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.

Eosinophils and chronic obstructive pulmonary diseases (COPD) in hospitalized COVID-19 patients.

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.

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.

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.

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.

In vitro activity of eight antifungal drugs against Chaetomiaceae.

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 ß 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 ß-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.

In vitro activities of 8 antifungal drugs against 126 clinical and environmental Exophiala isolates.

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 MIC90 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.

Molecular Diversity of Aspergilli in Two Iranian Hospitals.

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.

Targeting novel genes for simultaneous detection of five fungal and bacterial agents from BAL samples using multiplex PCR assay.

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.

Antifungal susceptibility, genotyping, resistance mechanism, and clinical profile of Candida tropicalis blood isolates.

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.

Phylogenetic Analysis of Clinically Relevant Fusarium Species in Iran.

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.

Low Level of Antifungal Resistance in Iranian Isolates of Candida glabrata Recovered from Blood Samples in a Multicenter Study from 2015 to 2018 and Potential Prognostic Values of Genotyping and Sequencing of PDR1.

Establishing an effective empirical antifungal therapy requires that national surveillance studies be conducted. Herein, we report the clinical outcome of infections with and the microbiological features of Iranian isolates of Candidaglabrata derived from patients suffering from candidemia. C. glabrata isolates were retrospectively collected from four major cities in Iran; identified by a 21-plex PCR, matrix-assisted laser desorption ionization-time of flight mass spectrometry, and large subunit of ribosomal DNA sequencing; and genotyped by amplified fragment length polymorphism (AFLP). Mutations in PDR1, ERG11, and hot spot 1 (HS1) of FKS1 and FKS2 were investigated, and antifungal susceptibility testing (AFST) was performed (by the CLSI M27-A3 and M27-S4 methods). Seventy isolates of C. glabrata were collected from 65 patients with a median age of 58 years. Fluconazole was the most widely used (29.23%) and least effective antifungal agent. The overall crude mortality rate was 35.4%. Only one strain was resistant to fluconazole, and 57.7% and 37.5% of the isolates were non-wild type (non-WT) for susceptibility to caspofungin and voriconazole, respectively. All isolates showed the WT phenotype for amphotericin B, posaconazole, and itraconazole. HS1 of FKS1 and FKS2 did not harbor any mutations, while numerous missense mutations were observed in PDR1 and ERG11 AFLP clustered our isolates into nine genotypes; among them, genotypes 1 and 2 were significantly associated with a higher mortality rate (P = 0.034 and P = 0.022, α < 0.05). Moreover, 83.3% of patients infected with strains harboring a single new mutation in PDR1, T745A, died despite treatment with fluconazole or caspofungin. Overall, Iranian isolates of C. glabrata were susceptible to the major antifungal drugs. Application of genotyping techniques and sequencing of a specific gene (PDR1) might have prognostic implications.

Comparative pathogenicity of opportunistic black yeasts in Aureobasidium.

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.

Trichophyton mentagrophytes and T interdigitale genotypes are associated with particular geographic areas and clinical manifestations.

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.

Predominance of non-fumigatus Aspergillus species among patients suspected to pulmonary aspergillosis in a tropical and subtropical region of the Middle East.

Non-fumigatus Aspergillus species are the leading cause of Aspergillus infections in the tropical and subtropical regions of the world. In a prospective study between 2015 and 2016, a total of 150 bronchoalveolar (BAL) specimens was collected from patients suspected to pulmonary aspergillosis (PA) underlying immunodeficiencies in Mashhad, Northeastern Iran, located in the Middle East. All Aspergillus strains were phylogenetically identified at the species level by PCR-sequencing of partial ß-tubulin gene. Overall, Aspergillus species were isolated from 20 specimens originating from 10 (50%) patients with cancer, 5 (25%) patients receiving corticosteroid therapy, 3 (15%) organ transplant recipients and 2 (10%) patients admitted to intensive care unit (ICU). A. flavus complex was the predominant 15 (75%) cause of probable invasive pulmonary aspergillosis (IPA), followed by A. tubingensis 3 (15%), and 2 (10%) A. fumigates complex. In conclusion, distribution of clinical Aspergillus species in the tropical region of the Middle East shows predominance of the non-fumigatus Aspergillus spp., which warrants further attention by health care professionals.

The effect of a vaginal suppository formulation of dill (Anethum graveolens) in comparison to clotrimazole vaginal tablet on the treatment of vulvovaginal candidiasis.

The goal of this study was to compare the effect of Anethum graveolens (dill) vaginal suppositories and 100 mg clotrimazole vaginal tablets on vulvovaginal Candidiasis. This study was a single centre, single-blind, randomised, placebo-controlled trial, in which 60 women with microbiology-confirmed vulvovaginal candidiasis were randomly assigned to dill and clotrimazole groups. At the end of the study, the estimated prevalence of leucorrhoea, burning, and itching was 23%, 23% and 20% in dill users, respectively. This figure was 20%, 10% and 16.7% for the clotrimazole group, respectively. The difference between the two groups was not significant. 13% of suppository patients, compared with 10% of clotrimazole-treatment patients, had a positive culture, which was not significant (p = .68). According to findings, 2% dill vaginal suppositories were as effective as clotrimazole vaginal tablets in reducing both clinical and microbiological symptoms of Candidiasis. Studies with larger sample sizes are required to confirm current findings. Impact statement What is already known on the subject? Based on results from in vivo and in vitro animal studies, dill (Anethum graveolens) has anti-candida activity. What do the results of this study add? It appears that 2% dill vaginal suppositories were as effective as 100 mg clotrimazole vaginal tablets in reducing both the clinical and microbiological symptoms. What are the implications of these findings for clinical practice and further research? Obstetricians and gynaecologists can offer dill as a useful alternative to chemical drugs, especially in women who are often interested in herbal medicine, or in women who are resistant or are not allowed to use antifungal drugs.

