Opportunistic Fungal Infections Research Articles

Rapidly Developing and Elusive Rhino-Orbital-Cerebral Mucormycosis

Purpose: To report a case of rapidly progressing rhino-orbital cerebral mucormycosis that was particularly difficult to diagnose, initially presenting as orbital apex syndrome. Major findings: In this case, a 59-year-old male patient with uncontrolled diabetes presented with a history of facial pain with no ocular involvement. Within 1 day of hospitalization, the patient developed complete ophthalmoplegia and total visual impairment of the right eye. Over the course of 2 hospital stays, several biopsies resulted in no significant histopathological findings, and several cultures resulted in growth of only a single colony of rhizopus mucor from the sinonasal mucosa. Given the high clinical suspicion of an invasive fungal infection, a universal PCR test was performed from a rapidly developing abscess in the frontal lobe and confirmed a diagnosis of mucormycosis. Conclusions: Orbital apex syndrome is a significant diagnosis that can be caused by a variety of factors, including those of fungal, bacterial, neoplastic, or inflammatory origin. Fungal infections, are a particularly concerning cause of orbital apex syndrome, given their ability to penetrate in and through the orbit to the brain, often resulting in an alarmingly high mortality rate. Mucormycosis, specifically rhino-orbital cerebral mucormycosis, is a very severe opportunistic invasive fungal infection, most often afflicting the immunocompromised. A clinician must be very thorough in their workup so as to not miss such a devastating diagnosis. Histopathology and cell cultures are currently the gold standard for diagnosis, with the potential to augment their technical success through the use of molecular techniques, such as universal PCR.

Photogallery. Fungal lesions of skin and nails infections in HIV-associated immunodeficiency

Against the background of any immunodeficiency, including that caused by HIV infection, the risk of developing superficial and invasive fungal diseases increases. Among people living with HIV, the most common fungal skin lesions are candidiasis, rubromycosis, and pityriasis versicolor. As immunosuppression worsens in HIV-positive patients not on antiretroviral therapy, the frequency and severity of mycoses increases. Thus, rubromycosis can spread beyond the feet, covering large areas of skin; sometimes the smooth skin of the hands, large folds, and areas of long hair growth are affected. In this case, the peripheral inflammatory ridge along the edge of the lesions, characteristic of rubromycosis, is sometimes absent. According to some reports, over half of patients in the secondary disease stage of HIV infection suffer from onychomycosis. The progression of the disease often occurs in a short time. In addition to the nail plates of the feet, the nails on the hands are often affected. In patients with HIV infection who do not receive antiretroviral therapy, difficult-to-treat onychomycosis occurs. Cryptococcosis is an opportunistic mycosis caused by yeast-like fungi Cryptococcus spp. It usually develops in HIV-positive individuals with a CD4+ T-lymphocyte level of less than 100 cells/μl. Skin lesions are usually secondary and indicate cryptococcal dissemination. Dermatological manifestations of cryptococcosis are varied. These may include papules and nodules surrounded by erythema and prone to ulceration, vesicular, pustular, herpetiform, acne-like rashes, ulcerative-necrotic lesions. We present to your attention a photogallery of cases of fungal skin lesions that developed against the background of HIV-associated immunosuppression.

SIADH secondary to rhino-orbito-cerebral mucormycosis: A case report.

