Radiological differentiation between bacterial orbital cellulitis and invasive fungal sino-orbital infections.

PURPOSE: Invasive fungal orbital infections (IFOI) may be difficult to differentiate from sinogenic bacterial orbital cellulitis (OC). This study investigates the features differentiating OC from IFOI on magnetic resonance imaging (MRI). METHODS: Retrospective study of adult patients with sinogenic OC and IFOI with pre-intervention MRI. Patients without post-septal involvement, non-sinogenic OC (e.g.: secondary to trauma) and poor-quality scans were excluded. Independent Sample's t test and Fisher's exact test were conducted with p < 0.05 deemed statistically significant. RESULTS: Eleven cases each of OC (Mean age: 41.6 ± 18.4 years-old, Male: 10) and IFOI (Mean age: 65.0 ± 16.6 years-old, Male: 9) between 2006 and 2023. IFOI patients were older, more likely immunocompromised and had a lower mean white-cell count (p value = 0.005, 0.035 and 0.017, respectively). The ethmoid and maxillary sinuses were most commonly involved in both entities. Pre-septal and lacrimal gland involvement were more common in OC (p = 0.001 and 0.008, respectively). Infiltrative OC orbital lesions were poorly demarcated, whilst those in IFOI were expansile/mass-like invading the orbit from the adjacent paranasal sinuses. Specific IFOI features included loss-of-contrast-enhancement (LoCE) of paranasal sinus tissues with orbital extension. Extra-orbital and -sinonasal extension indicative of IFOI included contiguous skull base or pterygopalatine fossa involvement, retro-antral and masticator space stranding and vasculitis. CONCLUSION: This study describes the key MRI features of IFOI including differentiating markers from OC. These specific features, such as LoCE of the paranasal and orbital soft tissues, the location and pattern of contiguous soft-tissue involvement, provide expedient identification of IFOI which necessitate early surgical intervention for microbiological confirmation of an invasive fungal pathology.

Mucorales: A systematic review to inform the World Health Organization priority list of fungal pathogens.

The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal priority pathogens list (FPPL). This systematic review aimed to evaluate the epidemiology and impact of invasive fungal disease due to Mucorales. PubMed and Web of Science were searched to identify studies published between January 1, 2011 and February 23, 2021. Studies reporting on mortality, inpatient care, complications and sequelae, antifungal susceptibility, risk factors, preventability, annual incidence, global distribution, and emergence during the study time frames were selected. Overall, 24 studies were included. Mortality rates of up to 80% were reported. Antifungal susceptibility varied across agents and species, with the minimum inhibitory concentrations lowest for amphotericin B and posaconazole. Diabetes mellitus was a common risk factor, detected in 65%-85% of patients with mucormycosis, particularly in those with rhino-orbital disease (86.9%). Break-through infection was detected in 13.6%-100% on azole or echinocandin antifungal prophylaxis. The reported prevalence rates were variable, with some studies reporting stable rates in the USA of 0.094-0.117/10 000 discharges between 2011 and 2014, whereas others reported an increase in Iran from 16.8% to 24% between 2011 and 2015. Carefully designed global surveillance studies, linking laboratory and clinical data, are required to develop clinical breakpoints to guide antifungal therapy and determine accurate estimates of complications and sequelae, annual incidence, trends, and global distribution. These data will provide robust estimates of disease burden to refine interventions and better inform future FPPL.

Aspergillus fumigatus-a systematic review to inform the World Health Organization priority list of fungal pathogens.

Recognizing the growing global burden of fungal infections, the World Health Organization established a process to develop a priority list of fungal pathogens (FPPL). In this systematic review, we aimed to evaluate the epidemiology and impact of invasive infections caused by Aspergillus fumigatus to inform the first FPPL. The pre-specified criteria of mortality, inpatient care, complications and sequelae, antifungal susceptibility, risk factors, preventability, annual incidence, global distribution, and emergence were used to search for relevant articles between 1 January 2016 and 10 June 2021. Overall, 49 studies were eligible for inclusion. Azole antifungal susceptibility varied according to geographical regions. Voriconazole susceptibility rates of 22.2% were reported from the Netherlands, whereas in Brazil, Korea, India, China, and the UK, voriconazole susceptibility rates were 76%, 94.7%, 96.9%, 98.6%, and 99.7%, respectively. Cross-resistance was common with 85%, 92.8%, and 100% of voriconazole-resistant A. fumigatus isolates also resistant to itraconazole, posaconazole, and isavuconazole, respectively. The incidence of invasive aspergillosis (IA) in patients with acute leukemia was estimated at 5.84/100 patients. Six-week mortality rates in IA cases ranged from 31% to 36%. Azole resistance and hematological malignancy were poor prognostic factors. Twelve-week mortality rates were significantly higher in voriconazole-resistant than in voriconazole-susceptible IA cases (12/22 [54.5%] vs. 27/88 [30.7%]; P = .035), and hematology patients with IA had significantly higher mortality rates compared with solid-malignancy cases who had IA (65/217 [30%] vs. 14/78 [18%]; P = .04). Carefully designed surveillance studies linking laboratory and clinical data are required to better inform future FPPL.

