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To assess population diversities among 81 strains of fungi in the genus Fonsecaea that had been identified down to species level, we applied amplified fragment-length polymorphism (AFLP) technology and sequenced the internal transcribed spacer regions and the partial cell division cycle, beta-tubulin, and actin genes. Many species of the genus Fonsecaea cause human chromoblastomycosis. Strains originated from a global sampling of clinical and environmental sources in the Western Hemisphere, Asia, Africa, and Europe. According to AFLP fingerprinting, Fonsecaea isolates clustered in 5 groups corresponding with F. pedrosoi, F. monophora, and F. nubica: the latter 2 species each comprised 2 groups, and F. pedrosoi appeared to be of monophyletic origin. F. pedrosoi was found nearly exclusively in Central and South America. F. monophora and F. nubica were distributed worldwide, but both showed substantial geographic structuring. Clinical cases outside areas where Fonsecaea is endemic were probably distributed by human migration. [ABSTRACT FROM AUTHOR]

Candidemia is a major cause of morbidity and mortality in health care settings, and its epidemiology is changing. In the last two decades, the proportion of non- albicans Candida (NAC) yeasts in candidemia has increased. These yeasts more often display resistance to common antifungals. In many western countries, candidemia is mainly caused by susceptible C. albicans , while in resource-limited countries, including Iran, the candidemia species distribution is studied less often. Here, we investigated the species distribution, resistance levels, and characteristics of patients with candidemia in five hospitals in Mashhad (northeast Iran) for two years (2019-2021). Yeast isolates from blood were identified with MALDI-TOF MS and subjected to antifungal susceptibility testing (AFST) using the broth microdilution method, while molecular genotyping was applied to Candida parapsilosis isolates. In total, 160 yeast isolates were recovered from 160 patients, of which the majority were adults (60%). Candidemia was almost equally detected in men (48%) and women (52%). Almost half of patients ( n = 67, 49%) were from intensive care units (ICUs). C. parapsilosis ( n = 58, 36%) was the most common causative agent, surpassing C. albicans ( n = 52, 33%). The all-cause mortality rate was 53%, with C. albicans candidemia displaying the lowest mortality with 39%, in contrast to a mortality rate of 59% for NAC candidemia. With microbroth AFST, nearly all tested isolates were found to be susceptible, except for one C. albicans isolate that was resistant to anidulafungin. By applying short tandem repeat (STR) genotyping to C. parapsilosis, multiple clusters were found. To summarize, candidemia in Mashhad, Iran, from 2019 to 2021, is characterized by common yeast species, in particular C. parapsilosis , for which STR typing indicates potential nosocomial transmission. The overall mortality is high, while resistance rates were found to be low, suggesting that the high mortality is linked to limited diagnostic options and insufficient medical care, including the restricted use of echinocandins as the first treatment option.

People with metabolically healthy obesity (MHO) are at risk of developing cardiometabolic diseases. We investigated the prevalence of MHO and factors influencing its transition into a metabolically unhealthy state (MUS). This study was conducted as part of the Kerman Coronary Artery Disease Risk Factor Study (KERCADRS). From 2014 to 2018, 9997 people were evaluated. The obesity and metabolic status of the MHO participants were re-examined after 5 years of their initial participation in the study. Out of 347 MHO, 238 individuals were accessed at follow-up. Twenty-nine (12.2%) had metabolic unhealthy normal weight (MUNW), 169 (71.0%) had metabolic unhealthy obesity (MUO), and the others had healthy metabolic state. Among age, total cholesterol, diastolic blood pressure and triglyceride (TG) variables, the baseline serum TG level was associated with a significant increase in the risk of developing MUS during 5 years (p <.05). The TG level optimal cut-off point for predicting the development into MUS was 107 mg/dL with 62.1% sensitivity and 77.5% specificity (AUC = 0.734, p <.001). A high percentage of MHO people transit into MUS during 5 years. A TG level higher than 107 mg/dL can help to identify people at a higher risk of developing into MUS., (© 2024 World Obesity Federation.)

Background: The emergence of coronavirus disease 2019 (COVID-19) as a global health emergency necessitates continued investigation of the disease progression. This study investigated the relationship between eosinophilia and the severity of COVID-19 in chronic obstructive pulmonary disease (COPD) patients., Methods: This cross-sectional study was conducted on 73 COPD patients infected by COVID-19 in Afzalipour Hospital, Iran. Peripheral blood samples were collected for hematological parameter testing, including eosinophil percentage, using Giemsa staining. Eosinophilia was defined as≥ 2% and non-eosinophilia as< 2%. The severity of pulmonary involvement was determined based on chest CT severity score (CT-SS) (based on the degree of involvement of the lung lobes, 0%: 0 points, 1-25%: 1 point, 26-50%: 2 points, 51-75%: 3 points, and 76-100%: 4 points). The CT-SS was the sum of the scores of the five lobes (range 0-20)., Results: The average age of patients was 67.90±13.71 years, and most were male (54.8%). Non-eosinophilic COPD patients were associated with more severe COVID-19 (P= 0.01) and lower oxygen saturation (P= 0.001). In addition, the study revealed a significant difference in the chest CT severity score (CT-SS) between non-eosinophilic (9.76±0.7) and eosinophilic COPD patients (6.26±0.63) (P< 0.001). Although non-eosinophilic COPD patients had a higher mortality rate, this difference was not statistically significant (P= 0.16)., Conclusions: Our study demonstrated that reduced peripheral blood eosinophil levels in COPD patients with COVID-19 correlate with unfavorable outcomes. Understanding this association can help us identify high-risk COPD patients and take appropriate management strategies to improve their prognosis., (© 2024. The Author(s).)

Our understanding of fungal epidemiology and the burden of antifungal drug resistance in COVID-19-associated candidemia (CAC) patients is limited. Therefore, we conducted a retrospective multicenter study in Iran to explore clinical and microbiological profiles of CAC patients. Yeast isolated from blood, were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and subjected to antifungal susceptibility testing (AFST) using the broth microdilution method M27-A3 protocol. A total of 0.6% of the COVID-19 patients acquired CAC (43/6174). Fluconazole was the most widely used antifungal, and 37% of patients were not treated. Contrary to historic candidemia patients, Candida albicans and C. tropicalis were the most common species. In vitro resistance was high and only noted for azoles; 50%, 20%, and 13.6% of patients were infected with azole-non-susceptible (ANS) C. tropicalis, C. parapsilosis, and C. albicans isolates, respectively. ERG11 mutations conferring azole resistance were detected for C. parapsilosis isolates (Y132F), recovered from an azole-naïve patient. Our study revealed an unprecedented rise in ANS Candida isolates, including the first C. parapsilosis isolate carrying Y132F, among CAC patients in Iran, which potentially threatens the efficacy of fluconazole, the most widely used drug in our centers. Considering the high mortality rate and 37% of untreated CAC cases, our study underscores the importance of infection control strategies and antifungal stewardship to minimize the emergence of ANS Candida isolates during COVID-19., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Background: In April 2020, an association between multisystem inflammatory syndromes (MIS-C) was observed in children with severe acute respiratory syndrome coronavirus infection (SARS-CoV-2). Most patients had heart involvement alone, and most patients had pericardial effusion. This study aimed to express and emphasize cardiac involvement in pediatric patients with respiratory symptoms who were diagnosed with COVID-19., Methods: This study was conducted in July 2021 in Kerman province, Southeastern Iran, during a notable surge in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. The study included 904 pediatric patients diagnosed with COVID-19. Data collection involved a comprehensive assessment of clinical symptoms and manifestations. Patients with fever lasting more than five days were admitted to the hospital. Echocardiography was utilized for cardiac involvement diagnosis, with 47 patients undergoing this diagnostic procedure., Results: Of the 904 patients, most of them had high fevers (74%). Fifty-five patients had a fever for more than five days and were hospitalized. Of the 47 patients who underwent echocardiography, 45 (81%) had heart involvement. In 75% of patients, pericardial effusion was the only cardiac involvement. Patients with pericardial effusion were treated with dexamethasone up to 3 mg every 8 h for 72 h., Conclusions: MIS-C has a wide range of clinical symptoms. In cases where the fever is prolonged and there are gastrointestinal symptoms, physicians have clinical suspicion to diagnose this syndrome. Most cases of pericardial effusion are alone and improve with treatment with glucocorticosteroids., (© 2024. The Author(s).)

