Minimal inhibitory concentration distributions and epidemiological cutoff values of five antifungal agents against Sporothrix brasiliensis

Almeida‐Paes, Rodrigo; Brito‐Santos, Fabio; Figueiredo-Carvalho, Maria Helena Galdino; Machado, Adriana Rodrigues; Oliveira, Manoel Marques Evangelista; Pereira, Sandro Antônio; Gutierrez-Galhardo, Maria Clara; Zancopé‐Oliveira, Rosely Maria

doi:10.1590/0074-02760160527

Cited by 34 publications

(33 citation statements)

References 29 publications

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“…Significant differences in antifungal susceptibilities have been observed among the four pathogenic species of the genus Sporothrix. In general, antifungal drugs show a good response against Sporothrix isolates from Brazil, especially terbinafine [23,[47][48][49][50]. In our reports, terbinafine was effective in vitro and in vivo, with remission of all clinical signs initially presented, as previously described in most cases of sporotrichosis in humans treated with this drug [21,22,[51][52][53][54].…”

Section: Discussionsupporting

confidence: 77%

Successful Treatment of Canine Sporotrichosis with Terbinafine: Case Reports and Literature Review

Viana¹,

Figueiredo²,

Gremião³

et al. 2017

Mycopathologia

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Sporotrichosis occurs worldwide, and the metropolitan region of Rio de Janeiro, Brazil, is a main endemic area, with a large number of human and animal cases in the last 19 years. This mycosis is more frequently described in cats rather than in dogs. There are a limited number of oral antifungal agents for the treatment of sporotrichosis in animals. In this context, the effectiveness of terbinafine in the treatment of sporotrichosis in humans, as well as the promising results of in vitro susceptibility tests, inspired us to use this drug in the therapy of this mycosis in dogs. We reported for the first time the use of terbinafine in the treatment of two dogs with sporotrichosis caused by Sporothrix brasiliensis. Moreover, we provided an overview of therapeutic features of canine sporotrichosis cases reported since the 1960s. One of the dogs presented the fixed cutaneous form of the disease, while the other patient presented hyperemia of the nasal mucosa and respiratory signs only. Terbinafine showed high antifungal activity in vitro against the canine Sporothrix isolates. The dogs were successfully treated with terbinafine, with remission of all clinical signs initially presented. The current reports indicate that this drug can emerge as a therapeutic option for canine sporotrichosis.

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Section: Discussionsupporting

confidence: 77%

Successful Treatment of Canine Sporotrichosis with Terbinafine: Case Reports and Literature Review

Viana¹,

Figueiredo²,

Gremião³

et al. 2017

Mycopathologia

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“…ECVs should distinguish the two populations (WT and non-WT) that are present in the MIC/MEC distribution of a species and agent combination. ECVs for S. brasiliensis and some agents were recently reported using data from a single laboratory (28). However, the definition of ECVs using data from multiple laboratories allows the evaluation of modal (more frequent values in each MIC/MEC distribution) compatibility among the individual distributions included in the pool (a CLSI requirement) (24).…”

Section: Resultsmentioning

confidence: 99%

Multicenter, International Study of MIC/MEC Distributions for Definition of Epidemiological Cutoff Values for Sporothrix Species Identified by Molecular Methods

