Five-year surveillance study of clinical and environmental Triazole-Resistant Aspergillus fumigatus isolates in Iran.

BACKGROUND: Invasive aspergillosis is one of the most common fungal infections and azole resistance in Aspergillus fumigatus (ARAf) is a growing medical concern in high-risk patients. To our knowledge, there is no comprehensive epidemiological surveillance study on the prevalence and incidence of ARAf isolates available in Iran. OBJECTIVES: The study aimed to report a five-year survey of triazole phenotypes and genotype patterns concerning the resistance in clinical and environmental A. fumigatus in Iran. METHODS: During the study time frame (2016-2021), a total of 1208 clinical and environmental Aspergillus species were collected. Isolates were examined and characterised by in vitro antifungal susceptibility testing (CLSI M38 broth microdilution) and cyp51A sequencing. RESULTS: In total, 485 Aspergillus section Fumigati strains were recovered (clinical, n = 23; 4.74% and environment, n = 462; 95.26%). Of which A. fumigatus isolates were the most prevalent species (n = 483; 99.59%). Amphotericin B and the echinocandins demonstrated good in vitro activity against the majority of isolates in comparison to triazole. Overall, 16.15% (n = 78) of isolates were phenotypically resistant to at least one of the azoles. However, 9.73% of A. fumigatus isolates for voriconazole were classified as resistant, 89.03% were susceptible, and 1.24% were intermediate. While, for itraconazole and posaconazole, using the epidemiological cut-off value 16.15% and 6.83% of isolates were non-wild types, respectively. Remarkably, in 21.79% (n = 17) phenotypically resistant isolates, no mutations were detected within the cyp51A gene. CONCLUSION: Although the incidence of ARAf varies from country to country, in Iran the rate has ranged from 3.3% to 18%, significantly increasing from 2013 to 2021. Strikingly, a quarter of the phenotypically resistant isolates harboured no mutations in the cyp51A gene. It seems that other mechanisms of resistance are importantly increasing. To fill a gap in our understanding of the mechanism for azole resistance in the non-cyp51A strains, we highly recommend further and more extensive monitoring of the soil with or without exposure to fungicides in agricultural and hospital areas.

Global prevalence and subgroup analyses of coronavirus disease (COVID-19) associated Candida auris infections (CACa): A systematic review and meta-analysis.

BACKGROUND: Increased hospitalisation rates in the Coronavirus disease 19 (COVID-19) era lead to a new wave of hospital-acquired infections such as emerging multidrug-resistant Candida auris. We aimed to evaluate and estimate the global prevalence of coronavirus-associated C. auris infection (CACa). METHODS: We searched related databases between December 2019 and April 2022 for studies that reported data about CACa. Meta-analysis was performed using MedCalc software version 20.104 according to the DerSimonian and Laird method applying the random-effects model. We evaluated heterogeneity using the χ2 -based Q statistic (significant for p-value < .1) and the I2 statistic (>75% indicative of 'notable' heterogeneity). Moreover, if possible, an odds ratio (OR) analysis was performed for eligible data. RESULTS: Our meta-analysis includes ten eligible studies, including 1942 patients hospitalised with COVID-19; 129 were C. auris cases. The overall pooled prevalence of CACa was estimated at 5.7%. The mortality rate of CACa was estimated at 67.849%. Hypertension was the most prevalent comorbidity (59.374%), followed by diabetes mellitus (52.898%) and cardiovascular diseases (31.392%). Men with a prevalence rate of 80.012% were 3.27 (OR) times more prone to getting infected by C. auris. CONCLUSION: We concluded that the prevalence of C. auris infections decreased during the COVID-19 pandemic and the prevalence gradient changed from Asia to America. Unfortunately, there are many descriptive studies with duplicate content in the field of epidemiology of C. auris infections which are increasing every day. We suggest further non-descriptive studies to accurately establish the cause-and-effect relationships between C. auris and COVID-19 infections.

Lack of association between vitamin D insufficiency and clinical outcomes of patients with COVID-19 infection.

