Modest efficacy of voriconazole against murine infections by <i>Sporothrix schenckii</i> and lack of efficacy against <i>Sporothrix brasiliensis</i>

Fernández-Silva, Fabiola; Capilla, Javier; Mayayo, Emilio; Guarro, Josep

doi:10.1111/myc.12112

Cited by 26 publications

(13 citation statements)

References 29 publications

(43 reference statements)

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“…Voriconazole (40 mg/kg) has been demonstrated to only reduce fungal load in mice infected with S. schenckii s. str. , and to have no activity against S. brasiliensis [52]. No studies to date have linked the dissimilar phylogenetic species to in vitro and in vivo data.…”

Section: Discussionmentioning

confidence: 99%

Genetic diversity and antifungal susceptibility profiles in causative agents of sporotrichosis

et al. 2014

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BackgroundSporotrichosis is a chronic subcutaneous mycosis of humans and animals, which is typically acquired by traumatic inoculation of plant material contaminated with Sporothrix propagules, or via animals, mainly felines. Sporothrix infections notably occur in outbreaks, with large epidemics currently taking place in southeastern Brazil and northeastern China. Pathogenic species include Sporothrix brasiliensis, Sporothrix schenckii s. str., Sporothrix globosa, and Sporothrix luriei, which exhibit differing geographical distribution, virulence, and resistance to antifungals. The phylogenetically remote species Sporothrix mexicana also shows a mild pathogenic potential.MethodsWe assessed a genetically diverse panel of 68 strains. Susceptibility profiles of medically important Sporothrix species were evaluated by measuring the MICs and MFCs for amphotericin B (AMB), fluconazole (FLC), itraconazole (ITC), voriconazole (VRC), posaconazole (PCZ), flucytosine (5FC), and caspofungin (CAS). Haplotype networks were constructed to reveal interspecific divergences within clinical Sporothrix species to evaluate genetically deviant isolates.ResultsITC and PCZ were moderately effective against S. brasiliensis (MIC90 = 2 and 2 μg/mL, respectively) and S. schenckii (MIC90 = 4 and 2 μg/mL, respectively). PCZ also showed low MICs against the rare species S. mexicana. 5FC, CAS, and FLC showed no antifungal activity against any Sporothrix species. The minimum fungicidal concentration ranged from 2 to >16 μg/mL for AMB against S. brasiliensis and S. schenckii, while the MFC90 was >16 μg/mL for ITC, VRC, and PCZ.ConclusionSporothrix species in general showed high degrees of resistance against antifungals. Evaluating a genetically diverse panel of strains revealed evidence of multidrug resistant phenotypes, underlining the need for molecular identification of etiologic agents to predict therapeutic outcome.

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Section: Discussionmentioning

confidence: 99%

Genetic diversity and antifungal susceptibility profiles in causative agents of sporotrichosis

et al. 2014

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“…Although the increase in the number of cases has been accompanied by problems for the health system, it has created opportunities to produce knowledge and to deepen the study of human and animal cases that were previously scarce. In this context, a variety of previously non-existent or unaware information has emerged in recent years such as studies focused on the understanding of the higher susceptibility of cats aimed at controlling the infection in these animals [ 1 , 11 , 21 , 33 ]; the description of the circulation of new species and complexity in some geographic areas [ 10 , 33 , 34 , 35 , 36 , 37 , 38 ]; studies about the mechanisms involved in infection and the establishment of lesions in humans and animals by trying to understand the dynamic of fungus–vertebrate interaction [ 35 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ]; the evaluation of new and old drugs for the treatment and resistance of some isolates have been initiated [ 41 , 46 , 47 , 48 , 49 ] as well as some correlation attempts between the susceptibility and severity of disease [ 50 , 51 ]. However, much more needs to be done.…”

Section: The Global Increase Of Sporotrichosis Creates New Problemmentioning

confidence: 99%

Immunopathogenesis of Human Sporotrichosis: What We Already Know

Conceição-Silva

Morgado

2018

JoF

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Sporotrichosis is a subacute/chronic mycosis caused by dimorphic fungus of the genus Sporothrix. This mycosis may affect both human and domestic animals and in the last few years, the geographic dispersion and increase of sporotrichosis worldwide has been observed. The occurrence of cases related to scratching/bites of domestic felines have increased, characterizing the disease as predominantly a zoonosis. In humans, sporotrichosis mainly involves the cutaneous tegument of infected patients, but other tissues may also present the infection. The main forms of clinical presentation are lymphocutanous sporotrichosis (LC) and fixed sporotrichosis (F). Although less common, mucosal, cutaneous disseminated, and extracutaneous forms have also been described. Multiple factors from the fungus and host can play a role in driving the clinical evolution of sporotrichosis to benign or severe disease. In this review, we discuss the immunopathological aspects involved in human sporotrichosis. Putting together the two branches of knowledge—host immune response and fungal evading mechanisms—we may perceive new possibilities in understanding the fungus–host interaction in order to be in a position to go further in the control of sporotrichosis.

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“…Posaconazole has shown efficacy for S. brasiliensis and S. schenckii sensu stricto infections in experimental murine models [ 101 ]. Voriconazole had not shown antifungal activity against S. brasiliensis and had only fungistatic effect in mice infected with S. schenckii sensu stricto [ 102 ].…”

Section: Treatment Optionsmentioning

confidence: 99%

Sporotrichosis: An Overview and Therapeutic Options

Mahajan¹

2014

Dermatology Research and Practice

190

207

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Sporotrichosis is a chronic granulomatous mycotic infection caused by Sporothrix schenckii, a common saprophyte of soil, decaying wood, hay, and sphagnum moss, that is endemic in tropical/subtropical areas. The recent phylogenetic studies have delineated the geographic distribution of multiple distinct Sporothrix species causing sporotrichosis. It characteristically involves the skin and subcutaneous tissue following traumatic inoculation of the pathogen. After a variable incubation period, progressively enlarging papulo-nodule at the inoculation site develops that may ulcerate (fixed cutaneous sporotrichosis) or multiple nodules appear proximally along lymphatics (lymphocutaneous sporotrichosis). Osteoarticular sporotrichosis or primary pulmonary sporotrichosis are rare and occur from direct inoculation or inhalation of conidia, respectively. Disseminated cutaneous sporotrichosis or involvement of multiple visceral organs, particularly the central nervous system, occurs most commonly in persons with immunosuppression. Saturated solution of potassium iodide remains a first line treatment choice for uncomplicated cutaneous sporotrichosis in resource poor countries but itraconazole is currently used/recommended for the treatment of all forms of sporotrichosis. Terbinafine has been observed to be effective in the treatment of cutaneous sporotrichosis. Amphotericin B is used initially for the treatment of severe, systemic disease, during pregnancy and in immunosuppressed patients until recovery, then followed by itraconazole for the rest of the therapy.

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Modest efficacy of voriconazole against murine infections by Sporothrix schenckii and lack of efficacy against Sporothrix brasiliensis

Cited by 26 publications

References 29 publications

Genetic diversity and antifungal susceptibility profiles in causative agents of sporotrichosis

Genetic diversity and antifungal susceptibility profiles in causative agents of sporotrichosis

Immunopathogenesis of Human Sporotrichosis: What We Already Know

Sporotrichosis: An Overview and Therapeutic Options

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