Fungal Infections In Immunocompromised Patients Research Articles

A rare case of fatal sepsis caused by Trichosporon asahii in an immunocompetent chronic obstructive pulmonary disease patient

Trichosporon asahii is an yeast-like organism that is emerging as an important cause of invasive fungal infection in immunocompromised patients, especially in patients with cancer and neutropenia. Invasive infections due to T.asahii in immunocompetent patients are rarely reported. We describe a 62-year-old COPD (chronic obstructive pulmonary disease) patient who contracted severe sepsis from T.asahii without any prior history of immunosuppression. He was successfully treated with voriconazole and was discharged from the hospital.

CURVULARIA PULMONARY FUNGAL INFECTION ASSOCIATED WITH IMMUNOCOMPROMISED PATIENT: HOW CT SCAN COULD HELP IN MAKING DIAGNOSIS

Pulmonary fungal infections can be found in immunocompetent and immunocompromised patients. The Curvularia species of fungi are rarely seen in humans. These fungi can be clinically significant and cause a range of disease processes, particularly in immunocompromised patients. We present a 24-year-old male patient diagnosed with SLE 5 years ago, complaining of fever five days before hospital administration concerning pneumonia. A CT scan revealed consolidation and multiple lung nodules compatible with a fungal pulmonary infection. The result of the sputum culture indicated Curvularia. A chest radiograph showed infiltrates with consolidation in the middle-lower lobes of both lungs. Early and second CT-scan findings revealed ground-glass opacity surrounding multiple irregular nodules (halo signs), cavitary nodules, and reverse halo signs. Afterward, the result of the patient’s sputum culture demonstrated fungal growth of the Curvularia species. The patient then underwent fungal treatment with fluconazole and voriconazole. The patient showed improvements, and a follow-up chest CT scan revealed the resolution of the lesion after fungal treatment. CT-scan examination, clinical condition, and microbiology culture can help diagnose Curvularia pulmonary fungal infection in immunocompromised patients. Keyword: Phaeohyphomycosis; Curvularia; Halo sign; Reverse halo sign

Alarming Increase of Azole-Resistant Candida Causing Blood Stream Infections in Oncology Patients in Egypt

Candidemia is a life-threatening invasive fungal infection in immunocompromised patients. The widespread use of azoles and the shift toward non-albicans Candida (NAC) species remarkably increase azole resistance in developing countries. We aimed to study candidemia trends and associated risk factors in oncology patients since they vary geographically, and rapid and appropriate treatment improves outcomes. Vitek 2 was used to identify the Candida species, and the E-test determined their susceptibility to azoles. Candida was the cause of 3.1% (n = 53/1701) of bloodstream infections (BSIs) during a 1-year study. Candida tropicalis was the most predominant species among the 30 candidemia episodes studied (36.7%), followed by C. albicans (33.3%). However, C. krusei, C. guilliermondii, C. pelliculosa, C. parapsilosis, C. famata, and C. inconspicua accounted for 30.0% of the isolates. An increased risk of NAC BSI was significantly associated with chemotherapy and leucopenia (P = 0.036 and 0.016, respectively). However, the multivariable analysis revealed that leucopenia was the only independent risk factor (P = 0.048). Fluconazole and voriconazole resistance were 58.3% and 16.7%, with NAC species showing higher resistance rates than C. albicans. Both fluconazole and voriconazole minimum inhibitory concentration (MIC) median values were higher in NAC than in C. albicans, but only voriconazole was significantly higher (0.220 versus 0.048 μg/ml, P = 0.047). In conclusion, the increased prevalence of NAC BSIs and incredibly high fluconazole resistance rates in cancer patients emphasize the necessity of antifungal stewardship to preserve voriconazole effectiveness, continued surveillance of candidemia, and future studies into azole resistance molecular mechanisms.

Biofilm Formation and Phospholipase and Proteinase Production in Cryptococcus neoformans Clinical Isolates and Susceptibility towards Some Bioactive Natural Products.

