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.

COVID-19 Associated Rhino-Orbital-Cerebral Mucormycosis: Clinical Features, Antifungal Susceptibility, Management and Outcome in a Tertiary Hospital in Iran.

BACKGROUND: Despite the unprecedented surge in the incidence of mucormycosis in the COVID-19 era, the antifungal susceptibility patterns (ASPs) of COVID-19 associated mucormycosis (CAM) isolates have not been investigated so far and it is unclear if the high mortality rate associated with CAM is driven by decreased susceptibility of Mucorales to antifungal drugs. OBJECTIVES: To describe the clinical, mycological, outcome and in vitro ASPs of CAM cases and their etiologies from Iran. PATIENTS/METHODS: A prospective study from January 2020 to January 2022 at a referral tertiary hospital in Tehran, Iran was conducted for screening mucormycosis through histopathology and mycological methods. The identity of Mucorales isolates was revealed with ITS-panfungal PCR& sequencing and MALDI-TOF. The AS for amphotericin B, itraconazole, isavuconazole and posaconazole was cleared according to the EUCAST antifungal susceptibility testing protocol. RESULT: A total of 150 individuals were diagnosed with CAM. Males constituted 60.7% of the population. The mean age was 54.9 years. Diabetes was the leading risk factor (74.7%). The median interval between diagnosis of COVID-19 and CAM was 31 days. The recovery rate of culture was as low as 41.3% with Rhizopus arrhizus being identified as the dominant (60; 96.7%) agent. Amphotericin B (MIC50 = 0.5 µg/ml) demonstrated the highest potency against Mucorales. CONCLUSION: Majority of the cases had either diabetes, history of corticosteroid therapy or simultaneously both conditions. Accordingly, close monitoring of blood glucose should be considered. The indications for corticosteroids therapy are recommended to be optimized. Also, an anti Mucorales prophylaxis may be necessitated to be administrated in high risk individuals. Although amphotericin B was the most active agent, a higher rate of resistance to this antifungal was noted here in comparison with earlier studies on mucormycetes from non-CAM cases.

In vitro combination of antifungal drugs with tacrolimus (FK506) holds promise against clinical Candida species, including Candida auris.

In vitro interactions between tacrolimus, a calcineurin inhibitor, and fluconazole, itraconazole, caspofungin, or anidulafungin were evaluated against Candida auris, C. albicans, C. parapsilosis, and C. glabrata (each five strains). Tacrolimus-itraconazole, tacrolimus-caspofungin, and tacrolimus-fluconazole combinations resulted in synergistic interactions against 95%, 90%, and 60% of Candida isolates, respectively. However, tacrolimus-anidulafungin resulted in only a 35% synergistic effect. A combination of tacrolimus and itraconazole was most potent with synergy against 100% of C. auris, C. parapsilosis, and C. glabrata isolates. Of note, no antagonistic interaction was found.

Corrigendum to "Pneumocystis pneumonia in COVID-19 patients: A comprehensive review" [Heliyon 9(2) (February 2023) e13618].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e13618.].

Fungal keratitis in Iran: Risk factors, clinical features, and mycological profile.

Introduction: This study was intended to investigate the clinical features and predisposing factors of fungal keratitis (FK), as well as molecular identification and antifungal susceptibility of causative agents in Tehran, Iran. Methods: This cross-sectional study was carried out from April 2019 to May 2021. All fungi isolates were identified using conventional methods and were confirmed by DNA-PCR-based molecular assays. Matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) was used to identify yeast species. Minimum inhibitory concentrations (MIC) of eight antifungal agents were assessed according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) microbroth dilution reference method. Results: Fungal etiology was confirmed in 86 (7.23%) of 1189 corneal ulcers. A significant predisposing factor for FK was ocular trauma caused by plant materials. Therapeutic penetrating keratoplasty (PKP) was required in 60.4% of cases. The predominant fungal species isolated was Fusarium spp. (39.5%) followed by Aspergillus spp. (32.5%) and Candida spp. (16.2%). Discussion: The MIC results indicate that amphotericin B may be appropriate for treating FK caused by Fusarium species. FK caused by Candida spp. can be treated with flucytosine, voriconazole, posaconazole, miconazole, and caspofungin. In developing countries such as Iran, corneal infection due to filamentous fungi is a common cause of corneal damage. In this region, fungal keratitis is observed primarily within the context of agricultural activity and subsequent ocular trauma. Fungal keratitis can be managed better with understanding the "local" etiologies and antifungal susceptibility patterns.