Features and global impact of invasive fungal infections caused by Pneumocystis jirovecii: A systematic review to inform the World Health Organization fungal priority pathogens list.

This systematic review evaluates the current global impact of invasive infections caused by Pneumocystis jirovecii (principally pneumonia: PJP), and was carried out to inform the World Health Organization Fungal Priority Pathogens List. PubMed and Web of Science were used to find studies reporting mortality, inpatient care, complications/sequelae, antifungal susceptibility/resistance, preventability, annual incidence, global distribution, and emergence in the past 10 years, published from January 2011 to February 2021. Reported mortality is highly variable, depending on the patient population: In studies of persons with HIV, mortality was reported at 5%-30%, while in studies of persons without HIV, mortality ranged from 4% to 76%. Risk factors for disease principally include immunosuppression from HIV, but other types of immunosuppression are increasingly recognised, including solid organ and haematopoietic stem cell transplantation, autoimmune and inflammatory disease, and chemotherapy for cancer. Although prophylaxis is available and generally effective, burdensome side effects may lead to discontinuation. After a period of decline associated with improvement in access to HIV treatment, new risk groups of immunosuppressed patients with PJP are increasingly identified, including solid organ transplant patients.

Hope on the Horizon? Aptamers in Diagnosis of Invasive Fungal Infections.

Despite remarkable advances in the diagnosis of invasive fungal infections (IFIs), rapid, specific, sensitive, and cost-effective detection methods remain elusive. Due to their stability, ease of production, and specificity to signature molecules of fungal pathogens, short single-stranded sequences of DNA, RNA, and XNA, collectively called aptamers, have emerged as promising diagnostic markers. In this perspective, we summarize recent progress in aptamer-based diagnostic tools for IFIs and discuss how these tools could potentially meet the needs and provide economical and simple solutions for point-of-care for better management of IFIs.

Clinical features of pediatric mucormycosis: role of metagenomic next generation sequencing in diagnosis.

Background: Mucormycosis is an uncommon invasive fungal infection that has a high mortality rate in patients with severe underlying diseases, which leads to immunosuppression. Due to its rarity, determining the incidence and optimal treatment methods for mucormycosis in children is challenging. Metagenomic next-generation sequencing (mNGS) is a rapid, precise and sensitive method for pathogen detection, which helps in the early diagnosis and intervention of mucormycosis in children. In order to increase pediatricians' understanding of this disease, we conducted a study on the clinical features of mucormycosis in children and assessed the role of mNGS in its diagnosis. Methods: We retrospectively summarized the clinical data of 14 children with mucormycosis treated at the First Affiliated Hospital of Zhengzhou University from January 2020 to September 2023. Results: Of the 14 cases, 11 case of mucormycosis were classified as probable, and 3 cases were proven as mucormycosis. Most children (85.71%) had high-risk factors for mucormycosis. All 14 children had lung involvement, with 5 cases of extrapulmonary dissemination. Among the 14 cases, 4 cases underwent histopathological examination of mediastinum, lung tissue or kidney tissue, in which fungal pathogens were identified in 3 patients. Fungal hyphae was identified in 3 cases of mucormycosis, but only 1 case yielded a positive culture result. All patients underwent mNGS testing with samples from blood (8/14), bronchoalveolar lavage fluid (6/14), and tissue (1/14). mNGS detected fungi in all cases: 7 cases had Rhizomucor pusillus, 4 cases had Rhizopus oryzae, 3 cases had Rhizopus microsporus, 1 case had Lichtheimia ramosa, and 1 case had Rhizomucor miehei. Coinfections were found with Aspergillus in 3 cases, bacteria in 3 cases, and viruses in 5 cases. Conclusion: Children with mucormycosis commonly exhibit non-specific symptoms like fever and cough during the initial stages. Early diagnosis based on clinical symptoms and imaging is crucial in children suspected of having mucormycosis. mNGS, as a supplementary diagnostic method, offers greater sensitivity and shorter detection time compared to traditional mucormycosis culture or histopathological testing. Additionally, mNGS enables simultaneous detection of bacteria and viruses, facilitating timely and appropriate administration of antibiotics and thereby enhancing patient outcomes.