Invasive fungal mucormycosis and its outcome as SIADH and orbital apex syndrome is uncommon. Mucormycosis in paranasal sinuses can even lead to intracranial invasion and its treatment with the use of amphotericin B can cure improve the prognosis of the disease. Early diagnosis and prompt treatment with antifungal, endoscopic surgery, and controlling of diabetes can be beneficial. Mucormycosis is an opportunistic invasive fungal infection which is rare and fatal and can even cause intracranial invasion leading to SIADH. The infrequency with which mucormycosis with SIADH is encountered makes it a formidable diagnostic challenge. 70-year-old women uncontrolled diabetes mellitus presented with bilious vomiting and persistent headache with ptosis, proptosis, absence of extraocular movement, pupillary light reflex, and light perception of left eye. Radiographic investigation, KOH mount, and Biopsy showed mucormycosis in sinus with intracranial extension leading to SIADH. Further investigation revealed hyponatremia, decreased plasma osmolality. Then, when diabetes was controlled and hydrocortisone and amphotericin was given along with Endoscopic sinus debridement, SIADH was well controlled. This case illustrates the potential of mucormycosis in paranasal sinuses can even lead to intracranial invasion and its treatment with the use of amphotericin B can cure improve the prognosis of the disease. Prompt diagnosis through clinical history, radiological investigation, and laboratory parameters are important and its treatment is crucial for the better prognosis.

Mucormycosis and COVID-19: Unraveling the Interplay of Fungal Infection in a Global Health Crisis: An Overview.

The healthcare system has been greatly affected by the COVID-19 pandemic, result-ing in an increase in secondary and co-infections among patients. Factors like pulmonary dam-age and weakened immune systems make patients more susceptible to fungal infections. Mu-cormycosis, an opportunistic fungal infection, prospers in environments with limited oxygen, and elevated glucose levels due to conditions such as diabetes and steroid use, as well as in acidic environments from metabolic acidosis and diabetic ketoacidosis, where it demonstrates heightened germination ability. Recognizing these complications is critical to minimize harm to patients. The insights gained from this review can improve our understanding of how fungal infections develop in connection to COVID-19, leading to better predictive algorithms, tailored care plans, enhanced antifungal treatments, quicker diagnostics, and improved management strategies.

Suspected nocardiosis in an immunosuppressed patient: a case report highlighting diagnostic challenges and management strategies

Nocardiosis is a rare but potentially fatal opportunistic infection caused by Nocardia species, predominantly affecting immunocompromised individuals. This case report details the clinical course, diagnostic workup, and management of a 63-year-old female with a history of renal transplantation. Initial investigations, including imaging studies, revealed multiple cavitary pulmonary nodules and a solitary brain lesion, raising concerns for disseminated infection. The diagnostic challenge was compounded by the broad differential diagnosis in this patient population, including fungal, mycobacterial, and other opportunistic infections. Empirical antimicrobial therapy was initiated, and subsequent microbiological confirmation of Nocardia asteroides from bronchoalveolar lavage specimens established the diagnosis. Despite initial therapeutic response, the patient developed worsening neurological symptoms indicative of CNS involvement, necessitating prolonged treatment with a combination of trimethoprim-sulfamethoxazole and imipenem. This report underscores the importance of early recognition, comprehensive diagnostic evaluation, and individualized therapeutic approaches in managing suspected nocardiosis in immunocompromised patients. Furthermore, it discusses the diagnostic pitfalls, highlights the need for a high index of suspicion, and reviews current therapeutic recommendations for both pulmonary and disseminated nocardiosis, providing a valuable reference for clinicians managing similar cases.

3D Printable Alginate-Chitosan Hydrogel Loaded With Ketoconazole Exhibits Anticryptococcal Activity.

Natural polymers have recently been investigated for various applications, such as 3D printing and healthcare, including treating infections. Among microbial infections, fungal diseases remain overlooked, with limited therapeutic options and high recurrence. Cutaneous cryptococcosis is an opportunistic fungal infection triggered by mechanical inoculation or hematogenous dissemination of the yeast that causes cryptococcal pneumonia and meningitis. Every year, Cryptococcus neoformans endanger the lives of immunosuppressed hosts, resulting in 180,000 deaths per year. Nonetheless, healthy individuals can also be affected by this fungal infection. Cryptococcosis has a restricted and expensive therapeutic regimen with no topical approach to skin manifestations. This study sought to create a 3D printable biodegradable polymeric hydrogel carrying ketoconazole, a low-cost antifungal drug with reported anticryptococcal activity. The developed hydrogel exhibited good 3D printability and rheological properties, including a pseudoplastic behavior. The FTIR spectra of cross-linked hydrogels revealed interactions between alginate and Ca+2, referred to as the egg-box model, indicated by the decrease in peaks at 1600 and 1410 cm-1. Furthermore, the hydrogel loaded with ketoconazole showed remarkable antifungal activity against C. neoformans strains indicated by inhibition zones, which cross-linking did not seem to affect its antifungal performance. The developed material remained structurally stable for up to 12 days (288 h) in swelling studies, and preliminary cytotoxicity performed with V79 cells indicates potential for invivo studies and topical application.