Cryptococcosis is one of the most common fungal infections in immunocompromised patients, which is caused by Cryptococcus neoformans. However, relatively little is known about the virulence factors of C. neoformans and the incidence of antifungal drug resistance in C. neoformans is rapidly increasing. This study was undertaken to investigate the virulence factors in C. neoformans, thymol, curcumin, piperine, gallic acid, eugenol, and plumbagin for their potential antimicrobial activity against C. neoformans. The production of phospholipase and proteinase was detected using standard methods. Biofilm formation was determined using the microtiter plate method. The broth microdilution method was used to determine the antifungal activity. The antibiofilm activity was assessed using the safranin staining method. All isolates of C. neoformans produced biofilms with optical density values ranging from 0.16 to 0.89. A majority of C. neoformans isolates that were tested exhibited strong phospholipase (7/8) and proteinase (5/8) production. Plumbagin (with minimum inhibitory concentration values ranging from 4 to 16 μg/mL) showed the highest antifungal activity followed by thymol (with minimum biofilm inhibitory concentration values ranging from 8 to 64 μg/mL). In addition, plumbagin showed the highest antibiofilm activity with minimum biofilm inhibitory concentration and minimum biofilm eradication concentration values ranging from 4 to 16 μg/mL and 32 to 256 μg/mL, respectively. Plumbagin, compared to other natural products studied, was the most efficient in terms of antifungal and antibiofilm activities. Hence, plumbagin could be used in combination with antifungals for the development of new anticryptococcal drugs.

Alginate oligosaccharides enhance the antifungal activity of nystatin against candidal biofilms.

The increasing prevalence of invasive fungal infections in immuno-compromised patients is a considerable cause of morbidity and mortality. With the rapid emergence of antifungal resistance and an inadequate pipeline of new therapies, novel treatment strategies are now urgently required. The antifungal activity of the alginate oligosaccharide OligoG in conjunction with nystatin was tested against a range of Candida spp. (C. albicans, C. glabrata, C. parapsilosis, C. auris, C. tropicalis and C. dubliniensis), in both planktonic and biofilm assays, to determine its potential clinical utility to enhance the treatment of candidal infections. The effect of OligoG (0-6%) ± nystatin on Candida spp. was examined in minimum inhibitory concentration (MIC) and growth curve assays. Antifungal effects of OligoG and nystatin treatment on biofilm formation and disruption were characterized using confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM) and ATP cellular viability assays. Effects on the cell membrane were determined using permeability assays and transmission electron microscopy (TEM). MIC and growth curve assays demonstrated the synergistic effects of OligoG (0-6%) with nystatin, resulting in an up to 32-fold reduction in MIC, and a significant reduction in the growth of C. parapsilosis and C. auris (minimum significant difference = 0.2 and 0.12 respectively). CLSM and SEM imaging demonstrated that the combination treatment of OligoG (4%) with nystatin (1 µg/ml) resulted in significant inhibition of candidal biofilm formation on glass and clinical grade silicone surfaces (p < 0.001), with increased cell death (p < 0.0001). The ATP biofilm disruption assay demonstrated a significant reduction in cell viability with OligoG (4%) alone and the combined OligoG/nystatin (MIC value) treatment (p < 0.04) for all Candida strains tested. TEM studies revealed the combined OligoG/nystatin treatment induced structural reorganization of the Candida cell membrane, with increased permeability when compared to the untreated control (p < 0.001). Antimicrobial synergy between OligoG and nystatin against Candida spp. highlights the potential utility of this combination therapy in the prevention and topical treatment of candidal biofilm infections, to overcome the inherent tolerance of biofilm structures to antifungal agents.

