Experimental murine model of disseminated infection by<i>Saksenaea vasiformis</i>: successful treatment with posaconazole

Salas, Valentina; Pastor, Francisco; Sutton, Deanna A.; García-Hermoso, Dea; Mayayo, Emilio; Dromer, Françoise; Fothergill, A.; Álvarez, Enrique José Varela; Guarro, Josep

doi:10.3109/13693786.2012.673137

Cited by 14 publications

(7 citation statements)

References 21 publications

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“…(32). A more recent study showed a poor outcome of POS treatment of neutropenic mice infected with M. circinelloides (54), while the drug was effective, even more than amphotericin B, in treating immunocompetent mice infected intravenously with Apophysomyces variabilis (55) or Saksenaea vasiformis (56). We and others found that DKA or neutropenic mice infected intravenously with R. oryzae had limited benefit from POS treatment (27,57,58) despite the in vitro susceptibility of the used R. oryzae to POS (59,60).…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Liposomal Amphotericin B and Posaconazole in Intratracheal Models of Murine Mucormycosis

Luo

Gebremariam

Lee

et al. 2013

Antimicrob Agents Chemother

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e Mucormycosis is a life-threatening fungal infection almost uniformly affecting diabetics in ketoacidosis or other forms of acidosis and/or immunocompromised patients. Inhalation of Mucorales spores provides the most common natural route of entry into the host. In this study, we developed an intratracheal instillation model of pulmonary mucormycosis that hematogenously disseminates into other organs using diabetic ketoacidotic (DKA) or cyclophosphamide-cortisone acetate-treated mice. Various degrees of lethality were achieved for the DKA or cyclophosphamide-cortisone acetate-treated mice when infected with different clinical isolates of Mucorales. In both DKA and cyclophosphamide-cortisone acetate models, liposomal amphotericin B (LAmB) or posaconazole (POS) treatments were effective in improving survival, reducing lungs and brain fungal burdens, and histologically resolving the infection compared with placebo. These models can be used to study mechanisms of infection, develop immunotherapeutic strategies, and evaluate drug efficacies against life-threatening Mucorales infections. Mucormycoses are uncommon life-threatening fungal infections caused by fungi of the order Mucorales (1-3). These infections almost uniformly afflict the immunocompromised hosts, those with diabetic ketoacidosis (DKA) or other forms of acidosis, and trauma patients (e.g., victims of the recent natural disasters of the Joplin tornado [4] and the Indian tsunami [5]) (6, 7). Due to the rising prevalence of diabetes, cancer, and organ transplantation in aging populations, as well as the recent increase in natural disasters, the number of patients at risk for this deadly infection is significantly rising and is expected to continue to rise (8-10).Fungi belonging to the order Mucorales are distributed into six families, all of which can cause cutaneous and hematogenously disseminated infections (1, 6). Species belonging to the family Mucoraceae are isolated more frequently from patients with mucormycosis than any other family. Among the Mucoraceae, Rhizopus spp. are the most common cause of mucormycosis and are responsible for approximately 70% of all infections and 90% of rhinocerebral cases (6,11,12). However, recently more cases caused by the previously less frequent species of Lichtheimia (formerly Absidia) corymbifera, Apophysomyces elegans, and Mucor species have been reported (4, 6, 13-17). Increasing numbers of cases of mucormycosis have been also reported due to infection with Cunninghamella spp. (18)(19)(20).Despite disfiguring surgical debridement and adjunctive antifungal therapy, the overall mortality of mucormycosis remains approximately 50%. In the absence of surgical removal of the infected focus, antifungal therapy alone is rarely curative, resulting in a 100% mortality rate for patients with hematogenously disseminated disease (1,9,(21)(22)(23)(24). Clearly, new strategies to prevent and treat mucormycosis are urgently needed. Because of the rarity of the disease, controlled clinical trials are hard to conduct. Consequently...

