Acremonium strictum: Report of a Rare Emerging Agent of Cutaneous Hyalohyphomycosis with Review of Literatures

We present a case of cutaneous hyalohyphomycosis due to Acremonium strictum in an immunocompetent individual along with an overview of fungal infections caused by A. strictum. The diagnosis was confirmed by the presence of hyphae in microscopic examination of cutaneous biopsy and discharge, positive culture for A. strictum and sequencing of the isolate at reference centre. The infection resolved with itraconazole and terbinafine. Cutaneous or subcutaneous infections of A. strictum have rarely been reported. Fungemia or disseminated infection often with fatal outcome in immunocompromised patients was the most common presentation of A. strictum infection found in the literatures. The studies also reveal worldwide variation in the treatment regime and outcome of the treatment.     

The Use of (1–3) β-Glucan Along with Itraconazole Against Canine Refractory Sporotrichosis

Sporotrichosis, caused by the Sporothrix schenckii fungal complex, is a zoonotic mycosis distributed worldwide. Itraconazole is the treatment of choice for domestic animals although some fungal isolates have shown resistance to this drug. The objective of this study was to report, for the first time, the use of (1–3) β-glucan along with itraconazole in the treatment of a canine with sporotrichosis caused by Sporothrix brasiliensis. The animal had ulcerated and crusted lesions, especially on the nasal planum. Clinical samples were collected for a complete blood count, cytological analysis of the lesion, and fungal culture. Based on the results of the laboratory examination, and after the fungal culture, antibiotic therapy and treatment with itraconazole were initiated. Two additional fungal cultures were performed, which were positive. After 7 months of the animal treatment with itraconazole, the S. brasiliensis culture was still positive, so that the itraconazole was associated with (1–3) β-glucan. After four weekly applications of glucan, the complete elimination of the fungus was observed based on the fungal culture negative results. The results show, therefore, that (1–3) β-glucan with itraconazole promoted the case resolution, and it may be considered a promising alternative for the treatment of sporotrichosis in cases of resistance to conventional therapy.     

How I Treat Histoplasmosis

Histoplasmosis is an endemic mycosis caused by the dimorphic fungus Histoplasma capsulatum. Some important manifestations of infection include acute or chronic pulmonary disease, histoplasmomas, progressive disseminated histoplasmosis, and central nervous system infection. Depending on the clinical presentation, site of infection and severity of disease, either amphotericin B preparations followed by itraconazole, or itraconazole alone have become the preferred treatments. Because prolonged therapy (6 weeks to 24 months) may be required, careful monitoring for nephrotoxicity in patients on amphotericin B preparations is necessary. In addition, in patients receiving itraconazole, vigilance for drug interactions and pharmacokinetic properties is warranted. Histoplasma antigen testing has improved rapidity of diagnosis and the ability of long-term monitoring for clinical response in patients with histoplasmosis.     

Direct Extraction of DNA from Positive Transparent Dressing and Swab to Identify Candida albicans Infection in Intertriginous Candidiasis in the Inguinal Region

We report a case of a patient infected by Candida albicans which was identified by direct extraction of DNA from a positive transparent dressing and a swab. The patient was a 32-year-old male who complained of erosion in his inguinal region. Large patches of erythema and erosion were present in his inguinal and perianal region, with soya-bean like residue discharge. He was diagnosed with erythrasma and treated with antibiotics but his clinical condition did not improve. KOH examination furnished a positive result for candidiasis. Morphologic characteristics confirmed his infection was caused by Candida albicans. Sequencing of the internal transcribed spacer (ITS) 1/4 polymerase chain reaction products, amplified from positive transparent dressing and cotton swab with discharge and from primary culture isolates, established the Candida albicans lineage. The patient was cured by treatment with itraconazole 200?mg twice a day orally in combination with topical wash with 2?% ketoconazole shampoo and topical use of 1?% naftifine–0.25?% ketoconazole cream.     

