amphotericin-b and Sporotrichosis

Sporotrichosis is a rare fungal infection in transplant patients; among these patients, it occurs mostly in renal transplant patients. Sporothrix schenkii is the primary pathogen responsible. A high index of suspicion is required to make the diagnosis keeping important differential diagnoses in mind. History of trauma through recreational or occupational exposure to the fungus may assist in making the diagnosis. Treatment is difficult, with long-term use of potentially nephrotoxic and cytochrome P450 inhibitor antifungal agents leading to potential calcineurin inhibitors toxicity. We describe two renal transplant patients presenting with distinct sporotrichosis infection: "Case 2" being only the second reported case ever of meningeal sporotrichosis. We subsequently review the general aspects of sporotrichosis, specifically in renal transplant patients as described in the medical literature.. Case 1, a 43-year-old mixed ancestry male patient presented with a non-healing ulcer on the left arm for 1 year, he was diagnosed with cutaneous sporotrichosis and was successfully treated with itraconazole monotherapy. Case 2, a 56-year-old mixed ancestry male patient presented with a slow decline in functions, confusion, inappropriate behavior, rigors and significant loss of weight and appetite over the past 4 months, he was diagnosed with meningeal sporotrichosis and was successfully treated with a combination of deoxycholate amphotericin B and itraconazole.. Physicians taking care of renal transplant patients should have a high index of suspicion for sporotrichosis infection particularly when conventional therapy for common conditions fails. Susceptibility testing is recommended to identify the most effective antifungal agent and its dose. The slow nature of growth of Sporothrix schenkii necessitates patients to be on amphotericin B until the time results are available. Finally, there is a need to be aware of potential drug-drug interactions of the azoles with calcineurin inhibitors and the required dose adjustments to prevent therapy related adverse events.

Topics: Adult; Amphotericin B; Antifungal Agents; Deoxycholic Acid; Drug Combinations; Humans; Itraconazole; Kidney Transplantation; Male; Meningitis, Fungal; Middle Aged; Opportunistic Infections; Skin Ulcer; Sporotrichosis; Transplant Recipients

Sporotrichosis is an implantation mycosis caused by. To systematically review and analyse data from published literature with a view to comparing clinical outcomes between exogenous and endogenous endophthalmitis caused by. Case reports of intraocular sporotrichosis, published from 1960 to 2016, were retrieved from MEDLINE, Embase, Cochrane, LILACS and SciELO databases. The entire data set was divided into two patient groups: (1) exogenous endophthalmitis and (2) endogenous endophthalmitis. Primary outcomes were differences in ocular findings and clinical ocular outcomes between the two groups.. From 16 publications retrieved, a total of 8 eyes of 8 patients with exogenous endophthalmitis and 13 eyes of 10 patients with endogenous endophthalmitis were identified. Compared with exogenous endophthalmitis, endogenous endophthalmitis was more common in patients infected with HIV (p=0.001) and those from hyperendemic areas (p=0.036). Anterior uveitis (p=0.015) and posterior uveitis (p=0.04) were more common in the exogenous and endogenous endophthalmitis groups, respectively. The majority of patients with endogenous endophthalmitis had partial or full clinical resolution of ocular lesions with systemic amphotericin B alone or in combination with an oral antifungal, whereas patients with exogenous endophthalmitis had poor outcomes with irreversible vision loss, enucleation and evisceration.. Anterior uveitis is more common in exogenous endophthalmitis with worse overall outcomes and complications, compared with endogenous endophthalmitis where posterior uveitis is the most common clinical manifestation, especially in patients infected with HIV and those from hyperendemic areas.

Topics: Administration, Ophthalmic; Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Child; Drug Therapy, Combination; Endophthalmitis; Eye Infections, Fungal; Female; Glucocorticoids; Humans; Intravitreal Injections; Male; Middle Aged; Risk Factors; Sporothrix; Sporotrichosis; Treatment Outcome; Visual Acuity; Voriconazole; Young Adult

Feline sporotrichosis has been reported in Malaysia since the 1990's. Since then, studies have revealed that clinical clade D, Sporothrix schenckii sensu stricto, of a single clonal strain is the most common cause of this disease in Malaysia. The prevalence of a single clonal strain from a clinical clade was never before reported in Asia in a specific geographical niche. This raises the possibility of a process of purifying selection and subsequent clonal proliferation. While agricultural practices may serve as the selective pressure, direct causality has yet to be established. Studies into the thermo-tolerability of the Malaysian clonal strain of S. schenckii sensu stricto revealed that a small minority of clinical isolates have the capacity to grow at 37℃, while the majority displayed low susceptibility to commonly used antifungals in clinical practice, such as itraconazole (ITZ) and terbinafine (TRB). Despite unestablished breakpoints, suspected resistance (MIC > 4 mg/mL) towards amphotericin B (AMB) and fluconazole (FLC) was recorded in the isolates. This explains the often lack of clinical response in feline patients treated with recommended doses of antifungals, including ITZ. Coupled with the potential zoonotic transmission to clients and veterinarians, protracted treatment period, and subsequent cost of treatment, prognosis of feline sporotrichosis is often regarded to be poor. The use of a higher dose of ITZ has been reported, and an adoption of this high-dose treatment regime is reported in this manuscript, with complete cure achieved in cases of recalcitrant and/or unresponsive feline sporotrichosis, which would otherwise be euthanized.

Topics: Amphotericin B; Animals; Antifungal Agents; Cat Diseases; Cats; Drug Resistance, Fungal; Fluconazole; Humans; Itraconazole; Malaysia; Naphthalenes; Prevalence; Sporothrix; Sporotrichosis; Terbinafine; Zoonoses

A case of cavitary pulmonary sporotrichosis without mucocutaneous involvement caused by Sporothrix schenckii is reported in a sexagenarian woman with a long smoking history. The patient was hospitalized for septic shock with multiorgan failure from a respiratory focus. The diagnosis was delayed due to the fungal etiological agent was not initially considered in the differential diagnosis. A good clinical and radiological evolution was obtained with the antifungal therapy. Occasional cases of primary pulmonary sporotrichosis have been reported in the literature. Due to its low incidence, this is a less-known and underestimated clinical form. Both clinical suspicion and microbiological studies are needed to reach pulmonary sporotrichosis diagnosis.

Topics: Aged; Amphotericin B; Antifungal Agents; Female; Humans; Itraconazole; Lung Diseases, Fungal; Pneumonia; Shock, Septic; Smoking; Sporothrix; Sporotrichosis

Feline sporotrichosis, which is caused by species of the Sporothrix schenckii complex, is endemic to Rio de Janeiro, Brazil. More than 4000 cases of the disease were diagnosed at Fundação Oswaldo Cruz, Brazil, between 1998 and 2012. Sporotrichosis in cats has been reported in several countries, but nowhere has an outbreak of animal sporotrichosis been as large as that seen in Brazil. The clinical manifestations of the disease range from an isolated skin lesion that can progress to multiple skin lesions and even fatal systemic involvement. Nodules and ulcers are the most common types of lesions, and respiratory signs and mucosa involvement are frequent. The definitive diagnosis depends on isolation of the etiologic agent in culture. Cytology, histopathology, and serology are useful tools for preliminary diagnosis. Severe pyogranulomatous inflammatory infiltrate, high fungal load, and extension of lesions to mucosa, cartilage, and bone in the nose of cats are indicative of an agent of high virulence in this endemic region. Itraconazole is the drug of choice, while, in refractory cases, amphotericin B or potassium iodide might be alternative treatments; however, recurrence after discharge may occur. Sporotrichosis persists as a neglected disease in Rio de Janeiro, and the treatment of cats remains a challenging and long-term endeavor.

Topics: Amphotericin B; Animals; Antifungal Agents; Brazil; Cat Diseases; Cats; Endemic Diseases; Itraconazole; Potassium Iodide; Sporothrix; Sporotrichosis

Granulomatous diseases are caused by multiple infectious and noninfectious causes. Deep fungal infections can present in the skin or extracutaneously, most commonly with lung manifestations. An Azole or amphotericin B is the universal treatment. Blastomycosis-like pyoderma is a clinically similar condition, which is caused by a combination of hypersensitivity and immunosuppression. Successful treatment has been reported with antibiotics and, more recently, the vitamin A analog, acitretin. Granuloma inguinale and lymphogranuloma venereum cause ulcerative genital lesions with a granulomatous appearance on histology. The Centers for Disease Control and Prevention recommens treatment of these genital infections with doxycycline.

Topics: Acitretin; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Azoles; Blastomycosis; Coccidioidomycosis; Cryptococcosis; Dermatomycoses; Doxycycline; Granuloma Inguinale; Histoplasmosis; Humans; Keratolytic Agents; Lymphogranuloma Venereum; Mycoses; Pyoderma; Sexually Transmitted Diseases; Sporotrichosis

Endemic mycoses remain a major public health problem in several countries and they are becoming increasingly frequent with the spread of HIV infection. Amphotericin B remains the drug of choice during the acute stage of life-threatening endemic mycoses occurring in both immunocompetent and immunocompromised hosts. Ketoconazole is effective in non-AIDS patients with non-life-threatening histoplasmosis, blastomycosis, or paracoccidioidomycosis. Itraconazole is the treatment of choice for non-life-threatening Histoplasma capsulatum or Blastomyces dermatitidis infections occurring in immunocompetent individuals and is the most efficient secondary prophylaxis of histoplasmosis in AIDS patients. Itraconazole is also effective in lymphocutaneous and visceral sporotrichosis, in paracoccidioidomycosis, for Penicillum marneffei infection, and is an alternative to amphotericin B for Histoplasma duboisii infection. Coccidioidomycosis may be effectively treated with prolonged and sometimes life-long itraconazole or fluconazole therapy. Fluconazole has relatively poor efficacy against histoplasmosis, blastomycosis and sporotrichosis. New antifungal agents have been tested in vitro or in animal models and may soon be evaluated in clinical trials.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Blastomycosis; Coccidioidomycosis; Histoplasmosis; Humans; Mycoses; Paracoccidioidomycosis; Sporotrichosis

The so-called exotic pulmonary mycoses are imported diseases in France. They are infrequent or exceptional and for this reason can be underdiagnosed or recognized with delay. Nevertheless, they are easily treatable infections with available antifungal agents. As a rule, the site of primary infection is the lung with ensuing clearance or chronic local infection and/or dissemination. Immunocompromised hosts are more prone to develop severe forms or reactivation of the disease.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Anti-Infective Agents; Antifungal Agents; Blastomycosis; Coccidioidomycosis; Diagnosis, Differential; Histoplasmosis; Humans; Itraconazole; Ketoconazole; Lung Diseases, Fungal; Paracoccidioidomycosis; Penicillium; Sporotrichosis; Sulfadiazine; Travel; Trimethoprim, Sulfamethoxazole Drug Combination

We report here the case of a 12-year-old girl with concomitant cutaneous and ocular sporotrichosis. Sporothrix schenckii was isolated from skin lesions and aqueous humour. The difficulty in the diagnosis and treatment of this form of mycosis is discussed and the data are compared with those published in the few reports available in the literature.

Topics: Amphotericin B; Anterior Chamber; Brazil; Child; Eye Infections, Fungal; Female; Fluconazole; Humans; Paracentesis; Potassium Iodide; Sporotrichosis; Timolol; Uveitis

The old therapies for sporotrichosis--saturated solution of potassium iodide (SSKI) and amphotericin B--have largely been supplanted by itraconazole treatment. Although SSKI is effective for the treatment of lymphocutaneous sporotrichosis, it is difficult to administer and is frequently associated with side effects; response rates of >90% are associated with itraconazole therapy for lymphocutaneous sporotrichosis. Patients with osteoarticular sporotrichosis rarely have systemic symptoms and can be effectively treated with a prolonged course of itraconazole, thus obviating the need for intravenous amphotericin B therapy with its associated toxic effects. Pulmonary sporotrichosis in patients infected with human immunodeficiency virus continue to be difficult therapeutic problems, but itraconazole appears to be at least as effective as amphotericin B as treatment for these forms of sporotrichosis.