BACKGROUND: A protective effect of vitamin D against COVID-19 infection is under investigation. We aimed to analyze the effect of vitamin D sufficiency on the clinical outcomes of patients infected with COVID-19. METHODS: In this cross-sectional study we analyzed the vitamin D levels of COVID-19 patients who were admitted to Razi Hospital (an infectious disease referral center in Mazandaran province in northern Iran) from February to March 2020. Overall, a cutoff point of 30 ng/mL was used for the definition of vitamin D sufficiency. RESULTS: One hundred fifty-three patients were analyzed in this study who had laboratory documentation of a 25(OH) D level at the time of hospitalization. The vitamin D levels of the patients were 27.19 ± 20.17 ng/mL. In total, 62.7% (n = 96) of the patients had a 25(OH) D level of less than 30 ng/mL and 37.25% (n = 57) had a 25(OH) D level of more than 30 ng/mL. In total, 49% (n = 75) of the patients suffered from at least one underlying disease. The univariate and multivariable regression showed that vitamin D sufficiency was not associated with a statistically significant lower risk of adverse clinical outcomes of COVID-19 such as duration of hospitalization and severity of infection (P > 0.05). CONCLUSIONS: Sufficient vitamin D levels were not found to be protective against adverse clinical outcomes in patients infected with COVID-19. Chronic disorders in COVID-19 patients were found to have greater relevance than vitamin D levels in determining the adverse outcomes of the infection. Further studies are needed to determine the role of vitamin D level in predicting the outcomes of COVID-19 infection.

MALDI-TOF MS characterisation, genetic diversity and antifungal susceptibility of Trichosporon species from Iranian clinical samples.

BACKGROUND: Trichosporonosis is an emerging fungal infection caused by Trichosporon species, a genus of yeast-like fungi, which are frequently encountered in human infections ranging from mild cutaneous lesions to fungemia in immunocompromised patients. The incidence of trichosporonosis has increased in recent years, owing to higher numbers of individuals at risk for this infection. Although amphotericin B, posaconazole and isavuconazole are generally effective against Trichosporon species, some isolates may have variable susceptibility to these antifungals. OBJECTIVES: Herein, we evaluated the species distribution, genetic diversity and antifungal susceptibility profiles of Trichosporon isolates in Iran. METHODS: The yeasts were identified by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS). Phylogenetic analysis was performed based on amplified fragment length polymorphism (AFLP). The in vitro susceptibilities of eight antifungal agents were analysed using the Clinical and Laboratory Standards Institute broth microdilution methods. RESULTS: The isolates belonged to the species T asahii (n = 20), T japonicum (n = 4) and T faecale (n = 3). A dendrogram of the AFLP analysis demonstrated that T asahii and non-asahii Trichosporon strains (T japonicum and T faecale) are phylogenetically distinct. While voriconazole was the most active agent (GM MIC = 0.075 µg/ml), high fluconazole MICs (8 µg/ml) were observed for a quarter of Trichosporon isolates. The GM MIC value of amphotericin B for T asahii and non-asahii Trichosporon species was 0.9 µg/ml. CONCLUSIONS: The distribution and antifungal susceptibility patterns of the identified Trichosporon species could inform therapeutic choices for treating these emerging life-threatening fungi.

First azole-resistant Aspergillus fumigatus isolates with the environmental TR46 /Y121F/T289A mutation in Iran.

BACKGROUND: Azole resistance in Aspergillus fumigatus is an emerging problem and reported from all continents. As triazole antifungals are the mainstay of therapy in the management of invasive aspergillosis, azole-resistant A fumigatus has become a major medical concern and with complicated clinical management. OBJECTIVE: Screening of environmental presence of azole-resistant A fumigatus in Iran. METHODS: Compost from Northern Iran, collected between 2017 and 2018, was screened for the presence of azole-resistant A fumigatus with azole-containing agar. Phenotypic MICs were obtained from selected, molecularly confirmed isolates. cyp51A gene sequencing and genotyping of azole-resistant isolates were done. RESULTS: Among 300 compost samples, three A fumigatus isolates had high voriconazole MICs (≥16 mg/L) and harboured the TR46 /Y121F/T289A mutation in the cyp51A gene. Microsatellite typing of these isolates showed that two strains had the same allele across all nine examined microsatellite loci and were genotypically related to Indian azole-resistant strains. The other isolate had a different genotype. CONCLUSION: This is the first report of A fumigatus with TR46 /Y121F/T289A mutation from the region. Monitoring and surveillance of antifungal susceptibility of clinical A fumigatus is warranted in Iran and elsewhere in the region.

Epidemiological features of nosocomial candidaemia in neonates, infants and children: A multicentre study in Iran.

