Study on invasive aspergillosis using galactomannan enzyme immunoassay and determining antifungal drug susceptibility among hospitalized patients with hematologic malignancies or candidates for organ transplantation.

The incidence of invasive aspergillosis (IA) has dramatically increased during the last decade. This infection is associated with high morbidity and mortality, ranging from 30% to 70%, especially in immunocompromised patients. Delay in diagnosis and treatment is usually associated with high mortality rates. This study was aimed to assess the diagnostic value of Galactomannan EIA (GM) for early diagnosis of aspergillosis in hospitalized patients with underlying conditions. Also, the antifungal drug susceptibility profiles of causative agents were investigated. In this descriptive cross-sectional study, during the period of 18 months starting from September 2017 until February 2019, 22 bronchoalveolar lavage (BAL) and 13 biopsies from infected sinuses were obtained from a total of 150 patients suffering from different types of hematologic malignancies. All the samples were subjected to microscopic examination and fungal culture. Also, serum specimens were obtained from all patients (n = 135). 22 serum and 17 BAL specimens were tested for the GM level. Fungal identified were confirmed through the PCR-sequencing of the ß-tubulin gene. The susceptibility to amphotericin B, itraconazole, voriconazole, posaconazole, ravuconazole, and caspofungin was evaluated according to the Clinical and Laboratory Standards Institute document M38-A2 (CLSI M38-A2) broth microdilution protocol. The results showed that the incident rate of IA was 23.33% and 35 patients with IA (12 proven cases and 23 probable cases) were diagnosed according to the European Organization for Research and Treatment of Cancer and Mycoses Study Group criteria. The 35 patients with IA in the current study comprised 19 men (54.29%) and 16 women (45.71%) with the median age of 42 years. AML (31.5%) was documented as the most prevalent risk factor among our subjects with IA and Aspergillus flavus (65.7%) was the most prevailing causal agent in this study. Among patients with IA, ague (71%) and cough (60%) were the most common symptoms. In the present study, a sensitivity of 94% and a specificity of 98% was reported for GM ELISA in BAL specimens. Also, a sensitivity of 58% and a specificity of 98% was reported for GM ELISA in serum samples. Among 6 tested antifungal drugs, the lowest minimum inhibitory concentration (MIC) values were observed for posaconazole and ravuconazole which showed the range of 0.008-0.0062 µgml and 0.031-0.125 µgml, respectively. The current study has demonstrated that determining the value of GM investigation in BAL and serum specimens can be promising in early diagnosis of IA, also molecular identification of the agents causing IA and their antifungal susceptibility patterns are essential issues for the targeted antifungal therapy and outcome improvement of patients with this life-threatening disease.

Study on the relationship between the concentration and type of fungal bio-aerosols at indoor and outdoor air in the Children's Medical Center, Tehran, Iran.

Fungal bio-aerosols are of concern due to their adverse health effects, especially in indoor environments. The aim of this study was to evaluate the relationship between the concentration and type of fungal bio-aerosols in the indoor and outdoor of Children's Medical Center in Tehran, Iran. In the present descriptive-analytical study, the fungal bio-aerosols' concentrations in both indoor and outdoor of the hospital air were measured. The measurements were carried out by the Anderson method using a Quick Take 30 pump at 28.3 L min-1 and 2.5 min sampling that was placed on a Sabouraud dextrose agar with chloramphenicol. The average concentrations of total fungal bio-aerosols in the hospital indoor and outdoor air were 40.48 and 119.6 CFU/m3, respectively. Onco-hematology and bone marrow transplantation wards were the most and least contaminated units, respectively (11.09 CFU/m3 vs 1.47 CFU/m3). The most common fungi isolated from the indoor environment were Penicillium spp. (45.86%) which was followed by Cladosporium spp. (31.92%), Aspergillus section Nigri (6.26%), sterilized mycelia (5.05%), and Aspergillus section Flavi (2.83%). Cladosporium spp. (61.10 CFU/m3) and Penicillium spp. (18.56 CFU/m3) had the highest mean concentrations in outdoor and indoor air, respectively. The indoor-to-outdoor ratio of fungal aerosols was < 1 at most sampling sites, indicating that the indoor fungal bio-aerosols may have originated from the outdoor environment.

Synthesis, Cytotoxicity Evaluation, and Antifungal Activity of Novel Nitroglycerin Derivatives against Clinical Candida albicans Isolates.