Topics: Amphotericin B; Animals; Antifungal Agents; Azoles; Humans; Itraconazole; Potassium Iodide; Sporotrichosis

Sporotrichosis is a fungal infection caused by the dimorphic organism, Sporothrix schenkii. This etiologic agent typically gains entrance into the skin by traumatic implantation of infected soil or plant materials. The majority of cases are of the fixed cutaneous or lymphangitic cutaneous varieties, and less commonly, hematogenous dissemination to skin or viscera occurs. Untreated, the disease may spontaneously resolve or persist and gradually progress over time, its virulence being less than that of other dimorphic fungi. Potassium iodide remains a favored treatment for uncomplicated cutaneous disease. Amphotericin B, with its high toxicity, has historically been reserved for recalcitrant cutaneous or disseminated disease. Itraconazole, the newest triazole antifungal to become available in the United States, seems to be highly effective against Sporothrix schenkii without significant adverse effects and will likely become the first line therapy for all forms of this disease in the future.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Diagnosis, Differential; Hot Temperature; Humans; Potassium Iodide; Risk Factors; Sporotrichosis

Multifocal systemic sporotrichosis (disseminated sporotrichosis) with lobar pulmonary involvement is uncommon. We describe successful treatment with amphotericin B in such a patient and review data from 1 other similar case previously reported and 7 with nonlobar pulmonary involvement.

Topics: Aged; Amphotericin B; Humans; Lung Diseases, Fungal; Male; Sporotrichosis

Topics: Age Factors; Aged; Amphotericin B; Blastomycosis; Coccidioidomycosis; Histoplasmosis; Humans; Ketoconazole; Recurrence; Sporotrichosis; United States

Four culture-documented cases of pulmonary sporotrichosis, three primary infections and one with multisystem involvement, are presented. Two of these patients are the first reported cases of primary lung disease treated with ketoconazole. This antifungal agent appears to be ineffective in eradicating this infection. The four cases, as well as a review of the literature, illustrate several important aspects of this rare disease. Pulmonary sporotrichosis is most commonly found in males with a history of alcohol abuse who are between the ages of 30 and 60. The infection is usually confined to the parenchyma of the lung but can involve hilar and mediastinal lymph nodes, pleura, skin, subcutaneous tissue, and joints. All but two cases have been reported in the United States, and the majority reside within states bordering the Missouri or Mississippi rivers. Direct occupational or environmental exposure appears to be an important predisposing risk factor. The onset of the disease is insidious, presenting in a manner similar to many other granulomatous or neoplastic diseases. Tuberculosis is the most common suspected diagnosis before confirmation of sporotrichosis. The chest radiograph most commonly demonstrates upperlobe cavitary disease with surrounding parenchymal infiltrates. The diagnosis can be suspected with high serologic titers or skin-test positivity, but needs to be confirmed by culture. The organism can usually be grown from sputum, as well as routine bronchoscopic procedures, open-lung biopsy specimens or pleural fluid. Histologic examination shows granulomas of both the caseating and noncaseating varieties. Frequently, organisms can be seen in necrotic areas of the lung tissue by diastase-modified GMS or PAS staining. Staining by direct fluorescent antibody technique can also be done and appears to be highly specific. Treatment is controversial, but total surgical resection of diseased lung as well as a perioperative regimen of SSKI or amphotericin B appears to be the most efficacious therapy. Medical therapy alone with SSKI or amphotericin B may be useful in selected cases but has been disappointing in the majority of reports. The imidazoles are usually ineffective, and the search for more effective medical therapy continues.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Diagnosis, Differential; Humans; Ketoconazole; Lung; Lung Diseases, Fungal; Male; Middle Aged; Pneumonectomy; Radiography; Sporotrichosis; Tuberculosis, Pulmonary

The deep mycoses are increasing in importance both as opportunistic infections and from exposure in geographically defined areas. Diagnosis may be difficult in both groups. Mucosal involvement may be non-specific (e.g., in disseminated candidiasis) or highly predictive of disseminated disease (e.g., histoplasmosis, blastomycosis and paracoccidioidomycosis). Skin involvement is generally uncommon in disseminated aspergillosis, mucormycosis and cryptococcosis but is more common in candidemia and coccidioidomycosis. Manifestations of mucosal and cutaneous lesions of the deep mycoses are reviewed and the need for an aggressive diagnostic approach stressed. Culture is more specific than histopathologic examination alone but the latter may have to suffice in some cases. Control of underlying disease and administration of amphotericin B remain the mainstays of therapy. Ketoconazole is being evaluated as an alternative in therapy of some deep mycoses.

Topics: Amphotericin B; Aspergillosis; Blastomycosis; Candidiasis; Candidiasis, Cutaneous; Coccidioidomycosis; Cryptococcosis; Dermatomycoses; Flucytosine; Histoplasmosis; Humans; Immunosuppression Therapy; Ketoconazole; Miconazole; Mouth Diseases; Mouth Mucosa; Mucormycosis; Mycoses; Paracoccidioidomycosis; Sporotrichosis; Travel

In the past 20 years, there has been a marked increase in the number of reported cases of meningitis and brain abscess due to fungi and yeasts. This increase is due in part to better diagnostic techniques and greater awareness of the possibility of fungal invasion of the nervous system; but the increase can also be attributed to a growing pool of severely compromised hosts, many of whom are undergoing treatment with adrenal glucocorticoids or immunosuppressive agents. The diagnosis and treatment of aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, cryptococcosis, infections caused by dematiaceous fungi, histoplasmosis, paracoccidioidomycosis, petriellidosis, and sporotrichosis, as well as relatively rare infections of the central nervous system caused by other fungi, are discussed. The efficacy of amphotericin B and 5-fluorocytosine in the treatment of CNS fungal and yeast infections is also evaluated.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Blastomycosis; Candidiasis; Central Nervous System Diseases; Chromoblastomycosis; Cladosporium; Coccidioidomycosis; Cryptococcosis; Female; Fungi; Histoplasmosis; Humans; Male; Meningitis; Meningoencephalitis; Middle Aged; Mucormycosis; Mycoses; Paracoccidioidomycosis; Phialophora; Sporotrichosis

Topics: Actinomycosis; Amphotericin B; Antifungal Agents; Aspergillosis; Blastomycosis; Candidiasis; Coccidioidomycosis; Cryptococcosis; Flucytosine; Histoplasmosis; Humans; Mucormycosis; Mycoses; Nocardia Infections; Sporotrichosis

Topics: Actinomycosis; Adolescent; Adult; Amphotericin B; Animals; Aspergillosis; Basidiomycota; Blastomycosis; Candidiasis; Cephalosporins; Child; Chromoblastomycosis; Coccidioidomycosis; Conjunctiva; Cryptococcosis; Drug Synergism; Eye Diseases; Female; Fungi; Geotrichosis; Guinea Pigs; Histoplasmosis; Humans; Male; Mucor; Mycetoma; Mycoses; Natamycin; Nystatin; Penicillium; Pityriasis; Rabbits; Rhinosporidiosis; Sporotrichosis; Tinea

Topics: Actinomycosis; Amphotericin B; Anti-Bacterial Agents; Aspergillosis; Blastomycosis; Candidiasis; Coccidioidomycosis; Cryptococcosis; Griseofulvin; Histoplasmosis; Humans; Iodides; Mucormycosis; Mycoses; Nocardia Infections; Nystatin; Penicillins; Sporotrichosis; Stilbamidines; Sulfadiazine; Surgical Procedures, Operative; Toxicology

Topics: Adult; Amphotericin B; Blastomycosis; Clinical Trials as Topic; Coccidioidomycosis; Cryptococcosis; Female; Histoplasmosis; Humans; Male; Middle Aged; Sporotrichosis

Sporotrichosis is a subcutaneous and chronic infection caused by traumatic inoculation of pathogenic sporothrix species, usually infecting the skins and subcutaneous tissues of humans and animals. However, the lack of epidemiological data required further molecular identification to describe the distribution of this fungus in our region. In this study, forty-eight clinical sporothrix isolated from Sun Yat-Sen Memorial Hospital were classified, and the susceptibility of each strain to seven antifungal agents was determined.. Forty strains of S. globosa and eight strains of S. shenkshii were identified via colony morphology and PCR sequencing of calmodulin gene.. Antifungal susceptibility tests of the mycelial phase in vitro showed terbinafine (TRB) and luliconazole (LULI) were the most effective, followed by itraconazole (ITZ) and amphotericin B (AMB). By contrast, voriconazole (VCZ), 5-flucytosine (5FC) and fluconazole (FCZ) have low efficacy with high MIC.. Our results showed a predominantly S. globosa infection trend in southern China. Simultaneously, sporothrix is sensitive to TRB, LULI, ITZ and AMB whereas resistant to FCZ. This study firstly reports antifungal sensitivity test in vitro and epidemiological correlation analysis of sporothrix in southern China, and also the first time to find that sporothrix is sensitive to LULI.

Topics: Amphotericin B; Animals; Antifungal Agents; China; Flucytosine; Humans; Itraconazole; Microbial Sensitivity Tests; Prevalence; Sporothrix; Sporotrichosis; Terbinafine

Feline sporotrichosis caused by the Sporothrix schenckii complex is a global subcutaneous mycosis, having higher prevalence in Latin America and Malaysia. However, its etiological agents have not been elucidated in Thailand, a neighboring country of Malaysia, where the cases are increasing. This study identified 38 feline isolates of S. schenckii from Southern Thailand, collected between 2018 and 2021, using phenotypic characterization and molecular identification using polymerase chain reaction (PCR)-sequencing of partial calmodulin (CAL) and ß-tubulin (Bt2) genes. Phenotypic characteristics proved that the isolates were S. schenckii sensu lato, with low thermotolerance. Based on partial CAL and Bt2-PCR sequencing, all isolates were identified as S. schenckii sensu stricto. Phylogenetic analyses revealed that the isolates were clustered with S. schenckii sensu stricto isolated from the cats in Malaysia. A low degree of genetic diversity was observed among the Thai feline isolates. The antifungal susceptibility of these isolates to antifungal agents, including itraconazole (ITC), ketoconazole (KTC), fluconazole (FLC), and amphotericin B (AMB), was investigated according to the M27-A3 protocol of the Clinical and Laboratory Standards Institute. Results showed low ITC, KTC, and AMB activities against S. schenckii sensu stricto isolates, with high minimum inhibitory concentration (MIC) ranges of 1-8, 1-8, and 2-16 μg/ml, respectively, whereas FLC exhibited MICs of 64 and > 64 μg/ml. This study indicated that S. schenckii sensu stricto is the causative agent responsible for feline sporotrichosis in Southern Thailand. Their phenotypic characteristics and in vitro antifungal susceptibility profiles will help to improve our understanding of this mycosis in Thailand.. Sporothrix schenckii sensu stricto is a causative agent of feline sporotrichosis in Southern Thailand identified by PCR-sequencing of calmodulin and ß-tubulin genes. Phenotypic tests are not recommended for species identification. All isolates showed low susceptibility to commonly used antifungals.