Nosocomial bloodstream candidaemia is a life-threatening fungal infection with high morbidity and mortality, especially among paediatric patients undergoing intensive immunosuppressive therapy. Limited data on the epidemiology of candidaemia and susceptibility profiles are available for Iran. To characterise candidaemia epidemiology, comorbidity risk factors, species distribution, and antifungal susceptibility profiles among paediatric patients in Iran. This observational cross-sectional study enrolled 26 189 patients <18 years old at three reference paediatric hospitals in Mazandaran and Tehran over 2 years. Blood samples from patients with suspected fungal bloodstream infection were analysed using the BACTEC culture system. Fungal isolates were identified using matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF) and DNA sequencing. Antifungal susceptibility testing was performed using the Clinical and Laboratory Standards Institute broth microdilution guideline. We observed 109 episodes of nosocomial candidaemia in paediatric patients with or without immunosuppressive therapy. The most common healthcare-associated factor was central vascular catheter use (97%). The all-cause mortality rate was 40%, of which 48% was attributable to candidaemia. While Candida albicans was the most frequent causative agent (49%), emerging and uncommon Candida species were also isolated. Candidaemia mortality by non-albicans Candida species was significantly higher than that by C. albicans (P < .05). All fluconazole-resistant species were non-albicans Candida species. Uncommon Candida species with reduced susceptibility to antifungals are emerging as major agents of nosocomial candidaemia in high-risk paediatric patients in Iran. Appropriate source control, antifungal regimens and improved antifungal stewardship are warranted for managing and decreasing the burden of nosocomial candidaemia.

Antifungal Activity of a Novel Triazole, Efinaconazole and Nine Comparators against 354 Molecularly Identified Aspergillus Isolates.

Management of superficial aspergillosis is a major challenge owing to the frequent relapses and treatment failure, which may pose a potential risk, thereby gradually developing resistant species. Therefore, necessitating the development of new antifungals with higher potency should be considered as alternative strategies for efficient management of infections. We aimed to investigate the susceptibility of Aspergillus isolates toward a novel triazole, efinaconazole, in comparison with various classes of antifungal drugs. Antifungal susceptibility testing was performed according to the Clinical and Laboratory Standards Institute M38-A2 guidelines. Efinaconazole exhibited poor activity against mutant A. fumigatus strains, A. niger sensu stricto, and A. tubingensis with GM MIC values of 3.62, 1.62, and 2 µg/ml, respectively; however, surprisingly, it efficiently inhibited the growth of A. terreus sensu stricto, followed by wild-type A. fumigatus and A. flavus with GM MIC values of 0.29, 0.42, and 0.52 µg/ml, respectively. Presumably, efinaconazole is inefficient in aspergillosis treatment due to the low susceptibility of A. niger sensu stricto, A. tubingensis, and mutant A. fumigatus; however, it may be effective in treating superficial aspergillosis caused by wild-type A. fumigatus, A. terreus sensu stricto, and A. flavus. Further studies are needed to determine how these findings may translate into in vivo efficacy.

Airway colonisation by Candida and Aspergillus species in Iranian cystic fibrosis patients.

Cystic fibrosis (CF) is associated with increased rates of morbidity and mortality due to fungal and bacterial colonisation of the airways or respiratory infections. The prevalence of fungi in Iranian CF population has been underestimated. Therefore, the current study was conducted to define the frequency of fungi in respiratory specimens obtained from Iranian CF patients based on conventional and molecular assays. Furthermore, in vitro antifungal susceptibility testing was performed on the obtained isolates according to the guidelines from the Clinical and Laboratory Standards Institute. A cohort of 42 CF patients, including 29 males and 13 females, were categorised according to the referenced diagnostic criteria. Candida albicans (n = 24, 80%), C. dubliniensis (n = 2, 6.6%), C. parapsilosis (n = 2, 6.6%), C. tropicalis (n = 1, 3.3%), C. glabrata (n = 1, 3.3%) and Meyerozyma caribbica (n = 1, 3.3%) were isolated from 73.8% of the CF patients. Aspergillus terreus (n = 3, 42.8%) was identified as the most common Aspergillus species, followed by A. fumigatus (n = 2, 28.5%), A. oryzae (n = 1, 14.2%) and A. flavus (n = 1, 14.2%). Bacterial and fungal co-colonisation was detected in 7 (16.6%) and 22 (52.3%) samples that were positive for Aspergillus and Candida species, respectively. However, Scedosporium species and Exophiala dermatitidis never were detected. In terms of geometric mean (GM) minimum inhibitory concentrations (MICs), posaconazole (0.018 µg/mL) and caspofungin (0.083 µg/mL) exhibited the highest antifungal activities against all Candida species. In addition, posaconazole exhibited the lowest MIC range (0.008-0.063 µg/mL) against all Aspergillus species, followed by caspofungin (0.016-0.125 µg/mL) and voriconazole (0.125-0.25 µg/mL). To conclude, it is essential to adopt a consistent method for the implementation of primary diagnosis and determination of treatment regimen for the CF patients. However, further studies are still needed to better define the epidemiology of fungal organisms in CF patients from the Middle East and the clinical significance of their isolation.