The inhibitory effects of tyrosol on clinical Candida glabrata planktonic and biofilm cells

Biofilm formation is an important problem in the healthcare industry and veterinary medicine and is very common in natural, industrial or hospital environments. Microorganisms can become very resistant to antimicrobials and environmental factors by biofilm forming on biotic or abiotic surfaces. There is a need to develop new, effective and specific antimicrobials that can reduce pathogenicity in biofilm formation that threatens public health due to their role in medical device-related or infectious diseases. Candida species are opportunistic pathogenic yeasts and can cause superficial or disseminated infections. Especially C. glabrata is one of the most common microorganisms causing fungal infections in immunocompromised patients and drug resistance is observed when associated with biofilm. Tyrosol (2-[4-hydroxyphenyl] ethanol) can act as both a quorum sensing molecule and an exogenous agent on Candida species. In this study, the antifungal activity of tyrosol against a clinical C. glabrata isolate was investigated on both planktonic and biofilm forms. Broth microdilution test results demonstrated the inhibitory effect of tyrosol on C. glabrata. Transmission electron microscopic findings showed that tyrosol affected the planktonic C. glabrata cells in a multi targeted manner, and in the groups treated with tyrosol, significant damage was observed in the cell wall, cell membrane, cytoplasm, nucleus and mitochondria. Also, scanning electron microscopic images confirmed biofilm reduction in pre-/post-biofilm applications as a result of tyrosol treatment. In conclusion, tyrosol may be a potential alternative candidate for reducing the C. glabrata biofilm.

Facile synthesis, pharmacological and In silico analysis of succinimide derivatives: An approach towards drug discovery

The hybrid heterocyclic scaffolds possess extensive medicinal values and significant pharmaceutical usage. A series of N-substituted-2,5-dioxopyrrolidine carboxamides/carbothioamides have been synthesized under aqueous conditions using clean microwave irradiation technology. The quantum chemical data and chemical reactivity parameters of the title compounds have been derived by DFT execution. The synthesized compounds have been screened for In vitro biological evaluation to ascertain their antimicrobial potential and radical scavenging ability. The promising antifungal activity of the synthesized compounds is further explored with molecular docking simulation revealing favorable binding interactions and good docking score against glucosamine-6-phosphate synthase (GlcN-6-P, PDB: 1JXA). The pharmacokinetics and drug analogy of the title compounds have been deduced by ADMET prediction and drug likeliness with the ‘Lipinski rule of 5′. The encouraging bioavailability plots permit the oral ingestion of the synthesized drug candidates. In vitro and In silico inspection of the lead molecules manifest them as potential antifungal agents with an appreciable antiradical ability that could be exploited in the future as a therapeutic alternate in fungal skin infections as well as in opportunistic fungal infections in immunocompromised patients.

P489 Anti-granulocyte-macrophage colony-stimulating factor (Anti-GM-CSF) autoantibodies—the underrecognized cause of Cryptococcosis in non-HIV individuals in Thailand: Case series from a single tertiary care hospital

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM BackgroundCryptococcosis is an opportunistic fungal infection in immunocompromised patients. Granulocyte-macrophage colony-stimulating factor (GM-CSF) regulates the functions of phagocytes and alveolar macrophages, which are crucial in cryptococcal control. Anti-granulocyte-macrophage colony-stimulating factor (Anti-GM-CSF) autoantibodies have been found to be associated with cryptococcosis in non-HIV individuals but this syndrome has never been described in Thai population.MethodsWe report here the case series of patients hospitalized in a tertiary care hospital in Northern Thailand.ResultsThree apparently immunocompetent patients, 34, 38, and 45 years old, were presented with neurological manifestations. Brain computed tomography scans and lumbar punctures were performed and the results showed evidence of cryptococcal meningoencephalitis. Two of the patients also had pulmonary cryptococcosis. We performed Anti-GM-CSF autoantibody ELISA assays in the patient's sera and all of three serum samples revealed a high titer of anti-GM-CSF autoantibodies. The patients were treated with amphotericin B deoxycholate with or without flucytosine for induction antifungal therapy, followed by fluconazole consolidation treatment. All patients were cured and had favorable outcomes.ConclusionsAnti-GM-CSF autoantibodies syndrome is underrecognized in Thai patients and is a new entity of immunodeficiency associated with cryptococcal meningoencephalitis and disseminated cryptococcosis in Thai patients.