Topics: Amphotericin B; Animals; Antifungal Agents; Calmodulin; Cat Diseases; Cats; Fluconazole; Itraconazole; Ketoconazole; Microbial Sensitivity Tests; Phylogeny; Sporothrix; Sporotrichosis; Thailand; Tubulin

The dimorphic fungus Sporothrix globosa is the predominant etiologic agent causing sporotrichosis in China, particularly in the northeast. It has been demonstrated that the incubation temperature and growth phase can influence in vitro antifungal susceptibility profiles of S. schenckii sensu stricto and S. brasiliensis (sibling species of S. globosa). Few studies have reported on the antifungal susceptibility of S. globosa, especially using large numbers of isolates. In this study, we assessed the susceptibility of 80 isolates of S. globosa originating from Jilin Province, northeastern China, to six antifungal agents (itraconazole, terbinafine, voriconazole, posaconazole, fluconazole, and amphotericin B), at varying incubation temperatures and in different fungal growth phases. The isolates were most sensitive to terbinafine (geometric mean [GM] of the minimum inhibitory concentration [MIC]: 0.0356 μg/ml for the mycelial phase at 30 °C, 0.0332 μg/ml for the mycelial phase at 35 °C, and 0.031 μg/ml for the yeast phase, respectively), followed by posaconazole (GM of the MIC: 4.2501 μg/ml for the mycelial phase at 30 °C, 1.4142 μg/ml for the mycelial phase at 35 °C, and 0.7195 μg/ml for the yeast phase, respectively) and itraconazole (GM of the MIC: 6.8448 μg/ml for the mycelial phase at 30 °C, 3.1383 μg/ml for the mycelial phase at 35 °C, and 1.0263 μg/ml for the yeast phase, respectively). The isolates were relatively resistant to fluconazole (GM of the MIC: 76.7716 μg/ml for the mycelial phase at 30 °C, 66.2570 μg/ml for the mycelial phase at 35 °C, and 24.4625 μg/ml for the yeast phase, respectively) and voriconazole (GM of the MIC: 26.2183 μg/ml for the mycelial phase at 30 °C, 13.6895 μg/ml for the mycelial phase at 35 °C, and 1.3899 μg/ml for the yeast phase, respectively). For all the tested azole drugs, the MICs at 30 °C were significantly higher than those at 35 °C (P < 0.001); for all agents except terbinafine, the MICs of S. globosa in the yeast phase were significantly lower than those of the strains in the mycelial phase (P < 0.001). These results show that the sensitivities of S. globosa to antifungal compounds are dependent on incubation temperature and growth phase. To the best of our knowledge, this is the largest study of antifungal susceptibility of S. globosa isolates reported to date. To establish epidemiological cutoff values for S. globosa, further antifungal susceptibility testing studies by independent laboratories located in differ

Topics: Amphotericin B; Antifungal Agents; China; Fluconazole; Humans; Itraconazole; Microbial Sensitivity Tests; Mycelium; Phylogeny; Saccharomyces cerevisiae; Sporothrix; Sporotrichosis; Terbinafine; Triazoles

The in vitro activity of ibuprofen, a nonsteroidal anti-inflammatory drug, was evaluated against Sporothrix brasiliensis and S. schenckii, either alone or in combination with amphotericin B, itraconazole, or terbinafine. The inhibitory activity of ibuprofen as a single agent was determined according to minimum inhibitory concentration (MIC) values, while the effect of ibuprofen combined with amphotericin B, itraconazole, or terbinafine was estimated by microdilution checkerboard methodology. The ultrastructural alterations of S. schenckii after exposure to the combination of ibuprofen and amphotericin B were evaluated by scanning electron microscopy (SEM) and flow cytometry analysis. As a single agent, ibuprofen inhibited Sporothrix growth with a MIC median of 256 μg/mL, while the MIC medians of ibuprofen in combination with antifungals were 16 μg/mL and 128 μg/mL. The MIC values of amphotericin B, itraconazole, and terbinafine were reduced when isolates were co-incubated with ibuprofen, mainly the polyene. The major alteration after treatment with the ibuprofen/amphotericin B combination was the increase in the presence of filamentous forms and high membrane damage with loss of plasma membrane integrity. In summary, we demonstrated that ibuprofen increases the in vitro activity of antifungals, mainly amphotericin B, against S. brasiliensis and S. schenckii. Future in vivo studies exploring combination therapy with ibuprofen and antifungals in animal models are needed to confirm its efficacy.

Topics: Amphotericin B; Anti-Inflammatory Agents, Non-Steroidal; Antifungal Agents; Cell Membrane; Drug Synergism; Humans; Ibuprofen; Microbial Sensitivity Tests; Reactive Oxygen Species; Sporothrix; Sporotrichosis; Terbinafine

Sporotrichosis, a mycosis caused by pathogenic species of the genus Sporothrix, affects diverse species of mammals. Until 2007, Sporothrix schenckii was considered the unique etiologic agent of sporotrichosis. Canine sporotrichosis is a poorly reported disease, and the majority of cases are from Rio de Janeiro, Brazil. There are scarce studies on the characterization of canine isolates of Sporothrix schenckii complex, as well as few antifungal susceptibility data available. The aim of this study was to characterize the clinical isolates of Sporothrix from dogs from Brazil at species level and evaluate their antifungal susceptibility profile. Polyphasic taxonomy was used to characterization at species level (morphological, phenotypical characteristics, and molecular identification). Antifungal susceptibility profiles (amphotericin B, itraconazole, ketoconazole, posaconazole, and terbinafine) were determined using the Clinical and Laboratory Standards Institute broth microdilution method (M38-A2). According to phenotypic identification and molecular analysis, 46 isolates included in this study were identified as S. brasiliensis and one as S. schenckii. Amphotericin B presented the highest minimum inhibitory concentration values, and the other drugs showed effective in vitro antifungal activity. This is the first report of S. schenckii in dogs from Brazil, since S. brasiliensis is the only species that has been described in canine isolates from Rio de Janeiro to date. Nevertheless, no differences were observed in the antifungal susceptibility profiles between the S. brasiliensis and S. schenckii isolates, and it is important to continuously study new canine clinical isolates from Rio de Janeiro, Brazil.

Topics: Amphotericin B; Animals; Antifungal Agents; Brazil; Dog Diseases; Dogs; Itraconazole; Ketoconazole; Microbial Sensitivity Tests; Phylogeny; Sporothrix; Sporotrichosis; Terbinafine

Sporotrichosis is an implantation mycosis highly prevalent in Brazil, associated with soil activities and contact with infected animals. It has numerous clinical manifestations and its disseminated cutaneous form is uncommon, found in approximately 4% of cases and usually related to immunosuppressive conditions. We report an alcoholic 56-year-old male patient with no other comorbidities, presenting with multiple cutaneous nodules and ulcers. The patient was diagnosed with disseminated cutaneous sporotrichosis based on the isolation and identification of Sporothrix spp. The patient was initially treated with amphotericin B with satisfactory results and then with itraconazole.

Topics: Alcoholism; Amphotericin B; Animals; Antifungal Agents; Brazil; Humans; Itraconazole; Male; Middle Aged; Sporothrix; Sporotrichosis; Treatment Outcome; Ulcer

In severe cases of sporotrichosis, it is recommended to use amphotericin B deoxycholate (D-AMB) or its lipid formulations and/or in association with itraconazole (ITC). Our aim was to evaluate the antifungal efficacy of a poly-aggregated amphotericin B (P-AMB), a nonlipid formulation, compared with D-AMB on systemic sporotrichosis caused by Sporothrix brasiliensis. In vitro assays showed that Sporothrix schenckii sensu stricto and S. brasiliensis yeast clinical isolates were susceptible to low concentrations of P-AMB and D-AMB. Although P-AMB presented a higher minimal inhibitory concentration (MIC) compared to D-AMB, its cytotoxic effect on renal cells and erythrocytes was lower. For the in vivo assays, male BALB/c mice were intravenously infected with S. brasiliensis yeasts, and P-AMB or D-AMB was administered 3 days post-infection. The efficacy of five therapeutic regimens was tested: intravenous monotherapy with P-AMB or D-AMB, intravenous pulsed-therapy with P-AMB or D-AMB, and intravenous therapy with P-AMB, followed by oral ITC. These treatments increased murine survival and controlled the fungal burden in the liver, spleen, lungs, and kidneys. However, only D-AMB monotherapy or the pulsed-therapies with D-AMB or P-AMB led to 100% survival of the mice 45 days post-infection; only pulsed administration of D-AMB was able to control the fungal load in all organs 45 days post-infection. Accordingly, the histopathological findings showed reductions in the fungal burden and inflammatory reactions in these treatment regimens. Together, our results suggest that the P-AMB formulation could be considered as an alternative drug to D-AMB for treating disseminated sporotrichosis.

Topics: Amphotericin B; Animals; Antifungal Agents; Cell Survival; Colony Count, Microbial; Deoxycholic Acid; Disease Models, Animal; Drug Combinations; Male; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Sporothrix; Sporotrichosis; Survival Rate

Sporothrix brasiliensis has emerged as an important cause of sporotrichosis, particularly associated with feline and zoonotic cases. Owing to the paucity of data on antifungal activity against this species, the present study aimed to evaluate the in vitro susceptibility of clinical isolates of S. brasiliensis in the mycelial and yeast phases to itraconazole (ITZ), terbinafine (TRB), and amphotericin B (AMB). Thirty-five isolates from an outbreak of feline sporotrichosis in Southern Brazil were used. All of them were assessed in the yeast and filamentous phases using the broth microdilution technique in accordance with the respective reference protocols M27-A3 and M38-A2 of the Clinical and Laboratory Standards Institute (CLSI). In our study, TRB was the most active antifungal against both the filamentous and yeast phases, showing GM of the MIC of 0.343 μg/ml and 0.127 μg/ml, respectively. In the yeast phase, the GM of the MIC for TRB was significantly lower than that for both ITZ (P = .009) and AMB (P < .001). However, in the filamentous phase, the GM of the MIC for TRB was significantly lower than that of AMB (P < .001), but not different from that of ITZ (P = .091). AMB was the antifungal with the highest GM of the MIC for both phases (1.486 μg/ml for the filamentous phase and 0.660 μg/ml for the yeast). Our results may contribute to a better understanding of antifungal susceptibility profiles of clinical isolates of S. brasiliensis in the mycelial and yeast phases in further studies.

Topics: Amphotericin B; Animals; Antifungal Agents; Brazil; Cat Diseases; Cats; Itraconazole; Life Cycle Stages; Microbial Sensitivity Tests; Mycelium; Naphthalenes; Sporothrix; Sporotrichosis; Terbinafine

Feline sporotrichosis is common in Malaysia. Thermosensitivity and effects of azole treatment on fungal susceptibility are unknown.. To evaluate thermotolerance and antifungal susceptibility of feline Malaysian Sporothrix isolates, compare microdilution (MD) and E-test results, and investigate changes in susceptibility during azole therapy.. Sporothrix schenckii sensu stricto was isolated from 44 cats. Thermotolerance was determined via culture at 37°C for 7 days. Susceptibility to itraconazole (ITZ), ketoconazole (KTZ) and terbinafine (TRB) was assessed in 40 isolates by MD; to amphotericin B (AMB), KTZ, ITZ, fluconazole (FLC) and posaconazole (POS) by E-test. Results were statistically compared by Pearson's Product Moment. In eight ketoconazole treated cats, susceptibility testing to itraconazole and ketoconazole was repeated every two months for six months.. Thermotolerance was observed in 36 of 44 (82%) isolates. Assuming that isolates growing at antifungal concentrations ≥4 mg/mL were resistant, all were resistant on E-test to FLC and AMB, 11 (28%) to POS, 6 (15%) to ITZ and 1 (3%) to KTZ. On MD, 27 of 40 (68%) were resistant to TRB, 2 (5%) to ITZ and 3 (8%) to KTZ. There was no correlation between E-test and MD results (KTZ r = 0.10, P = 0.54, and ITZ r = 0.11, P = 0.48). MD values for ITZ and KTZ did not exceed 4 mg/L during KTZ therapy.. The majority of feline isolates in Malaysia are thermosensitive. Lack of correlation between E-test and MD suggests that the E-test is unreliable to test antifungal susceptibility for Sporothrix spp. compared to MD. KTZ was the antifungal drug with the lowest MIC. Prolonged KTZ administration may not induce changes in antifungal susceptibility.

Topics: Amphotericin B; Animals; Antifungal Agents; Cat Diseases; Cats; In Vitro Techniques; Itraconazole; Ketoconazole; Malaysia; Microbial Sensitivity Tests; Naphthalenes; Sporothrix; Sporotrichosis; Terbinafine; Triazoles

Sporotrichosis is an emergent subcutaneous mycoses caused by species of the Sporothrix schenckii complex. Amphotericin B (AmB) remains the main antifungal drug for the treatment of systemic infections, but its use is limited by toxicity reasons. AFCo3 is a novel cochleate containing detoxified LPS, which exhibits drug delivery and immunomodulating properties. Here, AFCo3 was used as the vehicle for AmB to evaluate the immunomodulatory and antifungal efficacy against S. schenckii in vitro and in vivo.. The minimum inhibitory concentrations of AFCo3-AmB and AmB were 0.25 and 1μg/mL respectively. The minimum fungicidal concentration was 0.5μg/mL for AFCo3-AmB and 2μg/mL for AmB. AFCo3-AmB was less cytotoxic than AmB for peritoneal macrophages, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and reduced the AmB-induced hemolysis in murine erythrocytes. AFCo3-AmB improved the intracellular killing of phagocytized yeast and it enhanced the in vitro production of IL-1β, TNF-α and NO in peritoneal macrophages. Moreover, AFCo3-AmB was more effective than AmB in reducing spleen and liver fungal burden after repeated (five days) intraperitoneal administration of 5mg/kg of AmB, in a Balb/c model of systemic infection, associated to a significant induction of Th1/Th17 response. Finally, blood chemistry revealed that AFCo3-AmB did not cause changes suggestive of nephrotoxicity, such as increases in total proteins, albumin, creatinine and blood urea nitrogen that were caused by free AmB.. AFCo3-AmB exhibited a significant immunomodulator action, reduced toxicity and improved antifungal action against S. schenckii, suggesting a potential use as AmB delivery for systemic sporotrichosis treatment.