Pneumocystis pneumonia in COVID-19 patients: A comprehensive review.

The admitted patients of intensive care units with coronavirus disease 2019 (COVID-19) meet the challenges of subsequent infections. Opportunistic fungal infections such as Pneumocystis pneumonia (PCP) are among the important factors in the context of COVID-19 patients affecting illness severity and mortality. We reviewed the literature on COVID-19 patients with PCP to identify features of this infection. Although studies confirmed at least the presence of one immunosuppressive condition in half of PCP patients, this disease can also occur in immunocompetent patients who developed the immunosuppressive condition during Covid-19 treatment. The major risk factors associated with COVID-19 patients with PCP can be considered low lymphocyte counts and corticosteroid therapy. Diagnostic and treatment options are complicated by the overlapping clinical and radiologic characteristics of PCP and COVID-19 pneumonia. Therefore, physicians should comprehensively evaluate high-risk patients for PCP prophylaxis.

Clinical, epidemiological, and mycological features of patients with candidemia: Experience in two tertiary referral centers in Iran.

Background and Purpose: Candidemia is a major cause of morbidity and mortality among patients receiving immunosuppressive therapy and those hospitalized with serious underlying diseases. Here, we investigated the epidemiological, clinical, and mycological features of candidemia in Tehran, Iran. Materials and Methods: A prospective observational study of all patients diagnosed with candidemia was performed at two referral teaching hospitals in Tehran, Iran, from February to December 2018. Demographic characteristics, underlying diseases, risk factors, clinical symptoms, and laboratory analyses of candidemic patients with positive culture were mined. Candida isolates were molecularly identified by sequencing of the internal transcribed spacer region (ITS1-5.8S-ITS2). The antifungal susceptibility testing for fluconazole, itraconazole, voriconazole, posaconazole, amphotericin B, caspofungin, micafungin, and anidulafungin against the isolates was performed using CLSI broth microdilution reference method (M27-A3). Results: A total of 89 episodes were identified, with an incidence of 2.1 episodes/1000 admissions. The common underling disease were malignancy (46%), renal failure/dialysis (44%), and hypertension (40%). The overall crude mortality was 47%. C. albicans (44%) was the most frequent causative agent, followed by C. glabrata (21%), C. parapsilosis complex (15%), C. tropicalis (11%), and C. lusitaniae (3.5%). All the isolates were susceptible to amphotericin B. The activity of all four azoles was low against non-albicans Candida species, especially C. tropicalis. Conclusion: The increase in non-albicans Candida species with reduced susceptibility to antifungal drugs might be alarming in high-risk patients. Therefore, accurate knowledge of predisposing factors and epidemiological patterns in candidemia are effective steps for managing and decreasing the mortality rate in candidemia.

Proven pulmonary aspergillosis in a COVID-19 patient: A case report.

BACKGROUND AND PURPOSE: Coronavirus disease 2019 (COVID-19) has become a significant clinical challenge in healthcare settings all over the world. Critically ill COVID-19 patients with acute respiratory distress syndrome may be at increased risk of co-infection with pulmonary aspergillosis. This study aimed to describe a clinical case of proven pulmonary aspergillosis caused by Aspergillus tubingensis in a 59-year-old man with a history of hospitalization due to COVID-19 infection. CASE REPORT: The Covid-19 infection was confirmed by positive nasopharyngeal polymerase chain reaction. He had a cavitary lesion measured 20 mm in diameter with intracavitary soft tissue density in the left lung in the first chest computerized tomography scan. After 25 days, he showed two cavitary lesions in both lungs which raised suspicion of fungal infection; hence, the patient underwent a trans-thoracic biopsy of the cavitary lesion. The direct examination and culture of the biopsy material revealed Aspergillus species. To confirm the Aspergillus species identification, the beta-tubulin region was sequenced. The patient was treated with oral voriconazole. CONCLUSION: This report underlined the importance of early diagnosis and management of invasive fungal infections in severe COVID-19 patients.