Feline sporotrichosis: a case series of itraconazole-resistant Sporothrix brasiliensis infection

Nakasu, Ceres Cristina Tempel; Waller, Stefanie Bressan; Ripoll, Márcia Kutscher; Ferreira, Marcos Roberto Alves; Conceição, Fabrı́cio R.; Gomes, Angelita dos Reis; Osório, Luíza da Gama; Faria, Renata Osório de; Cleff, Marlete Brum

doi:10.1007/s42770-020-00290-5

Cited by 35 publications

(30 citation statements)

References 40 publications

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“…Although sporotrichosis is endemic in several countries, treatment remains restricted to a few options, relying mainly on itraconazole [ 4 ]. The emergence of clinical and feline-borne isolates with low in vitro susceptibility to itraconazole and the constantly reported therapeutic failure highlights the need to seek new options for sporotrichosis treatment [ 9 – 11 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of two potential inhibitors of Sporothrix brasiliensis and Sporothrix schenckii in the Pathogen Box collection

2020

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Sporotrichosis is a neglected endemic mycosis with a high incidence in Latin America, mainly in Brazil. Sporothrix schenckii is the most frequent species in Latin America, whereas Sporothrix brasiliensis is the predominant species observed in Brazil and is associated with both human and animal sporotrichosis. Sporotrichosis treatment remains restricted to a few options, itraconazole being the first choice for human and animal therapy. In this work, we screened the molecular library Pathogen Box (Medicines for Malaria Venture [MMV], Switzerland) in search of compounds with anti-Sporothrix activity. Our initial screen of the 400 compounds identified five compounds that inhibited more than 80% of S. brasiliensis and S. schenkii growth. Among those, three compounds (MMV675968, MMV102872, and MMV002817 (known as iodoquinol)) not previously described as antifungals or agrochemicals, were selected for further evaluation. MMV102872 and iodoquinol showed the most promising combination of antifungal activity (lower inhibitory concentration) and fungal selectivity (lower cytotoxicity in LLC-MK2 cells). Scanning electron microscopy and flow cytometry analyses revealed that MMV102872 and iodoquinol induced changes in cell morphology, membrane integrity, and the presence of neutral lipids, impairing fungal survival. Our results indicate that MMV102872 and iodoquinol are promising molecules for use as scaffolds for the development of new antifungal agents.

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Section: Introductionmentioning

confidence: 99%

Identification of two potential inhibitors of Sporothrix brasiliensis and Sporothrix schenckii in the Pathogen Box collection

2020

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“…The increase in disease prevalence is due to many factors including the virulence of the pathogen -S. brasiliensis is the most virulent species in the S. schenckii complex (ARRILLAGA-MONCRIEFF et al, 2009;FERNANDES et al, 2013;DELLA TORRE et al, 2017) -difficulty for treating this mycotic disease, therapeutic time frame, zoonotic potential, and the large numbers of non-domiciled and semidomiciled (stray) cats that are affected by this fungal infection. All these factors make sporothricosis a public health problem in Brazil, which is especially alarming in the States of Rio de Janeiro, Minas Gerais and Rio Grande do Sul (POESTER et al, 2018;GREMIÃO et al, 2020;MACÊDO-SALES et al, 2020;NAKASU et al, 2020;RODRIGUES et al, 2020).…”

Section: Sporotrichosismentioning

confidence: 99%

Thymomodulin in association with antifungal drugs in the therapy of cats with disseminated cutaneous sporotrichosis: a prospective study