Candida auris otomycosis in Iran and review of recent literature.

Candida auris is a multidrug-resistant yeast emerging in immunocompromised and in otherwise healthy individuals. Due to difficulties in microbiological identification of C. auris because of the lack of available laboratory technology in developing countries, the number of patients affected is most likely underestimated. We report the first case of C. auris otitis which now adds Iran as the fifth country around the Persian Gulf, in addition to Kuwait, Oman, United Arab Emirates and Saudi Arabia. Candida auris is an unknown pathogen in routine laboratories in Iran because most Candida isolates are probably misdiagnosed. Otomycosis seems to be a different clinical presentation of C. auris mainly involving isolates from the East-Asian clade. We compared the mycological and clinical details of the Iranian patient with other cases of otitis reported since the last review of C. auris otomycosis in 2017.

Candida infanticola and Candida spencermartinsiae yeasts: Possible emerging species in cancer patients.

Opportunistic infections due to Candida species occur frequently in intensive care settings. We investigated the prevalence of Candida species among 65 clinical specimens obtained from 200 cancer patients by phenotypic and molecular (ITS sequencing and AFLP) methods. Among the 65 yeast isolates, Candida albicans was the most commonly isolated species (n = 34, 52.3%), whereas other Candida species comprised 47.7% (n = 31) and consisted of Candida glabrata (n = 14, 21.5%), Candida tropicalis (n = 5, 7.7%) and uncommon Candida species (n = 12, 18.5%) such as Candida pelliculosa (n = 3, 4.6%), Pichia kudriavzevii (= Candida krusei, n = 2, 3.1%), Candida orthopsilosis (n = 2, 3.1%), Candida parapsilosis (n = 1, 1.5%), Candida infanticola (n = 2, 3.1%), Candida spencermartinsiae (n = 1, 1.5%), and Kluyveromyces marxianus (=Candida kefyr, n = 1, 1.5%). Candida infanticola and Candida spencermartinsiae were recovered from oral lesions of cancer patients. Matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) easily confirmed these isolates as less common Candida isolates (4.6%). The in vitro antifungal susceptibilities of C. spencermartinsiae and the two strains of C. infanticola were determined according to CLSI guidelines (M27-A3). MIC results among these isolates showed they were susceptible to isavuconazole, posaconazole and voriconazole, however, fluconazole and caspofungin had high MIC values. These Candida species that may occur more commonly in infections remain unnoticed using commonly used phenotypical methods in routine microbiology laboratories. MALDI-TOF MS proved to be a more fast and robust diagnostic technique for identification of the yeasts isolated from different clinical specimens of cancer patients.

Common malignant cutaneous conditions among albinos in Kenya.

Background: Albinos in Africa are at constant risk of developing skin cancer due to the damage caused by ultra-violet exposure. This study identifies the common skin conditions among albinos in Kenya as a country located along the equator. Methods: In this descriptive study on albino patients who were admitted to Mbagathi District Hospital in Nairobi, Kenya the census method was used for sampling and a total of 151 albinos were registered. All necessary data including age, gender, type, site and the number of skin lesions were recorded. Suspected patients with malignant and premalignant lesions were studied individually through skin biopsy and histopathological investigation. Finally, the collected data were analyzed using SPSS software. Results: Albinos with serious skin lesions were 121(80%) patients. Females were 64 (52.9%). The frequency of the following premalignant and malignant skin lesions including actinic-cheilitis, solar elastosis, actinic keratosis (AK), basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) were 17.88%, 11.92%, 37.08%, 7.94% and 5.29%, respectively. Hands (20.52%), face (19.20%), head (18.18%), shoulder (14.56%) and neck (7.94%) were the most affected areas by malignant and premalignant lesions. Conclusions: BCC was the most common type of cutaneous malignancy on the face and shoulders while AK was the most common cutaneous pre-malignancy on the hands and face in albinos in Kenya. Therefore, appropriate physical protection, avoiding any trauma when carrying sharp, heavy or rough instruments by the shoulder and hands, and finally urgent and quality treatment for any lesion even a small erosion and ulcer, especially on exposed areas in albinos, are recommended.