Opportunistic Infections among People Living with HIV in the Infectious Disease Department, the University Hospital of Fann in Dakar, Senegal

Aim: The aim of this study was to identify the main infections and opportunistic infections in hospitalized patients living with HIV and to determine the hospital lethality rate. Patients and Methods: This was a retrospective, descriptive study of patients hospitalized in the infectious diseases department of the University Hospital of Fann over a 02-year period from 1 January 2021 to 31 December 2022. Results: We recorded 308 cases, 296 of which were patients living with HIV, out of a total of 1208 patients admitted to the department, a hospital prevalence rate of 24.5%. The average age of the patients was 43.3 ± 13.3 years, with a sex ratio of 0.7. One hundred and thirty-one patients (44.26%) were married. 22.97% had no occupation and 35.5% of patients came from home. The average diagnostic period was 3.9 days ± 4.78 days. Two hundred and five patients (69.26%) were at WHO stage 4. Tuberculosis was the most common bacterial infection, with 114 cases (38.5%), followed by common bacterial pneumonia (7.77%) and septicemia (4.72%). With regard to viral infections, the prevalence of viral hepatitis B was 6.76%, followed by herpes (1.68%). Among parasitic infections, toxoplasmosis was noted in 6.41% and cryptosporidiosis in 2.02%. Candidiasis was the most common fungal opportunistic infection, affecting forty-three patients (14.52%), followed by pneumocystis (7.09%) and cryptococcosis (2.36%). More than a third of our patients (37.84%) had severe anaemia, with haemoglobin levels below 8g/dl. Nearly a quarter of patients (21.28%) had impaired kidney function. Conclusion: HIV infection occurs in young adults at a late stage. Mortality remains high due to opportunistic infection. It is essential to carry out early screening, but above all to make available diagnostic tools and certain molecules for treatment of opportunistic infections.

The first prevalence and antifungal susceptibility profile of Candida infections in Palestine, 2022

BackgroundCandida spp. are the most common cause of opportunistic fungal infections and are associated with a high mortality rate worldwide. In Palestine, the prevalence of Candida spp. infections remains elusive.MethodsWe performed our study at two hospitals in Palestine (Istishari Arab Hospital, and Najah National University Hospital). All patients diagnosed with candidiasis during the year 2022 have participated in the study. The prevalence of Candida spp., their distribution, and the activity of selected antifungals against Candida pathogens were assessed. In combination with phenotypic properties, Candida isolates were identified and tested for antifungal susceptibility using the colorimetric VITEK-2 Compact system.ResultsOur results showed that the prevalence of Candida spp. among infected samples was 11.6%. A total of eleven different Candida spp. were identified. Among these isolates, C. albicans (46.54%) was the most frequent, followed by C. glabrata (16.14%), C. tropicalis (13.83%), C. parapsilosis (4.82%), C. krusei (3.56%), C. dubliniensis (2.09%), C. ciferrii (1.67%), C. lusitaniae (0.83%), C. guilliermondii (0.62%), C. kefyer (0.41%) and C. spherica (0.20%). Among C. albicans, all isolates were 100% susceptible to fluconazole and micafungin. The susceptibility rates to Amphotericin B and flucytosine were 95% and 99%, respectively. The susceptibility rates of non-albicans Candida spp. (NAC) to fluconazole, voriconazole, amphotericine B, caspofungin, flucytosine and micafungin were 70%, 99%, 97%, ,72%, 92% and 100%, respectively. The incidence of Candida infections was higher in the intensive care unit and surgery department as compared to other hospital departments.ConclusionsFour pathogens are responsible for the most invasive infections: C. albicans, C. glabrata, C. tropicalis, and C. parapsilosis. A notable characteristic of this study was the high frequency of NAC species which were often more resistant to antifungal agents. A quick and accurate system like Vitek 2 compact was suggested for the careful species identification of clinical isolates of Candida. We suggest that continued surveillance of species distribution and susceptibility to antifungals will enhance future burden estimates and assist in evaluating preventative measures’ effectiveness.

