Clinical and mycological implications of cryptococcal meningitis in Iran.

Cryptococcal meningitis (CM) is an uncommon and severe infection that tends to affect both immunocompromised and immunocompetent hosts. To gain insights into the clinical and epidemiological characteristics of CM in Iran, this study evaluated patients with subacute or chronic meningitis referred to 15 Iranian hospitals. Relevant clinical and epidemiological characteristics of the patients were analyzed. Diagnosis of CM cases was performed by microscopic examination, culture, latex agglutination assay, lateral flow assay, and multiplex PCR on cerebrospinal fluid (CSF) samples. The isolates were processed and subjected to molecular identification and in vitro susceptibility antifungal profile. Among the 272 evaluated patients, 7 (2.6 %) CM cases were diagnosed. Out of seven CM cases, 6 (86 %) were male with a median age of 36 years. The most common neurological signs were headache (100 %), followed by nausea and vomiting (71.4 %). All CSF samples from CM patients exhibited positive results across all mycological tests conducted. The isolates were identified as Cryptococcus neoformans (86 %) and Cryptococcus gattii (14 %). All isolates were susceptible to voriconazole and fluconazole, while resistance was observed with itraconazole (MIC value of 0.5 µg/mL) and amphotericin B (MIC values of 4 and 1 µg/mL). The highest mortality (6/7, 86 %) was observed among patients. While a comprehensive study on this subject is currently lacking in Iran, the data acquired through this research play a crucial role in enhancing the clinical and epidemiological understanding of this infection, particularly within low-income countries. Moreover, these findings will serve as a cornerstone for future international comparative studies in this field.

Drug Resistance and Biofilm Formation in Candida Species of Vaginal Origin.

Background: Candida species are normal vaginal flora in healthy women, which can cause vulvovaginal candid-iasis (VVC). The formation of biofilm is a cause of drug resistance in Candida species of vaginal origin. We aimed to specify Candida species cause VVC, detect their biofilm-forming ability, and antifungal susceptibility pattern. Methods: Overall 150 vaginal samples were collected from suspected cases of referring to Bahar Hospital of Shahroud, Iran between Jan 2018 and Jan 2019. Samples were cultured on Sabouraud dextrose agar (SDA), Chrome gar Candida and Corn meal agar (CMA). PCR-RFLP was performed to confirm the identification. Bio-film formation of the identified species was measured by the Crystal Violet method. The susceptibility to fluconazole, clotrimazole, and miconazole was determined based on the CLSI document M27-A3. Results: Of 50 women (33.3%) were suffering from VVC. C.albicans was the predominant species isolated in this study (n=39, 78%) followed by C. glabratia (n=11, 22%). In addition, in 25 (50%) of positive samples, bio-film formation was determined. The mean MIC of fluconazole and clotrimazole for C. albicans was 5.02 µg/mL and 3.92 µg/mL, respectively. Furthermore, the mean MIC related to these drugs for C. glabrata was 12.45 µg / mL and 4.1µg / mL, respectively. The mean diameter of miconazole inhibition zone for C. albicans and C. glabra isolates was 25.13 mm and 24.5mm, respectively and all of them were susceptible to this drug. Conclusion: C.albicans was the predominant Candida species isolated from patients with VVC and also was the predominant biofilm producer species.

Molecular Characterization of Fungal Colonization on the Provox™ Tracheoesophageal Voice Prosthesis in Post Laryngectomy Patients.