Clinical and laboratory manifestation and outcome of icterohemorrhagic leptospirosis patients in Northern Iran.

BACKGROUND: Icterohemorrhagic form of leptospirosis has a high mortality rate. In this study, the clinical manifestations, epidemiologic and laboratory findings and outcome of Weil's disease were investigated. METHODS: A descriptive cross- sectional study was conducted on 66 consecutive patients with icterohemorrhagic leptospirosis who were admitted to Razi Hospital (The Therapeutic Center of Infectious Diseases in the North of Iran) in 2013. The inclusion criteria were as follows: All patients who had clinical and epidemiological data suggestive of leptospirosis and displayed icterohemorrhagic form at the time of admission or during hospitalization. All patients were visited on admission, one, two and six weeks later. Demographic data, clinical, laboratory features and complications were evaluated, and statistical analysis was performed using SPSS version 13.0. RESULTS: Among 66 patients, 89.4% (n = 59) were male, 60% (n = 40) were farmers and 9.1% (n= 6) had a history of swimming in rivers. The most common complaints were fever and jaundice, respectively. The most common clinical symptoms were fever (90.9%), myalgia (75.8%), chills (70.8%) and headache (65.1%). Hyponatremia and hypernatremia were seen in 7.6% and 72.8% of the participants, respectively. Also, hypokalemia was observed in two patients (3%). Approximately, half of the cases had leukocytosis and 90% had thrombocytopenia. Rise of AST, ALT, ALP and bilirubin were seen in 95.2%, 93.6%, 76.2% and 100% of the patients, respectively. Of the patients, 42.4% experienced complications of icterohemorrhagic leptospirosis including acute renal failure (30.3%) pneumonia (25.8%), pancreatitis (4.5%), subarachnoid hemorrhage (1.5%) and gastrointestinal bleeding (1.5%). Three cases (4.5%) died, 42 cases (63.7%) were discharged with residual effects and 52 patients (78.8%) had positive serology. CONCLUSION: The most significant biochemical abnormalities were thrombocytopenia, hyperbilirubinemia, hyponatremia and hypernatremia and azotemia and the latter remained stable in 2% of the patients at least until the end of the 6-week period.

In-vivo efficiency of the novel azole compounds (ATTAF-1 and ATTAF-2) against systemic candidiasis in a murine model.

BACKGROUND: Antifungal resistance is the main health concern in the control of invasive fungal infections. This research was designed to further assess the antifungal activity of aryl-1,2,4-triazole-3-ylthio analogs of fluconazole (ATTAFs) against Candida albicans systemic candidiasis in the murine model. MATERIALS & METHODS: The murine model of systemic candidiasis was designed via the inoculation of 1 × 106 CFU of Candida albicans. The treatment dosages of 3.5 and 35 mg/kg per day were selected for ATTAFs and fluconazole, respectively. The median survival time (MST) was assayed for 30 days post-infection. The quantitative and qualitative (via histopathology staining) fungal burden was also assessed. Furthermore, immunohistochemistry and biochemistry assays were performed to monitor anti-inflammatory activity using the Cyclooxygenase-2 (Cox-2) marker and changes in serum protein levels. RESULTS: ATTAFs considerably improved the survival of the murine model (P < 0.003). Compared with fluconazole, the antifungal activity of ATTAFs and their MST showed no difference (P > 0.05). However, these compounds decreased the fungal burden in the kidneys, spleen, and liver. CONCLUSION: Our research indicates that ATTAF-1 and ATTAF-2 are effective therapeutic agents due to their fungal clearing and increasing the MST in the murine model of systemic candidiasis. Although we concluded that these components are novel and promising candidates for the management of invasive candidiasis, further studies are warranted to correlate these findings with clinical outcomes.

