Pulmonary co‐infections by Pneumocystis jirovecii and Aspergillus fumigatus in non‐HIV patients: A report of two cases and literature review

Pneumocystis jirovecii is the causative agent of Pneumocystis pneumonia (PcP), a common and often life‐threatening opportunistic infection in HIV‐infected patients. However, non‐HIV, immunocompromised patients are at risk of PcP as well, whereas the mortality appears to be higher among these patients. Pneumocystis co‐infections with other microorganisms are less frequent and only sparse reports of combined PcP and invasive pulmonary fungal infections exist in the literature, especially in the non‐HIV patients. Two cases of pulmonary co‐infections by P. jirovecii and Aspergillus fumigatus are presented. Both patients were non‐HIV infected, the first one was suffering from crescentic IgA nephropathy under immunosuppressive treatment and the second from resistant non‐Hodgkin lymphoma under chemotherapy. Both patients were treated with intravenous trimethoprim/sulphamethoxazole (TMP/SMX) combined with voriconazole. The first patient showed gradual clinical improvement while the outcome for the second patient was unfavourable. In addition, a literature review of the previous published cases of co‐infection by P. jirovecii and other fungi in non‐HIV patients was performed. Our target was to provide comprehensive information on this kind of infections, highlighting the importance of clinical suspicion.     

Rhodotorula minuta as onychomycosis agent in a Chinese patient: first report and literature review

Onychomycosis is a common superficial fungal infection, which usually caused by dermatophytes, yeast and non‐dermatophytic moulds. Recently, we isolated a Rhodotorula minuta isolate from a 15‐year‐old immunocompetent girl student in Hangzhou (China) that was identified using microscopy, culture morphology, histological diagnosis, API 20C AUX Yeast Identification Kit and sequencing of the Internal Transcribed Spacer region. In vitro, antifungal susceptibility tests showed that this yeast isolate was susceptible to low concentrations of amphotericin B, itraconazole, voriconazole and 5‐flvoriconaz but that it appeared to be dose‐dependent susceptible to fluconazole(MIC = 16 μg/ml). Furthermore, the effective result of therapy with itraconazole against R. minuta was consistent with that of susceptibility tests.     

Invasive pulmonary infection caused by Chrysosporium articulatum: the first case report

Chrysosporium species, saprobic soil fungi, comprise more than 60 species. There is some confusion regarding the taxonomy and nomenclature between Chrysosporium and Emmonsia since the causative agents of adiaspiromycosis, the development of big thick‐walled spores (adiaspores) in humans or animals, were previously thought to be Chrysosporium. Chrysosporium articulatum has never been reported to cause invasive infection in humans. We report herein the first case of invasive pulmonary infection caused by Chrysosporium articulatum in a 16‐year‐old man with acute T‐cell lymphoblastic leukaemia. He was successfully treated with voriconazole.     

First isolation of Candida wangnamkhiaoensis from the blood of immunocompromised paediatric patient

Candida wangnamkhiaoensis is a species clustered under the Hyphopichia clade has not ever been isolated from any clinical specimens. To the best of our knowledge, this is the first report of C. wangnamkhiaoensis associated with fungaemia in immunocompromised paediatric patient. The isolate was assigned a strain name as UZ1679/14, in which the identification was confirmed by a polymerase chain reaction‐sequencing of the internal transcribed spacer (ITS) and large subunit (LSU) regions of the rRNA gene. Antifungal susceptibility pattern showed that the isolate was sensitive to anidulafungin, caspofungin, fluconazole and voriconazole. The patient clinically improved after the antifungal treatment with caspofungin.     

Treatment of Paecilomyces variotii pneumonia with posaconazole: case report and literature review

The fungi Paecilomyces variotii is a potential pathogen in immunocompromised and immunocompetent patients. Their rare association with clinical disease results in scarce literature regarding susceptibility and treatment. Here, we discuss a case involving successful treatment of probable P. variotii pneumonia with posaconazole after treatment failure with voriconazole. The current literature related to antifungal susceptibility profiles, microbiological identification methods and clinical management of infections caused by this organism is also reviewed.     