Metagenomic next-generation sequencing could play a pivotal role in validating the diagnosis of invasive mold disease of the central nervous system.

Background: Invasive mold diseases of the central nervous (CNS IMD) system are exceedingly rare disorders, characterized by nonspecific clinical symptoms. This results in significant diagnostic challenges, often leading to delayed diagnosis and the risk of misdiagnosis for patients. Metagenomic Next-Generation Sequencing (mNGS) holds significant importance for the diagnosis of infectious diseases, especially in the rapid and accurate identification of rare and difficult-to-culture pathogens. Therefore, this study aims to explore the clinical characteristics of invasive mold disease of CNS IMD in children and assess the effectiveness of mNGS technology in diagnosing CNS IMD. Methods: Three pediatric patients diagnosed with Invasive mold disease brain abscess and treated in the Pediatric Intensive Care Unit (PICU) of the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2023 were selected for this study. Results: Case 1, a 6-year-old girl, was admitted to the hospital with "acute liver failure." During her hospital stay, she developed fever, irritability, and seizures. CSF mNGS testing resulted in a negative outcome. Multiple brain abscesses were drained, and Aspergillus fumigatus was detected in pus culture and mNGS. The condition gradually improved after treatment with voriconazole combined with caspofungin. Case 2, a 3-year-old girl, was admitted with "acute B-lymphoblastic leukemia." During induction chemotherapy, she developed fever and seizures. Aspergillus fumigatus was detected in the intracranial abscess fluid by mNGS, and the condition gradually improved after treatment with voriconazole combined with caspofungin, followed by "right-sided brain abscess drainage surgery." Case 3, a 7-year-old girl, showed lethargy, fever, and right-sided limb weakness during the pending chemotherapy period for acute B-lymphoblastic leukemia. Rhizomucor miehei and Rhizomucor pusillus was detected in the cerebrospinal fluid by mNGS. The condition gradually improved after treatment with amphotericin B combined with posaconazole. After a six-month follow-up post-discharge, the three patients improved without residual neurological sequelae, and the primary diseases were in complete remission. Conclusion: The clinical manifestations of CNS IMD lack specificity. Early mNGS can assist in identifying the pathogen, providing a basis for definitive diagnosis. Combined surgical treatment when necessary can help improve prognosis.

One Case of Drug-Resistant Invasive Fungal Infection after Myelodysplastic Syndrome Chemotherapy.

BACKGROUND: The aim of this study was to evaluate the therapeutic regimen of a patient with myelodysplastic syndrome (MDS) who developed invasive fungal infections caused by drug-resistant Candida tropicalis after chemotherapy and to investigate the effect of drug treatment. METHODS: We referred to the Diagnostic Criteria and Treatment Principles of invasive fungal diseases in patients with hematological diseases and malignant tumors (2013, fourth revised edition) and the Expert Consensus on Clinical Application of Posaconazole (2022 Edition). In addition, the drug treatment regimens of drug-resistant Candida tropicalis were reviewed. The doctors in charge were involved in the drug treatment process, and the ra-tional drug use was selected according to evidence-based medicine. RESULTS: After 4 months of use, the nodules around the body disappeared, and there was no further fever during follow-up. After 6 months of use, posaconazole was discontinued, and the patient continued to follow-up for 1 month without further fever or nodules. CONCLUSIONS: The combination of posaconazole, amphotericin B liposome, and micafungin is effective in the treatment of fluconazole-resistant Candida tropicalis infection.

Performance of rapid on-site evaluation of touch imprints of bronchoscopic biopsies or lung tissue biopsies for the diagnosis of invasive pulmonary filamentous fungi infections in non-neutropenic patients.