P488 Successful treatment of breakthrough invasive aspergillosis in an immunocompetent individual based on therapeutic drug monitoring: A case report

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PMBackground: Invasive aspergillosis (IA) is an opportunistic fungal infection in immunocompromised patients with high mortality. Aspergillus flavus is the second pathogen of IA. Breakthrough IA was defined as any IA occurring during exposure to an antifungal drug.Case presentation: A 22-year-old female college student was admitted severely unwell with dizziness and left limb weakness. She was healthy previously and did not take any medication. Magnetic resonance imaging showed a right intracranial space-occupying lesion. The postoperative pathological and morphological examinations suggested Aspergillus flavus. The anti-fungal medication, voriconazole, was administered immediately. Unfortunately, her condition deteriorated, and she experienced coma after about 1 month of antifungal treatment. The emergency craniotomy revealed a large amount of pus and the culture of pus confirmed Aspergillus flavus. Antifungal regimen was developed by infectious disease specialists, and drug concentration was monitored continuously. This patient received antifungal treatment for 2 years. No recurrence was observed after 6 months of antifungal drug withdrawal, and she can take care of herself.See Figures below.ConclusionBreakthrough IA occurs in patients who lack high risk factors, making diagnosis more difficult and leading to a higher risk of mortality. Therapeutic drug monitoring is crucial for therapeutic success. Meanwhile, multidisciplinary therapeutics can improve the survival rate.

P279 Invasive Trichosporonosis: an emerging blood stream fungal infection in immunocompromised patients

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PM Trichosporon is a genus of yeast-like fungi. It is perhaps most widely known as the cause of white piedra, a benign superficial mycosis seen in immunocompetent individuals in tropical and subtropical regions. However, the incidence of invasive trichosporonosis has increased in immunocompromised patients, most notably those with hematologic malignancies. Invasive infections due to Trichosporon species are considered rare so far, but during the past two decades, they have emerged as important opportunistic pathogens in immunocompromised individuals. All patients with blood culture positive for Trichosporon species from January 2020 to August 2020 at Woodlands Multispecialty Hospital, Kolkata, India were evaluated. In vitro susceptibility testing was performed using the reference broth micro-dilution method. Clinical co-relation was done with the positive culture report and patient's clinical condition to rule out colonization/contamination. A total of 7 patients were found to have blood culture positive for Trichosporon species among which five were true infections. Various predisposing factors previously reported to be associated with invasive trichosporonosis were also considered in the present study. All the cases were associated with either post radiotherapy/chemotherapy with renal failure requiring dialysis via hemodialysis catheter or use of central venous catheter or chemoport. Underlying malignancy was found in all patients. Susceptibility testing has been performed for 5-FC, amphotericin B, and Azoles. Azoles had good in vitro activity, whereas amphotericin B had higher MIC values. The all-cause mortality rate was 43%. Invasive Trichosporon infection is a rare, life-threatening infection in immunocompromised patients. Our study highlights the association of central venous catheter and hemodialysis catheter with Trichosporon fungemia and its high mortality. Therefore, strict infection control measures while handling these devices are recommended to prevent these infections. Species identification and susceptibility testing are to be attempted for all relevant clinical isolates in view of demonstrable resistance to certain antifungal drugs. Echinocandins are not effective in the treatment of trichosporon infection. Amphotericin B should also be avoided. Azoles, in particular, voriconazole is the drug of choice.