Superior Sagittal Sinus Thrombosis Secondary to Cerebral Aspergillosis with Ventriculitis in an Immunocompetent Patient: A Case Report

AbstractCerebral aspergillosis is an opportunistic fungal infection that is exceedingly rare in immunocompetent patients. The primary etiological locations for these infections typically involve the nasal cavity and hematological dissemination. A 62-year-old male, focused on wellness, presented with intermittent, nonprogressive headaches in the occipital region, generalized clonic–tonic seizures, and altered consciousness. A computed tomography scan revealed multiple small rim-enhancing lesions in both occipital lobes, with vasogenic edema in both occipital lobes adjacent to the confluence of the sinuses and the posterior superior sagittal sinus. In this case, superior sagittal sinus thrombosis secondary to cerebral aspergillosis was discovered, a condition not previously diagnosed in this specific location but manageable through surgical intervention. A combination of surgical resection and antifungal therapy resulted in favorable outcomes. The prognosis for patients depends significantly on early diagnosis and prompt, aggressive treatment.

Complete genome sequence of a Circovirus pigeon strain in lymphocyte-depleted bursa of Fabricius of a Common Raven (Corvus corax).

A necropsy was performed on a Common Raven (Corvus corax) presenting an opportunistic fungal respiratory infection and a bursal lymphoid depletion with inclusion bodies, suggestive of a circovirus infection. High-throughput sequencing of circular DNA in the bursa of Fabricius revealed a complete genome sequence of a Circovirus pigeon strain.

Implementation of Antigen-Based Diagnostic Assays for Detection of Histoplasmosis and Cryptococcosis among Patients with Advanced HIV in Trinidad and Tobago: A Cross-Sectional Study.

The Caribbean continues to have high HIV prevalence globally with concurrently high mortality rates due to opportunistic Infections. This study addresses the prevalence of histoplasmosis and cryptococcosis among patients living with advanced HIV disease (AHD) in Trinidad and Tobago, focusing on the implementation of antigen-based diagnostic assays. Conducted as a cross-sectional survey across five HIV treatment sites, 199 participants with advanced HIV disease were enrolled between July 2022 and September 2023. Diagnostic testing was performed using the Clarus Histoplasma Galactomannan Enzyme Immunoassay (EIA), and the Immy CrAg® LFA Cryptococcal Antigen Lateral Flow Assay on urine and blood samples, respectively. Results revealed that 14.6% of participants were found to be co-infected with either histoplasmosis or cryptococcosis, with histoplasmosis being more prevalent (10.5%) than cryptococcosis (4.0%). The study found no significant demographic differences between newly diagnosed and previously diagnosed participants. However, a lower median CD4 count was associated with a higher risk of fungal opportunistic infections. The findings underscore the critical role of systematic use of fungal antigen-based diagnostic assays among patients with AHD to improve the timely diagnosis and treatment of fungal infections among people living with HIV in resource-limited settings and to improve patient outcomes and survival.

ROLE OF FUNGI IN COVID-19 PATIENTS WITH CHRONIC LUNG DISEASE IN RANI DURGAVATI MEDICAL COLLEGE, BANDA (FORMERLY GOVERNMENT ALLOPATHIC MEDICAL COLLEGE, BANDA 210001 (UP) INDIA.)

