Successful treatment of a disseminated Sporothrix schenckii infection and in vitro analysis for antifungal susceptibility testing

Kohler, Lidiane Meire; Hamdan, Júnia Soares; Ferrari, Teresa Cristina Abreu

doi:10.1016/j.diagmicrobio.2006.11.002

Cited by 19 publications

(16 citation statements)

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“…As demonstrated experimentally (16) and corroborated in clinical reports (19,26), amphotericin B is effective for the treat- ment of disseminated sporotrichosis. It should be noted that Sporothrix infections are frequently chronic and consequently require long-term therapy.…”

Section: Discussionmentioning

confidence: 58%

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Efficacy of Posaconazole in Murine Experimental Sporotrichosis

Fernández-Silva

Capilla

Mayayo

et al. 2012

Antimicrob Agents Chemother

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We developed a murine model of systemic sporotrichosis by using three strains of each of the two commonest species causing sporotrichosis, i.e., Sporothrix schenckii sensu stricto and Sporothrix brasiliensis, in order to evaluate the efficacy of posaconazole (PSC). The drug was administered at a dose of 2.5 or 5 mg/kg of body weight twice a day by gavage, and one group was treated with amphotericin B (AMB) as a control treatment. Posaconazole, especially at 5 mg/kg, showed good efficacy against all the strains tested, regardless of their MICs, as measured by prolonged survival, tissue burden reduction, and histopathology. Sporotrichosis is the most common and cosmopolitan subcutaneous mycosis (13). The most usual clinical manifestation of the disease is the subacute or chronic lymphocutaneous form, followed by fixed cutaneous infections (5); however, disseminated infections have also been described for those with underlying alcoholism and for immunosuppressed patients, especially those with AIDS or those receiving chemotherapy or corticoids (11,13,17). Sporotrichosis is caused by a group of species belonging to the Sporothrix schenckii complex which have various individual in vitro responses to antifungal agents. The differential antifungal activity among Sporothrix species could explain the variability in antifungal susceptibility reported for S. schenckii in studies prior to the recent recognition of the S. schenckii complex (5,20,21).The recommended procedures for the management of sporotrichosis include local measures such as hyperthermia and systemic measures such as administration of a saturated solution of potassium iodide or administration of azoles (itraconazole and fluconazole), amphotericin B, or terbinafine (15). Itraconazole has become the drug of choice for treatment of the lymphocutaneous and cutaneous forms. In those patients with intolerance to itraconazole, fluconazole is the recommended alternative. Amphotericin B is the first choice for the treatment of disseminated sporotrichosis, and itraconazole is recommended as the stepdown therapy after patients respond to the initial treatment with amphotericin B (18).Posaconazole has shown activity in vitro against the species of the S. schenckii complex (21, 25). Since treatment options for disseminated sporotrichosis are limited and there is only scarce information on the effectiveness of posaconazole in vivo, we evaluated the response to this drug in a murine model of disseminated sporotrichosis. MATERIALS AND METHODSFungi were stored in slant cultures covered with sterile paraffin oil and subcultured on potato dextrose agar (PDA) plates at 30°C for 7 days.In vitro antifungal susceptibility to posaconazole of 5 isolates of S. brasiliensis and 10 of S. schenckii sensu stricto was determined using a broth microdilution method according to the CLSI guidelines for filamentous fungi (8).For the in vivo studies, strains of S. brasiliensis (n ϭ 3) and S. schenckii sensu stricto (n ϭ 5) showing different MIC values were chosen. The inocula were prepared by...

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Section: Discussionmentioning

confidence: 58%

“…Although cases of systemic sporotrichosis are fortunately not frequent, several cases have been described (1,3,15,19,22,26). Amphotericin B is the most common drug used in the treatment of disseminated sporotrichosis, but the dosage is limited by its toxicity and by the long-term therapy required.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Posaconazole in Murine Experimental Sporotrichosis

Fernández-Silva

Capilla

Mayayo

et al. 2012

Antimicrob Agents Chemother

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“…After the skin, bone tissue is the most affected. The osteoarticular form may occur by contiguity or hematogenous spread (120,170). The lesions may vary from small granulomas to large lytic lesions identical to osteomyelitis (125).…”

Section: Pathogenesis and Clinical Forms Human Diseasementioning

confidence: 99%

Sporothrix schenckii and Sporotrichosis

Barros

Paes²,

Schubach³

2011

Clin Microbiol Rev

532

677

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SUMMARY Sporotrichosis, which is caused by the dimorphic fungus Sporothrix schenckii , is currently distributed throughout the world, especially in tropical and subtropical zones. Infection generally occurs by traumatic inoculation of soil, plants, and organic matter contaminated with the fungus. Certain leisure and occupational activities, such as floriculture, agriculture, mining, and wood exploitation, are traditionally associated with the mycosis. Zoonotic transmission has been described in isolated cases or in small outbreaks. Since the end of the 1990s there has been an epidemic of sporotrichosis associated with transmission by cats in Rio de Janeiro, Brazil. More than 2,000 human cases and 3,000 animal cases have been reported. In humans, the lesions are usually restricted to the skin, subcutaneous cellular tissue, and adjacent lymphatic vessels. In cats, the disease can evolve with severe clinical manifestations and frequent systemic involvement. The gold standard for sporotrichosis diagnosis is culture. However, serological, histopathological, and molecular approaches have been recently adopted as auxiliary tools for the diagnosis of this mycotic infection. The first-choice treatment for both humans and cats is itraconazole.

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“…Four equidistant holes were made in each agar-extract dish with sterile Durham tubes; 30 µL of the spore suspension were placed in each hole, incubated al 27°C for 21 days for S. schenckii and 28 days for F. pedrosoi; as controls, dishes containing 35% ethanol (growth 100%) and 100 µg/mL amphotericin B (growth 0%) were prepared. Amphotericin B was chosen as positive control since it is used as drug for the treatment of both fungi (Kohler et al, 2007;López Martínez & Mendez Tovar, 2007). The colony diameter was measured in millimeter using a vernier and an extract was considered active when it showed 75% inhibition of the colony diameter in comparison with the control.…”

Section: Antifungal Assaymentioning

confidence: 99%

“…It occurs globally in tropical and subtropical regions and is characterized by nodular lesions, associated with lymphadenopathy ( Morris-Jones, 2002;Ramos-e-Silva et al, 2007), which become disseminated in AIDS patients (Ware et al, 1999). The available therapy in the majority of patients consists of treatment with terbinafine (Hull & Vismer, 1992), potassium iodide (Sandhu & Gupta, 2003), amphotericin B (Kohler et al, 2007), itraconazole and ketoconazole (Alvarado-Ramírez & Torres-Rodríguez, 2007).…”

Section: Introductionmentioning

confidence: 99%