Rate, Risk Factors, and Outcomes of Invasive Fungal Infections in Patients with Hematologic Malignancies.

Background: Invasive fungal infections (IFIs) are a significant cause of mortality and morbidity in patients with hematological malignancies. Given the considerable prevalence and consequences of IFIs, hence revealing the exact cause of fungal infections, their rate, associated risk factors, and complications could contribute to reducing both financial and life costs, choosing targeted antifungal treatment, and avoiding unnecessary toxic treatments in individuals who are not suffering from mycoses. Materials and Methods: This prospective cross-sectional study was conducted in the first semester of 2019. All patients with hematologic malignancies (HM) admitted to Dr. Shariati Hospital were studied. Only those with probable/proven IFIs defined according to the last update of EORTC/MSG criteria were included in the study. The demographic and clinical data were recorded from the hospital information registration system using a questionnaire. Statistical analysis was performed using SPSS software version 24. Results: Out of 1109 HM patients hospitalized during the study period, 67 (6.04%) IFIs were diagnosed. Of these, 57 (85.04%) were aspergillosis, 7 (10.4%) were mucormycosis, and 3 patients developed other fungal infections. Males constituted 67.2% of the entire IFI population. The mean±SD age of the samples was 43.16 ± 13.8 years. The most common type of malignancy was AML. Lung imaging showed lesions associated with fungal infections in 52 cases (77.6%), with multiple nodules as the most prevalent pattern being observed in 64.2% of cases. Sinus involvement was evidenced in the PNS CT scan of 46 (68.6%) patients. The attributable mortality rate for IFIs was 62.7%. Both the types of IFI and malignancies had no significant relationship with the outcome of patients. Central venous catheter, mucositis, and antibiotic use were the most frequent risk factors. Conclusion:  IFI represents a frequent complication for HM patients with high mortality. Aspergillus species are the predominant etiology in these settings. Considering our results, in high-risk patients, manifestations of warning signs in the sinus and lungs, which would not be cleared despite receiving antibiotics, should raise the possibility of IFIs.

Screening Candida auris through a multiplex stepwise PCR algorithm directly from clinical samples of patients suspected of otomycosis in south of Iran; Detection of five cases.

BACKGROUND: Otomycosis is an infection of the external auditory canal caused by molds and yeasts with descending frequency. Laboratory diagnosis is usually confirmed by microscopy and culture. However, they are not specific enough to reliably differentiate the causative agents, especially for rare pathogens such as Candida auris. The purpose of the current study was to the molecular screening of C. auris species from direct clinical samples of patients with suspected otomycosis in Southern of Iran. MATERIALS AND METHODS: A total of 221 ear aspirates collected from 221 patients with suspected otomycosis over a four-year period. All the ear aspirations were examined with pan-fungal primers, then those with a positive result was included in two separate reaction mixtures simultaneously to identify the most clinically relevant Aspergillus and Candida species. The validity of positive samples for C. auris was assessed by sequencing. RESULTS: Of the 189 pan-fungal positive PCRs, 78 and 39 specimens contained Aspergillus spp. and Candida spp., respectively. Furthermore, 65 specimens showed simultaneous positive bands in both Candida and Aspergillus species-specific multiplex PCR including five samples/patients with positive result for C. auris (5/189; 2.6%). Four out of five cases with C. auris species-specific PCR were reconfirmed by sequencing, while none were positive for C. auris in culture. CONCLUSION: Unfortunately, due to high treatment failure rates of antifungal classes against C. auris species, rapid and accurate identification of patients colonised with C. auris is critical to overcome the challenge of preventing transmission. This PCR assay can be successfully applied for rapid and accurate detection of C. auris directly in patient samples and is able to differentiate C. auris from closely related Candida species.

COVID-19 Associated Rhino-Orbital-Cerebral Mucormycosis: Clinical Features, Antifungal Susceptibility, Management and Outcome in a Tertiary Hospital in Iran.

