Orbital apex syndrome caused by Alternaria species: A novel invasive fungus and new treatment paradigm.

Orbital apex syndrome as a result of invasive fungal sinusitis is a disease entity most commonly found in immunocompromised patients. Infectious invasion affecting the orbital apex can have devastating visual and life-threatening consequences. Mucormycosis and Aspergillus species are the most common causes of such infections. Alternaria fungal sinusitis is a known entity, but its ability to cause an orbital apex syndrome has not yet been reported. Here, we present a case of orbital apex syndrome in an immunocompromised patient with invasive fungal sinusitis caused by Alternaria species. The patient underwent sinus washout and placement of an intraorbital catheter for local instillation of amphotericin B for 10 days, in addition to systemic antifungal treatment, with clinical resolution of infection. The use of an intraorbital catheter for local treatment of fungal infection may offer an exenteration-sparing treatment option in these patients.

Polyphasic identification of three new species in Alternaria section Infectoriae causing human cutaneous infection.

BACKGROUND: Cutaneous phaeohyphomycosis is an emerging disease in immunocompromised patients, being Alternaria one of the most common genera reported as a causative agent. Species identification is not carried out mainly due to the complexity of the genus. Analysis of the ITS barcode has become standard for fungal identification, but in Alternaria it is only able to discriminate among species-groups or sections. METHODS: We present three cases of cutaneous infection caused by Alternaria isolates morphologically identified as belonging to section Infectoriae. They have been morphologically characterised and phylogenetically delineated with five molecular markers (ITS, ATPase, gapdh, rpb2 and tef1). RESULTS: Mycotic infections have been diagnosed by repeated cultures and histopathological examination in two of the cases. The polyphasic approach has allowed to delineate three new species of Alternaria section Infectoriae, that is A anthropophila, A atrobrunnea and A guarroi. ATPase has been the only locus able to discriminate most of the species (29 out of 31) currently sequenced in this section, including A infectoria the commonest reported species causing alternariosis. Susceptibility test showed different antifungal patterns for the three species, although terbinafine was the most active in vitro drug against these fungi. CONCLUSIONS: The ATPase gene is recommended as an alternative barcode locus to identify Alternaria clinical isolates in section Infectoriae. Our results reinforce the relevance of identification of Alternaria isolates at the species level and the necessity to carry out antifungal susceptibility testing to determine the most adequate drug for treatment.

Queratitis por Alternaria alternata / Alternaria alternata keratitis

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[A case of pulmonary alternariosis complicated with aspergillosis].

A 61-year-old woman with pulmonary alternariosis and aspergillosis was reported. The patient presented with recurrent hemoptysis and cough for 3 years. Alternaria was identified by fungal culture. Biopsy specimen showed pulmonary aspergillosis. The patient had been treated with voriconazole at 400 mg/d through intravenous guttae for 7 days, and then switched amphotericin B at 25 mg/d through intravenous guttae for 11 days. The patient was treated with voriconazole at 400 mg through oral when she was discharged from hospital. After the treatment, the clinical symptoms of hemoptysis and cough were recovered, and the lung CT examinations showed normal.

Unusual fungal sepsis of Alternaria alternata in acute lymphoblastic leukaemia in an adult patient.

We report a case of unusual fungal sepsis of Alternaria alternata in a patient of acute lymphoblastic leukaemia in 62-year-old male who presented with complaints of 'off and on' fever with decreased oral intake. On evaluation, haemogram showed low platelet count and 68% blast cells in peripheral blood. On flow cytometry of peripheral blood, the gated blasts (approximately 55%) highly express CD45, CD10, CD19, CD22 and condition was diagnosed as acute lymphoblastic leukaemia. He was started on standard induction treatment along with supportive therapies. During the course of treatment, two sets of paired blood cultures were sent 48 h apart. All of blood cultures were done on Bac-T alert 3D system. All of them yielded fungus. The fungus was then grown on Sabouraud's Dextrose agar media. It was identified as A. alternata. The patient condition worsened and later had cardiac arrest in ICU and could not be revived.

Alternaria is an Infrequent Cause of Keratitis: A Case Report and Review of the Literature.

OBJECTIVE: To report a case of fungal keratitis caused by Alternaria in a 49-year-old female who developed an acute onset of eye infection after ocular trauma caused by an olive leaf. METHODS: The clinical presentation, microbiological diagnosis, and therapeutic approaches are reported. RESULTS: The patient was referred to our university hospital clinic with corneal abscess in her left eye. Before the start of an empirical antibacterial therapy (both topical and systemic), a swab of the cornea was obtained which at microscopic examination revealed a few fragments of hyphal elements, probably for the paucity of material collected. After one week, the corneal abscess had increased in size, and the corneal stroma was filled with filamentous structures similar to fungal hyphae. Oral and topical voriconazole was administered because of the clinical picture and the response of microbiological laboratory whose examination of the material removed from the anterior chamber showed numerous hyphal fragments identified by culture as Alternaria spp. The corneal abscess healed in two weeks, but the patient now has a corneal scar and is awaiting a corneal transplant. CONCLUSIONS: Ophthalmologists and microbiologists must take fungi into greater consideration as a possible cause of keratitis as they are emerging as the cause of this infectious disease in many countries. Voriconazole spreads well in the eye and is effective in the cure of fungal keratitis including those caused by Alternaria.

