte transfusions have been increasingly used for refractory mycoses, including mucormycosis (Slavin et al 2002;Grigull et al 2006).…”

Section: Iron Chelation Therapy and Other Novel Approachesmentioning

confidence: 99%

Human Fungal Pathogens of Mucorales and Entomophthorales

Mendoza

Vilela

Voelz

et al. 2014

Cold Spring Harbor Perspectives in Medicine

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In recent years, we have seen an increase in the number of immunocompromised cohorts as a result of infections and/or medical conditions, which has resulted in an increased incidence of fungal infections. Although rare, the incidence of infections caused by fungi belonging to basal fungal lineages is also continuously increasing. Basal fungal lineages diverged at an early point during the evolution of the fungal lineage, in which, in a simplified four-phylum fungal kingdom, Zygomycota and Chytridiomycota belong to the basal fungi, distinguishing them from Ascomycota and Basidiomycota. Currently there are no known human infections caused by fungi in Chytridiomycota; only Zygomycotan fungi are known to infect humans. Hence, infections caused by zygomycetes have been called zygomycosis, and the term "zygomycosis" is often used as a synonym for "mucormycosis." In the four-phylum fungal kingdom system, Zygomycota is classified mainly based on morphology, including the ability to form coenocytic (aseptated) hyphae and zygospores (sexual spores). In the Zygomycota, there are 10 known orders, two of which, the Mucorales and Entomophthorales, contain species that can infect humans, and the infection has historically been known as zygomyEditors:

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“…Immune augmentation strategies are also considered in patients with refractory mycormycosis, including administration of cytokines (eg, granulocyte-macrophage colony-stimulating factor, interferon-␥). [68][69][70][71] In select neutropenic patients, granulocyte transfusion may be a useful bridge until neutrophil recovery, although the clinical benefit remains unproven; and serious adverse effects, including pulmonary toxicity and accelerated cavitation/bleeding, have been reported in patients with opportunistic lung mycoses. Therefore, there are limited data to support the routine use of these adjunct strategies at this time.…”

Section: Adjunct Treatmentsmentioning

confidence: 99%

How I treat mucormycosis

Kontoyiannis

Lewis

2011

Blood

320

311

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Unlike invasive aspergillosis, the prognosis and outcome of hematologic malignancy patients who develop invasive mucormycosis have not significantly improved over the past decade as a majority of patients who develop the infection still die 12 weeks after diagnosis. However, early recognition and treatment of invasive mucormycosis syndromes, as well as individualized approaches to treatment and secondary prophylaxis, could improve the odds of survival, even in the most persistently immunosuppressed patient receiving chemotherapy and/or of stem cell transplantation. Herein, we describe the subtle clinical and radiographic clues that should alert the hematologist to the possibility of mucormycosis, and aggressive and timely treatment approaches that may limit the spread of infection before it becomes fatal. Hematology patients with this opportunistic infection require integrated care across several disciplines and frequently highly individualized and complex sequence of decision-making. We also offer perspectives for the use of 2 antifungals, amphotericin B products and posaconazole, with activity against Mucorales. The availability of posaconazole in an oral formulation that can be administered safely for prolonged periods makes it an attractive agent for long-term primary and secondary prophylaxis. However, serum drug concentration monitoring may be required to minimize breakthrough infection or relapsing mucormycosis associated with inadequate blood concentrations. (Blood. 2011;118(5):1216-1224) IntroductionMucormycosis is the unifying term used to describe infections caused by fungi belonging to the order Mucorales. Zygomycosis, an alternative term used to describe these life-threatening infections, has become less accurate based on a recent taxonomic reclassification (based on molecular identification) that abolished Zygomycetes as a class. [1][2][3][4] Rhizopus, Mucor, and Rhizomucor species account for up to 75% of mucormycosis cases encountered in hematologic malignancy patients. [5][6][7] Mucorales typically cause acute, aggressive, and frequently angioinvasive infections, especially in immunosuppressed hosts with hematologic malignancy and/or stem cell transplantation (SCT). 8,9 This opportunistic, geographically broad mycosis was highlighted as a sporadic cause of death in leukemia patients in the 1950s 10 until the mid 1990s where there has been an apparent increase in the documented cases in hematology units throughout the Westernized world ( Figure 1). [4][5][6][7]11 These cases are typically considered community-acquired, as nosocomial cases are less common in modern SCT and transplant units. 12 However, the true incidence of mucormycosis is not known and probably underestimated because of difficulties in antemortem diagnosis and the low autopsy rates in contemporary patients who die in the setting of leukemia or SCT. 13 The predisposing factors for mucormycosis in patients with hematologic cancer are similar to ones encountered in other opportunistic mold infections, such as aspergillosis, includi...

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Interferon-?? and Colony-Stimulating Factors as Adjuvant Therapy for Refractory Fungal Infections in Children

Cited by 108 publications

References 28 publications

Novel Perspectives on Mucormycosis: Pathophysiology, Presentation, and Management

Novel Perspectives on Mucormycosis: Pathophysiology, Presentation, and Management

Human Fungal Pathogens of Mucorales and Entomophthorales

How I treat mucormycosis

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