BACKGROUND: Despite the unprecedented surge in the incidence of mucormycosis in the COVID-19 era, the antifungal susceptibility patterns (ASPs) of COVID-19 associated mucormycosis (CAM) isolates have not been investigated so far and it is unclear if the high mortality rate associated with CAM is driven by decreased susceptibility of Mucorales to antifungal drugs. OBJECTIVES: To describe the clinical, mycological, outcome and in vitro ASPs of CAM cases and their etiologies from Iran. PATIENTS/METHODS: A prospective study from January 2020 to January 2022 at a referral tertiary hospital in Tehran, Iran was conducted for screening mucormycosis through histopathology and mycological methods. The identity of Mucorales isolates was revealed with ITS-panfungal PCR& sequencing and MALDI-TOF. The AS for amphotericin B, itraconazole, isavuconazole and posaconazole was cleared according to the EUCAST antifungal susceptibility testing protocol. RESULT: A total of 150 individuals were diagnosed with CAM. Males constituted 60.7% of the population. The mean age was 54.9 years. Diabetes was the leading risk factor (74.7%). The median interval between diagnosis of COVID-19 and CAM was 31 days. The recovery rate of culture was as low as 41.3% with Rhizopus arrhizus being identified as the dominant (60; 96.7%) agent. Amphotericin B (MIC50 = 0.5 µg/ml) demonstrated the highest potency against Mucorales. CONCLUSION: Majority of the cases had either diabetes, history of corticosteroid therapy or simultaneously both conditions. Accordingly, close monitoring of blood glucose should be considered. The indications for corticosteroids therapy are recommended to be optimized. Also, an anti Mucorales prophylaxis may be necessitated to be administrated in high risk individuals. Although amphotericin B was the most active agent, a higher rate of resistance to this antifungal was noted here in comparison with earlier studies on mucormycetes from non-CAM cases.

A Comprehensive Review of Identification Methods for Pathogenic Yeasts: Challenges and Approaches.

Given the increasing incidence of yeast infections and the presence of drug-resistant isolates, accurate identification of the pathogenic yeasts is essential for the management of yeast infections. In this review, we tried to introduce the routine and novel techniques applied for yeast identification. Laboratory identification methods of pathogenic yeast are classified into three categories; I. conventional methods, including microscopical and culture-base methods II. biochemical/physiological-processes methods III. molecular methods. While conventional and biochemical methods require more precautions and are not specific in some cases, molecular diagnostic methods are the optimum tools for diagnosing pathogenic yeasts in a short time with high accuracy and specificity, and having various methods that cover different purposes, and affordable costs for researchers. Nucleotide sequencing is a reference or gold standard for identifying pathogenic yeasts. Since it is an expensive method, it is not widely used in developing countries. However, novel identification techniques are constantly updated, and we recommend further studies in this field. The results of this study will guide researchers in finding more accurate diagnostic method(s) for their studies in a short period of time.

In vitro combination of antifungal drugs with tacrolimus (FK506) holds promise against clinical Candida species, including Candida auris.

In vitro interactions between tacrolimus, a calcineurin inhibitor, and fluconazole, itraconazole, caspofungin, or anidulafungin were evaluated against Candida auris, C. albicans, C. parapsilosis, and C. glabrata (each five strains). Tacrolimus-itraconazole, tacrolimus-caspofungin, and tacrolimus-fluconazole combinations resulted in synergistic interactions against 95%, 90%, and 60% of Candida isolates, respectively. However, tacrolimus-anidulafungin resulted in only a 35% synergistic effect. A combination of tacrolimus and itraconazole was most potent with synergy against 100% of C. auris, C. parapsilosis, and C. glabrata isolates. Of note, no antagonistic interaction was found.

A study on the fungal rhinosinusitis: Causative agents, symptoms, and predisposing factors.