The diagnosis of invasive pulmonary fungal disease depends on histopathology and mycological culture; there are few studies on touch imprints of bronchoscopic biopsies or lung tissue biopsies for the diagnosis of pulmonary filamentous fungi infections. The purpose of the present study was to explore the detection accuracy of rapid on-site evaluation of touch imprints of bronchoscopic biopsies or lung tissue biopsies for the filamentous fungi, and it aims to provide a basis for initiating antifungal therapy before obtaining microbiological evidence. We retrospectively analyzed the diagnosis and treatment of 44 non-neutropenic patients with invasive pulmonary filamentous fungi confirmed by glactomannan assay, histopathology, and culture from February 2017 to December 2023. The diagnostic positive rate and sensitivity of rapid on-site evaluation for these filamentous fungi identification, including diagnostic turnaround time, were calculated. Compared with the final diagnosis, the sensitivity of rapid on-site evaluation was 81.8%, and the sensitivity of histopathology, culture of bronchoalveolar lavage fluid, and glactomannan assay of bronchoalveolar lavage fluid was 86.4%, 52.3%, and 68.2%, respectively. The average turnaround time of detecting filamentous fungi by rapid on-site evaluation was 0.17 ± 0.03 hours, which was significantly faster than histopathology, glactomannan assay, and mycological culture. A total of 29 (76.3%) patients received earlier antifungal therapy based on ROSE diagnosis and demonstrated clinical improvement. Rapid on-site evaluation showed good sensitivity and accuracy that can be comparable to histopathology in identification of pulmonary filamentous fungi. Importantly, it contributed to the triage of biopsies for further microbial culture or molecular detection based on the preliminary diagnosis, and the decision on early antifungal therapy before microbiological evidence is available.

Emerging trends of invasive yeast infections and azole resistance in Beijing intensive care units.

BACKGROUND: Invasive fungal infections pose a substantial threat to patients in healthcare settings globally. Recent changes in the prevalence of fungal species and challenges in conducting reference antifungal susceptibility testing emphasize the importance of monitoring fungi and their antifungal resistance. METHODS: A two-phase surveillance project was conducted in Beijing, China, involving 37 centres across 12 districts, from January 2012 to December 2013 and from January 2016 to December 2017. FINDINGS: We found that the proportion of Candida albicans in intensive care units (ICUs) during 2016-2017 exhibited a significant decline compared with the 2012-2013 period, although it remained the most predominant pathogen. In contrast, the prevalence of Nakaseomyces glabratus (formerly Candida glabrata) and Candida tropicalis notably increased during the two-phase surveillance. The high prevalence of C. tropicalis and its resistance to azole drugs posed a serious threat to patients in ICUs. The pathogens causing invasive fungal infections in Beijing were relatively sensitive to echinocandins. While C. albicans continued to exhibit susceptibility to azoles, the resistance and growth rates of C. tropicalis towards azoles were particularly prominent. Concerns were raised due to the emergence of multiple, short-term isolates of Clavispora lusitaniae and Candida parapsilosis complex in neonatal ICUs, given their similarity in antifungal susceptibilities. Such occurrences point towards the potential for transmission and persisting presence of these pathogens within the ICU environment. CONCLUSIONS: Our study complements existing data on the epidemiology of invasive fungal infections. It is imperative to exercise cautious medication management for ICU patients in Beijing, paying particular attention to azole resistance in C. tropicalis.

Universal digital high-resolution melting for the detection of pulmonary mold infections.