BACKGROUND: Tracheoesophageal voice prostheses (TVPs) have been the gold standard in rehabilitation, after laryngectomy, producing faster and premier voicing towards esophageal speech. Fungal colonization shortens the device's lifetime and leads to prosthesis dysfunction, leakage, and subsequent respiratory infection. Therefore, in the current study, we aimed to investigate the fungal colonization patterns and to propose prophylactic measures that shall increase the longevity of voice prosthesis. METHODS: Failed TVPs were removed - due to leakage and/or aspiration - from 66 post laryngectomy patients and examined. They were referred to Amiralam and Rasoul Hospital, the main centers of Ear, Nose, and Throat in Tehran, Iran from April 2018 to January 2020. Fungal colonization patterns were assessed using DNA sequencing techniques. Furthermore, the susceptibility to fluconazole, amphotericin B, nystatin, and white vinegar was evaluated according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. RESULTS: Resident fungal species from the upper airways colonized all the 66 TVPs (100%). Diabetes (31%) and smoking (98%) were the predominant underlying disease and predisposing factors, respectively. Among the 79 fungal agents isolated from the 66 TVPs, Candida glabrata (n=25, 31.7%) was the most common. A significant reduction in minimum inhibitory concentration (MIC) values were observed for white vinegar when used alone (P<0.05). CONCLUSION: White vinegar at a very low concentration could decrease the amount of fungal colonization on TVPs without any adverse effects; its wide accessibility and affordability ensure a decrease in the overall health cost.

First report of chronic invasive fungal rhinosinusitis in a patient with ovarian cancer caused by Didymella pedeiae and successful treatment with voriconazole: A case report.

BACKGROUND AND PURPOSE: Didymella pedeiae is a dematiaceous fungus that belongs to the Coelomycetes class. While species within this class are known to cause human infection,  D. pedeiae had previously only been known as phytopathogens and had never been isolated from a human sample. CASE REPORT: A 51-year-old Iranian female patient with ovarian cancer was admitted with unilateral lesions in paranasal sinuses and a five-month history of nasal obstruction, headache, postnasal drainage, swelling on the left side of the face, and orbital pain. Paranasal sinus computerized tomography scan revealed a soft tissue mass that filled the left nasal cavity, ethmoid, sphenoid, and frontal sinuses with more involvement in the maxillary and ethmoid sinuses. Antifungal treatment was simultaneously initiated with itraconazole+prednisolone 15 mg/day, and levofloxacin. Due to poor clinical response, IV voriconazole and amphotericin B were added to the treatment as well. The patient recovered completely after 10 weeks of therapy. CONCLUSION: Here, we report the first case of human D. pedeiae infection in a patient with ovarian cancer.

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

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

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

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

Molecular characterization of fungi causing colonization and infection in organ transplant recipients: A one-year prospective study.

BACKGROUND AND PURPOSE: Organ transplant recipients are vulnerable to fungal infections. The aim of this study was to determine the prevalence of fungal colonization and infections among patients who underwent various transplantations and molecularly characterize the etiological agents. MATERIALS AND METHODS: This study was conducted on candidates for transplantation in Imam Khomeini Hospital, Tehran, Iran, from April 2017 to April 2018. All patients were monitored for fungal colonization or infections before and after transplantation. Isolated fungi were identified using molecular methods. RESULTS: A total of 125 patients, including 86 males and 39 females, with the mean age of 52.2 years participated in the study (age range: 15-75 years). Out of 125 patients, 84 (67.2%) cases had fungal colonization that appeared pre- and post-transplantation in 21 and 63 cases, respectively (alone or concurrent with another infection in 55 and 29 cases, respectively). In addition, a total of 39 episodes of fungal infections were diagnosed in 36 (28.8%) recipients (alone or concurrent with colonization in 7 and 29 cases, respectively). Out of the 39 fungal infections, 9 cases appeared pre-transplantation, while the other 30 cases occurred post-transplantation. However, no fungal colonization or infection was observed in 34 (27.2%) patients. Oral candidiasis (n=20) was the most common type of infection, followed by funguria (n=7), onychomycosis (n=5), candidemia (n=3), rhinocerebral mucormycosis (n=1), cutaneous mucormycosis (n=1), cutaneous aspergillosis (n=1), and peritonitis (n=1). Six yeast species were recovered from colonization cases with the dominance of Candida albicans both before and after transplantation. The observed fungal infections were caused by 11 distinct species, including the members of Candida (i.e., C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, and C. krusei), Aspergillus (i.e., A. oryzae and A. candidus), Rhizopus (i.e., R. oryzae and R. microsporus), Trichosporon asahii, and Trichophyton interdigitale. The results also indicated that the development of a fungal infection post-transplantation was associated with fungal colonization (r=0.0184; P=0.043). CONCLUSION: Based on the results, fungal colonization was a common finding in transplant recipients at Imam Khomeini Hospital. However, the incidence of fungal infections was comparable with those of other centers. As the oral cavity was the most common site of colonization and infection, it might be beneficial to take further care about the oral health of patients using effective mouthwash.

