Successful Treatment of Chronic Mucocutaneous Candidiasis Caused by Azole-Resistant<i>Candida albicans</i>with Posaconazole

Firinu, Davide; Massidda, Orietta; Lorrai, Maria Maddalena; Serusi, Loredana; Peralta, Monica; Barca, Maria Pina; Serra, P.; Manconi, Paolo Emilio

doi:10.1155/2011/283239

Cited by 19 publications

(9 citation statements)

References 19 publications

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“…Previous studies had reported that patients with azole-resistant C . albicans infections can be cured with posaconazole [38], indicating a potential advantage of posaconazole against azole-resistant isolates. This feature was also supported by our finding that posaconazole treatment at a dose of 2 mg/kg (but not 0.5 mg/kg) exhibited therapeutic activity against the azole (especially fluconazole)-resistant isolate 12–99 (Figures 1B and 2B).…”

Section: Discussionmentioning

confidence: 99%

Posaconazole Exhibits In Vitro and In Vivo Synergistic Antifungal Activity with Caspofungin or FK506 against Candida albicans

et al. 2013

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The object of this study was to test whether posaconazole, a broad-spectrum antifungal agent inhibiting ergosterol biosynthesis, exhibits synergy with the β-1,3 glucan synthase inhibitor caspofungin or the calcineurin inhibitor FK506 against the human fungal pathogen Candida albicans. Although current drug treatments for Candida infection are often efficacious, the available antifungal armamentarium may not be keeping pace with the increasing incidence of drug resistant strains. The development of drug combinations or novel antifungal drugs to address emerging drug resistance is therefore of general importance. Combination drug therapies are employed to treat patients with HIV, cancer, or tuberculosis, and has considerable promise in the treatment of fungal infections like cryptococcal meningitis and C. albicans infections. Our studies reported here demonstrate that posaconazole exhibits in vitro synergy with caspofungin or FK506 against drug susceptible or resistant C. albicans strains. Furthermore, these combinations also show in vivo synergy against C. albicans strain SC5314 and its derived echinocandin-resistant mutants, which harbor an S645Y mutation in the CaFks1 β-1,3 glucan synthase drug target, suggesting potential therapeutic applicability for these combinations in the future.

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Section: Discussionmentioning

confidence: 99%

Posaconazole Exhibits In Vitro and In Vivo Synergistic Antifungal Activity with Caspofungin or FK506 against Candida albicans

et al. 2013

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“…However, this can lead to the development of drug‐resistant strains. Therefore, for this reason, other antifungals such as flucytosine, amphotericin, the new azoles such as voriconazole and posaconazole, and echinocandins have sometimes been used . Some patients with chronic mucocutaneous candidiasis also develop dermatophyte onychomycosis, which can also respond poorly to treatment.…”

Section: Treatmentsmentioning

confidence: 99%

British Association of Dermatologists' guidelines for the management of onychomycosis 2014

et al. 2014

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“…Systemic agents (e.g. azole agents, echinocandins) are used for extensive or uncontrolled disease and for cases not responding to topical agents [153]. Invasive Candida infections must be treated intravenously (e.g.…”

Section: Treatment Of Fungal Diseases In Card9-deficient Patientsmentioning

confidence: 99%

Inherited CARD9 Deficiency: Invasive Disease Caused by Ascomycete Fungi in Previously Healthy Children and Adults

2018

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• Inherited CARD9 deficiency (OMIM #212050) is an AR PID due to mutations that may be present in a homozygous or compound heterozygous state. • CARD9 is expressed principally in myeloid cells and transduces signals downstream from CLR activation by fungal ligands. • Endogenous mutant CARD9 levels differ between alleles (from full-length normal protein to an absence of normal protein). • The functional impacts of CARD9 mutations involve impaired cytokine production in response to fungal ligands, impaired neutrophil killing and/or recruitment to infection sites, and defects of Th17 immunity. • The key clinical manifestations in patients are fungal infections, including CMC, invasive (in the CNS in particular) Candida infections, extensive/deep dermatophytosis, subcutaneous and invasive phaeohyphomycosis, and extrapulmonary aspergillosis. • The clinical penetrance of CARD9 deficiency is complete, but penetrance is incomplete for each of the fungi concerned. • Age at onset is highly heterogeneous, ranging from childhood to adulthood for the same fungal disease. • All patients with unexplained IFD should be tested for CARD9 mutations. Familial screening and genetic counseling should be proposed. • The treatment of patients with CARD9 mutations is empirical and based on antifungal therapies and the surgical removal of fungal masses. Patients with persistent/relapsing Candida infections of the CNS could be considered for adjuvant GM-CSF/G-CSF therapy. The potential value of HSCT for CARD9-deficient patients remains unclear.

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Successful Treatment of Chronic Mucocutaneous Candidiasis Caused by Azole-ResistantCandida albicanswith Posaconazole

Cited by 19 publications

References 19 publications

Posaconazole Exhibits In Vitro and In Vivo Synergistic Antifungal Activity with Caspofungin or FK506 against Candida albicans

Posaconazole Exhibits In Vitro and In Vivo Synergistic Antifungal Activity with Caspofungin or FK506 against Candida albicans

British Association of Dermatologists' guidelines for the management of onychomycosis 2014

Inherited CARD9 Deficiency: Invasive Disease Caused by Ascomycete Fungi in Previously Healthy Children and Adults

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