Competing Interests: Competing Interests The authors declare no conflict of interest related to this work.

Background: To evaluate myopia progression during the novel coronavirus disease 2019 (COVID-19) pandemic and its risk factors., Methods: We searched PubMed, Scopus, and Web of Science to find literature until August 2022 related to COVID-19 pandemic and myopia progression. Outcomes of myopia progression included axial length (AL) and spherical equivalent (SE). Factors of screen time and outdoor activity time were analyzed., Results: Thirty-three studies were included in this meta-analysis. Compared to the same period before the COVID-19 pandemic, myopia prevalence increased (OR = 1.11; 95% CI, 1.05-1.18). The outcomes of SE decreased -0.61 diopter (95% CI, -0.98 to -0.23), and AL increased 0.42 mm (95% CI, 0.13-0.7). Mean screen time was increased 6.25 hours/day (95% CI, 4.84-7.66), and outdoor activity time was decreased -1.52 hours/day (95% CI, -3.20 to -0.15)., Conclusion: Establishing care policies is necessary to restrict behavioral changes and their consequences during the pandemic.

Objectives: This study aimed to evaluate the relationships between serum levels of 25-hydroxyvitamin D (25(OH)D) and short-term blood pressure variability (BPV) in newly diagnosed hypertensive patients., Methods: One hundred newly diagnosed patients with stage one essential hypertension were included and divided into two groups, the deficient and non-deficient groups, according to their 25(OH)D level. The blood pressure was recorded automatically by a portable ambulatory blood pressure monitor for 24 h., Results: In the present study, there was no significant relationship between vitamin D levels and short-term BPV or other parameters derived from ambulatory blood pressure monitoring (ABPM) (P > 0.05). Age (r = 0.260, P = 0.009), serum phosphorus (r = 0.271, P = 0.007), and cholesterol levels (r = 0.310, P = 0.011) were positively correlated with 25(OH)D levels, while glomerular filtration rate (r = -0.232, P = 0.021) negatively correlated with vitamin D levels. There was no crude or adjusted relationship between the levels of 25(OH)D and any parameters of ABPM in multiple linear regression analysis., Conclusion: Although the relationship between vitamin D levels and cardiovascular diseases has been confirmed, vitamin D deficiency does not cause an increase in cardiovascular risk by influencing the short-term BPV or other parameters derived from ABPM., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Atherosclerosis has an essential role in causing cardiovascular diseases. Various factors affect the risk of coronary artery atherosclerosis, and the increase in the carotid intima-media thickness (CIMT) is a primary marker for detecting atherosclerotic changes in the artery wall. Since opioid use is one of the leading social and health problems in many countries, this study aimed to detect the factors influencing the increase in CIMT in opium consumers., Methods: This cross-sectional study was conducted on 350 participants of the phase 2 of the KERCADRS cohort study who visited Besat clinic in Kerman and were divided into addicted and non-addicted groups. The participants in both groups underwent carotid artery ultrasound, and the Philips IU22 ultrasound machine was used to measure the CIMT., Findings: The mean age of the participants was 42.28±12.58 in the addicted group and 35.99±15.38 in the non-addicted group ( P =0.001). CIMT was similar in the two groups ( P =0.170). Moreover, CIMT had a significant positive correlation with age, waist circumference, systolic blood pressure (SBP), body mass index (BMI), fasting plasma glucose (FPG), and triglyceride in both addicted and non-addicted groups. Age, weight, waist circumference, SBP, and BMI in the multivariate model were significant determinants of CIMT in the addicted group., Conclusion: The results revealed that age, weight, waist circumference, SBP, and BMI were the factors influencing intima thickness in opium consumers, and no significant relationship was observed between addiction to opium and CIMT., Competing Interests: Competing Interests The authors have no conflict of interest., (© 2023 Kerman University of Medical Sciences.)

Background: Metabolic syndrome (MetS) is a global public health concern. Chronic inflammation plays a role in MetS; haematological inflammatory parameters can be used as MetS predicting factors., Objective: Hereditary and environmental factors play an important role in the development of MetS. This study aimed to determine the relationship between haematological parameters and MetS in the adult population of southeastern Iran, Kerman., Methods: This cross-sectional study was a sub-analysis of 1033 subjects who participated in the second phase of the Kerman Coronary Artery Disease Risk Factor Study (KERCADRS). Metabolic syndrome was diagnosed according to Adult Treatment Panel III (ATP III) definition. Pearson correlation coefficient was used to investigate the relationship between haematological parameters with age and components of metabolic syndrome. The role of WBC, neutrophil, lymphocyte and monocyte in predicting metabolic syndrome was evaluated using the receiver operating characteristic (ROC) curve., Results: White blood cell (WBC) and its subcomponent cells count, red cell distribution width (RDW), monocyte to HDL ratio (MHR) and Neutrophil to HDL ratio (NHR) had a significant positive correlation with the severity of MetS. The cut-off value of WBC was 6.1 (×10 3 /μL), the sensitivity was 70%, the specificity was 52.9% for females, the cut-off value of WBC was 6.3 (×10 3 /μL), the sensitivity was 68.2% and the specificity was 46.7%, for males., Conclusion: WBC and its subcomponent count, RDW, MHR and NHR parameters are valuable biomarkers for further risk appraisal of MetS in adults. These markers are helpful in early diagnoses of individuals with MetS., (© 2023 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Background: Fusarium species are opportunistic human pathogens that remarkably cause fungal infections ranging from superficial to fatal invasive disseminated infections. Fusarium species are notoriously resistant to the majority of antifungal agents., Objectives: Therefore, detailed studies regarding in vitro susceptibility are required and may lead to a better prognosis of severe infections., Methods: We evaluated 25 antifungal drugs in vitro against 282 clinical and environmental Fusarium isolates., Results: Fusarium species demonstrated high MICs/MECs values to the most commonly used antifungal drugs in clinical practice. The geometric mean (GM) MICs for luliconazole (0.004 μg/ml) and lanoconazole (0.012 μg/ml) were the lowest, followed by efinaconazole (0.98 μg/ml) and amphotericin B (1.04 μg/ml)., Conclusions: Efinaconazole, a novel triazole, may be a promising candidate for the treatment of superficial Fusarium infections. Furthermore, the development of systemic formulations of these drugs as well as further in vitro and in vivo investigations could aid in the treatment of systemic fusariosis., (© 2022 Wiley-VCH GmbH.)