Invasive mold infections (IMIs) are associated with high morbidity, particularly in immunocompromised patients, with mortality rates between 40% and 80%. Early initiation of appropriate antifungal therapy can substantially improve outcomes, yet early diagnosis remains difficult to establish and often requires multidisciplinary teams evaluating clinical and radiological findings plus supportive mycological findings. Universal digital high-resolution melting (U-dHRM) analysis may enable rapid and robust diagnoses of IMI. A universal fungal assay was developed for U-dHRM and used to generate a database of melt curve signatures for 19 clinically relevant fungal pathogens. A machine learning algorithm (ML) was trained to automatically classify these pathogen curves and detect novel melt curves. Performance was assessed on 73 clinical bronchoalveolar lavage samples from patients suspected of IMI. Novel curves were identified by micropipetting U-dHRM reactions and Sanger sequencing amplicons. U-dHRM achieved 97% overall fungal organism identification accuracy and a turnaround time of ~4 hrs. U-dHRM detected pathogenic molds (Aspergillus, Mucorales, Lomentospora, and Fusarium) in 73% of 30 samples classified as IMI, including mixed infections. Specificity was optimized by requiring the number of pathogenic mold curves detected in a sample to be >8 and a sample volume to be 1 mL, which resulted in 100% specificity in 21 at-risk patients without IMI. U-dHRM showed promise as a separate or combination diagnostic approach to standard mycological tests. U-dHRM's speed, ability to simultaneously identify and quantify clinically relevant mold pathogens in polymicrobial samples, and detect emerging opportunistic pathogens may aid treatment decisions, improving patient outcomes. IMPORTANCE: Improvements in diagnostics for invasive mold infections are urgently needed. This work presents a new molecular detection approach that addresses technical and workflow challenges to provide fast pathogen detection, identification, and quantification that could inform treatment to improve patient outcomes.

Kodamaea ohmeri: A rare yeast causing invasive infections in immunocompromised patients.

INTRODUCTION: Kodamaea ohmeri is a rare, recognized pathogen that has previously been isolated from environmental sources. The patients commonly affected by this yeast include immunocompromised as well as immunocompetent patients having several associated risk factors. METHODOLOGY: We report three cases in which K. ohmeri was isolated from blood using Bact T/ALERT. Identification was carried out by MALDI-TOF MS (Vitek-MS, BioMérieux, Marcy-l'Etoile, France) in addition to color characteristics on chromogenic media. The patients had diminished immune response on account of a multitude of comorbidities. RESULTS: K. ohmeri can be misidentified as Candida tropicalis, Candida albicans, or Candida hemolounii by conventional methods; correct and timely identification can be achieved by MALDI-TOF MS. Antifungal susceptibility breakpoints for K. ohmeri are currently not defined. An Echinocandin was added to the treatment regimen of all three of the cases. CONCLUSIONS: Identification of K. ohmeri using conventional methods is difficult and unusual yeasts should be carefully observed, especially upon prolonged incubation.

End-organ damage from neonatal invasive fungal infection: a 14-year retrospective study from a tertiary center in China.

BACKGROUND: Invasive fungal infection (IFI) has become an increasing problem in NICU neonates, and end-organ damage (EOD) from IFI is one of the leading causes of morbidity and mortality in neonates. This study was conducted to summarize clinical data on epidemiology, risk factors, causative pathogens, and clinical outcomes of IFI-associated EOD among neonates in a center in China for the sake of providing references for prevention and treatment of fungal infections in neonates in future. METHODS: The clinical data of IFI neonates who received treatment in a tertiary NICU of China from January 2009 to December 2022 were retrospectively analyzed, including causative pathogens and the incidence of EOD. The neonates were divided into EOD group and non-EOD (NEOD) group. The general characteristics, risk factors and clinical outcomes of the two groups were compared. RESULTS: Included in this study were 223 IFI neonates (137 male and 86 female) with a median gestational age (GA) of 30.71 (29,35) weeks and a median birth weight (BW) of 1470 (1120,2150) g. Of them, 79.4% were preterm infants and 50.2% were born at a GA of ≥ 28, <32 weeks, and 37.7% with BW of 1000-1499 g. Candida albicans (C. albicans) was the most common Candida spp. in these neonates, accounting for 41.3% of all cases, followed by C. parapsilosis (30.5%) and C. glabrata (7.2%). EOD occurred in 40 (17.9%) of the 223 cases. Fungal meningitis was the most common EOD, accounting for 13.5% of the 40 EOD cases. There was no significant difference in the premature birth rate, delivery mode, GA and BW between EOD and NEOD groups, but the proportion of male infants with EOD was higher than that without. There was no significant difference in antenatal corticosteroid use, endotracheal intubation, invasive procedures, use of antibiotics, total parenteral nutrition, blood transfusion, postnatal corticosteroid use, fungal prophylaxis and the incidence of necrotizing enterocolitis between the two groups, but the proportion of C. albicans infection cases in EOD group was higher than that in NEOD group (57.5% vs. 37.7%). Compared with NEOD group, the proportion of cured or improved infants in EOD group was significantly lower (P < 0.05), and the number of infants who died or withdrew from treatment was larger (P < 0.05). CONCLUSIONS: Our retrospective study showed that preterm infants were prone to fungal infection, especially very preterm infants. C. albicans was the most common Candida spp. for IFI, and was a high-risk factor for EOD. EOD can occur in both full-term and premature infants, so the possibility of EOD should be considered in all infants with IFI.