The effect of ACE inhibitors and ARBs on outcomes in hospitalized patients with COVID-19.

BACKGROUND: Contradictory opinions exist regarding the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in patients with hypertension, which is the most common comorbidity associated with COVID-19. Herein, the effects of ACEIs and ARBs on outcomes of COVID-19 patients were evaluated. METHODS: In this cross-sectional study, the outcomes of COVID-19 patients were compared between patients who received pretreatment ACEIs or ARBs and those who did not. RESULTS: The incidence of moderate and severe forms of COVID-19 was significantly higher in patients taking ACEI/ARB drugs (P-value = 0.012). Also, patients taking ACEI/ARB drugs (P-value = 0.034), patients with hypertension (P-value = 0.011), and patients with dyslipidemia (P-value = 0.011) experienced more severe forms of COVID-19. There was an association between increased length of hospital stay and dyslipidemia (P-value = 0.033) and the use of ACEI/ARB drugs (P-value = 0.041), while no correlation was found between other parameters in univariate linear regression analysis as well as multivariate linear regression. There was an association between increased mortality of patients with increasing age (P-value < 0.001), BMI greater than 30 kg/m2 (P-value = 0.02), asthma (P-value = 0.003), and dyslipidemia (P-value = 0.045). CONCLUSIONS: ACEI/ARB drugs put COVID-19 patients at high risk for moderate to severe forms of COVID-19 and higher length of hospital stay. Although, it is notable that these drugs did not significantly affect specific adverse outcomes of COVID-19, such as the need for admission to the intensive care unit (ICU), length of ICU stay, ventilation, and mortality.

In vitro interactions of nystatin and micafungin combined with chlorhexidine against Candida albicans isolates.

Background and Purpose: Oral candidiasis has become a growing problem in hospitals worldwide, and the development of antifungal drug resistance in Candida species constitutes a serious concern. This study aimed to evaluate the in vitro efficacy of nystatin, and micafungin with chlorhexidine against fluconazole-resistant and fluconazole-sensitive Candida albicans (C. albicans) isolates. Materials and Methods: In this experimental-laboratory study, a total of 20 fluconazole-resistant (n=10) and fluconazole-susceptible (n=10) C. albicans strains were obtained from the reference culture collection of the Invasive Fungi Research Center in Mazandaran University of Medical Sciences, Sari, Iran. In vitro combination of nystatin and micafungin with chlorhexidine was performed using a microdilution checkerboard method based on the Clinical and Laboratory Standards Institute guideline. Results: Micafungin had the highest antifungal activity against C. albicans susceptible and resistant strains, with a Geometric mean of (GM) =0.008µg/ml and GM=0.008µg/ml, followed by nystatin with GM=0.06µg/ml and GM=0.042µg/ml and chlorhexidine with GM=0.25µg/ml and GM=0.165µg/ml against C. albicans resistant and sensitive strains, respectively. The interaction of micafungin and nystatin with chlorhexidine showed a synergistic interaction against most C. albicans strains. In addition, no antagonistic interaction was observed between micafungin, nystatin, and chlorhexidine against C. albicans strains. Conclusion: The synergistic interaction of micafungin with chlorhexidine against azole-resistant C. albicans suggests an alternative approach to overcome antifungal drug resistance. However, further studies are needed for in vivo evaluation.

Mucormycosis, one month after recovery from COVID-19: A case report.

Introduction: and importance: There are increasing case reports of mucormycosis in patient with coronavirus disease 2019 (Covid-19). Herein, we describe the case of mucormycosis after recovery from Covid-19. Case presentation: The patient was a 73 years old woman with a history of chronic kidney disease, diabetes mellitus, hypertension, and dyslipidemia that referred to the emergency department with clinical presentation of Covid-19. On the third day of admission, the Covid-19 PCR test was negative, but the patient presented headache and pain in her upper jaw. Physical examination showed fever, erythema, and tenderness in the right cheek. Emergency biopsy and culture from sinus by subsection to mucormycosis conducted. and the diagnosis of mucormycosis was confirmed by the positive result of biopsy and culture. Despite anti-fungal treatment with Amphotericin B, patient developed severe diarrhea and became hemodynamically unstable. In the stool analysis, Strongyloides stercoralis was reported. Unfortunately, patient was expired on day thirty-two of this admission. Clinical discussion: Mucormycosis is a dangerous infection, and its rapid diagnosis is so important. On the other hand, Covid-19 may associated with many nonspecific sign and symptoms. These finding may overlap with other infections.In patients with prolonged mucormycosis infection, the development of strongyloidiasis should not be neglected. A single dose of ivermectin as strongyloidiasis prophylaxis should be given if the duration of the illness is prolonged. Conclusion: Clinicians should consider mucormycosis and its complications after Covid-19 treatment in diabetic and immunocompromised patients.