Background: In natural conditions, inhaled fungi are considered a part of the microflora of nasal cavities and sinuses. However, subsequent to the protracted use of corticosteroids and antibacterial agents, suppression of the immune system by chemotherapy, and poor ventilation, these fungi can become pathogens. Fungal colonization in the nose and paranasal sinuses is a prevalent medical issue in immunocompetent and immunosuppressed patients. In this study, we aimed to categorize fungal rhinosinusitis (FRS) among immunocompetent and immunosuppressed patients and identified the etiologic agents of disease by molecular methods. Materials and Methods: A total of 74 cases were evaluated for FRS. Functional endoscopic sinus surgery was performed for sampling. The clinical samples were examined by direct microscopy with potassium hydroxide 20% and subcultured on Sabouraud Dextrose Agar with chloramphenicol. Polymerase chain reaction sequencing was applied to identify causative agents. Results: Thirty-three patients (44.6%) had FRS. Principal predisposing factors were antibiotic consumption (n = 31, 93.9%), corticosteroid therapy (n = 22, 66.6%), and diabetes mellitus (n = 21, 63.6%). Eyesore (n = 22, 66.6%), proptosis (n = 16, 48.5%), and headache (n = 15, 45.4%) were the most common clinical manifestations among patients. Rhizopus oryzae (n = 15, 45.4%) and Aspergillus flavus (n = 10, 30.3%) were the most prevalent fungal species. Conclusion: Diagnosis and classification of FRS are crucial, and a lack of early precise diagnosis can lead to a delay in any surgical or medical management. Since there are a variety of treatments for FRS, accurate identification of etiologic agents should be performed based on phenotypic and molecular methods.

Phaeohyphomycosis caused by Neoscytalidiumdimidiatum in a COVID-19 patient.

BACKGROUND: Neoscytalidiumdimidiatum is an opportunistic dematiaceous fungus belonging to the class Dothideomycetes. CASE REPORT: We report a case of N. dimidiatum cerebral phaeohyphomycosis post COVID-19 infection in a 32-year-old male from Iran. The causative agent was identified by cytopathology, routine mycological methods, and DNA sequencing of the internal transcribed spacer (ITS) region of rDNA. Apart from COVID-19 complications and the corticosteroid therapy, no underlying condition was diagnosed. The symptoms suggesting the fungal infection were shown two weeks after being discharged from COVID-19 hospital stay. Magnetic resonance of the brain showed a multi-focal central nervous system infection. The delayed identification of the fungus and, thus, a late starting of the antifungal treatment with amphotericin B, might have affected the patient outcome as he finally died. CONCLUSIONS: Considering the rare incidence of N. dimidiatum infections, this case should aware us about them, leading to a timely antifungal management.

COVID-19-associated mucormycosis: A review of an emergent epidemic fungal infection in the era of COVID-19 pandemic.

At a time when the COVID-19's second wave is still picking up in countries like India, a number of reports describe the potential association with a rise in the number of cases of mucormycosis, commonly known as the black fungus. This fungal infection has been around for centuries and affects those people whose immunity has been compromised due to severe health conditions. In this article, we provide a detailed overview of mucormycosis and discuss how COVID-19 could have caused a sudden spike in an otherwise rare disease in countries like India. The article discusses the various symptoms of the disease, class of people most vulnerable to this infection, preventive measures to avoid the disease, and various treatments that exist in clinical practice and research to manage the disease.

Trends in the Prevalence of Amphotericin B-Resistance (AmBR) among Clinical Isolates of Aspergillus Species.

The challenges of the invasive infections caused by the resistant Aspergillus species include the limited access to antifungals for treatment and high mortality. This study aimed to provide a global perspective of the prevalence of amphotericin B resistance (AmBR), geographic distribution, and the trend of AmBR from 2010 to 2020. To analyze the prevalence of in vitro AmBR in clinical Aspergillus species, we reviewed the literature and identified a total of 72 articles. AmBR was observed in 1128 out of 3061 Aspergillus terreus (36.8%), 538 out of 3663 Aspergillus flavus (14.9%), 141 out of 2691 Aspergillus niger (5.2%), and 353 out of 17,494 Aspergillus fumigatus isolates (2.01%). An increasing trend in AmB-resistant isolates of A. fumigatus and a decreasing trend in AmB-resistant A. terreus and A. flavus isolates were observed between 2016 and 2020. AmB-resistant A. terreus and A. niger isolates, accounting for 40.4% and 20.9%, respectively, were the common AmB-resistant Aspergillus species in Asian studies. However, common AmB-resistant Aspergillus species reported by European and American studies were A. terreus and A. flavus isolates, accounting for 40.1% and 14.3% in 31 studies from Europe and 25.1% and 11.7% in 14 studies from America, respectively. The prevalence of AmB-resistant A. niger in Asian isolates was higher than in American and European. We found a low prevalence of A. terreus in American isolates (25.1%) compared to Asian (40.4%) and European (40.1%). Future studies should focus on analyzing the trend of AmBR on a regional basis and using the same methodologies.

