Posaconazole Is Effective as Salvage Therapy in Zygomycosis: A Retrospective Summary of 91 Cases

Burik, Jo Anne H. Van; Hare, R S; Solomon, Howard F.; Corrado, Michael L.; Kontoyiannis, Dimitrios P.

doi:10.1086/500212

Cited by 581 publications

(363 citation statements)

References 17 publications

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“…Nevertheless, even with aggressive therapy, the rate of mortality is often above 50% (4, 6). It is clear that new strategies for the treatment of zygomycosis are urgently needed.Posaconazole (POS) is a new broad-spectrum triazole with activity against many filamentous fungal pathogens, including zygomycetes (3,8,11,13,14). Experimental infection models and clinical data showed that POS might be useful for the treatment of zygomycosis (3,11,14).…”

mentioning

confidence: 99%

Posaconazole Prophylaxis in Experimental Systemic Zygomycosis

Barchiesi¹,

Spreghini²,

Santinelli³

et al. 2007

Antimicrob Agents Chemother

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Three isolates of zygomycetes belonging to two different genera (Rhizopus oryzae and Absidia corymbifera) were used to produce a systemic infection in neutropenic mice. On days ؊2 and ؊1 and at 2 h prior to infection, the mice received either posaconazole (POS) at doses ranging from 20 to 80 mg/kg of body weight/day or amphotericin B (AMB) at 1 mg/kg/day. Antifungal drug efficacy was assessed by determination of the prolongation of survival, determination of the percentage of infected organs (brain, lung, spleen, and kidney), and histological examination for the number of infection foci and their sizes in brain and kidney tissues. AMB significantly prolonged the survival of mice infected with all isolates. POS significantly prolonged the survival of mice infected with zygomycetes. Cultured organs from mice infected with R. oryzae were all positive, while treated mice challenged with A. corymbifera generally showed lower percentages of infected organs compared with the percentages for the controls. Zygomycete isolates established an active infection (the presence of hyphae) in the brains and the kidneys of all controls. In mice challenged with R. oryzae, both antifungal drugs were effective at reducing the number and the size of infection foci in the kidneys. Only AMB reduced the numbers, but not the sizes, of infection foci in the brain. Finally, both drugs significantly reduced the numbers and the sizes of infection foci in both tissues of mice infected with A. corymbifera. Our data suggest that prophylaxis with POS has some potential to prevent zygomycosis. Zygomycosis is a rare but highly aggressive filamentous fungal infection (4). The clinical manifestations of zygomycosis include primary rhinocerebral, pulmonary, gastrointestinal, cutaneous or subcutaneous, and allergic disease and disseminated disease (4, 6, 7, 13). The zygomycetes most commonly identified as etiologic agents of human diseases are Rhizopus species, Rhizomucor species, Mucor species, and Absidia species (13). The invasive forms of zygomycosis cause angioinvasion, followed by progressive, necrotic, and generally fatal infections in immunocompromised hosts, such as diabetic patients with ketoacidosis, neutropenic patients, patients taking corticosteroids, and subjects with burns or iron overload (4,6,7,12,13). The standard therapy for these life-threatening infections consists of removal of the predisposing factors, widespread surgical debridement, and high doses of intravenous amphotericin B (AMB) (13). Nevertheless, even with aggressive therapy, the rate of mortality is often above 50% (4, 6). It is clear that new strategies for the treatment of zygomycosis are urgently needed.Posaconazole (POS) is a new broad-spectrum triazole with activity against many filamentous fungal pathogens, including zygomycetes (3,8,11,13,14). Experimental infection models and clinical data showed that POS might be useful for the treatment of zygomycosis (3,11,14). No data on the effects of POS prophylaxis against these infections are available. Therefore, in th...

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confidence: 99%

Posaconazole Prophylaxis in Experimental Systemic Zygomycosis

Barchiesi¹,

Spreghini²,

Santinelli³

et al. 2007

Antimicrob Agents Chemother

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“…8 In a retrospective series of invasive mucormycosis, posaconazole therapy was successful in 60% of subjects with diabetes mellitus, and its overall success rate was 65% in those with pulmonary mucormycosis. 9 Despite motivation and pursuance, our patient could not continue posaconazole beyond 4 weeks because of cost. However, we ensured macroscopic clearance of the mass in repeat bronchoscopy 2 weeks after discontinuation of posaconazole, and he did not develop any symptoms of relapse until 1 month ago.…”

Section: Discussionmentioning

confidence: 90%

Pulmonary Mucormycosis Presenting as Nonresolving Pneumonia in a Patient With Diabetes Mellitus

Panigrahi

Rajaram²,

Kumar³

et al. 2014

Respir Care

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“…Newer drugs have been introduced namely: posaconazole, isuvaconzole and echinocandins. While posaconazole has shown promising outcomes, Amphotericin B remains the first-line drug with posaconazole used as a salvage therapy (17). However, it has been proven that management of mucormycosis is multi-modal with surgical management and treatment of the underlying condition as important in antifungal therapy.…”

Section: Case Reportmentioning

confidence: 99%