Background: Dermatophytes have the ability to invade the keratin layer of humans and cause infections. The aims of this study were the accurate identification of dermatophytes by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism method and sequencing and comparison between the in vitro activities of newer and established antifungal agents against them., Methods: Clinical specimens of patients from five Iranian university laboratories were entered in this study. Samples were cultured on sabouraud dextrose agar medium. For molecular identification, extracted DNAs were amplified by the universal fungal primers ITS1 and ITS4, and digested with MvaI enzymes. The antifungal susceptibility test for each isolate to terbinafine, griseofulvin, caspofungin, fluconazole, itraconazole, luliconazole, and isavuconazole was performed, according to the microdilution CLSI M38-A2 and CLSI M61 standard methods., Results: Two hundred and seven fungi species similar to dermatophytes were isolated of which 198 (95.6%) were dermatophytes by molecular assay. The most commonly isolated were Trichophyton mentagrophytes (76/198), followed by Trichophyton interdigitale (57/198), Trichophyton rubrum (34/198), Trichophyton tonsurans (12/198), Microsporum canis (10/198), Trichophyton simii (3/198), Epidermophyton floccosum (3/198), Trichophyton violaceum (2/198), and Trichophyton benhamiae (1/198). The GM MIC and MIC 90 values for all the isolates were as follows: terbinafine (0.091 and 1 μg/ml), griseofulvin (1.01 and 4 μg/ml), caspofungin (0.06 and 4 μg/ml), fluconazole (16.52 and 32 μg/ml), itraconazole (0.861 and 8 μg/ml), isavuconazole (0.074 and 2 μg/ml), and luliconazole (0.018 and 0.25 μg/ml)., Conclusion: Trichophyton mentagrophytes, Trichophyton interdigitale, and Trichophyton rubrum were the most common fungal species isolated from the patients. luliconazole, terbinafine, and isavuconazole in vitro were revealed to be the most effective antifungal agents against all dermatophyte isolates., (© 2023. The Author(s).)

In recent decades, the incidence of Candida infections has increased in immunocompromised patients. This multicenter study aimed to evaluate in vitro antifungal activities of 8 antifungal agents against the Candida species isolated from 10 university hospitals in Iran. During the period from Dec 2019 to Dec 2021, Candida species were collected from clinical samples of patients. The isolates were identified by PCR restriction fragment length polymorphism and sequencing methods. The antifungal susceptibility tests of each isolate to eight antifungal agents were performed according to the microdilution CLSI M27, M59, and M60 standard methods. A total of 598 Candida strains were isolated from clinical samples. The most commonly isolated Candida species was C. albicans, followed by C. glabrata, C. parapsilosis, Debaryomyces hansenii (Candida famata), C. tropicalis, Pichia kudriavzevii (Candida krusei), C. orthopsilosis, Meyerozyma guilliermondii (Candida guilliermondii), Kluyveromyces marxianus (Candida kefyr), and Clavispora lusitaniae (Candida lusitaniae). MIC 90 values in all Candida species were as follows: 0.25 μg/mL for caspofungin and voriconazole; 0.5 μg/mL for amphotericin B and isavuconazole; 2 μg/mL for itraconazole, luliconazole, and posaconazole; and 16 μg/mL for fluconazole. Although 30/285 C. albicans, 15/31 C. hansenii, 3/12 M. guilliermondii , 67/125 C. glabrata, 5/15 P. kudriavzevii , 6/60 C. parapsilosis, and 5/23 C. tropicalis isolates were multiazole resistant with resistance to 2 to 4 azoles, pan-azole resistance was not observed. According to our data, Candida albicans and C. glabrata were the most frequent species isolated from clinical samples in Iran. Caspofungin and voriconazole, with lower MIC 90 values, are the most effective than other antifungal agents for the treatment of Candida infections in this region. IMPORTANCE Candida species cause severe invasive infections of the heart, brain, eyes, bones, and other parts of the body. Knowledge of regional distributions of causative Candida agents and their antifungal susceptibility patterns can help to monitor resistance to antifungal agents of various species and support local and national surveillance programs. In the present study, C. albicans and C. glabrata were the most frequently isolated species from clinical samples in Iran. Increasing rates of non- albicans Candida isolates from the Iranian population should be looked at as alarming due to various levels of intrinsic MIC values or resistance to various antifungal drugs. Caspofungin and voriconazole are recommended over fluconazole for the treatment of Candida infections in the study region. However, amphotericin B and isavuconazole are also active against the most common Candida species isolated from patients. Pan azole-resistant Candida species were not observed in the present study.

The aim of this systematic review was to identify randomized controlled trials that looked at the effects of Nigella sativa in any form on different skin diseases. Up to March 2022, the online databases of Scopus, Web of Science, PubMed, Embase, Google Scholar, and Cochrane trials were searched. This study included 14 records of people who had experienced different types of skin disease including atopic dermatitis, vulgaris, arsenical keratosis, psoriasis, vitiligo, acute cutaneous leishmaniasis, warts, eczema, and acne. The mean SD age of the patients was 28.86 (4.49); [range: 18.3-51.4], with females accounting for 69% (506 out of 732) of the total. The follow-up mean SD was 8.16 (1.3) (ranged: 4 days to 24 weeks). The odds ratio (OR) was found to be 4.59 in a meta-analysis (95% CI: 2.02, 10.39). Whereas the null hypothesis in this systematic review was that lotion had no impact, OR 4.59 indicated that lotion could be effective. The efficacy of N. sativa essential oil and extract has been demonstrated in most clinical studies. However, more research is needed to completely evaluate and validate the efficacy or inadequacy of therapy with N. sativa , although it appears that it can be used as an alternative treatment to help people cope with skin problems., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Naser Nasiri et al.)

Background: Patients with Coronavirus disease 2019 (COVID-19) pneumonia are at risk of hypoxemic respiratory failure. Hence, many patients may require noninvasive positive pressure ventilation (NIPPV) during their hospital course. Using mechanical ventilation such as bilevel positive airway pressure or a ventilator to provide NIPPV may result in adverse events, including barotrauma., Case Report: We reported two cases (40- and 43-years-old men) of severe COVID-19 pneumonia and hypoxemic respiratory failure who underwent NIPPV for respiratory support. These cases were complicated with barotrauma in their course of hospital admission that manifested with pneumoscrotum., Conclusion: In the cases of pneumoscrotum, it is crucial to understand its underlying etiology and origin since this clinical finding may be the outcome of life-threatening illnesses requiring urgent treatment., Competing Interests: All authors declare that they had no conflict of interest., (Copyright© 2022, Galen Medical Journal.)