Topics: Amphotericin B; Animals; Antifungal Agents; Cell Survival; Cytokines; Drug Carriers; Erythrocytes; Hemolysis; Immunologic Factors; Lipopolysaccharides; Liver; Macrophages, Peritoneal; Male; Mice, Inbred BALB C; Microbial Sensitivity Tests; Nitric Oxide; Spleen; Sporothrix; Sporotrichosis

Sporothrix brasiliensis is a highly virulent member of the S. schenckii complex, which is responsible for the emergence of the epidemic sporotrichosis in southeastern Brazil over the last two decades. There are no in vivo studies on the sensitivity of S. brasiliensis to the therapeutic regimens used to treat sporotrichosis. Here, we evaluated the efficacy and safety of antifungal treatments against S. brasiliensis using a murine model of disseminated sporotrichosis. In vitro, S. brasiliensis yeasts were sensitive to low concentrations of amphotericin B-deoxycholate (AMB-d) and itraconazole (ITZ), the latter having greater selectivity toward the fungus. The following treatment regimens were tested in vivo: intravenous AMB-d for 7 days post-infection (p.i.), oral ITZ for up to 30 days p.i., and AMB-d followed by ITZ (AMB-d/ITZ). AMB-d and AMB-d/ITZ led to 100% survival of infected mice at the end of the 45-day experimental period. Although all treatments extended mice survival, only AMB-d and AMB-d/ITZ significantly reduced fungal load in all organs, but AMB-d/ITZ led to a more consistent decrease in overall fungal burden. No treatment increased the levels of serum toxicity biomarkers. Taken together, our results indicate that AMB-d/ITZ is the best therapeutic option for controlling disseminated sporotrichosis caused by S. brasiliensis.

Topics: Amphotericin B; Animals; Antifungal Agents; Colony Count, Microbial; Disease Models, Animal; Drug Therapy; Itraconazole; Male; Mice, Inbred BALB C; Sporothrix; Sporotrichosis; Survival Analysis; Treatment Outcome

The in vitro activity of the antifungal agents amphotericin B (AMB), itraconazole (ITC), posaconazole (PSC), voriconazole (VRC), and terbinafine (TRB) against 32 Brazilian isolates of Sporothrix brasiliensis, including 16 isolates from a recent (2011-2012) epidemic in Rio de Janeiro state, was examined. We describe and genotype new isolates and clustered them with 16 older (from 2004 or earlier) S. brasiliensis isolates by phylogenetic analysis. We tested both the yeast and the mycelium form of all isolates using broth microdilution methods based on the reference protocols M38-A2 and M27-A3 (recommended by the Clinical and Laboratory Standards Institute). Considering minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs), TRB was found to be the most active drug in vitro for both fungal forms, followed by PSC. Several isolates showed high MICs for AMB and/or ITC, which are currently used as first-line therapy for sporotrichosis. VRC displayed very low activity against S. brasiliensis isolates. The primary morphological modification observed on treated yeasts by transmission electron microscopy analysis was changes in cell wall. Our results indicate that TRB is the antifungal with the best in vitro activity against S. brasiliensis and support the use of TRB as a promising option for the treatment of cutaneous and/or lymphocutaneous sporotrichosis.

Topics: Amphotericin B; Antifungal Agents; Brazil; Calmodulin; Cell Wall; Cluster Analysis; Disease Outbreaks; DNA, Fungal; Fungal Proteins; Humans; Microbial Sensitivity Tests; Microbial Viability; Microscopy, Electron, Transmission; Molecular Sequence Data; Naphthalenes; Phylogeny; Sequence Analysis, DNA; Sporothrix; Sporotrichosis; Terbinafine

Sporotrichosis is a common mycosis caused by dimorphic fungi from the Sporothrix schenckii complex. In recent years, sporotrichosis incidence rates have increased in the Brazilian state of Rio de Janeiro, where Sporothrix brasiliensis is the species more frequently isolated from patients. The standard antifungals itraconazole and amphotericin B are recommended as first-line therapy for cutaneous/lymphocutaneous and disseminated sporotrichosis, respectively, although decreased sensitivity to these drugs in vitro was reported for clinical isolates of S. brasiliensis. Here, we evaluated the activity of the phospholipid analogue miltefosine - already in clinical use against leishmaniasis - towards the pathogenic yeast form of S. brasiliensis isolates with low sensitivity to itraconazole or amphotericin B in vitro. Miltefosine had fungicidal activity, with minimum inhibitory concentration (MIC) values of 1-2 µg ml(-1). Miltefosine exposure led to loss of plasma membrane integrity, and transmission electron microscopy (TEM) analysis revealed a decrease in cytoplasmic electron density, alterations in the thickness of cell wall layers and accumulation of an electron-dense material in the cell wall. Flow cytometry analysis using an anti-melanin antibody revealed an increase in cell wall melanin in yeasts treated with miltefosine, when compared with control cells. The cytotoxicity of miltefosine was comparable to those of amphotericin B, but miltefosine showed a higher selectivity index towards the fungus. Our results suggest that miltefosine could be an effective alternative for the treatment of S. brasiliensis sporotrichosis, when standard treatment fails. Nevertheless, in vivo studies are required to confirm the antifungal potential of miltefosine for the treatment of sporotrichosis.

Topics: Amphotericin B; Animals; Antifungal Agents; Brazil; Cell Line; Cell Membrane; Cell Survival; Cell Wall; Cytoplasm; Drug Resistance, Fungal; Epithelial Cells; Humans; Itraconazole; Macaca mulatta; Microbial Sensitivity Tests; Microbial Viability; Microscopy, Electron, Transmission; Phosphorylcholine; Sporothrix; Sporotrichosis

We evaluated the combination of posaconazole with amphotericin B in vitro and in a murine model of systemic infections caused by Sporothrix brasiliensis and Sporothrix schenckii sensu stricto. In vitro data demonstrated a synergistic effect, and although posaconazole alone was effective against sporotrichosis, efficacy in terms of survival and burden reduction was increased with the combination. This combination might be an option against disseminated sporotrichosis, especially when itraconazole or amphotericin B at optimal doses are contraindicated.

Topics: Amphotericin B; Animals; Antifungal Agents; Drug Resistance, Multiple, Fungal; Drug Therapy, Combination; Mice; Microbial Sensitivity Tests; Sporothrix; Sporotrichosis; Triazoles

We describe a case of disseminated Sporothrix schenckii infection in a man with underlying hairy cell leukemia. The immunological defects associated with this malignancy, as well as the management of refractory sporotrichosis are reviewed.

Topics: Adult; Amphotericin B; Antifungal Agents; Humans; Leg; Leukemia, Hairy Cell; Male; Skin; Sporothrix; Sporotrichosis; Triazoles

Sporotrichosis is endemic in Rio de Janeiro, Brazil, and cases have been reported to be associated with HIV. This article describes the clinical manifestations and evolution of sporotrichosis in HIV-positive patients and constitutes the largest case series reported to date. There were 21 HIV-positive patients with sporotrichosis diagnosed by the recovery of the etiologic agent from 1999-2009. Sixteen patients (76.2%) were men and five (23.8%) were women, with a mean age of 41.2 years. Seven of these individuals were previously unaware of their HIV infection. Mean CD4 count was 346.4 cells/μl. The most frequent clinical presentations of sporotrichosis in these patients were the lymphocutaneous and disseminated form (seven patients each, 33.3%), followed by the widespread cutaneous form in five (23.8%), and fixed form in the remaining two (9.5%). In patients with the disseminated forms, clinical manifestations involved the skin in six, mucosa (nasal, oral, or conjunctival) in four, bone in two, and meninges in two. Eleven (52.4%) patients received itraconazole and eight (38.1%) amphotericin B contributing to an overall cure rate of 81%. Spontaneous cure was observed in one patient. The clinical forms of sporotrichosis varied according to the patients' immune status. The results demonstrate the importance of sporotrichosis as an opportunistic infection associated with AIDS in countries where the mycosis occurs.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Brazil; Endemic Diseases; Female; Humans; Immunocompromised Host; Itraconazole; Male; Middle Aged; Sporotrichosis

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.

Topics: Administration, Oral; Amphotericin B; Animals; Antifungal Agents; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Histocytochemistry; Liver; Male; Mice; Microbial Sensitivity Tests; Species Specificity; Sporothrix; Sporotrichosis; Survival Rate; Treatment Outcome; Triazoles

Disseminated sporotrichosis occurs in individuals with impaired cellular immunity, such as in cases of neoplasia, transplantation, diabetes, and especially, acquired immunodeficiency syndrome. This report presents a 32-year-old Brazilian human immunodeficiency virus (HIV)-infected patient who developed a protracted condition of disseminated sporotrichosis with endocarditis, bilateral endophthalmitis, and lymphatic involvement. He needed cardiac surgery to replace the mitral valve. Sporothrix brasiliensis isolates were recovered from cultures of subcutaneous nodules and mitral valve fragments. Species identification was based on classical and molecular methods. The patient received amphotericin B for 52 days and subsequently, oral itraconazole. He remains asymptomatic, and he is on maintenance therapy with itraconazole. Despite his positive clinical outcome, he developed bilateral blindness. To our knowledge, this case is the first report of endocarditis and endophthalmitis caused by S. brasiliensis.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Antiretroviral Therapy, Highly Active; Brazil; Endophthalmitis; Eye; HIV; Hospitalization; Humans; Itraconazole; Male; Sporothrix; Sporotrichosis; Treatment Outcome; Vision, Ocular

Sporotrichosis is a subcutaneous fungal infection caused by a thermally dimorphic aerobic fungus, Sporothrix schenckii. It results from traumatic inoculation or contact with animals. Most cases were reported mainly in the tropics and subtropics..   The objective of our study is to assess the clinical characteristic of cutaneous sporotrichosis among our patients.. We performed a retrospective review of all cases diagnosed with cutaneous sporotrichosis from July 2004 to June 2010. Patients' medical records were retrieved and analyzed according to demography, preceding trauma, sites of lesions, clinical subtypes, treatment, and clinical response.. Nineteen cases were diagnosed with cutaneous sporotrichosis with a male/female ratio of 9:10. Thirteen cases (68.4%) were able to recall preceding trauma, and seven of them reported cat scratches or cat bites. Lymphocutaneous sporotrichosis was observed in 13 cases (68.4%) followed by four cases of fixed cutaneous sporotrichosis and two cases of disseminated sporotrichosis. Histologically, 11 cases (57.8%) demonstrated a granulomatous reaction. Sporothrix schenckii was cultured in 12 cases (63.2%). Thirteen cases (68.4%) were successfully treated with oral itraconazole alone for a mean duration of 15.6 weeks. Two cases with disseminated cutaneous sporotrichosis were treated with intravenous amphotericin B..   Lymphocutaneous sporotrichosis was the most common subtype of cutaneous sporotrichosis in our series, with cat scratches or bites being the most common preceding trauma. Oral itraconazole was highly effective for the localized subtypes, whereas intravenous amphotericin B was required in disseminated cutaneous sporotrichosis.