et al. 2021

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Feline sporotrichosis is a relevant mycose in veterinary medicine due to its severity and zoonotic potential and the fact that it can be difficult to treat. The immune status of the animal exerts influence on the prognosis of the disease and determines its clinical outcome. This study evaluated the efficacy of the immunomodulatory thymomodulin as an adjunct to antifungal therapy in cats with disseminated sporotrichosis; thymomodulin was used in association with itraconazole (ITL) and potassium iodide (KI) to treat this fungal disease in the feline patient. Thirty-one cats (n=31) diagnosed with disseminated cutaneous sporotrichosis were divided into two groups as follows: Group 1 (G1) (n=16), which included those animals that were treated with thymomodulin in association with ITL and KI, and Group 2 (G2) (n=15) which had pacientsthat received ITL and KI only. The response to different treatment modalities was assessed, considering the survival rate, time frame for the lesions to respond to therapy, and clinical improvement or deterioration according to a body condition score system. Animals from G1 had a survival rate of nearly 100% (93.6%) that was approximately twice higher than the survival rate of those animals from G2 (53%). Moreover, patients from G1 had a significantly better prognosis, improved body condition, and shorter time for remission of the extra cutaneous clinical signs (p<0.02). Our findings showed that the association of thymomodulin with ITL and KI improves the prognosis of cats with disseminated cutaneous sporotrichosis.

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“…This transmission can occur between animals, such as dogs and cats, or by zoonotic transmission to humans (Rodrigues et al, 2016). Cats often develop ulcerative and nodular lesions with scabs and secretions ranging from serous to bloody, which can be localized or disseminated throughout the body (Nakasu et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

“…Feline cases of sporotrichosis are frequently reported in all Brazilian regions, mainly in the South and Southeast, and this geographic expansion has been related to socioeconomic problems, making it difficult to control as well as its transmission to humans (Gremião et al, 2020). For the treatment, only few agents are effective being itraconazole (ITZ) a reference drug clinically available for treatment of both human and animal cases of sporotrichosis (Waller, Ripoll, et al, 2021) due to its broad spectrum with inhibitory activity on the ergosterol biosynthesis (Borgers and Van de Ben, 1989).…”

Section: Introductionmentioning

confidence: 99%

Bioisosteric modification on benzylidene‐carbonyl compounds improved the drug‐likeness and maintained the antifungal activity against Sporothrix brasiliensis

et al. 2021

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Considering the emergence of antifungal resistance on Sporothrix brasiliensis, we aimed to assess new benzylidene-carbonyl compounds against feline-borne S. brasiliensis isolates. The compounds were designed as bioisosteres from previously reported benzylidene-ketones generating the p-coumaric (1), cinnamic(2), p-methoxycinnamic (3) and caffeic acid (4) analogues. The corresponding compounds were tested against feline isolates of S. brasiliensis with sensitivity (n = 4) and resistance (n = 5) to itraconazole (ITZ), following the M38-A2 protocol (CLSI, Reference method for broth dilution antifungal susceptibility testing of filamentous fungi M38-A2 Guideline, 2008). Eleven analogues showed activity against all fungal strains with minimum inhibitory concentrations (MIC) ≤1 mg/ml (1a-d, 2e, 3b, 3e, 4, 4a and 5e) and fungicidal concentrations (MFC) ≤1 mg/ml (1b, 1d, 3e and 4a), whereas 3 was the less active with both MIC and MFC values above 1 mg/ml. Compound 3e (4-methoxy-N-butylcinnamamide) was the most potent (MIC range 0.08-0.16 mg/ml; MFC range 0.32-0.64 mg/ml) from the set, suggesting a different role of the substituents in ester and amide derivatives. The designed compounds proved to be important prototypes with improved drug-likeness to achieve compounds with higher activity against ITZ-resistant S. brasiliensis.

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Feline sporotrichosis: a case series of itraconazole-resistant Sporothrix brasiliensis infection

Cited by 35 publications

References 40 publications

Identification of two potential inhibitors of Sporothrix brasiliensis and Sporothrix schenckii in the Pathogen Box collection

Identification of two potential inhibitors of Sporothrix brasiliensis and Sporothrix schenckii in the Pathogen Box collection

Thymomodulin in association with antifungal drugs in the therapy of cats with disseminated cutaneous sporotrichosis: a prospective study

Bioisosteric modification on benzylidene‐carbonyl compounds improved the drug‐likeness and maintained the antifungal activity against Sporothrix brasiliensis

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