Introduction: Cardiovascular diseases are very common in the general population, and several factors play a role in their development. The purpose of this study was to investigate the relationship between hyperuricaemia and other cardiovascular disease risk factors., Methods: This cross-sectional study was conducted on 1008 people over the 15-year-old general population in Kerman, Iran. The blood samples of all patients were analysed for the uric acid serum level, and they completed a checklist including physical activity, previous history of hypertension and diabetes, smoking and opium., Results: A number of 1008 cases of people were entered into the study. According to the results of this study, 254 patients had uric acid levels above the 75th percentile (6 mg/dl in males, and 5 mg/dl in females). No significant difference was observed between gender (p = .249) and age groups (p = .125) of people with and without hyperuricaemia. The prevalence of overweight/obesity (p < .001), hypertension (p = .004) and low physical activity (p = .033) was significantly higher in patients with hyperuricaemia. The duration of hypertension was significantly higher in hyperuricaemic individuals (p = .022). Overweight/obesity (OR = 2.67; 95% CI = 1.87-3.82) and hypertension (OR = 1.40; 95% CI = 1.02-1.93) were two significant independent factors that contributed to the increased risk of hyperuricaemia in the subjects., Conclusion: The uric acid serum level is higher in people with hypertension and overweight/obesity. Hyperuricaemia increases the risk of cardiovascular events, which can be prevented by determining the appropriate strategy for the early diagnosis and treatment of this metabolic disorder., (© 2022 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Background: Pain associated with chest wall trauma is a major issue in the emergency department (ED). However, it may be challenging to select among the various analgesic procedures., Objective: Our aim was to compare single-shot erector spinae plane block (ESPB) with intercostal nerve block (ICNB) under ultrasound guidance for pain management in thoracic trauma., Methods: This study was a randomized nonblinded clinical trial performed in a level I urban trauma center. A convenience sample of patients with isolated chest wall trauma and initial Numeric Rating Scale pain scores (NRS 0) > 5 were included. Exclusion criteria were large pain area, surgical interventions, discharged from the ED, and presence of contraindications to lidocaine. Pain scores at 20 min and 60 min (NRS 20 and 60) and at disposition (disp) were recorded., Results: Twenty-seven patients in the ESPB and 23 in the ICNB groups were enrolled. Mean values of NRS 0, 20, 60, and disp for the ESPB vs. ICNB groups were 8.0 vs. 7.4, 5.2 vs. 6.1, 4.1 vs. 5.4, and 4.3 vs. 5.8, respectively (p = 0.07, p = 0.04, p = 0.001, and p < 0.001, respectively). Four patients in the ESPB and 8 patients in the ICNB groups required administration of adjunctive doses of fentanyl for satisfactory pain control (p = 0.09)., Conclusions: Ultrasound-guided ESPB was superior to ICNB regarding pain control during the ED stay period of patients with painful chest wall trauma. We recommend ESPB in the ED for pain control in blunt or penetrating thoracic trauma., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Fusarium species are filamentous fungi that cause a variety of infections in humans. Because they are commonly resistant to many antifungal drugs currently available in clinical settings, research into alternative targets in fungal cells and therapeutic approaches is required. The antifungal activity of miltefosine and four comparators, amphotericin B, voriconazole, itraconazole, and caspofungin, were tested in vitro against a collection of susceptible and resistant clinical ( n = 68) and environmental ( n = 42) Fusarium isolates. Amphotericin B (0.8 μg/mL) had the lowest geometric mean (GM) MICs/MECs values followed by miltefosine (1.44 μg/mL), voriconazole (2.15 μg/mL), caspofungin (7.23 μg/mL), and itraconazole (14.19 μg/mL). Miltefosine was the most effective agent against Fusarium isolates after amphotericin B indicating that miltefosine has the potential to be studied as a novel treatment for Fusarium infections.

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., (Copyright © 2022. Publicado por Elsevier España, S.L.U.)

Aspergillus species are a major cause of life-threatening invasive infections and noninvasive diseases. This study seeks to investigate the frequency of Aspergillus species among Iranian patients and their susceptibility to seven antifungals. In a cross-sectional study, 233 Aspergillus isolates were collected from 11 university hospitals in Iran between 2018 and 2021. Aspergillus isolates were identified based on colony morphology, microscopic characteristics, PCR-restriction fragment length polymorphism (RFLP), and sequencing of the beta-tubulin gene. The CLSI M38-A2 reference methodology was used for antifungal susceptibility testing of amphotericin B, voriconazole, posaconazole, itraconazole, luliconazole, isavuconazole, and caspofungin. Members of Aspergillus section Flavi (117/233, 50.2%), Aspergillus section Nigri (77/233, 33.1%), Aspergillus section Fumigati (21/233, 9%), Aspergillus section Terrei (14/233, 6%), Aspergillus pseudodeflectus (2/233, 0.85%), and Aspergillus melleus (2/233, 0.85%) were isolated from the samples. The lowest 0.25 MIC 90 values for all isolates tested were for luliconazole (0.016 μg/mL) and isavuconazole (0.250 μg/mL), and the highest value was observed for itraconazole (≥ 8μg/mL). The 90% minimum effective concentration (MEC 90 ) value for caspofungin was 0.125 μg/mL. MIC 90 values for voriconazole, amphotericin B, and posaconazole were 1, 2, and 2 μg/mL, respectively. The non-wild-type species were presented for amphotericin B (3%), voriconazole (1.3%), posaconazole (2.6%), luliconazole (1.3%), isavuconazole (1.7%), and caspofungin (4.7%). Positive correlations in the MIC values of azole antifungals were observed, and using one azole increases the MIC value rates of other ones. None of the species were pan-azole resistant. Species of Aspergillus section Flavi were the most common Aspergillus species isolated from Iranian samples. Luliconazole, caspofungin, and isavuconazole present the most effective antifungal agents for treatment of infection due to Aspergillus species. Susceptibility tests should be performed frequently in each region for the best management of patients. IMPORTANCE Aspergillus species are the leading cause of invasive aspergillosis in immunocompromised hosts. The susceptibility of Aspergillus species to antifungal agents might be different. Azole-resistant species have emerged worldwide. Performing susceptibility testing in each region can help in the best management of patients. Here, we show the epidemiology and distribution of Aspergillus species in Iran and their susceptibility patterns for seven antifungal agents. The significant points of the present study are that species of Aspergillus section Flavi are the most prevalent Aspergillus species isolated from 11 university hospitals. Luliconazole, caspofungin, and isavuconazole were effective antifungal agents against all Aspergillus species.