The Epidemiological, Clinical, Mycological, and Pathological Features of Rhino-cerebral Mucormycosis: A Systematic Review.

Cerebral mucormycosis (CM) is a life-threatening manifestation of mucormycosis, an angioinvasive fungal infection caused by Mucorales. We sought to systematically review all available case reports to describe epidemiologic features, clinical manifestations, predisposing factors, and diagnostic and treatment strategies of CM. A systematic search was conducted using a combination of the following keywords: "Mucor", "Zygomycetes", "mucormycosis", "cereb*", "brain", "central nervous system", and "intracranial", separately and in combination until December 31st 2018. Data sources included PubMed, Scopus, EMBASE, Web of Science, Science Direct, and Proquest without limiting the time of publication. We included 287 articles corresponding to 345 cases of CM. Out of the 345 cases, 206 (60%) were male with a median age of 44 years; 130 (38%) were reported from North America; 87 (25%) from Asia; and 84 (24%) from Europe. The median time from onset of symptoms to presentation was 3-7 days (65/345, 65%). The highest mortality was observed among patients with diabetes mellitus (P=0.003). Debridement of infected brain tissue was associated with improved survival in CM cases (OR 1.5; 95% CI 01.3-1.8; P<0.0001). The use of liposomal amphotericin B (L-AMB) was significantly associated with patients' recovery (OR 2.09; 95% CI 1.2-3.4; P=0.003). The combination of L-AMB and posaconazole (12.5%) was more effective than the monotherapy treatment of CM cases (P=0.009). Clinicians should consider DM as an important risk factor for CM. Moreover, surgical debridement and antifungal combination therapy could be an effective approach in the management of CM patients.

Evaluating a semi-nested PCR to support histopathology reports of fungal rhinosinusitis in formalin-fixed paraffin-embedded tissue samples.

BACKGROUND: Fungal rhinosinusitis (FRS) encompasses a various spectrum of diseases. Histopathology is the "reference method" for diagnosing FRS, but it cannot determine the genus and species. Moreover, in more than 50% of the histopathologically proven cases, the culture elicited no reliable results. This study was an attempt to evaluate the diagnostic efficiency of semi-nested polymerase chain reaction (PCR) from formalin-fixed paraffin-embedded (FFPE) functional endoscopic sinus surgery (FESS) in FRS patients. METHODS: One hundred ten specimens were subjected to DNA extraction and histopathology examination. The amplification of the ß-globin gene by conventional PCR was used to confirm the quality of extracted DNA. The semi-nested PCR was performed using ITS1, ITS2, and ITS4 primers during two steps. Sequencing the internal transcribed spacer region (ITS1-5.8S-ITS2) to identify causative agents was performed on PCR products. RESULTS: Sixty-four out of 110 samples were positive by histopathology evidence, of which 56 samples (87.5%) were positive by PCR. Out of 46 negative samples by histopathological methods, five samples (10.9%) yielded positive results by PCR. Sensitivity, specificity, positive predictive value, and negative predictive value of the semi-nested PCR method were reported 87.5%, 89.2%, 92.7%, and 85.2%, respectively. The kappa factor between PCR and histopathological methods was 0.76, indicating substantial agreements between these two tests. CONCLUSION: Due to the acceptable sensitivity and specificity of the present method, it might be used to diagnose fungal sinusitis infections along with microscopic techniques. This method is recommended to confirm the diagnose of suspected fungal sinusitis with negative histopathology results.

COVID-19 Associated Unilateral Diaphragm Paralysis: A Case Report.