Problemas clínicos en micología médica: problema número 46

A 49 year old-man, without known previous diseases, who suffered an acute lung infection, is presented. He was a smoker and belonged to a high socioeconomic class. He suddenly presented high fever, dry cough and legs’ pain. Thorax X-ray and CT scan showed two excavated pneumonic infiltrates in the lower part of the right lung. He was treated with antibacterial antibiotics without clinical response. A transparietal fine needle lung biopsy was performed and the histopathology and cytological studies revealed an epithelioid granuloma with capsulated yeasts. Cryptococcus neoformans antigenemia was positive 1/128, and brain MR, as well as CSF studies, allowed to rule out a central nervous system compromise. The patient was successfully treated with itraconazole by oral route at a daily dose of 400 mg during 6 months. Post-treatment thorax CT scan showed a thin walled lung cavity as a sequela.     

A Case Report of Penile Infection Caused by Fluconazole- and Terbinafine-Resistant <Emphasis Type="Italic">Candida albicans</Emphasis>

Candida albicans is the most common pathogen that causes balanoposthitis. It often causes recurrence of symptoms probably due to its antifungal resistance. A significant number of balanitis Candida albicans isolates are resistant to azole and terbinafine antifungal agents in vitro. However, balanoposthitis caused by fluconazole- and terbinafine-resistant Candida albicans has rarely been reported. Here, we describe a case of a recurrent penile infection caused by fluconazole- and terbinafine-resistant Candida albicans, as well as the treatments administered to this patient. The isolate from the patient was tested for drug susceptibility in vitro. It was sensitive to itraconazole, voriconazole, clotrimazole and amphotericin B, but not to terbinafine and fluconazole. Thus, oral itraconazole was administrated to this patient with resistant Candida albicans penile infection. The symptoms were improved, and mycological examination result was negative. Follow-up treatment of this patient for 3 months showed no recurrence.     

Treatment of Aspergillus fumigatus in patients with cystic fibrosis: a randomized, placebo-controlled pilot study

Background

Many patients with cystic fibrosis develop persistent airway infection/colonization with Aspergillus fumigatus, however the impact of A. fumigatus on clinical outcomes remains unclear. The objective of this study was to determine whether treatment directed against Aspergillus fumigatus improves pulmonary function and clinical outcomes in patients with cystic fibrosis (CF).

Methods

We performed a double-blind randomized placebo-controlled pilot clinical trial involving 35 patients with CF whose sputum cultures were chronically positive for A. fumigatus. Participants were centrally randomized to receive either oral itraconazole 5 mg/kg/d (N = 18) or placebo (N = 17) for 24 weeks. The primary outcome was the proportion of patients who experienced a respiratory exacerbation requiring intravenous antibiotics over the 24 week treatment period. Secondary outcomes included changes in FEV₁ and quality of life.

Results

Over the 24 week treatment period, 4 of 18 (22%) patients randomized to itraconazole experienced a respiratory exacerbation requiring intravenous antibiotics, compared to 5 of 16 (31%) placebo treated patients, P = 0.70. FEV₁ declined by 4.62% over 24 weeks in the patients randomized to itraconazole, compared to a 0.32% improvement in the placebo group (between group difference = −4.94%, 95% CI: −15.33 to 5.45, P = 0.34). Quality of life did not differ between the 2 treatment groups throughout the study. Therapeutic itraconazole blood levels were not achieved in 43% of patients randomized to itraconazole.

Conclusion

We did not identify clinical benefit from itraconazole treatment for CF patients whose sputum was chronically colonized with A. fumigatus. Limitations of this pilot study were its small sample size, and failure to achieve therapeutic levels of itraconazole in many patients.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00528190","term_id":"NCT00528190"}}NCT00528190     