Onychomycosis caused by Onychocola canadensis: the first report in Estonia and lessons to learn

We report the first case of onychomycosis caused by Onychocola canadensis in Estonia. We believe that the number of nail infections caused by this fungus is underestimated due to the current diagnostic algorithm of non‐dermatophytic onychomycosis. The need to define categories and criteria for ‘proven’ and ‘probable’ non‐dermatophyte mold infections to promote more extensive studies in the future is also discussed.     

Aspergillus specific nested PCR from the site of infection is superior to testing concurrent blood samples in immunocompromised patients with suspected invasive aspergillosis

Invasive aspergillosis (IA) is a severe complication in immunocompromised patients. Early diagnosis is crucial to decrease its high mortality, yet the diagnostic gold standard (histopathology and culture) is time‐consuming and cannot offer early confirmation of IA. Detection of IA by polymerase chain reaction (PCR) shows promising potential. Various studies have analysed its diagnostic performance in different clinical settings, especially addressing optimal specimen selection. However, direct comparison of different types of specimens in individual patients though essential, is rarely reported. We systematically assessed the diagnostic performance of an Aspergillus‐specific nested PCR by investigating specimens from the site of infection and comparing it with concurrent blood samples in individual patients (pts) with IA. In a retrospective multicenter analysis PCR was performed on clinical specimens (n = 138) of immunocompromised high‐risk pts (n = 133) from the site of infection together with concurrent blood samples. 38 pts were classified as proven/probable, 67 as possible and 28 as no IA according to 2008 European Organization for Research and Treatment of Cancer/Mycoses Study Group consensus definitions. A considerably superior performance of PCR from the site of infection was observed particularly in pts during antifungal prophylaxis (AFP)/antifungal therapy (AFT). Besides a specificity of 85%, sensitivity varied markedly in BAL (64%), CSF (100%), tissue samples (67%) as opposed to concurrent blood samples (8%). Our results further emphasise the need for investigating clinical samples from the site of infection in case of suspected IA to further establish or rule out the diagnosis.     

Disseminated Emmonsia pasteuriana infection in India: a case report and a review

We report here the first case of disseminated Emmonsia pasteuriana infection in a patient with AIDS in India. The patient presented with weight loss, dyspnoea, left‐sided chest pain and multiple non‐tender skin lesions over face and body for 3 months. Disseminated emmonsiosis was diagnosed on microscopic examination and fungal culture of skin biopsy and needle aspirate of lung consolidation. It was confirmed by sequencing internal transcribed spacer region of rDNA, beta tubulin, actin, and intein PRP8. The patient responded to amphotericin B and itraconazole therapy.     

Dermatophytosis and immunovirological status of HIV‐infected and AIDS patients from Sao Paulo city,Brazil

Over the past decades, more people became infected with human immunodeficiency virus (HIV) and developed acquired immunodeficiency syndrome (AIDS). Because of that the incidence of fungal infections rose dramatically. It happened because this virus can modify the course of fungal diseases, leading to altered clinical pictures. The aim of this study was to evaluate epidemiological and biological aspects of dermatophytosis in HIV‐positive and AIDS patients living in the city of São Paulo, Brazil. A total of 84 (44 HIV‐positive and 40 AIDS) patients were enrolled in this study. The patients were tested for dermatophyte infections, as well as for the CD4⁺/CD8⁺ and HIV viral load counts. Tinea unguium was most frequently observed in AIDS patients, whereas Tinea pedis was mostly observed in HIV‐positive patients. The most frequent dermatophyte species was Trichophyton rubrum. CD4⁺ counts and CD4⁺/CD8⁺ ratios were not associated with a higher risk for dermatophytosis. On the other hand, viral load higher than 100 000 copies/ml was associated with a higher frequency of dermatophytosis. The results suggest to that although dermatophytosis is common in HIV‐positive and AIDS patients, the degree of immunosuppression does not seems to correlate with increased risk of this fungal infection. In addition, high viral load as a predictive risk factor for dermatophyte infection should be subject of further evaluations.     