Diaphragm paralysis may be either idiopathic or associated with several medical conditions including viral and bacterial infection. The association of phrenic nerve palsy with viral infections is rare but well-appreciated in several case reports. Neuropathy, both central and peripheral, is a common neurological consequence of COVID-19. Here, we describe a case of diaphragm paralysis in a woman who was admitted to the hospital because of COVID-19 pneumonia. Post-COVID-19 unilateral paralyzed diaphragm was diagnosed with a chest X-ray for her and the disorder was attributed to COVID-19 because no other etiology was found to be associated. So far, phrenic neuropathy and diaphragmatic paralysis in a COVID-19-affected patient have not been reported from Iran.

Clinical, epidemiological, and mycological features of patients with candidemia: Experience in two tertiary referral centers in Iran.

Background and Purpose: Candidemia is a major cause of morbidity and mortality among patients receiving immunosuppressive therapy and those hospitalized with serious underlying diseases. Here, we investigated the epidemiological, clinical, and mycological features of candidemia in Tehran, Iran. Materials and Methods: A prospective observational study of all patients diagnosed with candidemia was performed at two referral teaching hospitals in Tehran, Iran, from February to December 2018. Demographic characteristics, underlying diseases, risk factors, clinical symptoms, and laboratory analyses of candidemic patients with positive culture were mined. Candida isolates were molecularly identified by sequencing of the internal transcribed spacer region (ITS1-5.8S-ITS2). The antifungal susceptibility testing for fluconazole, itraconazole, voriconazole, posaconazole, amphotericin B, caspofungin, micafungin, and anidulafungin against the isolates was performed using CLSI broth microdilution reference method (M27-A3). Results: A total of 89 episodes were identified, with an incidence of 2.1 episodes/1000 admissions. The common underling disease were malignancy (46%), renal failure/dialysis (44%), and hypertension (40%). The overall crude mortality was 47%. C. albicans (44%) was the most frequent causative agent, followed by C. glabrata (21%), C. parapsilosis complex (15%), C. tropicalis (11%), and C. lusitaniae (3.5%). All the isolates were susceptible to amphotericin B. The activity of all four azoles was low against non-albicans Candida species, especially C. tropicalis. Conclusion: The increase in non-albicans Candida species with reduced susceptibility to antifungal drugs might be alarming in high-risk patients. Therefore, accurate knowledge of predisposing factors and epidemiological patterns in candidemia are effective steps for managing and decreasing the mortality rate in candidemia.

Distribution, Prevalence, and Causative Agents of Fungal Keratitis: A Systematic Review and Meta-Analysis (1990 to 2020).

Objectives: This study aims to provide an overview of the prevalence, distribution, and causative agents of fungal keratitis. Methods: All the articles with data on the prevalence of fungal keratitis among various patient groups from January 1, 1990 to May 27, 2020 were retrieved through a systematic search in PubMed, Scopus, Web of Science, and Google Scholar. Data were extracted, and the pooled estimated prevalence of fungal keratitis, yeast/mold infection, the spectrum and frequency of various causative agents, and the pooled estimated prevalence of mixed infections were calculated in general and in various countries (wherever possible) using meta-analysis. Results: From 11,235 articles retrieved in the primary search step, 169 met the inclusion criteria. The 169 eligible articles were divided into six groups and analyzed separately. The pooled prevalence of fungal keratitis was variable with values ranging from 0.05% among postkeratoplasty patients to 43.01% among patients with a clinical suspicion of fungal keratitis. There was also a country-dependent variation in the prevalence (Paraguay: 50.1% (95% CI, 35.11, 65.00); Ireland: 1.1% (95% CI, 0.03, 6.04)). Except for postkeratoplasty cases (yeast: 51.80%), in all patient groups, molds were more common than yeasts. Although more than 50 distinct species of fungi have been found to cause fungal keratitis, Fusarium species followed by Aspergillus species were the most common causes of the disease. In general, 9.29% (95% CI, 6.52, 12.38) of fungal keratitis cases were mixed with bacterial agents. Conclusion: The prevalence of fungal keratitis can vary dramatically depending on the patient groups and geographical origin; however, the dominant causative agents are generally similar.