A joint PCR-based gene-targeting method using electroporation in the pathogenic fungus Trichosporon asahii

Trichosporon asahii is a pathogenic fungus that causes deep-seated fungal infections in immunocompromised patients. Established methods for generating gene-deficient T. asahii mutants exist, but the frequency of obtaining transformants by electroporation remains low. In the present study, we optimized the conditions for gene transfer by electroporation using a ku70 gene-deficient mutant with high recombination efficiency. Introducing a DNA fragment by electroporation into T. asahii cells on Sabouraud dextrose agar to generate a cnb1 gene-deficient mutant and incubating for 1 day led to the growth of approximately 100 transformants. When the incubation period was extended to 2 days or 5 days, however, only 2 or no transformants, respectively, were grown. The highest number of transformants was grown by electroporation when a square wave at 1.8 kV (9 kV/cm) was applied for 5 ms. In addition, the number of transformants increased with an increase in the length of the homologous region, and transformants did not grow when the homologous region was less than 500 base pairs. A DNA fragment was produced for deletion of the cnb1 gene by joint PCR, and the cnb1 gene-deficient mutant was obtained by introducing the DNA fragment by electroporation. These results indicate that DNA fragments produced by joint PCR can be used to generate gene-deficient mutants of T. asahii through gene transfer by electroporation.Graphical

A State-of-the-art Review and Prospective Therapeutic Applications of Prenyl Flavonoids as Chemosensitizers against Antifungal Multidrug Resistance in Candida albicans.

Multidrug resistance (MDR) in the opportunistic pathogen Candida albicans is defined as non-susceptibility to at least one agent in two or more drug classes. This phenomenon has been increasingly reported since the rise in the incidence of fungal infections in immunocompromised patients at the end of the last century. After the discovery of efflux pump overexpression as a principal mechanism causing MDR in Candida strains, drug discovery targeting fungal efflux transporters has had a growing impact. Chemosensitization aims to enhance azole intracellular concentrations through combination therapy with transporter inhibitors. Consequently, the use of drug efflux inhibitors combined with the antifungal agent will sensitize the pathogen. As a result, the use of lower drug concentrations will reduce possible adverse effects on the host. Through an extensive revision of the literature, this review aims to provide an exhaustive and critical analysis of the studies carried out in the past two decades regarding the chemosensitization strategy to cope with multidrug resistance in C. albicans. This work provides a deep analysis of the research on the inhibition of drug-efflux membrane transporters by prenylated flavonoids and the interactions of these phytocompounds with azole antifungals as an approach to chemosensitize multidrug-resistant C. albicans strains. We highlight the importance of prenylflavonoids and their particular chemical and pharmacological characteristics that make them excellent candidates with therapeutic potential as chemosensitizers. Finally, we propose the need for further research on prenyl flavonoids as inhibitors of drug-efflux mediated fungal resistance.

Computer-aided molecular design, synthesis and evaluation of antifungal activity of heterocyclic compounds

Outpatient complications for fungal infections in immunocompromised patients and the development of antimicrobial drug resistance mechanisms demonstrate the need to develop new antifungal agents. In this perspective, heterocyclic compounds namely thiazolylhydrazones, furan, tetrazole, triazole and thiadiazoline derivatives were synthesized and tested in vitro against seven clinical importance Cryptococcus and Candida species. In this study, virtual screening techniques were applied using a scaffold-hopping database, FDA approved drugs and a ZINC subset. Some of the compounds evaluated showed promising antifungal activity against C. albicans, C. glabrata, C. krusei, C. parapsilosis, C. tropicalis, C. neoformans and C. gatti, displaying minimal inhibitory concentration (MIC) values in the range of 0.12–250 µM.

CYP51 Mutations in the Fusarium solani Species Complex: First Clue to Understand the Low Susceptibility to Azoles of the Genus Fusarium.