PCR法评价伊曲康唑注射液治疗播散性白念珠菌病兔模型疗效

目的通过静脉内接种的方法,构建播散性白念珠菌感染的兔模型,并用PCR评价伊曲康唑注射液治疗播散性念珠菌病的疗效。方法在接种后24h,用伊曲康唑注射液5rag／kg对兔模型进行治疗,1次／d,共14d。在不同的时间段取兔模型的静脉血,进行血培养和真菌通用引物以及白念珠菌特异性引物的PCR检测,监测伊曲康唑注射液治疗播散性白念珠菌感染的疗效。结果在接种白念珠菌后1h、6h,外周血中用PCR方法就能检测到白念珠菌,且能持续到8—10d;实验兔外周血血培养1h后阳性,持续到18h。实验结束后解剖实验兔,治疗组较对照组内脏器官的组织培养阳性率及菌落数低。结论PCR是一种快速和敏感的检测播散性念珠菌病的方法,伊曲康唑注射液治疗播散性白念珠菌病有效,但是真菌的清除率特别是肾脏组织的真菌清除率并不理想,治疗结束7d后,组织匀浆真菌培养仍然阳性。     

Feline Nasal Granuloma Due to Cryptoccocus gattii Type VGII

The aims of this study are to make a more precise identification of the etiologic agent of a nasal granuloma in a cat, to verify the susceptibility to the antifungal drugs: ketoconazole, itraconazole, fluconazole, posaconazole, voriconazole, amphotericin B and the proper treatment. Part of the granuloma’s fragment was removed, added to a saline solution and sent to the Laboratory of Mycology. The solution was then seeded in Sabouraud dextrose agar, and the yeast was primarily identified by the traditional methods. The confirmation of the specie Cryptococcus gattii and its molecular type were performed using the PCR–RFLP molecular techniques. The antifungal susceptibility was verified by using the E-test method, and the cat was treated with itraconazole associated with 5-flucytosine. The isolated strain was identified as C. gattii type VGII and was susceptible to all antifungal drugs tested. The treatment with itraconazole associated with 5-flucytosine led to the cure of granulomatous lesions in the feline after 6 months. The characterization and molecular investigation of this microorganism are relevant because they could help us better understand the epidemiology of the infection and to guide us to treat properly the disease.     

A Case of Relapsed Chromoblastomycosis Due to Fonsecaea monophora: Antifungal Susceptibility and Phylogenetic Analysis

Chromoblastomycosis is a chronic cutaneous and subcutaneous mycosis. The management of this infection continues to be challenging because there is no consensus on the therapeutic regimen. We report here a case of a 69-year-old male patient with cauliflower-like lesions on his left leg and foot. He had already been treated with itraconazole at a dose of 200 mg/day for 5 months, with mycological cure for all the affected areas. However, the lesions relapsed at both sites, and treatment with itraconazole was resumed at the dose previously used. Initially, direct mycological examination, cultural, and microculture slide observation were performed. Afterward, sequencing of the ITS1-5.8S rDNA-ITS2 region of the fungal DNA and evaluation of its susceptibility to antifungal agents alone and in combination were performed. In direct mycological examination, the presence of sclerotic cells was verified, and the fungus was identified as Fonsecaea based on cultural and microscopic examinations. Identification as Fonsecaea monophora was confirmed after sequencing of the ITS region and phylogenetic analysis. The isolate was susceptible to itraconazole and terbinafine. The combinations of amphotericin B and terbinafine and terbinafine and voriconazole were synergistic. The use of drugs for which the causative agent is susceptible to singly or in combination may be an alternative for the treatment of mycosis. Furthermore, the identification of the agent by molecular techniques is important for epidemiological purposes. To the best of our knowledge, this is the first case of relapsed chromoblastomycosis caused by F. monophora in Brazil.     

马尔尼菲蓝状菌病致溶骨性损害合并Sweet样皮疹1例

本文报道广西医科大学第一附属医院皮肤性病科收治的马尔尼菲蓝状菌病致溶骨性损害合并Sweet样皮疹1例。免疫力正常人群较少患马尔尼菲蓝状菌病。本例患者既往体健,起初合并融骨性损害,在两性霉素B、伊曲康唑治疗过程中逐渐出现Sweet样皮疹。患者经两性霉素B、伊曲康唑、激素等治疗后,病情逐渐好转。     

Cutaneous and Mucosal Phaeohyphomycosis Caused by Exophiala spinifera in a Pregnant Patient: Case Report and Literature Review

We report a case of mucocutaneous phaeohyphomycosis caused by Exophiala spinifera. Crusty plaques and nodules were major clinical features. Histological examination revealed brown yeast-like cells and hyphae. Mycological and molecular data identified E. spinifera as etiologic agent. Oral itraconazole was effective, which was in accordance with the results of in vitro susceptibility testing. We speculated that her pregnancy may play a role of risk factor in the infection by E. spinifera.     

