[Saksenaea caused invasive infection in an immunocompetent patient after trauma]. / Saksenaea-svamp gav invasiv infektion hos frisk traumapatient.

This text discusses a rare case of soft tissue infection caused by the fungus Saksenaea in a young, immunocompetent woman following an all-terrain vehicle accident abroad. Despite initial treatment, her wound worsened, necessitating multiple surgical revisions and aggressive antifungal therapy with liposomal Amphotericin B. The interdisciplinary collaboration among orthopedic surgeons, infectious disease specialists, and plastic surgeons played a vital role in her successful treatment. Prompt identification of the fungus and immediate intervention were crucial. This case emphasizes the importance of awareness among healthcare providers regarding this rare condition and underscores the significance of early diagnosis and timely surgical and medical interventions for a positive outcome.

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.

Exploring European Consensus About the Remaining Treatment Challenges and Subsequent Opportunities to Improve the Management of Invasive Fungal Infection (IFI) in the Intensive Care Unit.

BACKGROUND: The global prevalence of invasive fungal infections (IFI) is increasing, particularly within Intensive Care Units (ICU), where Candida spp. and Aspergillus spp. represent the most important pathogens. Diagnosis and management of IFIs becomes progressively challenging, with increasing antifungal resistance and the emergence of rare fungal species. Through a consensus survey focused on assessing current views on how IFI should be managed, the aim of this project was to identify challenges around diagnosing and managing IFIs in the ICU. The current status in different countries and perceived challenges to date amongst a multidisciplinary cohort of healthcare professionals involved in the care of IFI in the ICU was assessed. METHODS: Using a modified Delphi approach, an expert panel developed 44 Likert-scale statements across 6 key domains concerning patient screening and minimal standards for diagnosis of IFIs in ICU; initiation and termination of antifungal treatments and how to minimise their side effects and insights for future research on this topic. These were used to develop an online survey which was distributed on a convenience sampling basis utilising the subscriber list held by an independent provider (M3 Global). This survey was distributed to intensivists, infectious disease specialists, microbiologists and antimicrobial/ICU pharmacists within the UK, Germany, Spain, France and Italy. The threshold for consensus was set at 75%. RESULTS: A total of 335 responses were received during the five-month collection period. From these, 29/44 (66%) statements attained very high agreement (≥ 90%), 11/44 (25%) high agreement (< 90% and ≥ 75%), and 4/44 (9%) did not meet threshold for consensus (< 75%). CONCLUSION: The results outline the need for physicians to be aware of the local incidence of IFI and the associated rate of azole resistance in their ICUs. Where high clinical suspicion exists, treatment should start immediately and prior to receiving the results from any diagnostic test. Beta-D-glucan testing should be available to all ICU centres, with results available within 48 h to inform the cessation of empirical antifungal therapy. These consensus statements and proposed measures may guide future areas for further research to optimise the management of IFIs in the ICU.

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.

Deciphering Unexpected Vascular Locations of Scedosporium spp. and Lomentospora prolificans Fungal Infections, France.

Scedosporium spp. and Lomentospora prolificans are emerging non-Aspergillus filamentous fungi. The Scedosporiosis/lomentosporiosis Observational Study we previously conducted reported frequent fungal vascular involvement, including aortitis and peripheral arteritis. For this article, we reviewed 7 cases of Scedosporium spp. and L. prolificans arteritis from the Scedosporiosis/lomentosporiosis Observational Study and 13 cases from published literature. Underlying immunosuppression was reported in 70% (14/20) of case-patients, mainly those who had solid organ transplants (10/14). Osteoarticular localization of infection was observed in 50% (10/20) of cases; infections were frequently (7/10) contiguous with vascular infection sites. Scedosporium spp./Lomentospora prolificans infections were diagnosed in 9 of 20 patients ≈3 months after completing treatment for nonvascular scedosporiosis/lomentosporiosis. Aneurysms were found in 8/11 aortitis and 6/10 peripheral arteritis cases. Invasive fungal disease--related deaths were high (12/18 [67%]). The vascular tropism of Scedosporium spp. and L. prolificans indicates vascular imaging, such as computed tomography angiography, is needed to manage infections, especially for osteoarticular locations.

Clinical performance of metagenomic next-generation sequencing for diagnosis of invasive fungal disease after hematopoietic cell transplant.