Members of Fusarium solani species complex (FSSC) are cosmopolitan filamentous fungi responsible for invasive fungal infections in immunocompromised patients. Despite the treatment recommendations, many strains show reduced sensitivity to voriconazole. The objective of this work was to investigate the potential relationship between azole susceptibility and mutations in CYP51 protein sequences. Minimal inhibitory concentrations (MICs) for azole antifungals have been determined using the CLSI (Clinical and Laboratory Standards Institute) microdilution method on a panel of clinical and environmental strains. CYP51A, CYP51B and CYP51C genes for each strain have been sequenced using the Sanger method. Amino acid substitutions described in multiple azole-resistant Aspergillus fumigatus (mtrAf) strains have been sought and compared with other Fusarium complexes’ strains. Our results show that FSSC exhibit point mutations similar to those described in mtrAf. Protein sequence alignments of CYP51A, CYP51B and CYP51C have highlighted different profiles based on sequence similarity. A link between voriconazole MICs and protein sequences was observed, suggesting that these mutations could be an explanation for the intrinsic azole resistance in the genus Fusarium. Thus, this innovative approach provided clues to understand low azole susceptibility in FSSC and may contribute to improving the treatment of FSSC infection.

Invasive Aspergillosis Manifesting As An Intracardiac Mass In A Heart Transplant Patient

<h3>Introduction</h3> Invasive aspergillosis (IA) is the third most common form of invasive fungal infections in immunocompromised patients, and has the second highest mortality rate at 30-70%. Invasion of lung parenchyma is the most common presentation, but can rarely present as aspergillus endocarditis. To our knowledge, IA presenting as a mass lesion in the heart is very rare and has never been reported in an orthotopic heart transplant (OHT) patient. We present a case of invasive aspergillus manifesting as an intracardiac mass in the right atrium (RA) in a heart transplant patient who survived. <h3>Patient presentation</h3> This is a 68 year-old-male with ischemic cardiomyopathy s/p OHT in June 2019 complicated by Aspergillus fumigatus sternal osteomyelitis requiring complete sternectomy on chronic antifungal therapy who was readmitted for right shoulder pain and failure to thrive. On admission, the patient was afebrile and hemodynamically stable. Pertinent workup showed transthoracic echocardiogram (TTE) with right atrial (RA) mass confirmed to be 3.5 × 3.3 cm by transesophageal echocardiogram (TEE) attached to interatrial septum. Initial malignancy workup was negative. Further infectious work up was remarkable for Aspergillus antigens. Intra-cardiac echocardiogram (ICE) and TEE techniques were utilized to locate and culture the mass. Argon epitome was placed into the mass under fluoroscopic and intracardiac echo guidance, extracting two specimens. Gross examination suggested identical specimens without any evidence of endocardium or lipomatous tissue. Initial pathology showed findings consistent with a thrombus but no evidence of fungal organisms, inflammation or malignancy. However, cultures from the specimen revealed Aspergillus fumigatus. Unfortunately, the patient was deemed a poor surgical candidate for resection due to other comorbidities and attempts are being made for long term antifungal therapy in management. <h3>Discussion</h3> Opportunistic infections such as invasive fungal infections are the leading cause of mortality in heart transplant recipients. Approximately 65% of OHT cases will have an infection within the first year of surgery. In a single institution, both incidence and mortality of IA in heart transplant recipients declined over the years. Despite this decrease, it remains a common pathogen observed in immunocompromised populations, specifically in solid organ transplantations. Most IA present as pulmonary disease as the route of entry for aspergillus conidia particles is inhalation, but rarely has intracardiac manifestations. To our knowledge, this is the first case report of invasive aspergillosis in a heart transplant recipient who had rare systemic manifestations including intra-cardiac mass and sternal osteomyelitis.

Opportunistic Fungal Infections in Immunocompromised Patients of a Tertiary Care Centre, Amritsar, India