Multiple Candida strains causing oral infection in COVID-19 patients under corticosteroids and antibiotic therapy: An observational study.

Introduction: The occurrence of oral candidiasis (OC) is expected in patients with COVID-19, especially those with moderate to severe forms of infection who are hospitalized and may be on long-term use of broad-spectrum antibiotics or prolonged corticosteroid therapy. We aimed to characterize clinical conditions, the prevalence profile of Candida species, and outcomes of COVID-19 patients with OC. Methods: In this observational study, oral samples were obtained from COVID-19 patients suspected of OC admitted to Razi teaching hospital. Patients with OC were monitored daily until discharge from the hospital. Species identification was performed by a two-step multiplex assay named YEAST PLEX, which identifies 17 clinically important uncommon to common yeast strains. Results: Among the 4133 patients admitted with COVID-19, 120 (2.90%) suffered from OC. The onset of signs and symptoms of OC in patients was, on average (2.92 ± 3.596 days) with a range (of 1-29 days). The most common OC presentation was white or yellow macules on the buccal surface or the tongue. In (39.16%) of patients suffering from OC multiple Candida strains (with two or more Candida spp.) were identified. The most common Candida species were C. albicans (60.57%), followed by C. glabrata (17.14%), C. tropicalis (11.42%), C. kefyr (10.83%) and C. krusei (3.42%). Notably, OC caused by multiple Candida strains was more predominant in patients under corticosteroid therapy (P <0.0001), broad-spectrum antibiotics therapy (P = 0.028), and those who used nasal corticosteroid spray (P <0.0001). The majority of patients who recovered from OC at the time of discharge were patients with OC by single Candida species (P = 0.049). Discussion: Use of corticosteroids and antimicrobial therapy in COVID-19 patients increases risk of OC by multiple Candida strains.

Non-effectiveness of Ivermectin on Inpatients and Outpatients With COVID-19; Results of Two Randomized, Double-Blinded, Placebo-Controlled Clinical Trials.

Background: Ivermectin which was widely considered as a potential treatment for COVID-19, showed uncertain clinical benefit in many clinical trials. Performing large-scale clinical trials to evaluate the effectiveness of this drug in the midst of the pandemic, while difficult, has been urgently needed. Methods: We performed two large multicenter randomized, double-blind, placebo-controlled clinical trials evaluating the effectiveness of ivermectin in treating inpatients and outpatients with COVID-19 infection. The intervention group received ivermectin, 0.4mg/kg of body weight per day for 3 days. In the control group, placebo tablets were used for 3 days. Results: Data for 609 inpatients and 549 outpatients were analyzed. In hospitalized patients, complete recovery was significantly higher in the ivermectin group (37%) compared to placebo group (28%; RR, 1.32 [95% CI, 1.04-1.66]; p-value = 0.02). On the other hand, the length of hospital stay was significantly longer in the ivermectin group with a mean of 7.98 ± 4.4 days compared to the placebo receiving group with a mean of 7.16 ± 3.2 days (RR, 0.80 [95% CI, 0.15-1.45]; p-value = 0.02). In outpatients, the mean duration of fever was significantly shorter (2.02 ± 0.11 days) in the ivermectin group versus (2.41 ± 0.13 days) placebo group with p value = 0.020. On the day seventh of treatment, fever (p-value = 0.040), cough (p-value = 0.019), and weakness (p-value = 0.002) were significantly higher in the placebo group compared to the ivermectin group. Among all outpatients, 7% in ivermectin group and 5% in placebo group needed to be hospitalized (RR, 1.36 [95% CI, 0.65-2.84]; p-value = 0.41). Also, the result of RT-PCR on day five after treatment was negative for 26% of patients in the ivermectin group versus 32% in the placebo group (RR, 0.81 [95% CI, 0.60-1.09]; p-value = 0.16). Conclusion: Our data showed, ivermectin, compared with placebo, did not have a significant potential effect on clinical improvement, reduced admission in ICU, need for invasive ventilation, and death in hospitalized patients; likewise, no evidence was found to support the prescription of ivermectin on recovery, reduced hospitalization and increased negative RT-PCR assay for SARS-CoV-2 5 days after treatment in outpatients. Our findings do not support the use of ivermectin to treat mild to severe forms of COVID-19. Clinical Trial Registration: www.irct.ir IRCT20111224008507N5 and IRCT20111224008507N4.