Espinel-Ingroff

Abreu

Almeida‐Paes

et al. 2017

Antimicrob Agents Chemother

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Clinical and Laboratory Standards Institute (CLSI) conditions for testing the susceptibilities of pathogenic species to antifungal agents are based on a collaborative study that evaluated five clinically relevant isolates of and some antifungal agents. With the advent of molecular identification, there are two basic needs: to confirm the suitability of these testing conditions for all agents and species and to establish species-specific epidemiologic cutoff values (ECVs) or breakpoints (BPs) for the species. We collected available CLSI MICs/minimal effective concentrations (MECs) of amphotericin B, five triazoles, terbinafine, flucytosine, and caspofungin for 301, 486 , 75, and 13 molecularly identified isolates. Data were obtained in 17 independent laboratories (Australia, Europe, India, South Africa, and South and North America) using conidial inoculum suspensions and 48 to 72 h of incubation at 35°C. Sufficient and suitable data (modal MICs within 2-fold concentrations) allowed the proposal of the following ECVs for and , respectively: amphotericin B, 4 and 4 μg/ml; itraconazole, 2 and 2 μg/ml; posaconazole, 2 and 2 μg/ml; and voriconazole, 64 and 32 μg/ml. Ketoconazole and terbinafine ECVs for were 2 and 0.12 μg/ml, respectively. Insufficient or unsuitable data precluded the calculation of ketoconazole and terbinafine (or any other antifungal agent) ECVs for , as well as ECVs for and These ECVs could aid the clinician in identifying potentially resistant isolates (non-wild type) less likely to respond to therapy.

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“…This heterogeneity could be related to the intra-species genetic variation and/or differences in gene expression. Almeida-Paes et al (2017) reported that S. brasiliensis isolates from human and cats with sporotrichosis had similar sensibility to azoles, but exhibited differences to amphotericin B and terbinafine susceptibilities ( Almeida-Paes et al, 2017 ). The lower sensitivity of feline-borne isolates to tacrolimus as monotherapy may stem from an adaptation of fungal isolates to the higher body temperature encountered in cats (compared with that found in humans).…”

Section: Discussionmentioning

confidence: 99%

Tacrolimus Increases the Effectiveness of Itraconazole and Fluconazole against Sporothrix spp.

et al. 2017

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Calcineurin inhibitors – such as the clinically used drug tacrolimus – are active against important fungal pathogens, particularly when combined with azoles. However, tacrolimus has not been tested against sporotrichosis, an endemic subcutaneous mycosis with worldwide distribution. Here, we evaluated the activity of tacrolimus and cyclosporine A in vitro – as monotherapy and in combination with itraconazole or fluconazole – against yeasts of Sporothrix brasiliensis and S. schenckii, the main sporotrichosis agents in Brazil. We also analyzed the effect of tacrolimus treatment on intracellular neutral lipid levels, which typically increase after azole treatment. Tacrolimus inhibited the growth of yeasts from S. brasiliensis and S. schenckii reference isolates, with minimum inhibitory concentration (MIC) values (required for ≥50% growth inhibition) of 1 and 2 mg/L, respectively. Importantly, the combination of tacrolimus and azoles exhibited high synergy toward reference Sporothrix isolates. Tacrolimus combined with itraconazole significantly increased neutral lipid accumulation in S. brasiliensis, but not in S. schenckii. Clinical isolates of S. brasiliensis and S. schenckii were more sensitive to tacrolimus as monotherapy than feline-borne isolates, however, synergy between tacrolimus and azoles was only observed for feline-borne isolates. Cyclosporine A was effective against S. brasiliensis and S. schenckii as monotherapy (MIC = 1 mg/L), but exhibited no synergy with itraconazole and fluconazole. We conclude that tacrolimus has promising antifungal activity against sporotrichosis agents, and also increases the activity of the current anti-sporotrichosis therapy (itraconazole and fluconazole) in combination assays against S. brasiliensis feline-borne isolates.

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Minimal inhibitory concentration distributions and epidemiological cutoff values of five antifungal agents against Sporothrix brasiliensis

Cited by 34 publications

References 29 publications

Successful Treatment of Canine Sporotrichosis with Terbinafine: Case Reports and Literature Review

Successful Treatment of Canine Sporotrichosis with Terbinafine: Case Reports and Literature Review

Multicenter, International Study of MIC/MEC Distributions for Definition of Epidemiological Cutoff Values for Sporothrix Species Identified by Molecular Methods

Tacrolimus Increases the Effectiveness of Itraconazole and Fluconazole against Sporothrix spp.

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