Topics: Adult; Aged; Amphotericin B; Animals; Antifungal Agents; Bites and Stings; Cats; Child; Female; Humans; Itraconazole; Malaysia; Male; Middle Aged; Retrospective Studies; Sporothrix; Sporotrichosis

Sporotrichosis is a subacute or chronic fungal infection caused by the ubiquitous fungus Sporothrix schenckii. Disseminated cutaneous sporotrichosis is an uncommon entity and is usually present in the immunosuppressed. Here, a case of disseminated cutaneous sporotrichosis in an immunocompetent patient is reported. This 70-year-old healthy woman presented with multiple painful ulcerated nodules on her face and upper and lower extremities of 6-month duration, associated with low-grade fever, night sweats, loss of appetite, and loss of weight. Histopathological examination of the skin biopsy revealed epidermal hyperplasia and granulomatous inflammation in the dermis, with budding yeast. Fungal culture identified S. schenckii. She had total resolution of the lesions after 2 weeks of intravenous amphotericin B and 8 months of oral itraconazole. All investigations for underlying immunosuppression and internal organ involvement were negative. This case reiterates that disseminated cutaneous sporotrichosis, although common in the immunosuppressed, can also be seen in immunocompetent patients.

Topics: Aged; Amphotericin B; Antifungal Agents; Biopsy; Female; Humans; Immunocompetence; Skin; Sporothrix; Sporotrichosis

OBJECTIVE To describe the use of intralesional amphotericin B in localised lesions for the treatment of 26 cats from Rio de Janeiro, Brazil, with sporotrichosis refractory to oral itraconazole. DESIGN Uncontrolled intervention study. METHOD The 26 cats in this study were diagnosed with sporotrichosis, confirmed by isolation of Sporothrix schenckii, and presented residual localised skin lesions refractory to treatment with oral itraconazole for a minimum period of 8 weeks. The animals received weekly applications of intralesional amphotericin B in conjunction with oral itraconazole. In cases of owner unavailability, a maximum of 2 weeks between the infiltrations was accepted. RESULTS Twenty-two (84.6%) of the 26 treated cats achieved clinical remission, 16 (72.7%) of which were cured, and in the remaining six (27.3%) the lesions recurred at the same site. Lack of clinical response was observed in one animal and three owners abandoned treatment. CONCLUSION The proposed therapeutic regimen is an adjunctive treatment option for cats with sporotrichosis presenting as residual skin lesions refractory to itraconazole.

Topics: Administration, Oral; Amphotericin B; Animals; Antifungal Agents; Brazil; Cat Diseases; Cats; Drug Therapy, Combination; Female; Injections, Intralesional; Itraconazole; Male; Sporotrichosis; Treatment Outcome

Fusarium species are hyaline hyphomycetes widely distributed in nature and documented agents of both superficial and systemic infections in humans. In this paper, we report a darkly-pigmented and initially non-sporulating isolate in the Fusarium solani species complex (FSSC) causing a post-traumatic sporotrichoid infection in an otherwise healthy, male patient. Sequencing of multiple loci showed that the isolate represented an otherwise unknown lineage, possibly corresponding to a separate species, within the multi-species F. solani complex. In prolonged culture, the non-sporulating isolate produced revertant wild-type subcultures with typical Fusarium conidiation. This suggests that the original dense, dark, non-sporulating isolate was a host-adapted form selected in vivo for characters compatible with human pathogenicity. The production of such forms by Fusarium species is increasingly recognized now that sequencing has allowed the identification of highly atypical isolates. In vitro antifungal susceptibility of the isolate was investigated against seven conventional and two newly approved antifungal agents. The isolate showed in vitro resistance to amphotericin B, but appeared susceptible to itraconazole and terbinafine. A cure was ultimately achieved with combined terbinafine/itraconazole therapy with prolonged itraconazole follow-up therapy.

Topics: Adult; Amphotericin B; Antifungal Agents; DNA, Fungal; DNA, Ribosomal; DNA, Ribosomal Spacer; Drug Therapy, Combination; Fungal Proteins; Fusarium; Humans; Itraconazole; Male; Microbial Sensitivity Tests; Molecular Sequence Data; Naphthalenes; Pigments, Biological; RNA Polymerase II; Sequence Analysis, DNA; Skin; Spores, Fungal; Sporotrichosis; Terbinafine; Treatment Outcome; Wound Infection

Sporotrichosis is a fungal disease usually restricted to the cutaneous and lymphatic systems. Visceral involvement is unusual. To date, only 21 cases of sporotrichosis meningitis have been reported, some of these associated with immunosuppression. According to the reported cases, difficulty establishing the correct diagnosis is almost the rule which, undoubtedly, is associated with a worse prognosis. In this report, two HIV infected patients are described who developed meningitis due to Sporothrix schenckii associated with immune reconstitution inflammatory syndrome. This is the first report of sporotrichosis meningitis associated with immune reconstitution inflammatory syndrome in AIDS patients.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Brain; Humans; Immune Reconstitution Inflammatory Syndrome; Male; Meningitis, Bacterial; Sporothrix; Sporotrichosis; Tomography, X-Ray Computed

The present report concerns a case of sporotrichosis in a 3-year-old male crossbred cat. After 9 months of oral itraconazole (20mg/kg) therapy, all skin lesions had resolved with the exception of a single nodular lesion located on the bridge of the nose. Therefore, a combined therapy that included intralesional (IL) amphotericin B (1mg/kg) was started. The lesion resolved completely after three weekly administrations of IL amphotericin B, given in concert with oral itraconazole. The cat remains well 1 year after discontinuing therapy, with no signs of recurrence.

Topics: Amphotericin B; Animals; Antifungal Agents; Brazil; Cat Diseases; Cats; Injections, Intralesional; Male; Nose Diseases; Sporotrichosis; Treatment Outcome

Ninety-two isolates belonging to five species of the Sporothrix schenckii complex were tested in vitro against 12 antifungal agents, using a reference microdilution method. There were significant differences among the species; Sporothrix brasiliensis was the species that showed the best response to antifungals, and S. mexicana had the worst response. In general, terbinafine was the most active drug, followed by ketoconazole and posaconazole.

Topics: Animals; Antifungal Agents; Drug Resistance, Fungal; Humans; Microbial Sensitivity Tests; Species Specificity; Sporothrix; Sporotrichosis

In this report, we describe a case of disseminated sporotrichosis that was diagnosed by fine-needle aspiration biopsy (FNAB). The cytologic smears exhibited a large number of macrophages, few polymorphonuclear neutrophils and numerous round or oval, sometimes elongated, isolated and scattered yeast-like structures localized extracellularly or inside macrophages. These structures were clearly visualized by Giemsa and Papanicolaou methods. Cultures from skin biopsy material revealed fungal colonies which were subsequently identified as Sporothrix schenckii. The cytologic aspects, the correlation with histologic findings and the differential cytologic diagnosis were reviewed.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Biopsy, Fine-Needle; Fatal Outcome; Humans; Male; Sporothrix; Sporotrichosis; Staining and Labeling

The in vitro susceptibility of Sporothrix schenckii to antifungal drugs has been determined with three different methods. Nineteen Peruvian clinical isolates of S. schenckii were tested against amphotericin B (AB), flucytosine (FC), fluconazole (FZ), itraconazole (IZ), voriconazole (VZ), and ketoconazole (KZ). Modified NCCLS M38-A, Sensititre YeastOne (SYO), and ATB Fungus 2 (ATBF2) methods were used to determine the MICs. ATCC isolates of Candida parapsilosis, Candida krusei, and Aspergillus flavus were used for quality control. Sporothrix inocula were prepared with the mycelial form growing on potato dextrose agar at 28 +/- 2 degrees C. MICs of AB, FC, FZ, and IZ were determined with all three methods, VZ with M38-A and SYO, and KZ with only SYO. The three methods showed high MICs of FZ and FC (MIC(90) of 0.5 microg/ml), being homogeneously lower than those of IZ and KZ. The M38-A method showed a variable MIC range of VZ (4.0 to 16 microg/ml); the geometric mean (GM) was 9.3 mug/ml. The MIC range of AB was wide (0.06 to 16 microg/ml), but the GM was 1.2 microg/ml, suggesting that the MIC is strain dependent. Agreement (two log(2) dilutions) between commercial techniques and the modified M38-A method was very high with FZ, IZ, and FC. In AB and VZ, the agreement was lower, being related to the antifungal concentrations of each method. The highest activity against S. schenckii was found with IZ and KZ. Lack of activity was observed with FZ, VZ, and FC. When AB is indicated for sporotrichosis, the susceptibility of the strain must be analyzed. Commercial quantitative antifungal methods have a limited usefulness in S. schenckii.

Topics: Amphotericin B; Antifungal Agents; Fluconazole; Flucytosine; Humans; In Vitro Techniques; Itraconazole; Ketoconazole; Microbial Sensitivity Tests; Pyrimidines; Quality Control; Sporothrix; Sporotrichosis; Triazoles; Voriconazole

Environmental fungi, in particular primary pathogens and Cryptococcus spp. can be responsible for skin lesions mimicking sporotrichosis. In this paper, we report a case of subcutaneous cryptococcosis in an apparently healthy, young male patient due to a non-C. neoformans Cryptococcus species, C. diffluens. The isolate showed in vitro phenotypic switching that may affect virulence and host inflammatory and immune responses, and in vitro resistance to amphotericin B and 5-flucytosin. This species shares several phenotypic traits with C. neoformans, and, therefore, decisive diagnosis should be based on biopsy and culturing results followed by molecular identification.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Base Sequence; Cryptococcosis; Cryptococcus; Diagnosis, Differential; DNA, Fungal; DNA, Ribosomal; DNA, Ribosomal Spacer; Drug Resistance, Fungal; Flucytosine; Humans; Male; Microbial Sensitivity Tests; Molecular Sequence Data; RNA, Ribosomal, 28S; Sequence Analysis, DNA; Sporotrichosis

We report a case of a diabetic patient with localized osteoarticular sporotrichosis followed by widespread dissemination of the infection, which was successfully treated with amphotericin B. In addition, we evaluated the in vitro antifungal activity of 4 agents against both the mycelial and the yeast forms of the isolated fungus.

Topics: Amphotericin B; Antifungal Agents; Diabetes Complications; Female; Humans; Microbial Sensitivity Tests; Middle Aged; Osteoarthritis, Knee; Sporothrix; Sporotrichosis; Treatment Outcome

A male patient with HIV and past history of tuberculosis and suspected neurotoxoplasmosis was admitted to the hospital with vomiting and small nodules through all his body. Few of the nodules were found forming chains of enlarged lymphatic vessels, especially on lesions located on the limbs. Some of the nodules were ulcerated with a serosanguineous discharge. Collected samples from ulcerated and the nodular lesions showed the presence of Sporothrix schenckii in culture. Although all hemocultures were negative, a spinal fluid collected from this patient and cultures from the cutaneous lesions were both positive for S. schenckii. The patient showed improvement after treatment with Amphotericin B. Sadly, he later died of complications not related to the S. schenckii infection. This case of disseminated sporotrichosis is a remainder that in patients with immunological disorders exotic forms of this fungal clinical entity could be expected.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Candidiasis, Oral; Cerebrospinal Fluid; Diagnosis, Differential; Fatal Outcome; Humans; Male; Meningitis, Fungal; Skin; Sporotrichosis; Toxoplasmosis, Cerebral

We describe a case of sporotrichosis that disseminated to involve multiple nerves after initiation of immunosuppressive therapy and then precipitously worsened after withdrawal of therapy. This case illustrates that multiple mononeuropathies are not always caused by vasculitis, and a correct pathological diagnosis should be established before treatment. Based on clinical and pathological features, the mechanism of neuropathy may have been due to either direct nerve infection or a bystander effect of inflammatory/immune damage or, perhaps more likely, to both mechanisms.