Fatal necrotising cutaneous mucormycosis due to novel Saksenaea species: a case study.

This case report describes the progressive wound infection in the left thigh of a 34-year-old man due to an old landmine explosion. The infection developed into rapidly spreading skin and soft tissue necrotising Saksenaea infection, despite antifungal therapy and surgical debridement. The report provides evidence that Saksenaea spp. should be added to the list of mucoralean fungi that can cause severe necrotising infection. It also highlights the need for improved early diagnostic procedures and enhanced understanding of Saksenaea virulence factors that contribute to necrotising infection.

Mucormycosis in patients with COVID-19: A cross-sectional descriptive multicentre study from Iran.

PURPOSE: The aim of the study was to report clinical features, contributing factors and outcome of patients with coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM). METHODS: A cross-sectional descriptive multicentre study was conducted on patients with biopsy-proven mucormycosis with RT-PCR-confirmed COVID-19 from April to September 2020. Demographics, the time interval between COVID-19 and mucormycosis, underlying systemic diseases, clinical features, course of disease and outcomes were collected and analysed. RESULTS: Fifteen patients with COVID-19 and rhino-orbital mucormycosis were observed. The median age of patients was 52 years (range 14-71), and 66% were male. The median interval time between COVID-19 disease and diagnosis of mucormycosis was seven (range: 1-37) days. Among all, 13 patients (86%) had diabetes mellitus, while 7 (46.6%) previously received intravenous corticosteroid therapy. Five patients (33%) underwent orbital exenteration, while seven (47%) patients died from mucormycosis. Six patients (40%) received combined antifungal therapy and none that received combined antifungal therapy died. CONCLUSION: Clinicians should be aware that mucormycosis may be complication of COVID-19 in high-risk patients. Poor control of diabetes mellitus is an important predisposing factor for CAM. Systematic surveillance for control of diabetes mellitus and educating physician about the early diagnosis of CAM are suggested.

Molecular identification and clinical features of fungal rhinosinusitis: A 3-year experience with 108 patients.

This study aimed to determine the prevalence, the causative agents, clinical features, and the risk factors associated with the fungal rhinosinusitis in a tertiary health center with a view to providing valid grounds that may guide healthcare professionals to effectively prevent, control, and treat fungal infections. All patients were subjected to diagnostic nasal endoscopy and CT scan of paranasal sinuses and FRS were confirmed by routine and complementary mycological and molecular methods. The inclusion criteria for invasive FRS were: confirmed diagnosis of IFRS according to the guidelines of the EORTC/MSG criteria (i.e., clinical, microbiological, and histological evidence of invasive fungal infection). From a total of 512 suspected patients, FRS was confirmed in 108 cases (21.1%). Our results showed FB (38/108; 35.2%) is the most common form of FRS followed by AIFRS (33/108; 30.6%), AFS (32/108; 29.6%), and CIFRS (5/108; 4.6%). A. flavus and Rhizopus oryzae were the most common causes of infection in AFS, FB, CIFRS, and AIFRS, respectively. Univariate analysis of variables predictive of AIFRS revealed 3 variables significantly associated with AIFRS. These included mucosal abnormalities of the middle turbinate and septum, and specifically, necrosis of the middle turbinate (P < .0001). Microbiological cultures, although useful for mycological speciation, are less sensitive. Furthermore, we used molecular methods to confirm the identity of some isolates that were not detectable using routine methods. Our data showed that the molecular methods and histologic diagnosis in all patients were more sensitive than the unenhanced sinus CT scan, and conventional microbiological methods.

Direct Detection and Identification of the Most Common Bacteria and Fungi Causing Otitis Externa by a Stepwise Multiplex PCR.