Background: Fungal infections of the lung have gained increasing recognition in the field of infectious disease and they are difficult to diagnosis. Advances in modern treatment like antibiotics corticosteroids, Immunosupressants and anticancer drugs have lead to increase in opportunistic fungal infections including bronchopulmonary Candidiasis and Bronchopulmonary aspergillosis has also increased, commonly occurs in COVID-19 patients of pre existing bronchial asthma. In India there is high prevalence of chronic lung diseases including bronchial Asthma, yet the diagnosis of aspergillosis and Candidiasis. An association between asthma and aspergillosis was noted and confirmed by isolation of Aspergillus species more commonly in sputum of Asthma patients (Lum et al., 2020 Singla, N. et al., 2019). Subject and Methods: To find out the role of fungi in 50 Corona virus (RTPCR test) positive patients of chronic lung disease (non tubercular) like COPD, Chronic Bronchitis with or without emphysema, Broncheichtasis, Bronchial Asthma were included. Patients were attended and admitted in Rani Durgavati Medical College (RDMC) and Hospital, Banda (UP) India, in a one year period was taken up from December 2020 till December 2021. The diagnosis of these cases v/as established by clinical features, radiological examination of chest, ECG, pulmonary function tests. Laboratory procedure for isolation and identification of fungi in bronchoalveoiar lavage. Each specimen of Bronchoalveloar Lavage (BAL) was subjected to various laboratory procedures for isolation and identification of fungi. Result: Different fungal species were cultured in 26% total cases. 20% isolates were positive for fungi alone whereas rest 6% cases showed both bacterial and fungal pathogens amongst fungi Candida was the predominant isolate in 16% cases followed by Aspergillus in 8% cases and Histopfasms capsulatum in just1(2%) case. Fungal isolates in bronchial aspirates were sensitive to Amphotericin B, Fluconazole, etc. Conclusion: COVID-19 Patients which are already containing chronic lung diseases especially COPD, bronchiectasis is more common in elderly males. The Bronchiectatic patients are also at risk of getting, fungal infections Patients of chronic lung disease who are on long-term antibiotic therapy, and or steroids are more predisposed to get these opportunistic infections. Another conclusion from it is clear that there is great need better and judicious use of antibiotics in patients to prevent drug resistance, to prevent further progression of the diseases.

Bioavailability of a novel sustained-release pellet formulation of 5-flucytosine in healthy-fed participants for use in patients with cryptococcal meningitis.

Cryptococcal meningoencephalitis (CM) is an opportunistic fungal infection and a major cause of death among people living with human immunodeficiency virus in sub-Saharan Africa. 5-flucytosine (5-FC) is a unique, brain-permeable antifungal agent used to reduce mortality from CM and to prevent disease in individuals carrying cryptococcal antigen. 5-FC has a short plasma half-life, requiring 6-hourly oral dosing with an immediate-release (IR) formulation, a significant challenge in hospital and outpatient settings, risking a lack of compliance. We recently reported the relative bioavailability in fasting conditions of a sustained release (SR) oral pellet formulation of 5-FC. In this phase I study, we assessed the safety and pharmacokinetic profiles of the new 5-FC SR formulation in a single dose (2 × 3000 mg), relative to 5-FC IR tablets (Ancotil®; 1500 mg b.i.d.) in healthy participants in fed conditions. This randomized, two-period crossover study was conducted in South Africa to confirm the dose of the identified 5-FC SR formulation for a twice-daily 5-FC regimen in patients. Thirty-six healthy participants were included. All treatments were well tolerated and no serious adverse event was reported. Cmax and AUC(0-t) for the SR formulation (49.2 ± 10.49 μg/mL and 640.4 ± 126.4 h.μg/mL, respectively) were significantly higher than for the IR formulation (36.8 ± 7.61 μg/mL and 456.6 ± 72.8 h.μg/mL, respectively). A physiological based pharmacokinetic model (PBPK) predicted that under fasting conditions, 6000 mg SR pellets would show a good overlap with the IR product (3000 mg b.i.d), thus 6000 mg SR 5-FC b.i.d. in fasting conditions is recommended.