BACKGROUND: Candida albicans remains the main cause of candidiasis in most clinical settings. Available drugs for candidiasis treatment have many side effects. In this work, novel nitroglycerin derivatives were synthesized and their cytotoxic and antifungal effects evaluated against fluconazole susceptible and resistant clinical C. albicans isolates. METHODS: This experimental study was performed in Tehran University of Medical Sciences and Baqiatallah University of Medical Sciences, Tehran, Iran between Feb to Dec 2019. The in vitro activities of two novel nitroglycerin derivatives (1b and 2b) against 25 clinical fluconazole-susceptible and resistant C. albicans isolates and four standard C. albicans strains were determined according to CLSI reference M27-A3 documents. The cytotoxicity of chemical compounds was investigated near the SNL76/7 cells by colorimetric assay. Real-time PCRs were performed to evaluate the alterations in the regulation of ERG11 and CDR1 genes under nitroglycerin derivatives-treated and untreated conditions. RESULTS: The derivatives 1b and 2b exhibited potent antifungal activity against C. albicans isolates; MICs and MFCs varied from 18 µg/ml to 72 µg/ml and 36 µg/ml to 144 µg/ml, respectively. The cell viability evaluation demonstrated that both chemical compounds are safe within 24h. The nitroglycerin derivatives were able to reduce the transcription level of CDR1 and ERG11 genes in all susceptible and resistant C. albicans isolates. CONCLUSION: Considering the potential and efficacy of these compounds against clinical C. albicans isolates, the complementary in vivo and clinical trials should be investigated.

A Mycological and Molecular Epidemiologic Study on Onychomycosis and Determination In Vitro Susceptibilities of Isolated Fungal Strains to Conventional and New Antifungals.

Background: Onychomycosis is one of the most common and recurrent dermatological diseases worldwide. The antimycotic activity of prescribed medications varies according to the causative agents, and treatment failure rates exceeding 30%. This study aimed to assess the epidemiological profile of onychomycosis in Iran. Also, the susceptibilities to conventional and new antifungals were investigated. Methods: In this descriptive cross-sectional study, during the period of 18 months starting from September 2019 until March 2020, 594 nail specimens were obtained from patients who presented nail changes compatible with a clinical diagnosis of onychomycosis. The patients were referred from different cities, including Tehran, Kermanshah, Arak, Kashan, Rasht, Qom, Urmia, Zahedan, Hamadan, Zanjan, Borujerd, Bushehr, and Yazd. All the samples were subjected to microscopic examination and fungal culture. Fungi identified were confirmed through the PCR-sequencing method. The susceptibility to itraconazole, fluconazole, terbinafine, griseofulvin, posaconazole, ravuconazole, efinaconazole, luliconazole, and tavaborole was evaluated according to the Clinical and Laboratory Standards Institute (CLSI) guidelines, document M38-A2 for filamentous fungi, and document M27-A3 for yeasts. Results: 594 patients were included. Of these, in 179 cases (30.1%) (95% CI:0.3 ± 0.037) onychomycosis was confirmed. The majority of patients were ≥ 60 years of age (n=58, 32.6%) and female (n=113, 63.1%). Saprophytic fungi accounted for the vast majority of the nail isolates (n=92, 51.4%) (95% CI:0.051 ± 0.0.073), followed by dermatophytes (n=45, 25.1%) (95% CI:0.25 ± 0.063), and yeasts (n=42, 23.5%) (95% CI:0.23 ± 0.061). Diabetes mellitus (77.3%), hypothyroidism (18.2%), and solid tumors (4.5%) were documented as the most prevalent underlying conditions. Antifungal susceptibility testing was performed against 60 fungal isolates (20 each of Candida species, saprophytic fungi, and dermatophytes). Efinaconazole, ravuconazole, and luliconazole were the most active agents against Candida species. Also, luliconazole, posaconazole, and efinaconazole were most potent against dermatophytes. Luliconazole had the greatest antifungal activity against saprophytic fungi. Conclusions: The prevalence of onychomycosis in Iranian patients was relatively high. LUL exhibited potent antifungal activity against the three groups of fungi tested, determining its broad-spectrum antimycotic activity and its probable use as the first-line therapy for onychomycosis.

Evaluation of phenotypes and genotypes of airborne Fungi during middle eastern dust storms.