Subcutaneous phaeohyphomycosis due to Alternaria infectoria in a renal transplant patient: surgical treatment with no long-term relapse / Feohifomicosis subcutánea debida a Alternaria infectoria en un paciente sometido a un trasplante renal: tratamiento quirúrgico sin recidivas a largo plazo

Background. Phaeohyphomycosis can be caused by a number of different species, being the most common Alternaria alternata and Alternaria infectoria. The biggest risk factor for the development of the infection is immunosuppression. Aims. We present the case of a 64-year-old male renal transplant patient who came to hospital for presenting a tumour in the Achilles region which had been gradually growing in size. Methods. A skin biopsy was taken for histological study and culture of fungi and mycobacteria. Blood tests and imaging studies were performed. Results. Histopathology study and cultures identified A. infectoria as the causal agent. Imaging studies ruled out internal foci of infection. The lesion was surgically removed with no signs of recurrence after 24 months of follow-up. Conclusions. There are no treatment guidelines at present for cutaneous and subcutaneous Alternaria spp. infections. Various systemic antifungals have been used, either in combination with surgical removal or alone, with varying results. Surgery alone could be useful in the treatment of solitary, localised lesions in transplant patients in whom there are difficulties in controlling immunosuppression (AU)

Antecedentes. La feohifomicosis está causada por diversas especies de hongos, siendo las más habituales Alternaria alternata y Alternaria infectoria. El factor de riesgo principal en la aparición de la infección es la inmunosupresión. Objetivos. Presentamos el caso de un hombre de 64 años de edad, sometido a un trasplante renal, que se presentó en el hospital con un tumor en la región del tendón de Aquiles que había aumentado gradualmente de tamaño. Métodos. Se obtuvo una biopsia de piel para estudio histológico y cultivo de hongos y micobacterias. Se efectuaron análisis de sangre y estudios de diagnóstico por imagen. Resultados. El estudio histopatológico y los cultivos permitieron la identificación de A. infectoria como del patógeno causal. Los estudios por imagen descartaron focos internos de infección. Se procedió a la exéresis quirúrgica de la lesión sin signos de recidiva después de 24 meses de seguimiento. Conclusiones. En la actualidad no se dispone de guías de tratamiento para las infecciones cutáneas y subcutáneas por Alternaria spp. Se han utilizado diversos antimicóticos sistémicos, combinados con la exéresis quirúrgica o solos, con diferentes resultados desiguales. La cirugía sola podría ser útil en el tratamiento de las lesiones localizadas, solitarias, en los pacientes sometidos a un trasplante en los que es difícil controlar la inmunosupresión (AU)

Incidence of non-candidal fungal infections in severe burn injury: an Australian perspective.

INTRODUCTION: Infection remains the primary cause of morbidity and mortality in the burns patient population. While candidal infection in burns patients is well described, there is dearth of information regarding non-candidal fungal infections in this setting. METHOD: All adult burns patients who developed non-candidal fungal infections over a period of 10 years (between January 2001 and June 2011) were included. Retrospective data analyzed included patient demographics, organisms cultured, antibiotic susceptibility patterns, treatment, length of stay and overall mortality. RESULTS: The incidence of non-candidal fungal infections at our centre over the time period studied was 0.04%. A total of 12 patients had a fungus other than Candida isolated. Of these 12 patients, seven were thought to have clinically significant fungal infections and were treated with targeted anti-fungal therapy. Between them, seven species of fungus were isolated: Aspergillus fumigatus (n=7), Scedosporium prolificans (n=2), Fusarium solani (n=2), Mucor spp. (n=2), Absydia corymbifera (n=1), Penicillium (n=1) and Alternaria spp. (n=1). Of those definitively treated, two died, although fungal infection was not believed to be a contributing factor to these deaths. CONCLUSION: We demonstrate a low incidence and attributable mortality of non-candidal fungal infections in the setting of early antifungal therapy and extensive surgical debridement at our state-wide Burns Service.

Innate type 2 response to Alternaria extract enhances ryegrass-induced lung inflammation.