Background: Timely diagnosis and appropriate antifungal therapy are critical for improving the prognosis of patients with invasive fungal disease (IFD) after hematopoietic stem cell transplantation (HSCT). We evaluated the performance of metagenomic next-generation sequencing (mNGS) and conventional microbiological testing (CMT), as well as the diagnosis, therapeutic management, and outcomes of IFD after HSCT. Methods: We retrospectively studied 189 patients who underwent HSCT and were considered at risk for IFD. In total, 46 patients with IFD were enrolled in this study. The IFD consensus was followed for classifying IFD incidents. Results: Forty-six patients were diagnosed with proven/probable (n = 12), possible (n = 27), and undefined (n = 7) IFD. Aspergillus was the most commonly detected fungal genus. Mucormycosis was found in 15 patients; two had Aspergillus, and one had Candida infections. Compared to CMT, mNGS significantly reduced the time required to identify pathogens (P = 0.0016). mNGS had a much higher sensitivity than CMT (84.78% vs. 36.96%; P < 0.0001). A total of 76.09% of patients received antifungal prophylaxis during fungal infections. All Pneumocystis infections occurred later than 100 days after transplantation. Among patients with Pneumocystis infection, 71.43% occurred following sulfonamide withdrawal, and subsequent treatment with sulfonamide alone or in combination with other drugs was effective. Based on the empirical antifungal treatment, the dosages, modes of administration, frequency of administration, or antifungal of 55.26% of the patients were changed according to the mNGS results. The 4-year overall survival rate of patients diagnosed with IFD after transplantation was 71.55% (95% CI, 55.18%-85.82%). Hypoproteinemia and corticosteroid use are independent risk factors for IFD. Conclusion: mNGS, which has a high sensitivity and a short detection time, aids in the diagnosis and prognosis of pathogenic fungi. As a powerful technology, mNGS can influence treatment decisions in patients with IFD following HSCT.

Identification of Irpex and Rhodotorula on surveillance bronchoscopy in a pediatric lung transplant recipient: A case report and review of literature of these atypical fungal organisms.

BACKGROUND: Invasive fungal disease (IFD) is a frequent complication in pediatric lung transplant recipients, occurring in up to 12% of patients in the first year. Risk factors for infection include impaired lung defenses and intense immunosuppressive regimens. While most IFD occurs from Aspergillus, other fungal conidia are continuously inhaled, and infections with fungi on a spectrum of human pathogenicity can occur. CASE REPORT: We report a case of a 17-year-old lung transplant recipient in whom Irpex lacteus and Rhodotorula species were identified during surveillance bronchoscopy. She was asymptomatic and deemed to be colonized by Irpex lacteus and Rhodotorula species following transplant. 2 years after transplantation, she developed a fever, respiratory symptoms, abnormal lung imaging, and histological evidence of acute and chronic bronchitis on transbronchial biopsy. After developing symptoms concerning for a pulmonary infection and graft dysfunction, she was treated for a presumed IFD. Unfortunately, further diagnostic testing could not be performed at this time given her tenuous clinical status. Despite the initiation of antifungal therapy, her graft function continued to decline resulting in a second lung transplantation. CONCLUSIONS: This case raises the concern for IFD in lung transplant recipients from Irpex species. Further investigation is needed to understand the pathogenicity of this organism, reduce the incidence and mortality of IFD in lung transplant recipients, and refine the approach to diagnosis and manage the colonization and isolation of rare, atypical fungal pathogens in immunocompromised hosts.

[Diagnostic approaches for invasive mycoses: what's hot?] / Diagnostik bei invasiven Mykosen: What's hot?

Invasive fungal infections are a significant cause of morbidity and mortality in immunocompromised patients. The primary and most frequent pathogens in Europe are Aspergillus and Candida species. However, other representatives such as Mucorales, Trichosporon, and Fusarium species are increasingly being identified. Confirming the diagnosis of an invasive mycosis is challenging; apart from imaging and clinical presentation, essential diagnostic elements include conventional fungal culture, microscopy, antibody/antigen detection tests, and molecular biology.

[Innovative therapies for treatment of invasive fungal diseases]. / Invasive Mykosen ­ Innovative Therapien.

Invasive fungal diseases (IFD) are difficult to treat and pose a significant threat to immunocompromised individuals. Current antifungal agents face limitations, including antifungal resistance and adverse effects. This review aims to give a comprehensive overview of emerging treatment strategies.Novel drugs in development are Ibrexafungerp, an orally available triterpenoid inhibiting glucan synthesis, and Rezafungin representing the echinocandins with extended half-life and improved tissue penetration, both recently licensed for certain indications. Fosmanogepix targets glycosylphosphatidylinositol biosynthesis, while Olorofim, an orotomide, inhibits fungal nucleic acid synthesis, both currently assessed in advanced clinical trials.Immunotherapeutic approaches include immune checkpoint inhibitors to enhance immune response in immunosuppressed individuals and fungal-specific allogeneic CAR-T cell therapy. For prophylactic purpose in high-risk populations to develop IFD, monoclonal antibodies against different virulence factors of Candida spp. have been discovered but are not yet seen in clinical trials. Vaccines against distinct fungal antigens as well as pan fungal vaccines to prevent IFD are under development in preclinical stages, notably for Candida spp., Cryptococcus spp., and Aspergillus spp., however, their clinical value is still discussed.In summary, major advances to treat IFD have been observed, but challenges for their establishment in the clinical routine persist.

