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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Clonal Expansion of Environmental Triazole Resistant Aspergillus fumigatus in Iran.

Azole-resistance in Aspergillus fumigatus is a worldwide medical concern complicating the management of aspergillosis (IA). Herein, we report the clonal spread of environmental triazole resistant A. fumigatus isolates in Iran. In this study, 63 A. fumigatus isolates were collected from 300 compost samples plated on Sabouraud dextrose agar supplemented with itraconazole (ITR) and voriconazole (VOR). Forty-four isolates had the TR34/L98H mutation and three isolates a TR46/Y121F/T289A resistance mechanism, while two isolates harbored a M172V substitution in cyp51A. Fourteen azole resistant isolates had no mutations in cyp51A. We found that 41 out of 44 A. fumigatus strains with the TR34/L98H mutation, isolated from compost in 13 different Iranian cities, shared the same allele across all nine examined microsatellite loci. Clonal expansion of triazole resistant A. fumigatus in this study emphasizes the importance of establishing antifungal resistance surveillance studies to monitor clinical Aspergillus isolates in Iran, as well as screening for azole resistance in environmental A. fumigatus isolates.

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.

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.

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.

Indifferent effect of nonsteroidal anti-inflammatory drugs (NSAIDs) combined with fluconazole against multidrug-resistant Candida auris.

BACKGROUND AND PURPOSE: Emergence and development of antifungal drug resistance in Candida species constitute a serious concern. Candida auris as an emerging multidrug-resistant fungus is the most important public health threat with high levels of mortality and morbidity. Almost all C. auris isolates are resistant to fluconazole, and there have been reports of elevated minimum inhibitory concentrations (MICs) to amphotericin B and echinocandins. To overcome the growing challenge of antifungal resistance, a valuable alternative option would be the use of drug combination. MATERIALS AND METHODS: The present study evaluated the in vitro combination of nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, diclofenac and aspirin with fluconazole against fluconazole-resistant C. auris in comparison to other fluconazole-resistant Candida species, including C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, and C. krusei originating from patients with candidiasis. RESULTS: The MIC ranges of fluconazole-ibuprofen and fluconazole-diclofenac decreased from 32-256 to 32-128 and 16-256 µg/ml, respectively and remained the same for fluconazole-aspirin against C. auris. However, the combination of fluconazole with ibuprofen resulted in a synergistic effect for 5 strains, including C. albicans (n=2), C. tropicalis (n=1), C. glabrata (n=1), and C. krusei (n=1), by decreasing the MIC of fluconazole by 2-3 log2 dilutions. CONCLUSION: Although the interaction of NSAIDs with fluconazole was not synergistic against fluconazole-resistant C. auris isolates, no antagonism was observed for any combinations. Therefore, combination with newer azole agents needs to be conducted.

Candidemia due to Candida guilliermondii in an immuno-compromised infant: a case report and review of literature.

BACKGROUND AND PURPOSE: Candidemia is a life-threatening fungal infection with significant mortality and morbidity in neutropenic individuals, immunosuppressive chemotherapy recipients, and broad-spectrum antibiotics consumers. The epidemiology and antifungal susceptibility testing of non-albicans Candida species have been poorly studied. These species are characterized by low susceptibility to azoles and echinocandins. Herein, we report the first pediatric case of candidemia due to C. guilliermondii in Iran and review the literature on fungemia caused by C. guilliermondii. CASE REPORT: We presented the first candidemia case due to C. guilliermondii in a 4-month-old male infant with neuroblastoma in Iran. This study also involves a comprehensive literature review on fungemia caused by C. guilliermondii during a period of 18 years (i.e., 2000-2018) to discuss the epidemiology, clinical features, and treatment of this disease. The literature review resulted in the identification of 501 cases of candidemia caused by C. guilliermondii. Most of the patients were adults and had multiple risk factors. However, the main risk factors were significantly related to cancer chemotherapy, followed by central venous catheter use and Intensive Care Unit admission. Mortality rate due to this disease had a range of 3.4-66.6%, in this regard, the patients with cancer had the highest mortality rate. CONCLUSION: Given the high mortality of candidemia, the early diagnosis of this infection and timely initiation of antifungal therapy significantly improve the patients' survival rate and result in better outcomes. Consequently, it is highly recommended to monitor the local epidemiology of this life-threatening infection and raise awareness in this regard.

A review on hypersensitivity reactions to fungal aeroallergens in patients with allergic disorders in Iran.

Fungal agents account for the clinical manifestation of allergic disorders. The aim of the present study was to review the prevalence of hypersensitivity reactions to fungal aeroallergens in patients with allergic disorders, including allergic rhinitis, asthma, urticaria, and eczema, in Iran. The initial literature search resulted in the identification of 50 records, 26 cases of which met the inclusion criteria. Regarding the methods adopted for the detection of fungal allergens, serum-specific IgE and skin prick tests were used in 6 and 20 studies, respectively. Aspergillus fumigatus and Alternaria alternata sensitization was the most common allergic sensitization among the patients with allergic disorders. According to the reviewed studies, despite the humid climate of the north of Iran, fungal sensitization has a prevalence range of 5-70% in this region. In other regions, such as central and southern Iran, which have a dry and warm climate, fungal sensitization reportedly has a prevalence range of 5-65%. The prevalence of fungal sensitizations varies in different allergic disorders due to the factors related to geographic and genetic issues, gender, sample size, test operator, and assessment method.