Background: Considering the importance of differential diagnosis of infectious otitis externa (OE), a stepwise PCR-based assay using universal and genus- or species-specific primers for the detection/identification of the most prevalent bacterial and fungal OE was developed and evaluated on the ear aspiration specimens of clinically suspected patients. Methods and Materials: A total of 120 ear aspiration specimens with otomycosis suspicion were subjected to manual DNA extraction using phenol-chloroform extraction after tissue digestion with a lysis buffer. The multiplex PCR was initially performed using pan-fungal and bacterial homemade primers. Pseudomonas and Staphylococcus specific primers were simultaneously used in one reaction mixture to identify the bacterial genera. Furthermore, for the identification of fungal agents, Candida species-specific multiplex primers targeting the most clinically important Candida species causing OE (i.e., C. albicans, C. parapsilosis, and C. auris), as well as Aspergillus related multiplex PCR identifying the most prevalent Aspergillus species were used in two separate reaction mixtures. All the results of multiplex PCR were interpreted based on the amplicon size. Results: The overall multiplex PCR-based detection rate of bacterial (n = 88; 73.3%) and fungal (n = 97; 81%) OE was documented to be 100% along with and complete consistency with the results of direct examination and Giemsa staining. Double amplicon bands of bacterial and fungal pathogens were evidenced in 76 specimens (63.3%). Moreover, the positivity rate of pan-fungal PCR was higher than that of the culture result. Out of 88 pan-bacterial positive PCR specimens, 66 and 47 ones were positive for Staphylococcus and Pseudomonas, respectively. In addition, 30 samples exhibited mixed infection of both, and five specimens remained negative. Out of 97 pan-fungal positive PCR specimens, 67 and 51 ones contained Candida and Aspergillus species, respectively. It should be noted that dual amplicon bands of Candida and Aspergillus-related multiplex PCR were yielded in 30 specimens. Conclusion: The stepwise multiplex PCR assay proved to be more sensitive, more rapid, as well as less cumbersome in detection and identification of fungal and bacterial OE, compared to culture.

Clinical and mycological characteristics of keratitis caused by Colletotrichum gloeosporioides: A case report and review of literature.

INTRODUCTION: Colletotrichum species are well-known plant pathogens, which have been increasingly reported as the cause of keratitis or subcutaneous lesions in humans. In this study we reported a rare case of fungal keratitis from Iran and reviewed the literature. CASE PRESENTATION: A 69-year-old man whose right eye was injured by herbal material was examined by slit-lamp biomicroscopy and mycology investigation of corneal scrapings was done. The grown filamentous fungal was identified as Colletotrichum gloeosporioides based on morphological characteristics and DNA sequence of the internal transcribed spacer region. The isolated strain was sensitive to amphotericin B, caspofungin, anidolafungin, micafungin, voriconazole, and relatively resistant to fluconazole, and itraconazole. Patient was successfully treated with voriconazole. CONCLUSIONS: This report highlights that the early and accurate identification and therapy can helpful to management keratitis caused by C. gloeosporioides.

The double-edged sword of systemic corticosteroid therapy in viral pneumonia: A case report and comparative review of influenza-associated mucormycosis versus COVID-19 associated mucormycosis.

Acute respiratory distress syndrome is a common complication of severe viral pneumonia, such as influenza and COVID-19, that requires critical care including ventilatory support, use of corticosteroids and other adjunctive therapies to arrest the attendant massive airways inflammation. Although recommended for the treatment of viral pneumonia, steroid therapy appears to be a double-edged sword, predisposing patients to secondary bacterial and invasive fungal infections (IFIs) whereby impacting morbidity and mortality. Mucormycosis is a fungal emergency with a highly aggressive tendency for contiguous spread, associated with a poor prognosis if not promptly diagnosed and managed. Classically, uncontrolled diabetes mellitus (DM) and other immunosuppressive conditions including corticosteroid therapy are known risk factors for mucormycosis. Upon the background lung pathology, immune dysfunction and corticosteroid therapy, patients with severe viral pneumonia are likely to develop IFIs like aspergillosis and mucormycosis. Notably, the combination of steroid therapy and DM can augment immunosuppression and hyperglycaemia, increasing the risk of mucormycosis in a susceptible individual. Here, we report a case of sinonasal mucormycosis in a 44-year-old woman with hyperglycaemia secondary to poorly controlled diabetes following dexamethasone therapy on a background of influenza pneumonia and review 15 available literatures on reported cases of influenza and COVID-19 associated mucormycosis.