Subcutaneous phaeohyphomycosis caused by Exophiala spinifera in a European patient with lymphoma: a rare occurrence case report and literature review

Exophiala spinifera is a dematiaceous fungus responsible for rare skin infections presenting as phaeohyphomycosis or chromoblastomycosis which has been primarily reported in tropical and subtropical areas (Asia, South and North America). We report the first case of E. spinifera phaeohyphomycosis in a European patient. The phaeohyphomycosis was limited to the skin, involving the finger of an immunocompromised patient presenting with a large B‐cell lymphoma treated by R‐mini‐CHOP regimen. Remission was initially achieved by surgical excision; however, a local subcutaneous relapse required treatment with itraconazole. We performed a literature review of the 32 previously published cases of E. spinifera phaeohyphomycosis highlighting its clinical phenotype: disseminated infection with extracutaneous involvement and poor prognosis were reported in young patients, of whom some were recently associated with CARD9 mutations, whereas cases in older immunocompromised patients were limited to the skin and showed better prognosis. There is currently no standard treatment for E. spinifera phaeohyphomycosis; however, itraconazole, alone or in combination, allowed partial or complete response in 16 out of 20 cases.     

A cluster of Geotrichum clavatum (Saprochaete clavata) infection in haematological patients: a first Italian report and review of literature

Invasive fungal infections, usually Aspergillus and Candida, represent a major cause of morbidity and mortality in patients with malignant haematological diseases, but in the last years rare fungal infections have more frequently been reported. Here, we report the clinical history of three patients affected with haematological malignancies who developed an infection caused by Geotrichum (G.) clavatum. Two out of three patients were affected by acute myeloid leukaemia (AML), and one by mantle cell lymphoma (MCL). All patients received cytarabine‐based chemotherapeutic regimens and developed G. clavatum infection within 3 weeks from therapy initiation. In all cases, G. clavatum was isolated from central venous catheter and peripheral blood cultures. In vitro susceptibility test confirmed an intrinsic resistance to echinocandins and, in all cases, visceral localisations (spleen, liver and lung) were documented by total body computed tomography (CT) scan. A prolonged antifungal therapy with high doses liposomal amphotericin‐B was necessary to obtain fever resolution. Only the patient with MCL died while the other two AML recovered, and one of them after received an allogeneic stem cell transplantation. We consecutively reviewed all published cases of infection caused by G. clavatum. Our experience and literature review indicate that G. clavatum can cause invasive infection in haematological patients, mainly in those with acute leukaemia.     

TP53 mutation at early stage of colorectal cancer progression from two types of laterally spreading tumors

Although most sporadic colorectal cancers (CRC) are thought to develop from protruded adenomas through the adenoma–carcinoma sequence, some CRC develop through flat lesions, so‐called laterally spreading tumors (LST). We previously analyzed epigenetic aberrations in LST and found that LST are clearly classified into two molecular subtypes: intermediate‐methylation with KRAS mutation and low‐methylation with absence of oncogene mutation. Intermediate‐methylation LST were mostly granular type LST (LST‐G) and low‐methylation LST were mostly non‐granular LST (LST‐NG). In the present study, we conducted a targeted exon sequencing study including 38 candidate CRC driver genes to gain insight into how these genes modulate the development of LST. We identified a mean of 11.5 suspected nonpolymorphic variants per sample, including indels and non‐synonymous mutations, although there was no significant difference in the frequency of total mutations between LST‐G and LST‐NG. Genes associated with RTK/RAS signaling pathway were mutated more frequently in LST‐G than LST‐NG (P = 0.004), especially KRAS mutation occurring at 70% (30/43) of LST‐G but 26% (13/50) of LST‐NG (P < 0.0001). Both LST showed high frequency of APC mutation, even at adenoma stage, suggesting its involvement in the initiation stage of LST, as it is involved at early stage of colorectal carcinogenesis via adenoma‐carcinoma sequence. TP53 mutation was never observed in adenomas, but was specifically detected in cancer samples. TP53 mutation occurred during development of intramucosal cancer in LST‐NG, but during development of cancer with submucosal invasion in LST‐G. It is suggested that TP53 mutation occurs in the early stages of cancer development from adenoma in both LST‐G and LST‐NG, but is involved at an earlier stage in LST‐NG.     