Introduction. Aspergillus sections Flavi and Nigri comprise clinically relevant and cryptic species that differ significantly in drug susceptibility, meaning that effective treatment depends on correct species identification. Hypothesis/Gap Statement. There are no comprehensive data for molecular identification and antifungal susceptibility testing (AFST) of clinically relevant and cryptic species of Aspergillus sections Flavi and Nigri as the main agents of invasive and non-invasive aspergillosis in Iran. We aimed to perform molecular identification and AFST of 213 clinical Aspergillus isolates belonging to sections Flavi and Nigri . Molecular identification of isolates was performed using sequencing of the β-tubulin gene and in vitro AFST was conducted according to the Clinical and Laboratory Standards Institute (CLSI) M38-A3 guidelines. Results. The most common isolates in sections Flavi and Nigri were Aspergillus flavus (110/113, 97.3 %) and Aspergillus tubingensis (49/100, 49.0 %), respectively. A total of 62/213 (29.1 %) isolates belonging to cryptic species were identified; among them, A. tubingensis was the most prevalent (49/62, 79.0%). Aspergillus flavus and A. niger isolates that responded to the minimum inhibitory concentrations (MICs) of itraconazole above the epidemiological cutoff values were the most frequently detected: 8/110 (7.3 %) and 3/41 (7.3 %), respectively. In section Flavi , Aspergillus alliaceus responded to amphotericin B at a high MIC (>16 µg mL -1 ) and in section Nigri , one of the three Aspergillus luchuensis/awamori isolates responded to itraconazole at an MIC >16 µg ml -1 . Interestingly, for all Aspergillus welwitschiae isolates, the MIC 50 and MIC 90 of itraconazole were both 16 µg ml -1 . Conclusion. A considerable presence of A. flavus and A. niger isolates showing non-wild-type responses to azoles in clinical cases of aspergillosis indicates the importance of classifying clinical Aspergillus isolates at the species level and performing antifungal susceptibility testing on the isolates, which would ensure appropriate treatment.

Background: Dermatophytosis is a common global superficial mycosis caused by a group of keratinophilic moulds known as dermatophytes that invade the skin and keratinized tissues such as hair and nails of humans and animals. This study takes identification of a collection of clinical dermatophyte isolates by using partial sequencing of translation elongation factor-1α ( Tef-1α ) gene aiming both to update the epidemiological status of dermatophytosis in Mashhad, Northeastern Iran and to corroborate the efficacy of Tef-1α for species-level identification of dermatophytes., Method: The demographic data related to 87 culture-positive dermatophytes isolated from patients clinically suspected to have dermatophytosis were collected. The dermatophyte isolates were subjected to a partial polymerase chain reaction (PCR)-sequencing of Tef-1α gene by using specific pan-dermatophyte primers. The data were analysed by SeqMan software, the sequences were compared and aligned with the GenBank database and the isolates were identified., Results: Identification based on Tef-1α partial sequence was successful for all isolates. The identified dermatophyte isolates in decreasing order were as Trichophyton interdigitale 19 (22%), T. tonsurans 19 (22%), T. mentagrophytes 13 (15%), T. persicum 10 (11.5%), Epidermophyton floccosum 9 (10.3%), Microsporum canis 7 (8%), T. rubrum 5 (5.7%), T. violaceum 2 (2.2%), Nannizzia fulva 2 (2.2%) and N. persicolor 1 (1.1%). The isolates have been associated with clinical forms of tinea corporis ( n = 38; 43.7%), tinea faciei ( n = 13; 15%), tinea cruris ( n = 12; 13.9%), tinea manuum ( n = 7; 8%), tinea unguium ( n = 7; 8%), tinea capitis ( n = 7; 8%) and tinea pedis ( n = 3; 3.4%)., Conclusion: Dermatophytosis has yet remained a public health problem in Northeastern Iran, and infection with new and less frequent species, e.g., T. persicum , N. fulva and N. persicolor have emerged. The Tef-1α gene partial sequencing reconfirmed the resolution power of this locus for the determination of species boundaries in dermatophytes., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Indian Journal of Dermatology.)

The incidence of infections caused by uncommon Chaetomiaceae (Chaetomium and related species) in humans has increased in the recent years. The in vitro activity of eight antifungal drugs (amphotericin B, five azoles, two echinocandins) against 42 morphologically identified Chaetomium strains was determined according to the Clinical and Laboratory Standards Institute (CLSI) guideline. The strains were subsequently identified based on sequences of the internal transcribed spacer 1 and 2 including the intervening 5.8S nrDNA region (ITS) and the partial β tubulin gene (tub2). Chaetomium globosum (n = 24), was the most frequently isolated species, followed by Amesia atrobrunnea (syn. Chaetomium atrobrunnea, n = 6), Dichotomopilus dolichotrichus (syn. Chaetomium dolichotrichum, n = 2) and Acrophialophora jodhpurensis, Chaetomium coarctatum, C. elatum, C. gracile, C. subaffine, C. tarraconense, C. unguicola, Dichotomopilus sp., Dichotomopilus variostiolatus, Ovatospora brasiliensis (all represented by a single strain). The geometric means of the minimum inhibitory concentrations/minimum effective concentrations (MICs/MECs) of the antifungals across all strains were (in increasing order): micafungin 0.12 µg/ml, itraconazole and posaconazole 0.21 µg/ml, amphotericin B 0.25 µg/ml, voriconazole 0.45 µg/ml, isavuconazole 0.54 µg/ml, caspofungin 2.57 µg/ml, and fluconazole 45.25 µg/ml. Micafungin had the lowest geometric mean followed by amphotericin B which had the largest range against tested isolates. All examined C. globosum strains had similar antifungal susceptibility patterns. Fluconazole and caspofungin could not be considered as an option for treatment of infections caused by Chaetomium and chaetomium-like species., Lay Summary: Infections caused by uncommon fungi such as Chaetomium have increased in the recent years. Chaetomium globosum has been reported from onychomycosis and phaeohyphomycosis. This species often induces superficial infections in immunocompetent patients. The taxonomy of Chaetomium spp. has changed dramatically in the last years. Antifungal treatment is a crucial step for managing these kinds of infections. Therefore, the in vitro activity of eight antifungal drugs against Chaetomium strains was determined and β-tubulin (tub2) sequencing was applied to identify the strains. Chaetomium globosum was the most frequent species in our dataset. Based on the results of susceptibility testing, micafungin had the lowest geometric mean followed by amphotericin B. Fluconazole and caspofungin cannot be considered a proper treatment option for infections caused by Chaetomium and chaetomium-like species., (© The Author(s) 2021. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Background: Exophiala is the main genus of black fungi comprising numerous opportunistic species. Data on antifungal susceptibility of Exophiala isolates are limited, while infections are potentially fatal., Materials and Methods: In vitro activities of eight antifungal drugs (AMB, five azoles, two echinocandins) against 126 clinical (n = 76) and environmental (n = 47) isolates from around the world were investigated. E. oligosperma (n = 58), E. spinifera (n = 33), E. jeanselmei (n = 14) and E. xenobiotica (n = 21) were included in our dataset., Results: The resulting MIC 90 s of all strains were as follows, in increasing order: posaconazole 0.063 μg/ml, itraconazole 0.125 μg/ml, voriconazole and amphotericin B 1 μg/ml, isavuconazole 2 μg/ml, micafungin and caspofungin 4 μg/ml, and fluconazole 64 μg/ml. Posaconazole, itraconazole and micafungin were the drugs with the best overall activity against Exophiala species. Fluconazole could not be considered as a treatment choice. No significant difference could be found among antifungal drug activities between these four species, neither in clinical nor in environmental isolates., Conclusion: Antifungal susceptibility data for Exophiala spp. are crucial to improve the management of this occasionally fatal infection and the outcome of its treatment., (© 2021 Wiley-VCH GmbH.)