First Case of Tritirachium oryzae as Agent of Onychomycosis and Its Susceptibility to Antifungal Drugs

The first case of Tritirachium oryzae isolated from an Iranian patient is reported. A 44-year-old woman with a lesion in her fingernail was examined for onychomycosis. Direct microscopic examination of the nail clippings revealed fungal filaments and inoculation of portions of the nail clippings on cultures media yielded T. oryzae after 8 days. The isolate was identified as Tritirachium spp. on the basis of gross morphological characteristics of the fungal colony and microscopic characterization of slide cultures. The diagnosis of T. oryzae was confirmed by PCR sequencing of the internal transcribed spacer domain of the rDNA gene. In vitro antifungal susceptibility test demonstrated that the fungus was susceptible to itraconazole and posaconazole. The patient was treated with oral itraconazole.     

Pulmonary Mucormycosis due to Lichtheimia ramosa in a Patient with HIV Infection

Mucormycosis is increasingly common in patients with risk factors such as diabetes mellitus, neutropenia, and corticosteroid therapy. However, mucormycosis seems to be less common in patients with human immunodeficiency virus (HIV) infection compared to patients with other risk factors. Despite their lower virulence, Lichtheimia species should be regarded as emerging pathogens among Mucoralean fungi. We report a fatal case of pulmonary mucormycosis due to Lichtheimia ramosa in a 52-year-old man with an end-stage HIV infection. He had a cachectic appearance and his CD4 count was 8 cells/mm³. The fungal infection was diagnosed based on a positive sputum culture with histopathologic confirmation. The fungus was resistant to caspofungin, anidulafungin, and voriconazole [minimum inhibitory concentration (MCI) >32 µg/ml], whereas the E test MIC values of itraconazole, posaconazole, and amphotericin B were 0.38, 0.38, and 0.5 µg/ml, respectively. Although intravenous drug use is the main risk factor for the development of mucormycosis in HIV-infected patients, it may also develop in patients with low CD4 count, opportunistic infections and/or additional diseases, such as Kaposi’s sarcoma or severe immunodeficiency, as in our case.     

Effects of Itraconazole and Micafungin on Aspergillus fumigatus Biofilms

Aspergillus fumigatus (A. fumigatus) is the most common airborne opportunistic fungal pathogen. Biofilm formation is one of the main pathogenic mechanisms of A. fumigatus. During the past decades, A. fumigatus azole resistance has become prevalent due to the medical and agricultural use of antifungal drugs and fungicides. Until now, the role of fungal biofilms in azole resistance of A. fumigatus remains unclear. In the present study, we compared biofilm drug susceptibility and biofilm formation under itraconazole of azole-resistant strains, sensitive strains, and standard strains, separately. The biofilm viability and matrix thickness at the early and the late stage were measured by XTT assay and Calcofluor white. Our results showed that the sessile minimum inhibitory concentration of itraconazole, which describing the inhibition of drugs on fungi sessile with biofilm, was much higher than the traditional minimal inhibitory concentration of itraconazole. Additionally, low concentrations of itraconazole inhibited biofilm formation of A. fumigatus strains. Notably, biofilm formation by azole-resistant strains could not be inhibited by high concentrations of itraconazole but could be effectively restrained by low concentrations of micafungin, revealing the efficacy of a cell-wall inhibitor to disrupt A. fumigatus biofilm formation. However, late-stage biofilms of both azole-resistant strains and standard strains were hard to disrupt using itraconazole. We found that itraconazole was effective to prevent A. fumigatus biofilm formation at the early stage. For the treatment of A. fumigatus biofilm, our findings suggest that an early-stage preventive strategy is preferred and micafungin is effective to control the azole-resistant strain infection.