Introduction: The incidence of opportunistic fungal infections has increased considerably in recent years. The clinical manifestations of these infections are non specific, and laboratory methods generally cannot diagnose infection at an initial phase.So,it is necessary to understand these infections for the treatment of immunocompromised patients adequately. Aim: To study the prevalence of common opportunistic fungal infections in immunocompromised patients in northern India. Materials and Methods: A prospective cross-sectional observational prevalence study was conducted in the Department of Microbiology, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, Punjab, India, from March 2020 to August 2021, on 185 immunocompromised patients. Follow-up was done for a period of six month. Weekly blood samples were drawn and presence of any fungal colonisation was identified with methods such as growth in sabouraud dextrose agar and Indian ink staining. Statistical tests used were prevalence and positive prevalence rate to estimate the most common opportunistic infection in immunocompromised individuals. Results: Out of 185 patients, oropharyngeal candidasis was found to be most common (143, 77.3%) in which opportunistic fungal infections caused by Candida spp. were found in 67 (46.8%) patients representing the most common causing agents followed by Pneumocystis jiroveci (12.5%) and Cryptococcus meningitis (38.2%). Conclusion: Oropharyngeal candidiasis was found to be most common opportunistic fungal infection. This study would help to extend the awareness to clinicians to come up with the right diagnosis and earlier treatment of those infections with the right management of the patients especially in resource limited regions in India.

Effectiveness of a real-time PCR for diagnosis of Pneumocystis pneumonia in immunocompromised patients – Experience from a tertiary care center, India

Pneumocystis jirovecii pneumonia (PCP) is a life-threatening fungal infection in immunocompromised patients. Traditionally, the laboratory diagnosis of PCP relied on the visualization of organisms by microscopy as Pneumocystis cannot be readily cultured in the laboratory. The polymerase chain reaction (PCR) method is preferred over the conventional microscopic methods as PCR is rapid and found to have higher sensitivity. This retrospective study aimed to analyze the diagnostic value of a real-time PCR (qPCR) for routine diagnosis of PCP in immunocompromised patients with various underlying conditions. The qPCR targets a 121 bp fragment of P.jirovecii mitochondrial large subunit rRNA gene. The study was conducted in a 2600-bed tertiary care hospital between January and December 2019. All patients whose respiratory samples were tested for PCP by qPCR were included. The clinical diagnosis was made for each patient and categorized into PCP and non-PCP based on multi-component clinical criteria by a multi-disciplinary team. The performance characteristics of qPCR were analyzed using clinical diagnosis as the reference. A total of 339 respiratory samples from 289 patients were tested for PCP by qPCR during the study period. The overall sensitivity and specificity of qPCR were 84.75% (95% CI, 73.01% to 92.78%) and 96.1% (95% CI, 92.7 to 98.2), respectively. The sensitivity was slightly higher among HIV-infected patients (91%) than the non- HIV group (81%). The PCR exhibited higher sensitivity in bronchoalveolar lavage (BAL) (94%) than in sputum samples (81%). The colonization can be ruled out with the cycle threshold (CT) value of below 34 with a sensitivity and specificity of 100% and 78%, respectively.The real-time PCR showed good sensitivity and specificity for routine diagnosis of PCP in patients with various underlying conditions. In addition, a cut-off CT value (≤ 34) was determined to exclude colonization from active pneumonia.

First case of Magnusiomyces capitatus endocarditis in South India

Magnusiomyces capitatus (previously known as Geotrichum capitatum or Trichosporon capitatum) is a rare cause of fungal infection in immunocompromised patients mainly seen in hematological malignancies. 1,2 We are presenting an extremely rare case of “Mcapitatus endocarditis” in an immunocompromised patient, a 15-year-old boy with Focal segmental glomerulosclerosis– Not otherwise specified, diagnosed after tricuspid valve vegetatectomy in south India. Fungal identification was performed at standard laboratory by phenotypic characteristics. He was successfully treated with combination of surgery and Inj. liposomal Amphotericin B with voriconazole. Keywords: Magnusiomyces capitatus, Geotrichum capitatum, Trichosporon captiatum, Endocarditis.

PULMONARY NODULES AND THE HALO SIGN: CAN WE THINK OF JUST ONE DIAGNOSIS?