Pathogens from the Trichophyton benhamiae complex are one of the most important causes of animal mycoses with significant zoonotic potential. In light of the recently revised taxonomy of this complex, we retrospectively identified 38 Trichophyton isolates that could not be resolved into any of the existing species. These strains were isolated from Iranian and Czech patients during molecular epidemiological surveys on dermatophytosis and were predominantly associated with highly inflammatory tinea corporis cases, suggesting possible zoonotic etiology. Subsequent phylogenetic (4 markers), population genetic (10 markers), and phenotypic analyses supported recognition of two novel species. The first species, Trichophyton persicum sp. nov., was identified in 36 cases of human dermatophytosis and one case of feline dermatophytosis, mainly in Southern and Western Iran. The second species, Trichophyton spiraliforme sp. nov., is only known from a single case of tinea corporis in a Czech patient who probably contracted the infection from a dog. Although the zoonotic sources of infections summarized in this study are very likely, little is known about the host spectrum of these pathogens. Awareness of these new pathogens among clinicians should refine our knowledge about their poorly explored geographic distribution. IMPORTANCE In this study, we describe two novel agents of dermatophytosis and summarize the clinical manifestation of infections. These new pathogens were discovered thanks to long-term molecular epidemiological studies conducted in Czechia and Iran. Zoonotic origins of the human infections are highly probable, but the animal hosts of these pathogens are poorly known. Further research is needed to refine our knowledge about these new dermatophytes.

The Aspergillus species are main causative agents of various infections such as invasive aspergillosis (IA) in immunocompromised patients and these infections have high mortality rates. In this study, we provide insight in the species causing aspergillosis in Iran based on morphology and sequence data. Clinical (n = 117) and environmental isolates (n = 54) collected during 2010-2016 from University hospitals in Mashhad and Tehran (Iran) were identified both morphologically and molecularly using partial calmodulin (CaM) gene sequences. Clinical cases were identified based on EORTC/MSG criteria. Aspergillus flavus (n = 96, 55%) was the most prevalent species among the clinical and environmental isolates while A. fumigatus (n = 13, 7.5%) ranked fourth after A. tubingensis (n = 23, 13%) and A. welwitchiae (n = 18, 10%). Species such as A. tubingensis, A. welwitschiae, A. fumigatus, A. sydowii, A. neoniger and A. terreus were present in both clinical and environmental samples indicating the possible environmental source of infections. Interestingly, A. niger was isolated only once. Furthermore, 13 other rare and cryptic Aspergillus species were detected. Pulmonary and respiratory disorders (n = 33), followed by transplantation (n = 23), invasive fungal rhinosinusitis (n = 14), and haematological malignancies (n = 12) were major predisposing factors. According to EORTC/MSG criteria, there were 43 probable cases identified followed by 36 cases for each of proven and possible ones. Correct molecular identification will be useful for further epidemiological studies., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

As a novel risk factor, COVID-19 has led to an increase in the incidence of candidemia and an elevated mortality rate. Despite being of clinical importance, there is a lack of data regarding COVID-19-associated candidemia (CAC) among Iranian patients. Therefore, in this retrospective study, we assessed CAC epidemiology in the intensive care units (ICUs) of two COVID-19 centers in Mashhad, Iran, from early November 2020 to late January 2021. Yeast isolates from patients' blood were identified by 21-plex polymerase chain reaction (PCR) and sequencing, then subjected to antifungal susceptibility testing according to the CLSI M27-A3 protocol. Among 1988 patients with COVID-19 admitted to ICUs, seven had fungemia (7/1988; 0.03%), among whom six had CAC. The mortality of the limited CAC cases was high and greatly exceeded that of patients with COVID-19 but without candidemia (100% (6/6) vs. 22.7% (452/1988)). In total, nine yeast isolates were collected from patients with fungemia: five Candida albicans , three C. glabrata , and one Rhodotorula mucilaginosa . Half of the patients infected with C. albicans (2/4) were refractory to both azoles and echinocandins. The high mortality of patients with CAC, despite antifungal therapy, reflects the severity of the disease in these patients and underscores the importance of rapid diagnosis and timely initiation of antifungal treatment.

Aspergillus species are emerging causative agents of non-dermatophyte mold onychomycosis. In this study, 48 Aspergillus isolates were obtained from patients with onychomycosis in Mashhad, Iran, during 2015-2018. The aim is to identify the Aspergillus isolates to the species level by using partial calmodulin and beta-tubulin gene sequencing and MALDI-TOF MS, and to evaluate their in vitro susceptibility to ten antifungal drugs: terbinafine, itraconazole, voriconazole, posaconazole, ravuconazole, isavuconazole, caspofungin, micafungin, anidulafungin and amphotericin B according to CLSI M38-A3. Our results indicate that A.flavus (n = 38, 79%) is the most common Aspergillus species causing onychomycosis in Mashhad, Iran. Other detected species were A. terreus (n = 3), A. tubingensis (n = 2), A. niger (n = 1), A. welwitschiae (n = 1), A. minisclerotigenes (n = 1), A. citrinoterreus (n = 1) and A. ochraceus (n = 1). Aspergillus flavus, A. terreus and A. niger isolates were correctly identified at the species level by MALDI-TOF MS, while all cryptic species were misidentified. In conclusion, A. flavus is the predominant Aspergillus species causing onychomycosis due to Aspergillus spp. in Mashhad, Iran. MALDI-TOF MS holds promise as a fast and accurate identification tool, particularly for common Aspergillus species. It is important that the current database of reference spectra, representing different Aspergillus species is expanded to increase the precision of the species-level identification. Terbinafine, posaconazole and echinocandins were in vitro most active against the studies Aspergillus isolates and terbinafine could be the first choice for treatment of onychomycosis due to Aspergillus.

Chromoblastomycosis is a chronic, cutaneous or subcutaneous mycosis characterized by the presence of muriform cells in host tissue. Implantation disease is caused by melanized fungi related to black yeasts, which, in humid tropical climates, are mainly members of the genus Fonsecaea . In endemic areas of Brazil, F. pedrosoi and F. monophora are the prevalent species. The current hypothesis of infection is traumatic introduction via plant materials, especially by plant thorns. However, isolation studies have demonstrated a low frequency of the agents in environmental substrates. The present study aimed to detect F. pedrosoi and F. monophora in shells of babassu coconuts, soil, plant debris, and thorns from endemic areas of chromoblastomycosis in Maranhão state, northern Brazil, using Rolling Circle Amplification (RCA) with padlock probes as a new environmental screening tool for agents of chromoblastomycosis. In addition to molecular screening, the environmental samples were analyzed by fungal isolation using mineral oil flotation. The limit of detection of the RCA method was 2.88 × 10 7 copies of DNA per sample for the used padlock probes, indicating that this represents an efficient and sensitive molecular tool for the environmental screening of Fonsecaea agents. In contrast, with isolation from the same samples using several selective methods, no agents of chromoblastomycosis were recovered.