Topics: Abscess; Amphotericin B; Anti-Bacterial Agents; Anti-Inflammatory Agents; Debridement; Dermatitis; Diagnostic Errors; Disease Progression; Forearm; Granulomatous Disease, Chronic; Humans; Immunosuppressive Agents; Inflammation; Male; Middle Aged; Muscle Weakness; Muscle, Skeletal; Pain; Peripheral Nerves; Peripheral Nervous System Diseases; Sporothrix; Sporotrichosis; Treatment Outcome; Wrist Joint

To describe an unusual case of disseminated sporotrichosis with intraocular involvement.. Interventional case report.. An 18-year-old man presented with disseminated ulcerated skin lesions. Fundus examination showed fluffy opacities in the vitreous and a retinal granuloma in the left eye. Biopsy of the skin lesion and lymph node showed the presence of numerous fungus cells. Culture was positive for the diagnosis of disseminated sporotrichosis.. Although intraocular infection due to Sporothrix schenckii is uncommon, it can occur in case of disseminated sporotrichosis. Systemic therapy is a successful means to control skin and ocular sporotrichosis.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Biopsy; Eye Diseases; Eye Infections, Fungal; Granuloma; Humans; Male; Retinal Diseases; Skin; Sporothrix; Sporotrichosis; Vitreous Body

A wide spectrum of oral lesions has been associated with human immunodeficiency viral infection (HIV), or AIDS. This report describes the case of an HIV-infected patient who developed a case of disseminated sporotrichosis whose first clinical sign was the presence of orofacial lesions. A histopathological study of this patient's biopsy specimens taken from the oropharyngeal lesions revealed a number of rounded and/or oval free-spore forms of Sporothrix schenkii, the identification of which was corroborated by culturing skin lesion exudate on Sabouraud's glucose agar. To the best of our knowledge to date, this is the first time a case of the oral manifestation of sporotrichosis in association with HIV infection has been described in the dental literature.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Biopsy; Facial Dermatoses; Gingival Hyperplasia; HIV Infections; Humans; Male; Mouth Diseases; Oropharynx; Periodontal Diseases; Pharyngeal Diseases; Sporothrix; Sporotrichosis

One hundred clinical isolates of Sporothrix schenckii were tested against voriconazole, itraconazole and amphotericin B using a modification of the NCCLS M27-A in vitro yeast susceptibility testing procedure. NCCLS M38-P for moulds was not used because yeast forms may have been present when the test isolates were incubated at 35 +/- 1 degrees C. The minimum inhibitory concentration (MIC) values were: voriconazole 0.5-8 (geometric mean titer 6.50) microg ml(-1) ; itraconazole 0.03-8 (geometric mean titer 1.56) microg ml(-1); and amphotericin B 0.25-2 (geometric mean titer 1.23) microg ml(-1). The minimum fungicidal concentration (MFC) values were: voriconazole 2-8 (geometric mean titer 7.67) microg ml(-1); itraconazole 0.125-8 (geometric mean titer 7.41) microg ml(-1); and amphotericin B 0.125-2 (geometric mean titer 1.53) microg ml(-1). Based upon MIC values, sensitivity to amphotericin B is strain-dependent. S. schenckii is more sensitive to itraconazole than voriconazole based upon a comparison of MIC geometric means, even though the MIC ranges were essentially the same.

Topics: Amphotericin B; Antifungal Agents; Humans; Itraconazole; Microbial Sensitivity Tests; Pyrimidines; Sporothrix; Sporotrichosis; Triazoles; Voriconazole

We report a case of multiple skin lesions, lymphadenopathy, and osteoarticular sporotrichosis in a man infected with human immunodeficiency virus (HIV). He subsequently died of tuberculosis after successful treatment for osteoarticular sporotrichosis with amphotericin B. We describe the unusual histopathology in disseminated sporotrichosis with acquired immunodeficiency syndrome (AIDS) and compare it with that seen in patients without AIDS. Although the optimal treatment of osteoarticular sporotrichosis in patients with AIDS is unknown, use of amphotericin B in our patient appeared successful. Culture and histologic stains of all tissues taken at autopsy were negative for sporotrichosis. Recent studies of similar cases have shown initial treatment with amphotericin B followed by long-term maintenance with itraconazole to be beneficial.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Biopsy; Bone Diseases, Infectious; Diabetes Complications; Fatal Outcome; Humans; Joint Diseases; Lymphatic Diseases; Male; Sporotrichosis; Substance Abuse, Intravenous; Synovial Fluid; Treatment Outcome; Tuberculosis

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Female; Fluconazole; Humans; Meningitis, Cryptococcal; Sporotrichosis

Topics: Amphotericin B; Anorexia; Antifungal Agents; Aspergillosis; Blastomycosis; Candidiasis; Coccidioidomycosis; Cryptococcosis; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme Inhibitors; Dose-Response Relationship, Drug; Drug Interactions; Fluconazole; Flucytosine; Gynecomastia; Histoplasmosis; Humans; Itraconazole; Ketoconazole; Kidney Diseases; Liposomes; Male; Mixed Function Oxygenases; Mucormycosis; Nausea; Paracoccidioidomycosis; Sporotrichosis; Teratogens

Sporotrichosis is endemic in temperate and tropical regions of the world, including Australia. Although uncommon, it is frequently encountered in Northern Australia, especially in Queensland. All ages are affected, although most cases occur from occupational exposure to vegetation or soil. This article reviews the cause, diagnosis and treatment options of this fungal disease which affects the skin and is often misdiagnosed. It classically presents in gardeners, especially those handling roses.

Topics: Adult; Amphotericin B; Child; Dose-Response Relationship, Drug; Humans; Itraconazole; Microbiological Techniques; Potassium Iodide; Skin; Sporothrix; Sporotrichosis

Twelve culture proven patients of sporotrichosis were seen over a period of 4 1/2 yr in the north-western region of this country. Most of the patients (75%) were from Himachal Pradesh, with slight female preponderance. The right upper limb was commonly (58.3%) involved; gardeners and housewives being the common sufferers. Localised lymphocutaneous variety was the commonest presentation (91.7%), except in one patient, where after initial involvement of the face, the lesion extended to the right upper limb and trunk. All but one patient responded to oral potassium iodide therapy; this patient with mixed infection of Sporothrix schenckii and Cladosporium species, required in addition, amphotericin B therapy.

Topics: Amphotericin B; Female; Humans; India; Male; Middle Aged; Occupational Diseases; Potassium Iodide; Sex Factors; Sporotrichosis

A 62-year-old woman had chronic cavitary pulmonary sporotrichosis refractory to medical management over an 8-year period. She was treated with oral itraconazole and had an apparent microbiologic and clinical response; however, the patient succumbed to progressive pulmonary hypertension. The early use of oral itraconazole for treatment of pulmonary sporotrichosis is advocated.

Topics: Amphotericin B; Antifungal Agents; Female; Humans; Itraconazole; Ketoconazole; Lung Diseases, Fungal; Middle Aged; Potassium Iodide; Sporotrichosis

Itraconazole is a lipophilic triazole with potent in vitro activity. It is also effective after topical, oral and parenteral administration. The antifungal activity of itraconazole has been evaluated against more than 6,500 different strains, belonging to more than 260 fungal species, using the serial decimal dilution test in fluid broth medium (brain-heart infusion broth). Candida spp., Torulopsis spp., Cryptococcus neoformans, Pityrosporum spp. (Dixon broth), various other yeasts, dermatophytes, Aspergillus spp., Penicillium spp., Sporothrix schenckii, dimorphic fungi (mycelium phase and yeast phase), Phaeohyphomycetes, Entomophthorales and various Hyalohyphomycetes are sensitive. Most strains of Fusarium and Zygomycetes are poorly sensitive. Itraconazole was administered orally and parenterally in normal and immunocompromised guinea-pigs infected with C. albicans, Cr. neoformans, Histoplasma duboisii, S. schenckii, P. marneffei and A. fumigatus. It was effective in terms of both survival of the animals and elimination of the fungi from the various tissues. Itraconazole was superior to fluconazole in candidosis, cryptococcosis, sporotrichosis and aspergillosis, and to amphotericin B and to flucytosine in candidosis, cryptococcosis and aspergillosis. No comparative studies have yet been undertaken for other deep mycoses. The results of combination therapy with itraconazole and fluconazole in cryptococcosis were indifferent; with flucytosine or amphotericin B, additive or synergistic effects were seen in systemic candidosis, cryptococcosis and aspergillosis. No drug-related side-effects were observed after oral or parenteral administration of itraconazole.

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Candidiasis; Cryptococcosis; Drug Therapy, Combination; Fluconazole; Flucytosine; Guinea Pigs; Immunocompromised Host; Itraconazole; Ketoconazole; Microbial Sensitivity Tests; Mycoses; Sporotrichosis

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Dermatomycoses; Fluconazole; Humans; Male; Meningitis, Fungal; Sporothrix; Sporotrichosis

Topics: Adult; Amphotericin B; Animals; Cats; Clinical Protocols; Diagnosis, Differential; Disease Vectors; Humans; Male; Potassium Iodide; Sporotrichosis; Texas

Sporotrichal arthritis is a rare disease entity. Diagnosis is often difficult and delayed. Presentation may be either monoarticular or polyarticular. A case of polyarticular sporotrichal arthritis which exemplifies these problems is reported.

Topics: Adult; Amphotericin B; Arthritis, Infectious; Humans; Male; Sporotrichosis; Synovectomy; Synovial Membrane

A 58-year-old, alcoholic, diabetic man presented with multiple, ulcerated skin lesions and polymicrobial septicemia. Sporothrix schenckii was recovered from blood cultures and was resistant to amphotericin B by in vitro testing. Amphotericin B therapy failed, but the patient responded dramatically to itraconazole therapy, only to relapse 3 months after therapy was stopped. Reinstitution of itraconazole therapy has produced another dramatic response. This report is noteworthy for three reasons. First, to our knowledge, it represents only the second reported instance of fungemia with S schenckii that responded to medical therapy. Second, it illustrates that in vitro antifungal susceptibility tests may predict clinical infection response to drug therapy. Third, it suggests that itraconazole has significant promise in treating systemic sporotrichosis.

Topics: Amphotericin B; Antifungal Agents; Drug Resistance, Microbial; Humans; Itraconazole; Ketoconazole; Male; Middle Aged; Sepsis; Sporothrix; Sporotrichosis

Arthritis caused by Sporothrix schenckii may not respond satisfactorily to a full course of intravenous amphotericin B therapy. Left untreated, the fungus continues to be recovered from cultures of joint fluid, and the patient typically has serious joint disability. We have shown in one patient with sporotrichosis of the knee that direct low-dose injections of amphotericin B can be performed safely, resulting in eradication of the fungus. The patient has had continued useful range of motion and weight bearing on the involved knee.

Topics: Amphotericin B; Arthritis, Infectious; Humans; Injections, Intra-Articular; Male; Middle Aged; Sporothrix; Sporotrichosis

Four antifungal agents, amphotericin B, SDZ 89-485, itraconazole, and terbinafine, were tested for efficacy in a murine model of systemic sporotrichosis. Survival in the groups treated with amphotericin B, SDZ 89-485, and itraconazole was significantly better than that of control infected mice. However, these agents did not wholly protect the infected mice, as tail and paw lesions, whole-body radiographs, and positive cultures from survivors showed evidence of dissemination. Terbinafine-treated mice had the same or poorer survival as control infected mice, despite documented drug absorption.

Topics: Amphotericin B; Animals; Antifungal Agents; Drug Evaluation, Preclinical; Itraconazole; Ketoconazole; Mice; Naphthalenes; Sporothrix; Sporotrichosis; Terbinafine; Triazoles

Joint infection secondary to sporotrichosis is quite rare. Recently there have been two reports of sporotrichosis arthritis in the literature. An early report of synovitis of the knee secondary to sporotrichosis without cutaneous or multifocal involvement appeared in 1957. Sporotrichosis is a fungal disease that commonly causes bone and joint infection in its extracutaneous form. This report discusses sporotrichosis of the knee joint in a 28-year-old patient.

Topics: Adult; Amphotericin B; Arthritis, Infectious; Female; Humans; Knee Joint; Radiography; Sporotrichosis

A patient with cryptogenic cirrhosis and disseminated sporotrichosis developed acute renal failure immediately following the administration of amphotericin B on four separate occasions. The abruptness of the renal failure and its reversibility within days suggests that there was a functional component to the renal dysfunction. We propose that amphotericin, in the setting of reduced effective arterial volume, may activate tubuloglomerular feedback, thereby contributing to acute renal failure.

Topics: Acute Kidney Injury; Adult; Amphotericin B; Creatinine; Hepatic Encephalopathy; Humans; Male; Respiratory Insufficiency; Sporotrichosis

Growth of the yeast form of Sporothrix schenckii (ATCC 14804) was determined in diffusion chambers with 0.45 and 3.0 micron pore size over a period of 24 to 192 h after subcutaneous implantation into mice. Numbers of S. schenckii in 0.45 micron chambers increased significantly by 192 h when inocula of 10(3) and 10(5) colony forming units were implanted. In chambers with a pore size of 3.0 microns, only a slight decrease of fungal growth occurred, although host cells readily passed the filter membrane and phagocytosed yeast-form cells. The activities of amphotericin B, ketoconazole, itraconazole, ICI 153.066, vibunazole and potassium iodide against S. schenckii in implanted chambers were determined in terms of their effects on S. schenckii. ICI 153.066, ketoconazole, itraconazole and amphotericin B significantly reduced the numbers of reisolated S. schenckii in both types of chambers. There was a slight activity with vibunazole but none with potassium iodide.