Lung adenocarcinoma concurrent with pulmonary cryptococcosis: a case report and literature review

Pulmonary cryptococcosis (PC) is a common opportunistic fungal infection caused by Cryptococcus neoformans or Cryptococcus gattii. PC primarily invades the respiratory system, followed by the central nervous system. Few clinical reports have examined the coexistence of PC and lung cancer. This study reports the case of a 54-year-old immunocompetent PC patient with lung adenocarcinoma. Chest CT revealed multiple nodules in the right lung, with the largest nodule located in the dorsal segment of the right lower lobe. 18 F‑FDG positron emission tomography-computed tomography (PET-CT) revealed elevated glucose metabolism in the dorsal segment of the right lower lobe, which suggested lung cancer. The metabolism level of the nodule in the basal segment of the right lower lobe and the anterior segment of the right upper lobe was not abnormally increased, but the possibility of a malignant tumour could not be excluded. The pulmonary nodules in the dorsal segment and the basal segment of the right lower lobe were simultaneously resected via video-assisted thoracic surgery (VATS), and the final histopathology revealed primary lung adenocarcinoma and pulmonary cryptococcal infection, respectively. After surgery, antifungal treatment was administered for 3 months. Over the 3-year follow-up, contrast-enhanced computed tomography (CT) revealed no recurrence of either disease. This case study highlights the possibility of dualism in the diagnosis of multiple pulmonary nodules on chest CT, such as the coexistence of lung cancer and PC. Surgical resection is recommended for micronodules that are not easy to diagnose via needle biopsy; in addition, early diagnosis and treatment are helpful for ensuring a good prognosis. This paper reports the clinical diagnosis and treatment of one patient with pulmonary cryptococcal infection of the right lung complicated with lung adenocarcinoma, including 3 years of follow-up, providing a reference for clinical practice.

Functional characterization of two survival factor 1 genes in Mucor lusitanicus.

Mucor lusitanicus is a widely used model organism to study various biological processes in the basal fungal group Mucorales. Several members of this group can be agents of mucormycosis, an opportunistic fungal infection, which is associated with high mortality, rapid progression, and wide resistance to the commonly used antifungal agents. Svf1 proteins have so far only been identified in fungi, where they have been involved in pathogenicity and resistance to antifungal agents in many cases. Only a limited number of factors affecting the stress response, antifungal resistance, and virulence of Mucorales fungi have been revealed. Elucidating the function of a fungus-specific protein that may regulate these processes may bring us closer to understanding the pathogenesis of these fungi.

Inflammatory cytokine signalling in vulvovaginal candidiasis: a hot mess driving immunopathology.

Protective immunity to opportunistic fungal infections consists of tightly regulated innate and adaptive immune responses that clear the infection. Immune responses to infections of the vaginal mucosa by Candida species are, however, an exception. In the case of vulvovaginal candidiasis (VVC), the inflammatory response is associated with symptomatic disease, rather than that it results in pathogen clearance. As such VVC can be considered an inflammatory disease, which is a significant public health problem due to its predominance as a female-specific fungal infection. Particularly, women with recurrent VVC (RVVC) suffer from a significant negative impact on their quality of life and mental health. Knowledge of the inflammatory pathogenesis of (R)VVC may guide more effective diagnostic and therapeutic options to improve the quality of life of women with (R)VVC. Here, we review the immunopathogenesis of (R)VVC describing several elements that induce an inflammatory arson, starting with the activation threshold established by vaginal epithelial cells that prevent unnecessary ignition of inflammatory responses, epithelial and inflammasome-dependent immune responses. These inflammatory responses will drive neutrophil recruitment and dysfunctional neutrophil-mediated inflammation. We also review the, sometimes controversial, findings on the involvement of adaptive and systemic responses. Finally, we provide future perspectives on the potential of some unexplored cytokine axes and discuss whether VVC needs to be subdivided into subgroups to improve diagnosis and treatment.