Background and Purpose: Keratinophilic fungi play an important role in the decomposition of keratinous substances in nature. This capacity induces dermatomycosis in both humans and livestock. The soil of livestock stables can be a reservoir of keratinophilic fungi. Therefore, the present study was conducted to isolate and identify keratinophilic fungi in the soil of the livestock stables located in Qayen, South Khorasan Province, Iran., Materials and Methods: This study was conducted on 62 soil samples collected from livestock stables. The samples were cultured by means of hair bait technique (HBT). The identification of the isolates was performed based on their morphological characteristics and then confirmed by polymerase chain reaction and sequencing of the ITS regions of ribosomal DNA., Results: A total of 118 isolates of 7 species from 5 genera were identified. Aphanoascus verrucosu (n=70, 59.36%) was detected as the dominant keratinophilic fungus, followed by Arthroderma quadrifidum (n=13, 11.01%), A. terreus (n=12, 10.16%), Acremonium (n=12, 10.16%), A. gertleri (n=5, 4.23%), Fusarium equiseti (n=3, 2.54%), and Uncinocarpus reesii (n=3, 2.54%)., Conclusion: Different keratinophilic fungi were isolated from the soil of livestock stables; however, A. verrucosu was found to be the dominant species., (Copyright: © 2020, Published by Mazandaran University of Medical Sciences on behalf of Iranian Society of Medical Mycology and Invasive Fungi Research Center.)

Melanized fungi and black yeasts in the family Herpotrichiellaceae (order Chaetothyriales) are important agents of human and animal infectious diseases such as chromoblastomycosis and phaeohyphomycosis. The oligotrophic nature of these fungi enables them to survive in adverse environments where common saprobes are absent. Due to their slow growth, they lose competition with common saprobes, and therefore isolation studies yielded low frequencies of clinically relevant species in environmental habitats from which humans are thought to be infected. This problem can be solved with metagenomic techniques which allow recognition of microorganisms independent from culture. The present study aimed to identify species of the family Herpotrichiellaceae that are known to occur in Brazil by the use of molecular markers to screen public environmental metagenomic datasets from Brazil available in the Sequence Read Archive (SRA). Species characterization was performed with the BLAST comparison of previously described barcodes and padlock probe sequences. A total of 18,329 sequences was collected comprising the genera Cladophialophora, Exophiala, Fonsecaea, Rhinocladiella and Veronaea, with a focus on species related to the chromoblastomycosis. The data obtained in this study demonstrated presence of these opportunists in the investigated datasets. The used techniques contribute to our understanding of environmental occurrence and epidemiology of black fungi.

A leading pharmacological strategy toward HIV cure requires "shock" or activation of HIV gene expression in latently infected cells with latency reversal agents (LRAs) followed by their subsequent clearance. In a screen for novel LRAs, we used fungal secondary metabolites as a source of bioactive molecules. Using orthogonal mass spectrometry (MS) coupled to latency reversal bioassays, we identified gliotoxin (GTX) as a novel LRA. GTX significantly induced HIV-1 gene expression in latent ex vivo infected primary cells and in CD4 + T cells from all aviremic HIV-1 + participants. RNA sequencing identified 7SK RNA, the scaffold of the positive transcription elongation factor b (P-TEFb) inhibitory 7SK small nuclear ribonucleoprotein (snRNP) complex, to be significantly reduced upon GTX treatment of CD4 + T cells. GTX directly disrupted 7SK snRNP by targeting La-related protein 7 (LARP7), releasing active P-TEFb, which phosphorylated RNA polymerase II (Pol II) C-terminal domain (CTD), inducing HIV transcription., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Candida tropicalis is one of the major candidaemia agents, associated with the highest mortality rates among Candida species, and developing resistance to azoles. Little is known about the molecular mechanisms of azole resistance, genotypic diversity, and the clinical background of C. tropicalis infections. Consequently, this study was designed to address those questions. Sixty-four C. tropicalis bloodstream isolates from 62 patients from three cities in Iran (2014-2019) were analyzed. Strain identification, antifungal susceptibility testing, and genotypic diversity analysis were performed by MALDI-TOF MS, CLSI-M27 A3/S4 protocol, and amplified fragment length polymorphism (AFLP) fingerprinting, respectively. Genes related to drug resistance (ERG11, MRR1, TAC1, UPC2, and FKS1 hotspot9s) were sequenced. The overall mortality rate was 59.6% (37/62). Strains were resistant to micafungin [minimum inhibitory concentration (MIC) ≥1 μg/ml, 2/64], itraconazole (MIC > 0.5 μg/ml, 2/64), fluconazole (FLZ; MIC ≥ 8 μg/ml, 4/64), and voriconazole (MIC ≥ 1 μg/ml, 7/64). Pan-azole and FLZ + VRZ resistance were observed in one and two isolates, respectively, while none of the patients were exposed to azoles. MRR1 (T255P, 647S), TAC1 (N164I, R47Q), and UPC2 (T241A, Q340H, T381S) mutations were exclusively identified in FLZ-resistant isolates. AFLP fingerprinting revealed five major and seven minor genotypes; genotype G4 was predominant in all centers. The increasing number of FLZ-R C. tropicalis blood isolates and acquiring FLZ-R in FLZ-naive patients limit the efficiency of FLZ, especially in developing countries. The high mortality rate warrants reaching a consensus regarding the nosocomial mode of C. tropicalis transmission., (© The Author(s) 2019. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

The main purpose of our study was to evaluate multiplex PCR assay targeting novel genes for detection of five fungal and bacterial agents in BAL samples; because many fungi and bacteria that cause respiratory infections have similar clinical symptoms, diagnosing and differentiating them are therefore essential to controlling and treating them. A total of 100 BAL specimens from a mycobacterium and mycology laboratory were collected from patients suspected of having TB or other respiratory diseases. Novel DNA targets for Aspergillus, Nocardia, Cryptococcus, and Streptomyces were found using modified comparative genomic analysis. Afterward, the primers were designed based on novel targets, and the sensitivity and specificity of the newly designed primers were evaluated. These primers, along with specific primers for M. tuberculosis (SDR), were used in a multiplex PCR assay. The results showed the culture test to be more sensitive than the PCR assay in detecting M. tuberculosis. However, in the detection of Aspergillus, the PCR assay was more sensitive than the culture test. We also found one positive culture and two positive PCR assays for Nocardiosis. Cryptococcal infections and Streptomyces associated with lung diseases were not identified by the culture test nor by the PCR assay. The multiplex PCR is one of the cheapest molecular diagnostic tests readily available for BAL samples in clinical laboratories. This assay can be used for early reports of the causative agents and for treating patients with appropriate drugs at an early stage.

Fungi of the genus Fusarium are well known as major plant pathogens but also cause a broad spectrum of human infections. Sixty-three clinical isolates, collected during 2014-2017, were identified using a part of the TEF1 gene as barcoding marker. Fusarium fujikuroi species complex (FFSC, n = 41, 65%) showed to be the dominant etiological agent, followed by F. solani species complex (FSSC, n = 14, 22%) and F. oxysporum species complex (FOSC, n = 7, 11%). There was one strain belonging to F. lateritium species complex (FLSC, n = 1, 1.5%). For final identification, a phylogenetic tree was constructed including the type strains of each species complex. Most cases of fusariosis were due to nail infection (n = 38, 60.3%), followed by keratitis (n = 22, 34%). Fusarium infections are difficult to be treated due to their intrinsic resistance to different azoles; however, accurate and fast identification of etiological agents may enhance management of the infection. We present the first phylogenetic study on clinical Fusarium spp. from Iran.