BACKGROUND: Exposure to the fungal allergen Alternaria alternata as well as ryegrass pollen has been implicated in severe asthma symptoms during thunderstorms. We have previously shown that Alternaria extract induces innate type 2 lung inflammation in mice. We hypothesized that the innate eosinophilic response to Alternaria extract may enhance lung inflammation induced by ryegrass. METHODS: Mice were sensitized to ryegrass allergen and administered a single challenge with A. alternata extract before or after final ryegrass challenges. Levels of eosinophils, neutrophils, Th2 cells, innate lymphoid cells (ILC2), interleukin (IL)-5 and IL-13 in bronchoalveolar lavage (BAL) as well as inflammation and mucus were assessed. RESULTS: Mice receiving ryegrass sensitization and challenge developed an eosinophilic lung response. A single challenge with Alternaria extract given 3 days before or 3 days after ryegrass challenges resulted in increased eosinophils, peribronchial inflammation and mucus production in the airways compared with ryegrass-only challenges. Type 2 ILC2 and Th2 cell recruitment to the airways was increased after Alternaria extract exposure in ryegrass-challenged mice. Innate immune challenges with Alternaria extract induced BAL eosinophilia, Th2 cell recruitment as well as ILC2 expansion and proliferation. CONCLUSIONS: A single exposure to Alternaria extract in ryegrass-sensitized and -challenged mice enhances the type 2 lung inflammatory response, including airway eosinophilia, peribronchial infiltrate, and mucus production, possibly through Th2 cell recruitment and ILC2 expansion. If translated to humans, exposure to both grass pollen and Alternaria may be a potential cause of thunderstorm-related asthma.

Alternaria alternata invasive fungal infection in a patient with Fanconi's anemia after an unrelated bone marrow transplant.

Alternaria spp. have emerged as opportunistic pathogens particularly in immunosuppressed patients, such as bone marrow transplant recipients. The authors present a case of Alternaria alternata in a patient with Fanconi's anemia, who received antifungal prophylaxis with posaconazole after an unrelated bone marrow transplantation, followed by empirical antifungal treatment with caspofungin when persistent fever emerged until cutaneous lesions eventually appeared. At that time there were clinical reasons to assume that the patient had an infection with an emerging fungus. This consideration triggered a change of the antifungal therapy from caspofungin to liposomal amphotericin B. After collecting sufficient evidence for the presence of an invasive fungal infection by A. alternata and given the severity of neutropenia and other immunosuppression, oral posaconazole was added to liposomal amphotericin B. The course of disease in this case suggests a possibly synergistic interaction between liposomal amphotericin B and posaconazole when administered simultaneously to treat an invasive systemic infection by Alternaria spp. in immunocompromised patients.

Delayed scleral buckle infection due to Alternaria species.

OBJECTIVE: To report a case of scleral buckle infection by Alternaria fungus. CASE REPORT: A 75-year-old male who underwent rhegmatogenous retinal detachment repair 11 years ago developed a scleral buckle infection during the course of serial injections of bevacizumab for the treatment of wet age-related macular degeneration. Removal of the scleral buckle was done and culture results revealed Alternaria species. RESULTS: The infected scleral buckle was removed and the patient received oral voriconazole. The patient's best corrected visual acuity changed from 20/50 preoperatively to 20/150 six months after the procedure. CONCLUSION: Alternaria species may be encountered as a cause of scleral buckle infection.

Phaeohyphomycosis caused by Alternaria infectoria presenting as multiple vegetating lesions in a renal transplant patient.

The genus Alternaria is one of the most common black moulds and appears to be increasing as a causative agent of subcutaneous phaeohyphomycosis, particularly among immunosuppressed patients. A 53-year-old patient who had received a kidney transplant presented with multiple verrucous lesions on the distal extremities. Positive histopathology and cultures, in addition to rDNA ITS region sequencing, identified the fungal isolate as Alternaria infectoria. Oral itraconazole was administered for 10 months. A follow-up at 15 months demonstrated no signs of infection. Clinical manifestations of cutaneous alternariosis vary significantly and only a few cases have been described in the literature. Although optimal treatment options remain controversial, this case of phaeohyphomycosis was successfully treated with itraconazole monotherapy.

Non-dermatophyte moulds as pathogens of onychomycosis.

OBJECTIVE: To determine the role and pattern of non-dermatophyte moulds as causative agents of onychomycosis. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: Department of Microbiology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from November 2009 to July 2010. METHODOLOGY: Nail clippings and nail scrapings were obtained from abnormal looking nails with treatment and detection failure for onychomycosis. Microscopic (40% potassium hydroxide mounts) examination and culture on Sabouraud's dextrose agar (SDA), SDA containing chloramphenicol, and SDA containing actidione and chloramphenicol were used for species identification. RESULTS: Non-dermatophyte moulds were isolated from 32 out of the total 47 culture positive cases (68%). Alternaria alternata was the commonest species (46%). Dermatophytes were isolated from only 7 patients (15%) belonging to genus Trichophyton. Yeasts were isolated in 8 (17%). There was no fungal growth in 53% of cases. CONCLUSION: The non-dermatophytes should be considered important in evaluating the culture negative cases for dermatophytes as well as those cases ending up in treatment failure after empirical treatment for dermatophyte infections.