Genetic diversity and antifungal susceptibilities of environmental Cryptococcus neoformans and Cryptococcus gattii species complexes

Cryptococcosis is an opportunistic systemic mycosis caused by Cryptococcus neoformans and C. gattii species complexes and is of increasing global importance. Maintaining continued surveillance of the antifungal susceptibility of environmental C. neoformans and C. gattii isolates is desirable for better managing cryptococcosis by identifying resistant isolates and revealing the emergence of intrinsically resistant species. Relevant research data from Egypt are scarce. Thus, this study aimed to report the genetic diversity of C. neoformans and C. gattii species complexes originating from different environmental sources in Egypt, antifungal susceptibility profiles, antifungal combinations, and correlations of susceptibility with genotypes. A total of 400 environmental samples were collected, 220 from birds and 180 from trees. Cryptococcus spp. were found in 58 (14.5%) of the samples, 44 (75.9%) of the isolates were recovered from birds and 14 (24.1%) from trees. These isolates were genotyped using M13 polymerase chain reaction-fingerprinting and URA5 gene restriction fragment length polymorphism analysis. Of the 31 C. neoformans isolates, 24 (77.4%), 6 (19.4%) and one (4.4%) belonged to VNI, VNII, and VNIII genotypes, respectively. The 27 C. gattii isolates belonged to VGI (70.4%), VGII (18.5%), and VGIII (11.1%) genotypes. Non-wild type C. neoformans and C. gattii isolates that may have acquired resistance to azoles, amphotericin B (AMB), and terbinafine (TRB) were observed. C. gattii VGIII was less susceptible to fluconazole (FCZ) and itraconazole (ITZ) than VGI and VGII. C. neoformans isolates showed higher minimum inhibitory concentrations (MICs) to FCZ, ITZ, and voriconazole (VRZ) than those of C. gattii VGI and VGII. Significant (P < 0.001) correlations were found between the MICs of VRZ and ITZ (r = 0.64) in both C. neoformans and C. gattii isolates, FCZ and TRB in C. neoformans isolates, and FCZ and TRB (r = 0.52) in C. gattii isolates.There is no significant differences in the MICs of TRB in combination with FCZ (P = 0.064) or in combination with AMB (P = 0.543) and that of TRB alone against C. gattii genotypes. By calculating the fractional inhibitory concentration (FIC) index, the combination of FCZ + AMB was synergistic against all tested genotypes. These findings expand our knowledge of ecological niches, genetic diversity, and resistance traits of C. neoformans and C. gattii genotypes in Egypt. Further investigations into how they are related to clinical isolates in the region are warranted.

Candida tropicalis PMT2 Is a Dispensable Gene for Viability but Required for Proper Interaction with the Host.

Candidemia is an opportunistic mycosis with high morbidity and mortality rates. Even though Candida albicans is the main causative agent, other Candida species, such as Candida tropicalis, are relevant etiological agents of candidiasis and candidemia. Compared with C. albicans, there is currently limited information about C. tropicalis' biological aspects, including those related to the cell wall and the interaction with the host. Currently, it is known that its cell wall contains O-linked mannans, and the contribution of these structures to cell fitness has previously been addressed using cells subjected to chemical treatments or in mutants where O-linked mannans and other wall components are affected. Here, we generated a C. tropicalis pmt2∆ null mutant, which was affected in the first step of the O-linked mannosylation pathway. The null mutant was viable, contrasting with C. albicans where this gene is essential. The phenotypical characterization showed that O-linked mannans were required for filamentation; proper cell wall integrity and organization; biofilm formation; protein secretion; and adhesion to extracellular matrix components, in particular to fibronectin; and type I and type II collagen. When interacting with human innate immune cells, it was found that this cell wall structure is dispensable for cytokine production, but mutant cells were more phagocytosed by monocyte-derived macrophages. Furthermore, the null mutant cells showed virulence attenuation in Galleria mellonella larvae. Thus, O-linked mannans are minor components of the cell wall that are involved in different aspects of C. tropicalis' biology.