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.

Demographic characteristics and risk factors for invasive fungal sinusitis in the context of COVID-19: A systematic review and meta-analysis.

OBJECTIVES: To identify the demographic characteristics and potential risk factors of invasive fungal sinusitis (IFS) patients with Coronavirus Disease in 2019 (COVID-19). METHODS: Web of Science, Embase, the Cochrane Library, and PubMed were searched from database inception to August 2023 using the combination of medical searching heading terms "invasive fungal sinusitis" and "COVID-19" and their free words. The research protocol was registered on PROSPERO (CRD42023467175). RESULTS: A total of 53 studies were included. The mean age of IFS patients with COVID-19 was 53.72 (95% credible interval [CI]: 51.08, 56.36), with 66% males (95% CI: 0.62, 0.70), and 81% diabetes (95% CI: 0.77, 0.86). The mean time from COVID-19 diagnosis to IFS onset was 19.09 days (95% CI: 16.96, 21.22). The percentage of patients with COVID-19 PCR positivity was 33% (95% CI: 0.21, 0.45). Overall, 71% of patients receiving steroid therapy during COVID-19 infection (95% CI: 0.63, 0.78). The odds ratio of diabetes mellitus, steroid administration, and COVID-19 PCR positivity were 6.09, 2.21, and 1.82, respectively. COVID-19 infection did not affect the IFS stage. CONCLUSION: IFS patients with COVID-19 had an average age of 53.72 years and were predominantly males, with a mean interval of 19.09 days from COVID-19 diagnosis to IFS onset. Diabetes, steroid administration, and COVID-19 PCR positivity were risk factors.

Safety and effectiveness of isavuconazole in real-life non-neutropenic patients.

OBJECTIVES: Information is scarce on clinical experiences with non-neutropenic patients with invasive fungal infection (IFI) receiving isavuconazole. We aimed to report the safety and effectiveness of this drug as a first-line treatment or rescue in real life. METHODS: A retrospective, observational multicentric study of non-neutropenic patients who received isavuconazole as an IFI treatment at 12 different university hospitals (January 2018-2022). All patients met criteria for proven, probable or possible IFI according to EORTC-MSG. RESULTS: A total of 238 IFIs were treated with isavuconazole during the study period. Combination therapy was administered in 27.7% of cases. The primary IFI was aspergillosis (217, 91.2%). Other IFIs treated with isavuconazole were candidemia (n = 10), mucormycosis (n = 8), histoplasmosis (n = 2), cryptococcosis (n = 2), and others (n = 4). Median time of isavuconazole treatment was 29 days. Only 5.9% (n = 14) of cases developed toxicity, mainly hepatic-related (10 patients, 4.2%). Nine patients (3.8%) had treatment withdrawn. Successful clinical response at 12 weeks was documented in 50.5% of patients. CONCLUSION: Isavuconazole is an adequate treatment for non-neutropenic patients with IFIs. Toxicity rates were low and its effectiveness was comparable to other antifungal therapies previously reported.

Current status and new experimental diagnostic methods of invasive fungal infections after hematopoietic stem cell transplantation.

Invasive fungal infections (IFIs) are common and life-threatening complications in post-hematopoietic stem cell transplantation (post-HSCT) recipients, Severe IFIs can lead to systemic infection and organ damage, which results in high mortality in HSCT recipients. With the development of the field of fungal infection diagnosis, more and more advanced non-culture diagnostic tools have been developed, such as glip biosensors, metagenomic next-generation sequencing, Magnetic Nanoparticles and Identified Using SERS via AgNPs+ , and artificial intelligence-assisted diagnosis. The advanced diagnostic approaches contribute to the success of HSCT and improve the overall survival of post-HSCT leukemia patients by supporting therapeutical decisions. This review provides an overview of the characteristics of two high-incidence IFIs in post-HSCT recipients and discusses some of the recently developed IFI detection technologies. Additionally, it explores the potential application of cationic conjugated polymer fluorescence resonance energy transfer (CCP-FRET) technology for IFI detection. The aim is to offer insights into selecting appropriate IFI detection methods and gaining an understanding of novel fungal diagnostic approaches in laboratory settings.

Invasive fungal disease in children with solid tumors: An Australian multicenter 10-year review.