     

Isolated Cutaneous Granuloma Caused by <Emphasis Type="Italic">Candida glabrata</Emphasis>: A Rare Case Report and Literature Review

The incidence of candidiasis due to non-albicans Candida species (especially Candida glabrata) has significantly increased in recent decades. Candida glabrata often invades immunocompromised hosts and causes systemic or mucosal infections, whereas cutaneous infections are rarely reported. We present a rare case of cutaneous infection caused by C. glabrata and review all similar cases available in the PubMed database. A patient was admitted to the hospital with a 2-month history of a plaque on the face. Histopathological examination displayed typical infectious granulomas in the deep dermis, and the pathogen was finally confirmed as C. glabrata using a series of microbial examinations (fungal culture, biochemical test, and PCR-directed sequencing). The patient was completely cured after 4 months of treatment with oral itraconazole combined with topical terbinafine. We reviewed similar reports of cutaneous infection caused by C. glabrata. All the data suggested that an accurate diagnosis of cutaneous candidiasis depends mainly on histological and fungal examinations, especially molecular biological assays. Antifungal agents based on microbial susceptibility tests are the first-line treatment choice for C. glabrata infection, but the prognosis might be more dependent on the basic condition of the host.     

Central Nervous System Paracoccidioidomycosis in an AIDS Patient: Case Report

Up to now, over 200 patients with paracoccidioidomycosis (PCM) associated to HIV infection have already been reported; however, the central nervous system involvement in this coinfection was rarely reported. This paper presents a 35-year-old Brazilian male AIDS patient who developed pulmonary PCM successfully treated with itraconazole. At the antiretroviral therapy starting, he had 32 CD4⁺ T cells baseline count and high viral load levels. After 9 months, he presented severe fungal meningoencephalitis diagnosed by sublenticular enhanced nodular lesion at computerized tomography and magnetic resonance brain imaging and a positive Paracoccidiodes brasiliensis smear and culture from cerebrospinal fluid. At the time, a sixfold increase in CD4⁺ T cell count and undetectable viral load level were evidenced. The patient received amphotericin B during 1 year presenting slow but progressive clinical improvement, and he is currently asymptomatic and without neurological disabilities. To our knowledge, this is the second case report of a patient with neuroparacoccidioidomycosis associated to HIV infection.     

Subcutaneous Phaeohyphomycosis Caused by <Emphasis Type="Italic">Exophiala oligosperma</Emphasis> in an Immunocompetent Host: Case Report and Literature Review

We report a case of subcutaneous infection caused by Exophiala oligosperma. Erythematous ulcerated plaque with exudate was major clinical features. Histopathological examination showed yeast-like cells and fungal hyphae. Mycological and molecular identification revealed E. oligosperma as etiologic agent. Local debridement and oral itraconazole were effective. To the best of our knowledge, this is the first report of phaeohyphomycosis caused by E. oligosperma in mainland China. This report highlights the potential role of E. oligosperma as an emerging cause of infection in immunocompetent patients.     

Problemas clínicos en micología médica: problema número 51

A 48 year-old immunocompetent woman, who had a nodular lesion in the neck and a dense infiltrate at the lower lobe of the left lung, presented at the Mycology Unit of Muñiz Hospital of Buenos Aires City. The pulmonary infiltrate disappeared spontaneously 3 months later. The histopathological study of the nodular lesion showed capsulated yeasts (mucicarmin and alcian blue positive stains) compatible with Cryptococcus. The mycological study of a new sample, obtained by a nodular puncture, allowed the isolation of yeasts, identified as Cryptococcus gattii (VGII). Latex test for Cryptococcus capsular antigen in serum was positive (1/100). CSF cultures rendered negative results. Fluconazole at a daily dose of 800 mg was given during 45 days with partial improvement; as cultures from a new clinical sample were positive for Cryptococcus, the antimycotic was changed to itraconazole 400 mg/day for 5 months, with an excellent clinical response.