The underlying factors of occurrence of Mucormycosis in post-COVID-19 patients – A meta-analysis of case histories

Mucormycosis is a life-threatening fungal infection caused by fungi of the order Mucorales. It usually affects people with weakened immune systems, such as those with uncontrolled diabetes, acquired immunodeficiency syndrome, iatrogenic immunosuppression, and hematological malignancies, as well as individuals who have had organ transplants. The type of mucormycosis a person suffers from is often determined by their underlying conditions. The most common types are rhino-cerebral mucormycosis, pulmonary mucormycosis, cutaneous mucormycosis, cerebral mucormycosis, gastrointestinal mucormycosis, and disseminated mucormycosis. The incidence of mucormycosis has been increasing over the years, with an overall mortality rate of 54%. Recent cases have shown a correlation between COVID-19 and mucormycosis. Using anti-inflammatory drugs to combat the cytokine storm associated with COVID-19 can weaken the immune system, making individuals more susceptible to opportunistic fungal infections like mucormycosis. Underlying health conditions further exacerbate the condition. This study reviewing 198 cases of mucormycosis and conducting a meta-analysis found that post-COVID-19 patients most commonly developed rhino-orbital-cerebral mucormycosis, followed by pulmonary and gastrointestinal mucormycosis. The study also identified diabetes as the most common underlying factor contributing to the development of mucormycosis in post-COVID-19 patients, followed by hypertension and obesity. The study also examined the influence of age, affected organs, and the use of certain drugs on the development of mucormycosis. Age was found to be a significant factor in the infection. This meta-analysis is one of the first to compare post-COVID mucormycosis cases with those from the pre-COVID era. The hope is that this study and analysis will help identify the determinants of mucormycosis in post-COVID patients and aid the scientific community in finding a solution to this problem.

Hospitalized COVID-19 Patients with Urinary Tract Infection in Iran: Candida Species Distribution and Antifungal Susceptibility Patterns.

Candida species, typically part of the human skin and mucous membrane flora, can cause opportunistic fungal infections, notably urinary tract infections (UTIs), which are on the rise among hospitalized COVID-19 patients. The lack of understanding of UTIs in this population, coupled with the emergence of multidrug-resistant strains, poses significant challenges for effective treatment and further investigations. In this study, urine samples were collected from 70 COVID-19 patients with UTIs in sterile containers for microbiology examination. After microscopic observation, the isolates were identified both by phenotypic and molecular techniques such as multiplex PCR. Antifungal susceptibility testing (AFST) against fluconazole (Flu), itraconazole (Itr), and amphotericin B (AMB) was performed according to CLSI M27/S4 standard methods, with the frequency of isolates including Candida albicans (n = 20, 51.3%), Candida tropicalis (n = 15, 38.4%), Nakaseomyces glabrata (previously Candida glabrata) (n = 2, 5.1%), Pichia kudriavzevii (previously Candida krusei), and Candida parapsilosis (n = 1, 2.5%). All isolates of C. albicans, C. tropicalis, C. glabrata, and C. parapsilosis were sensitive to amphotericin B, while C. kruzei was resistant to AMB. Around 70% of C. albicans isolates were sensitive to Flu; 20% of C. tropicalis were resistant to itraconazole, while 33% were resistant to fluconazole. C. albicans and C. tropicalis were the main causes of candiduria in infected cases and both Flu and AMB showed good results in AFST in these species. Performing drug susceptibility testing for clinical isolates of Candida spp. provided guidance for appropriate management and control, and timely antifungal treatment.