Topics: Amphotericin B; Animals; Antifungal Agents; Disease Models, Animal; Female; Itraconazole; Ketoconazole; Mice; Potassium Iodide; Sporothrix; Sporotrichosis; Triazoles

Topics: Amphotericin B; Animals; Cat Diseases; Cats; Female; Humans; Ketoconazole; Male; Potassium Iodide; Sporotrichosis; Zoonoses

Sporotrichosis is a fungal disease caused by Sporothrix schenckii, which is seen worldwide. Infection usually involves cutaneous and subcutaneous tissues. Articular involvement is rare. A 29-year-old man with ankle sporotrichosis is reported to demonstrate the differential diagnosis and treatment.

Topics: Adult; Amphotericin B; Arthritis, Infectious; Arthrodesis; Combined Modality Therapy; Drug Therapy, Combination; Humans; Male; Penicillin G; Radiography; Sporothrix; Sporotrichosis

Persons whose work or recreation exposes them to minor trauma out of doors are at risk for sporotrichosis. The disease is generally indolent, with the lymphocutaneous form being by far the commonest. Extracutaneous disease may affect the bones or joints, lungs, or other foci. Isolation of the fungus Sporothrix schenckii from involved tissue establishes the diagnosis. Saturated solution of potassium iodide is the first-line treatment of lymphocutaneous disease. Intravenous amphotericin B is used for lesions not responding to saturated solution of potassium iodide and, occasionally, excision of lesions is required. Amphotericin B also is the treatment of choice for extracutaneous sporotrichosis.

Topics: Adult; Amphotericin B; Arm Injuries; Hand Injuries; Humans; Injections, Intravenous; Male; Middle Aged; Potassium Iodide; Skin Transplantation; Sporotrichosis

Topics: Amphotericin B; Arthritis, Infectious; Diagnosis, Differential; Granuloma; Humans; Knee Joint; Male; Middle Aged; Myositis; Sporotrichosis

The laboratory diagnosis and therapeutic management of disseminated sporotrichosis can present many problems to the clinical laboratory and the clinician. Culturing of clinical specimens is necessary because the direct microscopic examination of specimens for Sporothrix schenckii often is not useful. Although this organism has been recovered from many specimen sites, recovery from blood has been rare. This report summarizes data concerning recovery of S. schenckii from clinical specimens and the use of serologic and fungal antimicrobial susceptibility data. It appears to be the first antemortem recovery of S. schenckii from blood reported since 1909.

Topics: Amphotericin B; Female; Humans; Ketoconazole; Middle Aged; Sepsis; Sporothrix; Sporotrichosis

Localized sporotrichosis can present a difficult diagnostic problem. It mimics many other skin diseases, some of which are far more common. Often the skin biopsy is not helpful. The disease tends to be chronic, requiring specific therapy with potassium iodide.

Topics: Administration, Oral; Adult; Amphotericin B; Chronic Disease; Dermatomycoses; Humans; Male; Potassium Iodide; Sporotrichosis

Mimicry by fungal infection of other chronic bone and joint diseases may easily result in a tardy diagnosis with subsequent needless surgery or permanent damage to the joint and its function. A case of sporotrichosis arthritis involving both wrists and knee joints is described. Diagnostic pitfalls and therapeutic dilemmas are outlined. The literature on this apparently 'rare' form of arthritis is reviewed.

Topics: Amphotericin B; Arthritis, Infectious; Humans; Injections, Intra-Articular; Male; Middle Aged; Sporotrichosis

Disseminate cutaneous and osseous sporotrichosis is reported in a patient who failed to respond to 6 months of iodide therapy. Although the patient showed improvement on a 2-month course of amphotericin B, he experienced a fulminant relapse 12 days after the amphotericin B was stopped. Cure was achieved after 6 months of 5-fluorocytosine (8 gm/day) in conjunction with amphotericin B (total, 4.8 gm). The fluorocytosine was continued for an entire year. Two years after all treatment was discontinued the patient remained in good health. The only complication was a marked photosensitivity associated with the 5-fluorocytosine therapy. This is the second case of such photosensitivity in the literature.

Topics: Adult; Amphotericin B; Bone Diseases; Cytosine; Drug Therapy, Combination; Flucytosine; Humans; Male; Photosensitivity Disorders; Skin; Skin Diseases, Infectious; Sporotrichosis

Topics: Amphotericin B; Humans; Lung Diseases, Fungal; Lymphadenitis; Male; Middle Aged; Potassium Iodide; Sporotrichosis

Three cases of disseminated cutaneous sporotrichosis are reported, including a rare presentation of the disease as vesicular dermatitis. The diagnosis was confirmed by culture of a skin biopsy specimen, and all patients responded well to amphotericin B therapy. The sporotrichosis slide latex agglutination titer was used to determine the end point of therapy.

Topics: Adult; Amphotericin B; Dermatomycoses; Female; Humans; Middle Aged; Sporotrichosis

Topics: Adult; Amphotericin B; Blastomycosis; Dermatomycoses; Diagnosis, Differential; Humans; Male; Sporotrichosis

Sporotrichosis is frequently primary in the lungs, caused by inhalation or aspiration of spores of Sporothrix schenckii. The clinical features and roentgenographic changes are nonspecific and usually indistinguishable from reactivated pulmonary tuberculosis. Therefore, pulmonary sporotrichosis should be considered when the tuberculin test and sputum cultures for Mycobacterium tuberculosis are persistently negative. Direct fluorescent antibody is a reliable, rapid, and specific method of identifying organisms in specimens and tissue biopsies. While the agglutination test is very sensitive in detecting sporotrichosis, it does not differentiate active disease from inactive disease. The complement fixation test, when positive, may suggest the presence of systemic sporotrichosis. Potassium iodide may be used initially in the nonimmunocompromised host with limited, noncavitary pulmonary disease. Amphotericin B should be given to patients who fail to respond to potassium iodide. Initial amphotericin B therapy is indicated in immunocompromised patients, in patients with multifocal systemic sporotrichosis. and in those with cavitary pulmonary sporotrichosis. Resectional surgery with perioperative medical therapy is indicated in patients with persistent cavitary disease unresponsive to amphotericin B, or when cavitary disease is associated with bleeding.

Topics: Adult; Amphotericin B; Diagnosis, Differential; Humans; Lung; Lung Diseases, Fungal; Male; Middle Aged; Potassium Iodide; Radiography; Sporotrichosis; Tuberculosis, Pulmonary

Topics: Administration, Oral; Adult; Amphotericin B; Cautery; Cryosurgery; Curettage; Cytosine; Dermatomycoses; Evaluation Studies as Topic; Flucytosine; Griseofulvin; Hand Dermatoses; Humans; Imidazoles; Male; Miconazole; Potassium Iodide; Sporotrichosis

Six cases of pulmonary sporotichosis were observed in 2 institutions in Oklahoma City, Okla. Three of the patients were treated with iodides with or without surgery. Although one patient required a second course of iodides, the patients have remained well after at least 34 months of follow-up. Three patients treated with amphotericin B, single course as well as multiple courses, and other antifungal agents (hydroxystilbamidine and miconazole) have all relapsed. These cases and a reviewed of more than 40 cases of pulmonary sporotrichosis susceptibilities of Sporothrix schenckii that we observed in vitro suggest that amphotericin B is not an effective agent for the treatment of pulmonary sporotrichosis. It is our opinion that the treatment of choice for pulmonary sporotrichosis is a supersaturated solution of potassium iodide. If the patient is allergic to the medication or fails to respond, then a combination of amphotericin B plus flucytosine may be tried.

Topics: Adult; Amphotericin B; Antifungal Agents; Female; Follow-Up Studies; Humans; In Vitro Techniques; Lung Diseases, Fungal; Male; Miconazole; Middle Aged; Oklahoma; Potassium Iodide; Sporothrix; Sporotrichosis; Stilbamidines

Management of four patients with sporotrichosis is summarized; one was treated medically and three were treated surgically. Thirty-seven cases from the literature are reviewed. The role of surgery in the management of pulmonary sporotrichosis is outlined as follows: (1) diagnosis of pulmonary infiltrates and/or pulmonary cavities of undetermined origin, (2) surgical intervention in patients with persistent infiltrates with cavitary lesions resulting from sporotrichosis, following failed medical treatment, and (3) resection of associated pulmonary cavitary lesions in patients in spite of adequte medical control of sporotrichosis. Surgical principles that must be observed in the management of pulmonary sporotrichosis follows:(1) Resection is the procedure of choice. The magnitude ranges from segmental resection to pneumonectomy. Clean resection is necessary. (2) Antifungal drug therapy--preferably with amphotericin B--is advisable preoperatively and postoperatively, since the major cause of late death is progression of the disease when clean resection has not been feasible. (3) Resection combined with drug therapy can be curative without increased risk in physiologically operable and anatomically resectable disease. (4) Thoracoplasty can be a lifesaving procedure for bilateral cavitary lesions with severe hemoptysis in patients with impaired pulmonary functions.

Topics: Adult; Amphotericin B; Humans; Lung Diseases, Fungal; Male; Methods; Middle Aged; Sporothrix; Sporotrichosis

Primary sporotrichosis of the eye is very rare; most infections are limited to the conjunctiva or adnexa. We report a case of Sporothrix endophthalmitis associated with necrotizing ethmoid sinusitis developing in a young diabetic man with ketoacidosis. The infection clinically resembled rhino-ophthalmic mycormycosis. Cure followed evisceration and an abbreviated course (215 mg) of amphotericin B. Sporothrix must now be regarded as another fungal agent capable of causing primary rhino-ophthalmic infection similar to Mucor.

Topics: Adult; Amphotericin B; Debridement; Diabetes Complications; Diagnosis, Differential; Endophthalmitis; Humans; Male; Mucormycosis; Sporotrichosis

A 34-year-old alcoholic and drug addict developed cavitary pulmonary sporotrichosis that progressed slowly during 6 years. Pulmonary resection and pre- and postoperative therapy with amphotericin B were associated with prompt clinical improvement with no evidence of relapse during a 2-year follow-up. Histologic examination of lung revealed granulomatous inflammation with organisms consistent with Sporothrix schenckii, and interstitial talc (magnesium silicate) granulomas. The latter finding was consistent with the history of intravenous drug abuse. Although the presence of silicates in lung enhances the pathogenicity of some microorganisms, the relation of these findings to the pathogenesis of sporotrichosis in our patient is unclear.

Topics: Adult; Alcoholism; Amphotericin B; Humans; Lung; Lung Diseases, Fungal; Male; Sporotrichosis; Substance-Related Disorders

The fungus Sporotrichum schenckii caused chronic meningitis in a 48-year-old man. Only three other firmly diagnosed cases were reported previously.

Topics: Amphotericin B; Humans; Male; Meningitis; Middle Aged; Sporotrichosis

Topics: Amphotericin B; Antifungal Agents; Blastomycosis; Clotrimazole; Flucytosine; Humans; Miconazole; Mycoses; Potassium Iodide; Sporotrichosis; Stilbamidines

Topics: Amphotericin B; Humans; Joint Diseases; Male; Middle Aged; Sporotrichosis

Two unusual cases of sporotrichosis are presented. One patient had disseminated vesicular skin lesions which yielded Sporothrix schenckii on culture. The other, with extensive pulmonary sporotrichosis, continued to have sputum cultures positive for S schenckii during three years of intensive chemotherapy.