Antifungal susceptibility testing of Candida species isolated from the immunocompromised patients admitted to ten university hospitals in Iran: comparison of colonizing and infecting isolates.

BACKGROUND: Antifungal susceptibility testing is a subject of interest in the field of medical mycology. The aim of the present study were the distributions and antifungal susceptibility patterns of various Candida species isolated from colonized and infected immunocompromised patients admitted to ten university hospitals in Iran. METHODS: In totally, 846 Candida species were isolated from more than 4000 clinical samples and identified by the API 20 C AUX system. Antifungal susceptibility testing was performed by broth microdilution method according to CLSI. RESULTS: The most frequent Candida species isolated from all patients was Candida albicans (510/846). The epidemiological cutoff value and percentage of wild-type species for amphotericin B and fluconazole in Candida albicans, Candida tropicalis, Candida glabrata and Candida krusei were 0.5 µg/ml (95%) and 4 µg/ml (96%); 1 µg/ml (95%) and 8 µg/ml (95%); 0.5 µg/ml (99%) and 19 µg/ml (98%); and 4 µg/ml (95%) and 64 µg/ml (95%), respectively. The MIC90 and epidemiological cutoff values to posaconazole in Candida krusei were 0.5 µg/ml. There were significant differences between infecting and colonizing isolates of Candida tropicalis in MIC 90 values of amphotericin B, and isolates of Candida glabrata in values of amphotericin B, caspofungin, and voriconazole (P < 0.05). CONCLUSIONS: Our findings suggest that the susceptibility patterns of Candida species (colonizing and infecting isolates) in immunocompromised patients are not the same and acquired resistance was seen in some species.

Morpho-Molecular Characterization of Soil Inhabitant Dermatophytes from Ahvaz, Southwest of Iran, a High Occurrence of Microsporum fulvum.

Occurrence and diversity of dermatophyte mycoflora in 298 soil samples from Ahvaz, Southwest of Iran was investigated by using the hair-baiting technique. The samples were collected during spring (n = 210) and autumn (n = 88) of 2015, and the fungal isolates were identified based on the macro- and micro-morphology of colonies and with further ITS-rDNA RFLP and sequencing. Totally, 60 soil samples (20.1%) were positive for dermatophyte growth whose pH varied from 7.0 to 7.9. The highest (26.6%) and the lowest (14.3%) recovery rates were from the animal resorts and the streets soils samples, respectively. Seasonally, 16.7% of the spring samples and 28.4% of the autumn samples were positive. Based on molecular identification, three species of two genera were identified viz. M. fulvum (n = 57), M. canis (n = 2) and zoophilic Trichophyton interdigitale (n = 1). As a specific goal in the study, differentiation of the species in Microsporum gypseum complex was established by measuring the mean length and width of macroconidia in some strains of M. gypseum, M. fulvum and M. incurvatum. Mean size for macroconidia length and width in three species showed that M. gypseum and M. incurvatum can morphologically be differentiated from M. fulvum but not from each other. M. fulvum was the most abundant species isolated from the soils of Ahvaz; however, to comprehensively specify the distribution pattern of geophilic dermatophytes in the soils of this city further investigations are needed. Identification based on micro-morphometric is not effective for species distinction in M. gypseum complex, while molecular procedures based on sequencing of certain DNA regions are the most reliable and applicable strategies for this purpose.

Acute invasive fungal rhinosinusitis: our experience with 18 cases.

Acute invasive fungal rhinosinusitis (AIFRS) is a rapidly progressive life threatening infection that is seen most commonly among immunocompromised patients. We present a case series of 18 patients clinically and histopathologically diagnosed with AIFRS with a mean follow-up of 9.11 ± 2.51 months (range 6-17). Demographic data, apparent symptoms and signs, underlying disorders, and outcomes are discussed. The mean age was 39.56 ± 20.66 years (range 2-75). The most common underlying diseases were diabetes mellitus (50 %) and leukemia (44.44 %). Mucosal biopsy confirmed fungal invasion of the nasal mucosa in all cases. The main fungi were Rhizopus oryzae (55.56 %), Absidia mucor (16.67 %), and Aspergillus fumigatus (27.78 %). Headache and facial pain (77.8 %), facial paresthesia (55.6 %), and ophthalmoplegia (33.3 %) were the most common symptoms and signs. Computed tomography and endoscopic findings showed various stages of sinonasal (100 %), pterygopalatine fossa (55.56 %), orbital (44.45 %), and cerebral (5.56 %) involvement. All patients underwent serial surgical debridement (3.78 ± 1.80 times; range 2-8) simultaneously with systemic antifungal therapy and proper management of the underlying disease. The most extreme case with brain involvement survived and recovered with no evidence of recurrent disease following treatment. All patients were considered cured after two endoscopic negative histopathologic evaluations. Three patients (16.67 %) died, one from uncontrolled leukemia and two due to renal failure. AIFRS is a potentially fatal condition, however, early diagnosis and management of the underlying disease accompanied with systemic antifungal and aggressive serial surgical intervention appears to be effective in reducing mortality in most patients.