Microbial species such as bacteria and fungi can be transported by dust storms over long distances, and may change the mycobiota in downwind. This study aimed to evaluate phenotypes and genotypes of airborne fungi during the Middle Eastern dust (MED) events and normal days in Khorramabad, Iran. The samples were collected regularly every six days at three locations during April 2018-March 2019, with additional samplings during MED days. For phenotypic analyses, the Petri dishes were incubated at 25 °C for 72-120 h. Molecular identification of fungi was carried out using polymerase chain reaction (PCR). The average (±SD) of total fungal concentration was 460.9 (±493.2) CFU/m3. The fungi with the highest average concentrations included Cladosporium cladosporioides, Penicillium brevicompactum, and Cladosporium iridis, respectively. The average concentration of fungi during dust days (967.65 CFU/m3) was 3.6 times higher than those in normal days (267.10 CFU/m3). During normal and dust days, 61 and 45 species were detected, respectively. Aspergillus and Cladosporium spp. were relatively more dominant during normal and dust days, respectively. Eight fungal species were only observed during MED days, including Talaromyces albobiverticillius that was detected for the first time in Iran. Despite air temperature, relative humidity and wind speed were associated to the fungal concentrations. Dust events lead to the changes in the air pollutants composition and mycobiota, identification of new fungi, and elevated fungal concentrations that may extremely affect the public health.

Candiduria in Hospitalized Patients and Identification of Isolated Candida Species by Morphological and Molecular Methods in Ilam, Iran.

BACKGROUND: Candiduria in hospitalized patients may represent contamination, colonization, or urinary tract infections. On the other hand, candidemia and upper urinary tract infection could be the complications of candiduria. The aim of this study was to determine candiduria in hospitalized patients and identify isolated Candida species by conventional and molecular methods. METHODS: This cross-sectional study was conducted on hospitalized patients in Imam Khomeini and Mostafa Khomeini hospitals in Ilam, western Iran from Jan to Dec 2016. Urine samples of hospitalized patients were collected during a period of 4 months for diagnosis of candiduria. Primary identification was done by conventional methods. PCR profile was carried out using phenol-chloroform method and confirmed using restriction fragment length polymorphism (PCR-RFLP) technique by MspI restriction enzyme. RESULTS: Candiduria was diagnosed in 18 (9.2%) cases from a total of 195 patients. Isolated yeasts were identified as C. albicans (n: 13), C. glabrata (n: 5), and C. parapsilosis (n: 1) in the one case both C. albicans and C. glabrata were isolated from a urine sample. CONCLUSION: Candida urinary tract infection is becoming increasingly common in hospitalized patients but, differentiation fungal colonization from infection and identification of etiologic agents for optimal treatment is necessary.

Investigation of Intertriginous Mycotic and Pseudomycotic (Erythrasma) Infections and Their Causative Agents with Emphasize on Clinical Presentations.

BACKGROUND: Intertrigo is an erythematous inflammatory condition with multiple etiologies including fungi and bacteria. Intertrigo manifests in different clinical forms with various complaints. This study was conducted to evaluate the causative agents of intertriginous infections with emphasize on clinical presentations. METHODS: This descriptive cross-sectional study was carried out in 2015-2016, on 188 patients with clinical suspicion of superficial and cutaneous intertriginous infections in Tehran, Iran. Demographic and additional related data were obtained by questionnaire from all participants. Specimens were collected by gentle scraping of the affected areas. Direct examination and culture were performed for all specimens and grown colonies were identified based on the macroscopic and microscopic features. Supplementary tests were done whenever needed. Data were analyzed in SPSS. RESULTS: Overall, 80 (42.5%) cases with the mean age of 43.5 yr were confirmed for intertrigo. Dermatophytosis was the predominant cause in this study with 36 (45%) cases followed by erythrasma (28 cases, 35%), tinea versicolor (10 cases, 12.5%) and candidiasis (6 cases, 7.5%). Intertrigo lesions with dermatophytic agents significantly were observed in groin in comparison to different infections among body sites (P<0.05). Itching was the most common clinical presentation (57 cases, 71.3%) and also significant association between different infections and clinical manifestations were observed (P<0.05). CONCLUSION: Different clinical manifestations may be observed in infectious intertrigo. Regarding the significant association observed in this study, some clinical features can be used for presumptive diagnosis of diseases but further studies are required to make it clear.