Novel antifungals and treatment approaches to tackle resistance and improve outcomes of invasive fungal disease.

SUMMARYFungal infections are on the rise, driven by a growing population at risk and climate change. Currently available antifungals include only five classes, and their utility and efficacy in antifungal treatment are limited by one or more of innate or acquired resistance in some fungi, poor penetration into "sequestered" sites, and agent-specific side effect which require frequent patient reassessment and monitoring. Agents with novel mechanisms, favorable pharmacokinetic (PK) profiles including good oral bioavailability, and fungicidal mechanism(s) are urgently needed. Here, we provide a comprehensive review of novel antifungal agents, with both improved known mechanisms of actions and new antifungal classes, currently in clinical development for treating invasive yeast, mold (filamentous fungi), Pneumocystis jirovecii infections, and dimorphic fungi (endemic mycoses). We further focus on inhaled antifungals and the role of immunotherapy in tackling fungal infections, and the specific PK/pharmacodynamic profiles, tissue distributions as well as drug-drug interactions of novel antifungals. Finally, we review antifungal resistance mechanisms, the role of use of antifungal pesticides in agriculture as drivers of drug resistance, and detail detection methods for antifungal resistance.

Dynamics and prognostic value of plasma cell-free DNA PCR in patients with invasive aspergillosis and mucormycosis.

Aspergillus species and Mucorales agents are the primary etiologies of invasive fungal disease (IFD). Biomarkers that predict outcomes are needed to improve care. Patients diagnosed with invasive aspergillosis and mucormycosis using plasma cell-free DNA (cfDNA) PCR were retested weekly for 4 weeks. The primary outcome included all-cause mortality at 6 weeks and 6 months based on baseline cycle threshold (CT) values and results of follow-up cfDNA PCR testing. Forty-five patients with Aspergillus and 30 with invasive Mucorales infection were retested weekly for a total of 197 tests. Using the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORTC/MSG) criteria, 30.7% (23/75), 25.3% (19/75), and 38.7% (29/75) had proven, probable, and possible IFD, respectively. In addition, 97.3% (73/75) were immunocompromised. Baseline CT increased significantly starting at week 1 for Mucorales and week 2 for Aspergillus. Aspergillosis and mucormycosis patients with higher baseline CT (CT >40 and >35, respectively) had a nonsignificantly higher survival rate at 6 weeks, compared with patients with lower baseline CT. Mucormycosis patients with higher baseline CT had a significantly higher survival rate at 6 months. Mucormycosis, but not aspergillosis patients, with repeat positive cfDNA PCR results had a nonsignificantly lower survival rate at 6 weeks and 6 months compared with patients who reverted to negative. Aspergillosis patients with baseline serum Aspergillus galactomannan index <0.5 and <1.0 had significantly higher survival rates at 6 weeks when compared with those with index ≥0.5 and ≥1.0, respectively. Baseline plasma cfDNA PCR CT can potentially be used to prognosticate survival in patients with invasive Aspergillus and Mucorales infections. IMPORTANCE: We show that Aspergillus and Mucorales plasma cell-free DNA PCR can be used not only to noninvasively diagnose patients with invasive fungal disease but also to correlate the baseline cycle threshold with survival outcomes, thus potentially allowing the identification of patients at risk for poor outcomes, who may benefit from more targeted therapies.

Utility of an in-house real-time PCR in whole blood samples as a minimally invasive method for early and accurate diagnosis of invasive mould infections.