Recurrent eumycetoma caused by novel species Madurella pseudomycetomatis: A case report.

Mycetoma is a chronic-granulomatous disease characterized by the inflammation, swollen organ, draining sinuses containing blood, pus, and grains. We present a case of madura foot with novel etiologic agent Madurella pseudomycetomatis. Diagnosis was based on morphologic, physiologic, histipathologic and molecular methods. In vitro antifungal susceptibility tests revealed that MIC values for itraconazole, amphotericin B, and posaconazole were 0.0313 µg/ml, 0.0313 µg/ml, and 0.004 µg/ml, respectively. The patient was treated and recovered by itraconazole(400 mg/day) after prolonged course.

Effects of omega-3 polyunsaturated Fatty acids on heart function and oxidative stress biomarkers in pediatric patients with dilated cardiomyopathy.

OBJECTIVES: Dilated cardiomyopathy is the most prevalent type of cardiomyopathy in children, which results in congestive heart failure and causes significant morbidity and mortality. This study, aims to investigate the effect of supplementation with omega-3 polyunsaturated fatty acids (n-3 PUFA) on heart function and oxidative stress biomarkers in these patients. METHODS: The present research was a case-control study on pediatric patients with dilated cardiomyopathy, who received n-3 PUFA and anti-failure therapy for 6 months (group 1, n = 6), or anti-failure therapy alone for 6 months (group 2, n = 6), as well as age matched normal individuals (group 3, n = 6), and evaluated the cardiac function and biomarkers of oxidative stress. RESULTS: Echocardiographic parameters, such as left ventricular ejection fraction, shortening fraction, tissue Doppler Ea and Aa waves of lateral annulus of tricuspid valve, and Ea and S wave of septum, were significantly improved in group 1 after n-3 PUFA compared to pre- treatment status, while they were not changed after treatment in group 2. Antioxidant enzymes, including catalase and glutathione peroxidase activities in erythrocytes were slightly decreased, while plasma 8-iso-prostaglandin F2α concentrations were somewhat increased in group 1 compared to groups 2 and 3, however these changes were not statistically significant. Total antioxidant capacity of plasma was similar in all 3 groups. CONCLUSIONS: The results indicate that some echocardiographic parameters were significantly improved in patients receiving omega-3 fish oil. However, omega-3 had no significant effect on oxidative stress biomarkers.

Alterations in oxidative stress biomarkers associated with mild hyperlipidemia and smoking.

Oxidative stress may increase the risk of atherosclerosis. The association of mild forms of hyperlipidemia, particularly primary hypertriglyceridemia, with oxidative stress has not been fully investigated. The aim of this study was to assess the alterations in oxidative stress biomarkers associated with three major types of mild untreated hyperlipidemia (hypercholesterolemia, hypertriglyceridemia and combined hyperlipidemia) in nonsmoker and smoker individuals. Five biomarkers were measured in 139 adult healthy men (83 nonsmokers and 56 smokers, ages 18-75), which included normolipidemic and hyperlipidemic subjects. Triglyceride levels were associated with a significant main effect on ferric reducing antioxidant power (FRAP) and 8-iso-prostaglandin F2α (iPF2α) levels in plasma (p<0.05 and p<0.005, respectively). Smokers with hypercholesterolemia, hypertriglyceridemia and combined hyperlipidemia had alterations in 1, 3 and 2 oxidative stress biomarkers compared to nonsmoker normolipidemics. Smokers (including normolipidemics and hyperlipidemics) had higher plasma FRAP (120.8 vs. 102.0 µM quercetin/l, p<0.05) and erythrocyte catalase activity (5125 vs. 4093 U/g Hb, p<0.01), while they had lower erythrocyte glutathione peroxidase activity (20.3 vs. 23.0 U/g Hb, p<0.05) compared to nonsmokers. These findings show that mild forms of hyperlipidemia, particularly in smokers, are associated with alterations in some oxidative stress biomarkers.