Invasive fungal disease (IFD) occurs less frequently during treatment for solid compared to hematological malignancies in children, and risk groups are poorly defined. Retrospective national multicenter cohort data (2004-2013) were analyzed to document prevalence, clinical characteristics, and microbiology of IFD. Amongst 2067 children treated for solid malignancy, IFD prevalence was 1.9% overall and 1.4% for proven/probable IFD. Of all IFD episodes, 42.5% occurred in patients with neuroblastoma (prevalence 7.0%). Candida species comprised 54.8% of implicated pathogens in proven/probable IFD. In children with solid tumors, IFD is rare, and predominantly caused by yeasts.Routine prophylaxis may not be warranted.

Surgical treatment of invasive fungal infection in pediatric oncology.

BACKGROUND: Invasive fungal disease (IFD) is typically aggressive and related with high mortality in children with a hematological malignancy. The association of medical and surgical treatment may ameliorate the outcome. The aim of this study was to analyze the surgical treatment of fungal infections in pediatric oncological populations. METHODS: Retrospective study (2000-2022) of a single-center experience. We reviewed the medical record of all patients with hematologic malignancies and IFD, analyzing the outcome. RESULTS: From the 70 pediatric cases of hematologic malignancies with the diagnosis IFD over 22 years, we included in the present study 44 cases who required surgical approaches for either diagnosis or treatment. Twenty-one patients were males and the mean age was 11 (range 1-23) years. The main indications for surgery were lack of improvement following medical treatment and/or progression of fungal infection (80%) and diagnosis confirmation (20%). Only five patients needed an emergency operation for rapid worsening of symptoms. The most common site of infection was the lung (80%) and the most frequently identified pathogen was Aspergillus (75%). The most common surgical procedures were lobectomy (performed in 17 patients) and atypical lung resection (10). Complications of surgery were mostly treated by medical approach. The mean time of resumption of oncological treatment was 40 (range 0-150) days. CONCLUSIONS: Surgery is an important step in the multimodal treatment of invasive fungal infection with excellent resolution rate. Overall mortality depends on the underlying malignancy.

Systematic review on efficacy and safety of empirical versus pre-emptive antifungal therapy among children with febrile neutropenia reveals paucity of data.

BACKGROUND: Two approaches are used to manage invasive fungal disease (IFD) in febrile neutropenic patients viz. empirical therapy (without attempting to confirm the diagnosis), or pre-emptive therapy (after screening tests for IFD). OBJECTIVE: This systematic review was undertaken to compare these approaches in children. METHODS: We searched PubMed, EMBASE, Cochrane Library, Scopus, Web of Science, CINAHL, Clinical Trial Registries and grey literature, for randomized controlled trials (RCT) comparing empirical versus pre-emptive antifungal therapy in children with FN suspected to have IFD. We used the Cochrane Risk of bias 2 tool for quality assessment, and evaluated the certainty of evidence using the GRADE approach. RESULTS: We identified 7989 citations. Stepwise screening identified only one relevant RCT that administered empirical (n = 73) or pre-emptive (n = 76) antifungal therapy. There were no significant differences in all-cause mortality (RR 1.56, 95% CI: 0.46, 5.31), IFD mortality (RR 1.04, 95% CI:0.15, 7.20) and other clinically important outcomes such as duration of fever, duration of hospitalization and proportion requiring ICU admission. There were no safety data reported. The number of days of antifungal therapy was significantly lower in the pre-emptive therapy arm. The certainty of evidence for all outcomes was 'moderate'. CONCLUSIONS: This systematic review highlighted the paucity of data, comparing empirical versus pre-emptive antifungal therapy in children with febrile neutropenia having suspected invasive fungal disease. Data from a single included trial suggests that both approaches may be comparable in research settings. Robust trials are warranted to address the gap in existing knowledge about the optimal approach in clinical practice.

Multi-organ involvement caused by Scedosporium apiospermum infection after near drowning: a case report and literature review.

BACKGROUND: Scedosporium apiospermum (S. apiospermum) is a rare fungal pathogen that causes disseminated infections. It rarely affects immunocompetent individuals and has a poor prognosis. CASE PRESENTATION: A 37-year-old woman presented with multiple lesions in the lungs, brain, and eyes, shortly after near drowning in a car accident. The primary symptoms were chest tightness, limb weakness, headache, and poor vision in the left eye. S. apiospermum infection was confirmed by metagenomic next-generation sequencing (mNGS) of intracranial abscess drainage fluid, although intracranial metastases were initially considered. After systemic treatment with voriconazole, her symptoms improved significantly; however, she lost vision in her left eye due to delayed diagnosis. CONCLUSION: While S. apiospermum infection is rare, it should be considered even in immunocompetent patients. Prompt diagnosis and treatment are essential. Voriconazole may be an effective treatment option.