INTRODUCTION: Invasive mould infections (IMIs) are a leading cause of death in patients with compromised immune systems. Proven invasive mould infection requires detection of a fungus by histopathological analysis of a biopsied specimen, sterile culture, or fungal DNA amplification by PCR in tissue. However, the clinical performance of a PCR assay on blood samples taken from patients suspected of invasive mould disease has not been fully evaluated, particularly for the differential diagnosis of invasive aspergillosis (IA) and invasive Mucormycosis (IM). OBJECTIVES: To assess the diagnostic utility of our previously validated in-house real-time PCR in blood samples for diagnosis of invasive aspergillosis and mucormycosis in patients with suspected invasive mould infection. METHODS: All patients with suspected invasive mould infection were prospectively enrolled from May 2021 to July 2021. Conventional fungal diagnosis was performed using tissue and respiratory samples. In-house PCR was performed on blood samples and its diagnostic performance evaluated. RESULTS: A total of 158 cases of suspected invasive mould infection were enrolled in the study. The sensitivity and specificity of in-house PCR performed on blood samples was found to be 92.5% and 81.4% respectively for diagnosis of probable IA, and 65% and 84.62% respectively for diagnosis of proven and probable IM. It was also able to detect 3 out of 5 cases of possible IM where no other microbiological evidence of IM was obtained. CONCLUSIONS: This assay could be helpful in minimally invasive diagnosis of IMIs for patients in whom invasive sampling is not feasible, especially as a preliminary or screening test. It can help in early diagnosis, anticipating conventional laboratory confirmation by days or weeks. Possible correlation between fungal load and mortality can help in initiating aggressive treatment for patients with high initial fungal load.

Increase in the incidence of invasive fungal infections due to Volvariella Volvacea.

PURPOSE: We aimed to show the increasing incidence of invasive fungal infections due to Volvariella Volvacea in patients with immunosuppression. METHODS: We present a case of an invasive fungal infection caused by Volvariella volvacea, and summarize the clinical and pathological features based on this case and a review of the literature. RESULTS: A total of seven patients with IFIs due to Volvariella Volvacea have been reported in the literature. The majority of cases have been obtained between 2019 and 2022. Including our case, they all had acquired immunosuppression. The lung and brain were the most commonly affected organs. All eight of these patients received antifungal therapy, but five still died one to seven months after occurrences of IFIs. CONCLUSION: The incidence of invasive fungal infections due to Volvariella Volvacea is increasing in recent years. It mainly occurred in patients with immunosuppression, especially in patients with malignant hematological cancers, and increased mortality.

Overview of invasive fungal infections in children in South America - the threat of resistant Candida species and the role of climate change in the new geographic distribution of endemic systemic mycosis.

PURPOSE OF REVIEW: Invasive fungal infection (IFI) in children is a growing problem with crescent morbidity and mortality, well recognized in developed countries, affecting mainly immunocompromised children, including neonates and children in intensive care units. The burden of IFI in South American children is less well comprehended. In addition, the current epidemiology of endemic systemic mycoses in children may have changed over time. RECENT FINDINGS: Candida spp. infections are very prevalent in South America hospitalized children, especially in neonates, in a rate far superior compared to developed countries. C. auris, has already been responsible for outbreaks in neonates and children in Venezuela and Colombia. Sporotrichosis is well established as an urban zoonosis in impoverish families. Paracoccidioidomycosis and histoplasmosis are affecting new areas of Brazil, probably due to climate change, deforestation, and human migration. SUMMARY: This review aims to unveil the real dimension of these infections in South American children. Hopefully, the awareness brought by this review will help healthcare professionals to recognize IFI more easily and it will provide support for getting more resources for IFI treatment and prevention.

Therapeutic drug monitoring of antifungal therapies: do we really need it and what are the best practices?

INTRODUCTION: Despite advancements, invasive fungal infections (IFI) still carry high mortality rates, often exceeding 30%. The challenges in diagnosis, coupled with limited effective antifungal options, make managing IFIs complex. Antifungal drugs are essential for IFI management, but their efficacy can be diminished by drug-drug interactions and pharmacokinetic variability. Therapeutic Drug Monitoring (TDM), especially in the context of triazole use, has emerged as a valuable strategy to optimize antifungal therapy. AREAS COVERED: This review provides current evidence regarding the potential benefits of TDM in IFI management. It discusses how TDM can enhance treatment response, safety, and address altered pharmacokinetics in specific patient populations. EXPERT OPINION: TDM plays a crucial role in achieving optimal therapeutic outcomes in IFI management, particularly for certain antifungal agents. Preclinical studies consistently show a link between therapeutic drug levels and antifungal efficacy. However, clinical research in mycology faces challenges due to patient heterogeneity and the diversity of fungal infections. TDM's potential advantages in guiding Echinocandin therapy for critically ill patients warrant further investigation. Additionally, for drugs like Posaconazole, assessing whether serum levels or alternative markers like saliva offer the best measure of efficacy is an intriguing question.