Isolation of Candida auris from 9 patients in Central America: Importance of accurate diagnosis and susceptibility testing

Candida auris is an emerging multidrug‐resistant (MDR) fungus associated with invasive infections and high mortality. This report describes 9 patients from whom C. auris was isolated at a hospital in Panama City, Panama, the first such cases in Central America, and highlights the challenges of accurate identification and methods for susceptibility testing.     

Primary deep cutaneous candidiasis caused by Candida duobushaemulonii in a 68‐year‐old man: the first case report and literature review

Superficial candida infections of the skin are common, but deep cutaneous candidiasis, including secondary dissemination to the skin from systemic candidiasis, candidaemia or primary invasion due to skin defects such as trauma, is rare. These patients are usually immunosuppressed, but immunocompetent hosts can be affected as well. Candida albicans is the most common pathogen. However, non‐albicans Candida species can cause deep skin invasion in rare circumstances. We report a case of deep cutaneous candidiasis caused by Candida duobushaemulonii in a 68‐year‐old man. Deep tissue invasion was confirmed by skin histopathology examination. The pathogen was initially identified as C. haemulonii using the VITEK^® 2 system for microbial identification, but was later determined to be C. duobushaemulonii based on sequencing of the internal transcribed spacer region of ribosomal DNA and D1/D2 region of 26S rDNA. The patient was successfully treated with amphotericin B, followed by fluconazole and surgical intervention. To the best of our knowledge, this is the first case of deep cutaneous infection by C. duobushaemulonii.     

Effects of intranasally dosed posaconazole on fungal load and biomarkers in Aspergillus fumigatus infected immunocompromised mice

Although anti‐fungal triazoles are dosed orally or systemically for Aspergillus fumigatus infection, systemic adverse events and limited exposure of the lung cavity would make a topical treatment for the lung an attractive option. In this study, we examined the effects of intranasally dosed posaconazole on survival rates and biomarkers in A. fumigatus (itraconazole susceptible: ATCC13073 [Af]; or resistant: NCPF7100 [AfR]) infected, temporarily neutropenic A/J mice. Once daily treatment produced a dose‐dependent improvement of survival of Af‐infected mice (ED₅₀: 0.019 mg/mouse [approx. 0.755 mg/kg, in]), similar to its potency (ED₅₀: 0.775 mg/kg, po) after once daily oral dosing. For AfR infection, either intranasal or oral posaconazole was largely ineffective on survival, although the highest dose of intranasal treatment (0.35 mg/mouse) achieved 75% survival rate. Early intervention (treated on days 0, 1, 2 and 3 postinfection) and late intervention (treated on days 1, 2 and 3) with intranasal posaconazole (0.014‐0.35 mg/mouse) demonstrated potent inhibition of lung fungal load and galactomannan levels in both bronchoalveolar lavage fluid (BALF) and serum as well as inflammatory cells, IFN‐γ, IL‐17 and malondialdehyde (MDA) in BALF. Thus, posaconazole when dosed intranasally once daily showed an improvement of survival equivalent to or better than oral treatment, and produced potent inhibition of fungal load and biomarkers.     

The first cases of Candida auris candidaemia in Oman

Candida auris has been recognised as a problematic healthcare‐associated emerging yeast which is often misidentified as Candida haemulonii by commercial systems. Correct early identification of C. auris is important for appropriate antifungal treatment and implementing effective infection control measures. Here we report emergence of the first C. auris cases in Oman, initially misidentified as C. haemulonii.     

Otomastoiditis caused by Candida auris: Case report and literature review

Fungal otomastoiditis is a rare disease, but can be fatal for immunocompromised patients. Recently, there have been increasing cases of otologic infection caused by Candida auris. Candida auris can be easily misdiagnosed for other species and treatment is difficult due to multidrug resistance. Clinician should be aware of this rare pathogen, and it should be treated with appropriate antifungal agent with surgical debridement.