Side effects and Immunogenicity following administration of the Sputnik V COVID-19 vaccine in health care workers in Iran.

The Sputnik V is a COVID- 19 vaccine developed by the Gamalia institute of epidemiology and microbiology and released on August 11, 2020. We provided independent evidence on side effects and immunogenicity following the administration of the Sputnik V COVID-19 in Iran. In this observational study, the healthcare workers who were vaccinated with the Sputnik V COVID-19 vaccine within February and April 2021 were evaluated. Among a total of 13,435 vaccinated healthcare workers, we received 3236 self-declaration reports of Sputnik V associated adverse events with the mean age 39.32 ± 10.19 years old which 38.8% were men and 61.2% were women. Totally 68.8% of females versus 66.2% of males reported side effects after receiving the first dose and 31.2% of females versus 33.8% of males reported side effects after the second dose of vaccine. The most common side effect was a pain in the injection site (56.9%), fatigue (50.9%), body pain (43.9%), headache (35.7%), fever (32.9%), joint pain (30.3%), chilling (29.8%) and drowsiness (20.3%). Side effects of the vaccine were significantly more frequent in females and younger individuals. Among a total of 238 participants, more than 90% after the first and second dose of vaccine had a detectable level of SARS-CoV-2 RBD antibody and SARS-CoV-2 neutralizing antibody. Although the overall rate of adverse effects was higher than the interim results from randomized controlled trials, our findings support the manufacturer's reports about the high humoral immunogenicity of vaccine against COVID-19.

Clinical features and para-clinical findings of cryptococcal meningitis in the North of Iran during 2011-19.

BACKGROUND AND PURPOSE: Cryptococcal meningitis (CM) is a serious fungal infection that especially affects patients with human immunodeficiency virus (HIV). In this regard, the present retrospective study aimed to analyze the clinical and laboratory features and therapeutic outcomes of patients with CM admitted to two teaching referral centers in the north of Iran during 2011-19. MATERIALS AND METHODS: This study was performed on all the hospitalized patients diagnosed with CM in two therapeutic centers of infectious diseases in the north of Iran. The required data, such as demographic characteristics and clinical and paraclinical features of patients, were extracted and entered in the information forms. Finally, the collected data were analyzed in SPSS software (version 16). RESULTS: For the purpose of the study, records of 12 confirmed CM patients were evaluated in this research. Based on the results, 75% of the patients were male. Moreover, the average age of the subjects was 40.33± 8.93 years old and 66.6% of them (n=8) were HIV-positive. Other underlying diseases among HIV-positive patients included infection with hepatitis C virus (25%) and a history of tuberculosis (25%). In total, three HIV-negative patients suffered from Hodgkin lymphoma (25%), sarcoidosis (25%), and asthma (25%) and one patient (25%) had no underlying disease. Headache (75%), weakness, and fatigue (75%) were the most common symptoms among the participants. The cluster of differentiation 4 (CD4) count in all HIV-positive patients was less than 100 cells/µl. There was no significant difference between symptoms in HIV-positive and HIV-negative patients. Besides, no significant difference was observed between the groups of HIV-positive and HIV-negative patients regarding the period between the onset of symptoms and diagnosis of CM, the length of hospital stay, and the duration of antifungal medication consumption. In total, three patients (25%) expired, and six patients recovered. The CM recurred in two HIV-negative and one HIV-positive subjects; the two HIV-negative patients were treated, while the HIV-positive patient expired due to this recurrence. CONCLUSION: Clinical features and cerebrospinal fluid parameters were not different in HIV-positive and HIV-negative participants. Despite the fact that CM is not common in Iran, due to the increasing number of immunosuppressive patients, the differential diagnosis of CM should be considered for patients with signs and symptoms of infection in the central nervous system.