TOPIC: Imaging TYPE: Medical Student/Resident Case Reports INTRODUCTION: The halo sign in computed tomography (CT) scan of the chest consists of ground-glass opacity around pulmonary lesions. It has been linked to a wide variety of pathological processes #1. CASE PRESENTATION: Male, 66 years old, admitted for hyperglycemia; he had no respiratory symptoms. At physical examination he presented with jaundice, choluria and acholia. The laparoscopic pancreatic biopsy confirmed the presence of pancreatic cancer. Chest-abdomen-pelvis CT scan were performed for staging, and identified numerous bilateral pulmonary nodules, infracentrimetic, with a circular area of ground-glass attenuation (halo sign), being hypothesized invasive pulmonar aspergillosis or metastatic lesions with associated bleeding, the last one being less likely because the primary lesion had hypovascular behavior. He was subsequently submitted to bronchofibroscopy, whose cytology of the bronchoalveolar lavage was negative for neoplastic cells, identifying the existence of fungal hyphae; the mycological examination was negative. The galactomannan survey was also negative. He repeated bronchofibroscopy in an attempt to identify the fungus, however, the result was also negative. It was decided to perform a transthoracic lung biopsy, which confirmed the presence of metastases. The patient died a few weeks later, due to systemic progression of the neoplasm. DISCUSSION: The halo sign was initially believed to be a specific sign of invasive pulmonary aspergillosis, but it has already been associated with multiple other pathologies, such as, inflammation, infection or cancer #2. CONCLUSIONS: In this case, it is highlighted the difficulty in establishing a definitive diagnosis and the importance of placing multiple hypotheses of diagnosis in the presence of some characteristic radiological signs, such as the halo sign, very suggestive of invasive pulmonary fungal infections in immunocompromised patients, but not specific. REFERENCE #1: Lee YR, Choi YW, Lee KJ, Jeon SC, Park CK, Heo JN. CT halo sign: the spectrum of pulmonary diseases. Br J Radiol 2005; 78:862–5 REFERENCE #2: Parrón M, Torres I, Pardo M, Morales C, Navarro M, Martínez-Schmizcraft M. Signo del halo en la tomografía computarizada de tórax: diagnóstico diferencial con correlación anatomopatológica [The halo sign in computed tomography images: differential diagnosis and correlation with pathology findings]. Arch Bronconeumol. 2008 Jul;44(7):386-92. Spanish. PMID: 18727892. DISCLOSURES: No relevant relationships by Mariana Argel, source=Web Response No relevant relationships by Marta Sousa, source=Web Response No relevant relationships by António Torres, source=Web Response

EQUAL Score Scedosporiosis/Lomentosporiosis 2021: a European Confederation of Medical Mycology (ECMM) tool to quantify guideline adherence.

BackgroundInvasive scedosporiosis and lomentosporiosis are life-threatening fungal infections in immunocompromised patients with complex diagnostic and treatment patterns.ObjectivesTo develop a scoring tool to facilitate and quantify adherence to current guideline recommendations for diagnosis, treatment and follow-up of invasive scedosporiosis and lomentosporiosis.MethodsExperts from European Confederation of Medical Mycology (ECMM) excellence centres reviewed current guidelines for scedosporiosis and lomentosporiosis. Recommendations for diagnosis, treatment and follow-up were summarized, assembled and weighted according to their strength of recommendation and level of evidence (strongly recommended = 3 points; moderately recommended = 2 points; marginally recommended = 1 point; recommended against = 0 points). Additional items considered of high importance for clinical management were also weighted.ResultsA total of 170 recommendations were identified. A 21-item tool was developed and embedded into the EQUAL score card. Nine items for diagnosis with 18 achievable points were assembled. For treatment, three general recommendation items with a maximal score of 9 were identified, while for specific antifungal treatment the two fungal pathogens were separated. Three and four items were established for scedosporiosis and lomentosporiosis, respectively, with a maximum achievable score of 3 due to the separation of different treatment options with the maximum point value of 3 for voriconazole-based treatment. Follow-up comprised two items (4 points maximum). Key recommendations for clinical outcome were weighted accordingly.ConclusionsWe propose the EQUAL Score Scedosporiosis/Lomentosporiosis to quantify adherence to current guideline recommendations for management of these rare infections. The score remains to be validated in real-life patient cohorts and correlated with patient outcome.