Topics: Adult; Amphotericin B; Dermatomycoses; Female; Humans; Lung Diseases, Fungal; Male; Middle Aged; Potassium Iodide; Sporotrichosis

Intravenous miconazole, an investigational, broad-spectrum, antifungal imidazole drug, was clinically effective when used for the first time in a patient with life-threatening sporotrichosis. Miconazole was used after drug resistance and treatment failure occurred in a patient with extensive, cavitary, pulmonary infection with Sporotrichum schenckii. He had first been treated with amphotericin B, and then with amphotericin B and flucytosine in combination. Side effects of miconazole included itching, diarrhea, and phlebitis. Clinical improvement occurred despite plasma concentrations below those needed for complete inhibition of the patient's organisms in vitro.

Topics: Amphotericin B; Dose-Response Relationship, Drug; Drug Resistance, Microbial; Drug Therapy, Combination; Flucytosine; Humans; Imidazoles; Lung Diseases, Fungal; Male; Miconazole; Middle Aged; Radiography; Recurrence; Sporothrix; Sporotrichosis

Topics: Africa; Amphotericin B; Blastomycosis; Central America; Histoplasmosis; Humans; Paracoccidioidomycosis; South America; Sporotrichosis

Topics: Amphotericin B; Animals; Blastomyces; Clotrimazole; Cryptococcosis; Cryptococcus; Cryptococcus neoformans; Flucytosine; Imidazoles; Male; Mice; Sporothrix; Sporotrichosis

Topics: Actinomycosis; Amphotericin B; Blastomycosis; Candida albicans; Candidiasis, Cutaneous; Chromoblastomycosis; Coccidioidomycosis; Cryptococcosis; Dermatomycoses; Flucytosine; Griseofulvin; Histoplasmosis; Mucormycosis; Mycetoma; Sporotrichosis; Tinea Capitis; Tinea Pedis; Tinea Versicolor

A 48-year old, retired mounted policeman was followed for 4 years through 4 hospitalizations for progression of his bilateral, cavitary lung disease. His sputum was always negative for acid-fast bacilli and fungi. Subsequently, a painful perianal swelling appeared that was incised and drained of purulent material. Five years after first seen, sputum and rectal drainage revealed Sporothrichum schenckii in many cultures. Serologic evidence of sporotrichosis was also present. With amphotericin B therapy, the patient showed marked clinical improvement. Unfortunately, he died from an episode of acute respiratory failure. Although most patients with primary cutaneous or primary pulmonary sporotrichosis are horticulturists, the writers believe that this disease should be considered in any undiagnosed, chronic, cavitary lung disease, even in the absence of this occupational history.

Topics: Abscess; Amphotericin B; Environmental Exposure; Humans; Lung Diseases, Fungal; Male; Middle Aged; Occupational Diseases; Radiography; Rectal Diseases; Sporotrichosis; Sputum

Topics: Amphotericin B; Antifungal Agents; Antigens, Fungal; Aspergillosis; Biopsy; Blastomycosis; Candidiasis; Coccidioidomycosis; Complement Fixation Tests; Cryptococcosis; Fluorescent Antibody Technique; Fungi; Histoplasmin; Histoplasmosis; Humans; Immunity, Maternally-Acquired; Immunodiffusion; Immunosuppression Therapy; Lung; Methods; Mycoses; Precipitin Tests; Silver; Skin Tests; Sporotrichosis; Staining and Labeling; Stilbamidines

Topics: Adult; Amphotericin B; Humans; Lung Diseases, Fungal; Male; Plants; Potassium Iodide; Sporotrichosis; Stilbamidines; Tomography, X-Ray

Topics: Amphotericin B; Antifungal Agents; Blastomycosis; Coccidioidomycosis; Cryptococcosis; Flucytosine; Histoplasmosis; Humans; Meningitis; Mycoses; Natamycin; Nocardia Infections; Penicillin G; Potassium Iodide; Sporotrichosis; Stilbamidines; Sulfonamides

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Blastomycosis; Candidiasis; Coccidioidomycosis; Cryptococcosis; Flucytosine; Histoplasmosis; Humans; Iodides; Mycoses; Nystatin; Sporotrichosis

Topics: Amphotericin B; Dermatitis, Occupational; Humans; Male; Middle Aged; Occupational Diseases; Rheumatic Diseases; Sporotrichosis

Topics: Actinomycosis; Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Child; Female; Flucytosine; Fungi; Humans; Infant; Male; Middle Aged; Mycoses; Natamycin; Nocardia asteroides; Nocardia Infections; Potassium Iodide; Sporotrichosis; Stilbamidines; Sulfonamides

Topics: Aged; Amphotericin B; Arthritis; Bursitis; Diagnosis, Differential; Elbow; Gout; Humans; Injections, Intravenous; Iodides; Male; Radiography; Sporothrix; Sporotrichosis

Topics: Amphotericin B; Anti-Bacterial Agents; Humans; Potassium Iodide; Sporothrix; Sporotrichosis; Yugoslavia

Topics: Adult; Amphotericin B; Female; Humans; Iodides; Lung Diseases, Fungal; Male; Middle Aged; Radiography; Sporotrichosis; Sputum

Topics: Adult; Amphotericin B; Arthritis, Infectious; Hand; Humans; Male; Radiography; Sporotrichosis; Synovectomy; Tenosynovitis

Topics: Amphotericin B; Bone Diseases; Humans; Immunodiffusion; Male; Middle Aged; Occupational Diseases; Potassium Iodide; Radiography; Skin Tests; Sporothrix; Sporotrichosis; Sulfadimethoxine

Topics: Amphotericin B; Blood Urea Nitrogen; Coccidioidomycosis; Fever; Histoplasmosis; Humans; Injections, Intramuscular; Injections, Intravenous; Methods; Nausea; Pain; Procaine; Sporotrichosis; Stimulation, Chemical; Vomiting

Topics: Amphotericin B; Animals; Aspergillosis; Blastomycosis; Candidiasis; Cat Diseases; Cats; Coccidioidomycosis; Cryptococcosis; Dog Diseases; Dogs; Histoplasmosis; Mycoses; Sporotrichosis

Topics: Adult; Amphotericin B; Arthritis, Infectious; Female; Humans; Male; Middle Aged; Potassium Iodide; Sarcoidosis; Sporotrichosis

Topics: Adult; Aged; Amphotericin B; Arthritis, Infectious; Dermatomycoses; Humans; Hypersensitivity, Delayed; Iodides; Lung Diseases, Fungal; Male; Middle Aged; Skin Tests; Sporotrichosis

Topics: Adult; Amphotericin B; Animals; Cycloserine; Diagnosis, Differential; Ethambutol; Ethionamide; Female; Fishes; Hobbies; Humans; Male; Middle Aged; Mycobacterium; Mycobacterium Infections; Skin; Skin Diseases, Infectious; Sporotrichosis; Vancomycin

Topics: Amphotericin B; Animals; Griseofulvin; Humans; Lung Diseases, Fungal; Mice; Sporotrichosis

Topics: Amphotericin B; Dermatomycoses; Griseofulvin; Humans; Lung Diseases, Fungal; Potassium Iodide; Sporotrichosis

Topics: Adult; Aged; Amphotericin B; Female; Griseofulvin; Humans; Iodides; Lung Diseases, Fungal; Male; Middle Aged; Sporotrichosis; Stilbamidines

Topics: Amphotericin B; Child; Child, Preschool; Humans; Potassium Iodide; Sporotrichosis

Topics: Agglutination Tests; Amphotericin B; Diagnosis, Differential; Humans; Lung; Lung Diseases, Fungal; Male; Middle Aged; Sporothrix; Sporotrichosis; Sputum; Stilbamidines; Tuberculosis, Pulmonary

Topics: Adult; Amphotericin B; Bacteriological Techniques; Biopsy; Brain Abscess; Cerebrospinal Fluid Proteins; Hemiplegia; Humans; Isoniazid; Joint Diseases; Lung Diseases; Male; Meningitis; Nocardia Infections; Polymyxins; Prednisone; Pseudomonas Infections; Sarcoidosis; Skin Diseases; Sporotrichosis; Tetracycline

Topics: Actinomycosis; Amphotericin B; Animals; Antifungal Agents; Atropine; Chorioretinitis; Conjunctivitis; Eye Diseases; Hot Temperature; Humans; Laser Therapy; Light Coagulation; Mycoses; Natamycin; Nocardia Infections; Nystatin; Penicillins; Rabbits; Sporotrichosis; Streptomycin; Sulfacetamide; Sulfadiazine; Vitreous Body

Topics: Amphotericin B; Humans; Lung Diseases, Fungal; Lymphatic Diseases; Male; Middle Aged; Pneumonectomy; Postoperative Complications; Pseudomonas Infections; Sporothrix; Sporotrichosis

Topics: Actinomycosis; Amphotericin B; Antifungal Agents; Blastomycosis; Candidiasis; Coccidioidomycosis; Cryptococcosis; Histoplasmosis; Mucormycosis; Mycoses; Nocardia Infections; Sporotrichosis

Topics: Amphotericin B; Diagnosis, Differential; Female; Humans; Lung Diseases; Lung Diseases, Fungal; Middle Aged; Occupational Diseases; Sarcoidosis; Sporotrichosis; Tuberculosis, Pulmonary

Topics: Adult; Amphotericin B; Follow-Up Studies; Humans; Iodides; Leg Ulcer; Lung Diseases, Fungal; Male; Occupational Diseases; Ohio; Pneumonectomy; Radiography; Sarcoidosis; Sporothrix; Sporotrichosis; Sputum; Steroids; Tomography; Tuberculosis, Pulmonary; Vegetables

Topics: Amphotericin B; Diagnosis, Differential; Humans; Lung Diseases, Fungal; Sporotrichosis; Tuberculosis, Pulmonary

Topics: Amphotericin B; Diagnosis, Differential; Hexachlorophene; Humans; Male; Middle Aged; Potassium Iodide; Prednisolone; Pyoderma; Silver Nitrate; Skin Ulcer; Sporothrix; Sporotrichosis

Topics: Adult; Amphotericin B; Facial Dermatoses; Female; Humans; Male; Middle Aged; Potassium Iodide; Sporotrichosis

Topics: Actinomycosis; Adult; Amphotericin B; Aspergillosis; Blastomycosis; Candidiasis, Vulvovaginal; Child; Cryptococcosis; Dermatomycoses; Female; Griseofulvin; Humans; Lung Diseases, Fungal; Mycetoma; Mycoses; Nails; Nocardia Infections; Nystatin; Skin Diseases; Sporotrichosis; Stilbamidines; Thallium; Tinea Pedis

Topics: Amphotericin B; Cerebrospinal Fluid; Fluorescent Antibody Technique; Humans; Male; Meningitis; Middle Aged; Sporotrichosis

Topics: Amphotericin B; Biomedical Research; Blastomycosis; Chlorpromazine; Coccidioidomycosis; Cryptococcosis; Drug Therapy; Fever; Histoplasmosis; Humans; Lactose; Nausea; Pentobarbital; Sporotrichosis; Toxicology; Vomiting

Topics: Amphotericin B; Humans; Nephrocalcinosis; Sporotrichosis; Toxicology

Topics: Actinomycosis; Amphotericin B; Biomedical Research; Blastomycosis; Candidiasis; Coccidioidomycosis; Cryptococcosis; Cycloserine; Erythromycin; Histoplasmosis; Humans; Mycoses; Nocardia Infections; Penicillins; Pharmacology; Sporotrichosis; Stilbamidines; Sulfamerazine; Tetracycline

Topics: Actinomycosis; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Aspergillosis; Blastomycosis; Candidiasis; Coccidioidomycosis; Cryptococcosis; Histoplasmosis; Humans; Iodides; Lung Diseases, Fungal; Nocardia Infections; Penicillin G; Sporotrichosis; Stilbamidines; Sulfonamides; Toxicology

Topics: Amphotericin B; Diagnosis; Drug Therapy; Humans; Potassium Iodide; Rosa; Sporotrichosis; Syndrome; Tendon Injuries; Tendons; Wrist Joint

Topics: Amphotericin B; Animals; Liver Diseases; Male; Mice; Myositis; Sporotrichosis; Temperature

Topics: Amphotericin B; Humans; Iodides; Knee; Sporotrichosis; Surgical Procedures, Operative; Synovitis

Topics: Amphotericin B; Diagnosis; Humans; Iodides; Potassium; Sporotrichosis; Stilbamidines

Topics: Amphotericin B; Animals; Antifungal Agents; Fungicides, Industrial; Griseofulvin; Mice; Sporotrichosis