Eradication of Invasive Mucormycosis--Effectiveness of the Echinocandin FK463

Jacobs, P; Wood, Lucille; Toit, Andrew du; Esterhuizen, Ken

doi:10.1080/1024533031000090810

Cited by 21 publications

(13 citation statements)

References 23 publications

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“…Voriconazole and fluconazole do not have significant in vitro activity against zygomycosis (7,19,33,45). Reports from uncontrolled studies of combination therapy with azoles, echinocandins, or both plus amphotericin B show various outcomes http://aac.asm.org/ (15,18,39,48). Breakthrough zygomycosis has been described for patients receiving voriconazole, fluconazole, itraconazole, and caspofungin (17,28,30,37,40).…”

Section: Discussionmentioning

confidence: 99%

Posaconazole as Salvage Therapy for Zygomycosis

Greenberg

Mullane

Burik

et al. 2006

Antimicrob Agents Chemother

496

306

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Zygomycosis, an infection that is associated with significant morbidity and mortality, is becoming common in immunocompromised patients. Posaconazole is a new extended-spectrum azole antifungal that has demonstrated in vitro and in vivo activity against zygomycetes. This report provides the results from the first 24 patients with active zygomycosis who were enrolled in two open-label, nonrandomized, multicentered compassionate trials that evaluated oral posaconazole as salvage therapy for invasive fungal infections. Posaconazole was usually given as an oral suspension of 200 mg four times a day or 400 mg twice a day. Eleven (46%) of the infections were rhinocerebral. Duration of posaconazole therapy ranged from 8 to 1,004 days (mean, 292 days; median, 182 days). Rates of successful treatment (complete cure and partial response) were 79% in 19 subjects with zygomycosis refractory to standard therapy and 80% in 5 subjects with intolerance to standard therapy. Overall, 19 of 24 subjects (79%) survived infection. Survival was also associated with surgical resection of affected tissue and stabilization or improvement of the subjects' underlying illnesses. Failures either had worsening of underlying illnesses or requested all therapy withdrawn; none of the failures received more than 31 days of posaconazole. Posaconazole oral solution was well tolerated and was discontinued in only one subject due to a drug rash. Posaconazole appears promising as an oral therapy for zygomycosis in patients who receive required surgery and control their underlying illness.Zygomycosis (also known as mucormycosis) is an infection caused by saprophytic fungi of the class Zygomycetes, which are primarily opportunists that invade immunocompromised hosts and produce angioinvasive disease (49). Transmission is mainly through inhalation of small airborne spores, by traumatic skin implantation, or by ingestion and translocation of the organism through the gut. Patients at highest risk for zygomycosis are those with (i) immunosuppression related to neutropenia, corticosteroid use, hematologic malignancies, and solid-organ transplants, (ii) diabetes mellitus, especially those with ketoacidosis, (iii) conditions of iron overload with associated desferoxamine use, and (iv) skin disruption by trauma or other serious conditions, such as burns or heatstroke. In recipients of a hematopoietic stem cell transplant (HSCT), infection often occurs during periods of graft-versus-host disease due to escalation of immunosuppressant regimens (1,4,12,21,25,27,36,41,44). Common sites of infection include pulmonary, rhinocerebral, or disseminated disease (36). The outcome of zygomycosis is closely related to the overall health of the patients and the control of their underlying diseases.Roden and associates analyzed 929 cases of zygomycosis reported since 1885 (38). Survival was reported in 65% of patients with no underlying condition, 56% with diabetes, and 34% with malignancy. Survival varied with infection site: localized skin, 90%; rhinocerebral, 38%; lung, 24...

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Section: Discussionmentioning

confidence: 99%

Posaconazole as Salvage Therapy for Zygomycosis

Greenberg

Mullane

Burik

et al. 2006

Antimicrob Agents Chemother

496

306

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“…In animal models, the combination of caspofungin and amphotericin B lipid complex was synergistic, improving the survival of mice (9). Few cases of IZ responded partially to the echinocandins, although we have so little clinical experience with caspofungin for the treatment of IZ (4,11). These data suggest that echinocandins may have a role as a second agent in combinations.…”

mentioning

confidence: 90%

Synergistic Effect of Posaconazole and Caspofungin against Clinical Zygomycetes

Guembe

Guinea

Peláez

et al. 2007

Antimicrob Agents Chemother

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“…As mentioned, there have also been reports of breakthrough mucormycosis in patients receiving either caspofungin alone (133) or caspofungin plus voriconazole (13). Conversely, the related experimental echinocandin micafungin has been added on a salvage basis to a patient failing antifungal therapy for craniofacial mucormycosis (67). The patient began responding to therapy shortly after the addition of micafungin and was ultimately cured.…”

Section: Antifungal Therapymentioning

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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Eradication of Invasive Mucormycosis--Effectiveness of the Echinocandin FK463

Abstract: Echinocandin FK463 is of documented value in managing invasive candidiasis and aspergillosis. This is believed to be the first case of successful outcome with one of the angiotrophic zygomycetes.

Cited by 21 publications

References 23 publications

Posaconazole as Salvage Therapy for Zygomycosis

Posaconazole as Salvage Therapy for Zygomycosis

Synergistic Effect of Posaconazole and Caspofungin against Clinical Zygomycetes

Novel Perspectives on Mucormycosis: Pathophysiology, Presentation, and Management

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