Clonal expansion of fluconazole resistant (FLZ-R) Candida parapsilosis isolates is increasingly being identified in many countries, while there is no study exploring the antifungal susceptibility pattern, genetic diversity, and clinical information for Iranian C. parapsilosis blood isolates. Candida parapsilosis species complex blood isolates ( n = 98) were recovered from nine hospitals located in three major cities, identified by MALDI-TOF MS, and their genetic relatedness was examined by AFLP fingerprinting. Antifungal susceptibility testing followed CLSI-M27-A3 and ERG11, MRR1 and hotspots 1/2 (HS1/2) of FKS1 were sequenced to assess the azole and echinocandin resistance mechanisms, respectively. Ninety-four C. parapsilosis and four Candida orthopsilosis isolates were identified from 90 patients. Only 43 patients received systemic antifungal drugs with fluconazole as the main antifungal used. The overall mortality rate was 46.6% (42/90) and death mostly occurred for those receiving systemic antifungals (25/43) relative to those not treated (17/47). Although, antifungal-resistance was rare, one isolate was multidrug-resistant (FLZ = 16 μg/ml and micafungin = 8 μg/ml) and the infected patient showed therapeutic failure to FLZ prophylaxis. Mutations causing azole and echinocandin resistance were not found in the genes studied. AFLP revealed five genotypes (G) and G1 was the main one (59/94; 62.7%). Clinical outcome was significantly associated with city ( P = 0.02, α <0.05) and Mashhad was significantly associated with mortality ( P = 0.03, α <0.05). Overall, we found a low level of antifungal resistance for Iranian C. parapsilosis blood isolates, but the noted MDR strain can potentially become the source of future infections and challenge the antifungal therapy in antifungal-naïve patients. AFLP typing results warrants confirmation using other resolutive typing methods., (Copyright © 2020 Arastehfar, Daneshnia, Najafzadeh, Hagen, Mahmoudi, Salehi, Zarrinfar, Namvar, Zareshahrabadi, Khodavaisy, Zomorodian, Pan, Theelen, Kostrzewa, Boekhout and Lass-Flörl.)

Background and Purpose: Dermatophytes are a group of fungi specialized in invading humans and other vertebrate keratinized tissues. These fungi cause a variety of skin, nail, and hair disorders, called dermatophytosis (tinea). In some cases, drug resistance to antifungals necessitates special treatment. Among the antifungal agents, sertaconazole (i.e., a third-generation imidazole) has a broad-spectrum against dermatophyte species. Regarding this, the present study was conducted to investigate the antifungal susceptibility of dermatophytes obtained from patients with dermatophytosis in Mashhad located in northeastern Iran., Materials and Methods: A total of 75 clinical dermatophyte isolates, including Trichophyton mentagrophytes (n=21), T. interdigital (n=18), T. tonsurans (n=16), Epidermophyton floccosum (n=11), Microsporum canis (n=5), Nannizzia fulvum (n=2), T. benhamiae (n=1), and T. verrucosum (n=1), were evaluated against five antifungal agents of sertaconazole , itraconazole, clotrimazole, terbinafine, and griseofulvin based on the CLSI M38-A2 guideline., Results: According to the results, the minimum inhibitory concentration (MIC) ranges of sertaconazole , terbinafine, griseofulvin, itraconazole, and clotrimazole were estimated at 0.125-16, 0.002-1, 0.5-4, 0.031-4, and 0.016-4 µg/ml, respectively, for dermatophyte species . In addition, the geometric mean (GM) values of the MIC of sertaconazole , terbinafine, griseofulvin, itraconazole, and clotrimazole were obtained as 3.39, 1, 1.44, 1.52, and 1.93, respectively., Conclusion: Among the tested antifungals, terbinafine and griseofulvin were the most effective agents against dermatophyte isolates. However, sertaconazole, a third-generation imidazole, did not show any significant effect. Furthermore, M. canis and E. floccosum showed the best response to the antifungal agents.

The fungi Trichophyton mentagrophytes and T interdigitale account for significant amount of dermatophytosis cases worldwide. These two dermatophytes form a species complex and have a number of ribosomal internal transcribed spacer (ITS) region genotypes, allowing simultaneous species identification and strain typing. Our aim was to describe the geographic distribution of T mentagrophytes/T interdigitale ITS region genotypes and find an association between the genotypes and clinical presentations of respective infections. We performed rDNA ITS region sequencing in 397 Iranian T mentagrophytes/T interdigitale isolates and analysed all available in GenBank entries with sequences of this kind. For the study, 515 clinical annotations were available. Statistical analysis was performed by chi-squared test and Spearman rank correlation analysis. A total of 971 sequences belonged to genotypes with at least 10 geographic annotations and were classified on the basis of exclusive occurrence in a particular region or high relative contribution to a regional sample. We discerned Asian and Oceanian ("KU496915" Type V, "KT192500" Type VIII, "KU315316"), European ("FM986750" Type III, "MF926358" Type III*, "KT285210" Type VI) and cosmopolitan ("FM986691" Type I, "JX122216" Type II, "KP132819" Type II* and "AF170453" Type XXIV) genotypes. There was statistically significant difference in the ITS genotype distribution between different affected body sites. Trichophyton mentagrophytes "KT192500" Type VIII correlated with tinea cruris, T mentagrophytes "KU496915" Type V correlated with tinea corporis, T interdigitale "JX122216" Type II correlated with tinea pedis and onychomycosis. Trichophyton mentagrophytes and T interdigitale genotypes can be associated with distinct geographic locations and particular clinical presentations., (© 2019 Blackwell Verlag GmbH.)

Aureobasidium pullulans and A. melanogenum are black-yeast-like surface colonisers and are commonly encountered as contaminants in the hospital. The species are able to produce melanin which play a role in protection against environmental stress and irradiation. Aureobasidium melanogenum shows higher frequency in opportunistic infections compared to A. pullulans. Comparative pathogenicity of opportunistic black yeasts between Aureobasidium pullulans and A. melanogenum to explain the observed differences in frequency in infection. Degrees of melanisation and thermotolerance were measured, and virulence of strains from different sources was examined in Galleria mellonela and murine infection models. Aureobasidium melanogenum responds with increased melanisation to temperature stress and generally survives at 37°C, A. pullulans on average scored less on these parameters. In the murine model, differences between species were not significant, but the melanised A. melanogenum group showed the highest virulence. This result was not reproducible in Galleria mellonella larvae at 25°C. The A. melanogenum black group showed higher pathogenicity in murine model, indicating that the combination of melanisation and thermotolerance rather than species affiliation is instrumental. Galleria larvae did not survive very well at 37°C, and hence, this model is judged insufficient to detect the small virulence differences observed in Aureobasidium., (© 2019 Blackwell Verlag GmbH.)