Multisystem inflammatory syndrome in children (MIS-C) post-COVID-19 in Iran: clinical profile, cardiac features, and outcomes.

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.

COVID-19 associated candidemia: From a shift in fungal epidemiology to a rise in azole drug resistance.

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.

Investigating the Relationship between Carotid Intima-Media Thickness (CIMT), Opium Addiction, and Components of the Metabolic Syndrome.

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.

The relationship between vitamin D and short-term blood pressure variability.

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.

Myopia Progression during the COVID-19 Era: A Systematic Review and Meta-analysis.

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.

Comparison of in vitro activities of newer triazoles and classic antifungal agents against dermatophyte species isolated from Iranian University Hospitals: a multi-central study.

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 MIC90 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.

Streptococcus-related acute suppurative thyroiditis in a COVID-19-positive child: A rare case report.

In this case report, we present a 10-year-old girl with acute suppurative thyroiditis (AST) symptoms, such as fever, sore throat, and swelling in the suprasternal region, who had a positive PCR test for COVID-19. The result of the secretions culture obtained from the abscess drainage was positive for nonhemolytic Streptococcus.

Investigating the relationship between haematological parameters and metabolic syndrome: A population-based study.

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 (×103 /µL), the sensitivity was 70%, the specificity was 52.9% for females, the cut-off value of WBC was 6.3 (×103 /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.

In vitro antifungal susceptibility profile of Iranian Fusarium isolates: Emphasising on the potent inhibitory effect of efinaconazole compared to other drugs.

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.

COMPARISON OF ULTRASOUND-GUIDED ERECTOR SPINAE PLANE BLOCK WITH INTERCOSTAL NERVE BLOCK FOR TRAUMA-ASSOCIATED CHEST WALL PAIN.

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.

The Therapeutic Effects of Nigella sativa on Skin Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

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.

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.

Epidemiology and Antifungal Susceptibility of Candida Species Isolated from 10 Tertiary Care Hospitals in Iran.

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). MIC90 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 MIC90 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.

Hyperuricaemia and its association with other risk factors for cardiovascular diseases: A population-based study.

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.

Update on dermatophytosis in Mashhad, Northeastern Iran, emergence of infection with Trichophyton persicum.

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.

In Vitro Antifungal Susceptibility Profile of Miltefosine against a Collection of Azole and Echinocandins Resistant Fusarium Strains.

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.

Multicenter Study of Susceptibility of Aspergillus Species Isolated from Iranian University Hospitals to Seven Antifungal Agents.

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 MIC90 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 (MEC90) value for caspofungin was 0.125 µg/mL. MIC90 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.

Molecular identification and antifungal susceptibility of clinically relevant and cryptic species of Aspergillus sections Flavi and Nigri.

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 ß-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 MIC50 and MIC90 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.