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Section: Discussionmentioning

confidence: 99%

Efficacy of Liposomal Amphotericin B and Posaconazole in Intratracheal Models of Murine Mucormycosis

Luo

Gebremariam

Lee

et al. 2013

Antimicrob Agents Chemother

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“…In immunocompetent mice amphotericin B prolonged survival, whereas for itraconazole and posaconazole there are heterogeneous effects depending on the fungal species used for infection [131][132][133]. The ECMM clinical registries reported successful first-line treatment with posaconazole in about 50-60% of patients [7,26].…”

Section: Recommendations On Treatment Of Mucormycosismentioning

confidence: 99%

ESCMID† and ECMM‡ joint clinical guidelines for the diagnosis and management of mucormycosis 2013

Cornely¹,

Arıkan-Akdağlı²,

Dannaoui³

et al. 2014

Clinical Microbiology and Infection

577

516

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These European Society for Clinical Microbiology and Infectious Diseases and European Confederation of Medical Mycology Joint Clinical Guidelines focus on the diagnosis and management of mucormycosis. Only a few of the numerous recommendations can be summarized here. To diagnose mucormycosis, direct microscopy preferably using optical brighteners, histopathology and culture are strongly recommended. Pathogen identification to species level by molecular methods and susceptibility testing are strongly recommended to establish epidemiological knowledge. The recommendation for guiding treatment based on MICs is supported only marginally. Imaging is strongly recommended to determine the extent of disease. To differentiate mucormycosis from aspergillosis in haematological malignancy and stem cell transplantation recipients, identification of the reverse halo sign on computed tomography is advised with moderate strength. For adults and children we strongly recommend surgical debridement in addition to immediate first-line antifungal treatment with liposomal or lipid-complex amphotericin B with a minimum dose of 5 mg/kg/day. Amphotericin B deoxycholate is better avoided because of severe adverse effects. For salvage treatment we strongly recommend posaconazole 4×200 mg/day. Reversal of predisposing conditions is strongly recommended, i.e. using granulocyte colony-stimulating factor in haematological patients with ongoing neutropenia, controlling hyperglycaemia and ketoacidosis in diabetic patients, and limiting glucocorticosteroids to the minimum dose required. We recommend against using deferasirox in haematological patients outside clinical trials, and marginally support a recommendation for deferasirox in diabetic patients. Hyperbaric oxygen is supported with marginal strength only. Finally, we strongly recommend continuing treatment until complete response demonstrated on imaging and permanent reversal of predisposing factors.

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“…[8,9]. In an experimental murine model of disseminated Saksenaea vasiformis infection, posaconazole demonstrated the greatest in vitro activity and was the most effective in prolonging survival in this model [10]. A high dose of 8 mg/kg liposomal amphotericin B was used in this case with early introduction of posaconazole, however there is limited evidence to guide management of Saksenaea infections.…”

Section: Discussionmentioning

confidence: 98%

Disseminated Saksenaea infection in an immunocompromised host associated with a good clinical outcome: a case report and review of the literature

et al. 2020

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Background Saksenaea species (spp.) are uncommon causes of mucormycosis but are emerging pathogens mostly associated with trauma and soil contamination often in immunocompetent hosts. Due to lack of sporulation in the laboratory, diagnosis and susceptibility testing is difficult so optimal treatment regimens are unknown. Case presentation A 67 year-old man from the Northern Territory in Australia, with a history of eosinophilic granulomatosis with polyangiitis, developed disseminated Saksenaea infection after initially presenting with symptoms consistent with bacterial pyelonephritis. Despite a delay in diagnosis; with aggressive surgical management and dual therapy with amphotericin B and posaconazole, he survived. Conclusions We describe an unusual case of disseminated infection with a favourable outcome to date.

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Experimental murine model of disseminated infection bySaksenaea vasiformis: successful treatment with posaconazole

Cited by 14 publications

References 21 publications

Efficacy of Liposomal Amphotericin B and Posaconazole in Intratracheal Models of Murine Mucormycosis

Efficacy of Liposomal Amphotericin B and Posaconazole in Intratracheal Models of Murine Mucormycosis

ESCMID† and ECMM‡ joint clinical guidelines for the diagnosis and management of mucormycosis 2013

Disseminated Saksenaea infection in an immunocompromised host associated with a good clinical outcome: a case report and review of the literature

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