Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 527
Filter
1.
Int Ophthalmol ; 44(1): 319, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38976107

ABSTRACT

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.


Subject(s)
Eye Infections, Bacterial , Eye Infections, Fungal , Magnetic Resonance Imaging , Orbital Cellulitis , Humans , Male , Orbital Cellulitis/microbiology , Orbital Cellulitis/diagnosis , Retrospective Studies , Eye Infections, Fungal/diagnosis , Eye Infections, Fungal/microbiology , Adult , Magnetic Resonance Imaging/methods , Middle Aged , Eye Infections, Bacterial/diagnosis , Eye Infections, Bacterial/microbiology , Aged , Diagnosis, Differential , Female , Young Adult , Aged, 80 and over , Invasive Fungal Infections/diagnosis , Invasive Fungal Infections/microbiology , Invasive Fungal Infections/diagnostic imaging
2.
Trials ; 25(1): 427, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38943201

ABSTRACT

BACKGROUND: Acute leukaemias (AL) are life-threatening blood cancers that can be potentially cured with treatment involving myelosuppressive, multiagent, intensive chemotherapy (IC). However, such treatment is associated with a risk of serious infection, in particular invasive fungal infection (IFI) associated with prolonged neutropenia. Current practice guidelines recommend primary antifungal (AF) prophylaxis to be administered to high-risk patients to reduce IFI incidence. AFs are also used empirically to manage prolonged neutropenic fever. Current strategies lead to substantial overuse of AFs. Galactomannan (GM) and ß-D-glucan (BG) biomarkers are also used to diagnose IFI. Combining both biomarkers may enhance the predictability of IFI compared to administering each test alone. Currently, no large-scale randomised controlled trial (RCT) has directly compared a biomarker-based diagnostic screening strategy without AF prophylaxis to AF prophylaxis (without systematic biomarker testing). METHODS: BioDriveAFS is a multicentre, parallel, two-arm RCT of 404 participants from UK NHS Haematology departments. Participants will be allocated on a 1:1 basis to receive either a biomarker-based antifungal stewardship (AFS) strategy, or a prophylactic AF strategy, which includes existing standard of care (SoC). The co-primary outcomes will be AF exposure in the 12-month post randomisation and the patient-reported EQ-5D-5L measured at 12-month post randomisation. Secondary outcomes will include total AF exposure, probable/proven IFI, survival (all-cause mortality and IFI mortality), IFI treatment outcome, AF-associated adverse effects/events/complications, resource use, episodes of neutropenic fever requiring hospital admission or outpatient management, AF resistance in fungi (non-invasive and invasive) and a Desirability of Outcome Ranking. The trial will have an internal pilot phase during the first 9 months. A mixed methods process evaluation will be integrated in parallel to the internal pilot phase and full trial, aiming to robustly assess how the intervention is delivered. Cost-effectiveness analysis will also be performed. DISCUSSION: The BioDriveAFS trial aims to further the knowledge of strategies that will safely optimise AF use through comparison of the clinical and cost-effectiveness of a biomarker-led diagnostic strategy versus prophylactic AF to prevent and manage IFI within acute leukaemia. The evidence generated from the study will help inform global clinical practice and approaches within antifungal stewardship. TRIAL REGISTRATION: ISRCTN11633399. Registered 24/06/2022.


Subject(s)
Antifungal Agents , Biomarkers , Cost-Benefit Analysis , Invasive Fungal Infections , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Humans , Antifungal Agents/therapeutic use , Antifungal Agents/economics , Invasive Fungal Infections/drug therapy , Invasive Fungal Infections/prevention & control , Invasive Fungal Infections/diagnosis , Biomarkers/blood , Galactose/analogs & derivatives , Mannans , Treatment Outcome , beta-Glucans , Antimicrobial Stewardship , Leukemia/drug therapy , Time Factors , Cost-Effectiveness Analysis
3.
Genes (Basel) ; 15(6)2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38927669

ABSTRACT

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.


Subject(s)
Aptamers, Nucleotide , Invasive Fungal Infections , Humans , Aptamers, Nucleotide/genetics , Invasive Fungal Infections/diagnosis , Invasive Fungal Infections/microbiology , Fungi/genetics , SELEX Aptamer Technique/methods
4.
Front Cell Infect Microbiol ; 14: 1393242, 2024.
Article in English | MEDLINE | ID: mdl-38912204

ABSTRACT

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.


Subject(s)
Antifungal Agents , Brain Abscess , High-Throughput Nucleotide Sequencing , Metagenomics , Humans , Female , Child , Metagenomics/methods , Brain Abscess/microbiology , Brain Abscess/diagnosis , Brain Abscess/drug therapy , Antifungal Agents/therapeutic use , Antifungal Agents/pharmacology , Invasive Fungal Infections/diagnosis , Invasive Fungal Infections/microbiology , Invasive Fungal Infections/drug therapy , Male , Central Nervous System Fungal Infections/diagnosis , Central Nervous System Fungal Infections/microbiology , Central Nervous System Fungal Infections/drug therapy , Child, Preschool , Aspergillus fumigatus/genetics , Aspergillus fumigatus/isolation & purification , Caspofungin/therapeutic use
5.
Mycopathologia ; 189(4): 56, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38869662

ABSTRACT

The incidence of breakthrough mold infections (bIMI) has been increasing, due to routine administration of broad-spectrum antifungal prophylaxis and an increasing pool of high-risk patient populations, with fungi more challenging to treat, resulting in a sustained high mortality, despite progress in diagnostic and therapeutic options. Pharmacokinetics of antifungal drugs, fungal, and host, including genetic, factors play a role in the emergence of bIMI. Suggested therapeutic approaches have included change of antifungal class treatment, with amphotericin-B products predominating as first-line empirical treatment and switching from one broad-spectrum azole to another remaining the most frequently used treatment modalities. Future perspectives include determining individual susceptibility to IMI to tailor prophylaxis and treatment strategies, improved diagnostic tests, and the introduction of new antifungal agents that may reduce morbidity and mortality caused by bIMI.


Subject(s)
Antifungal Agents , Invasive Fungal Infections , Humans , Invasive Fungal Infections/drug therapy , Invasive Fungal Infections/prevention & control , Invasive Fungal Infections/diagnosis , Antifungal Agents/therapeutic use , Fungi/drug effects , Incidence , Drug Resistance, Fungal
6.
Clin Lab ; 70(6)2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38868888

ABSTRACT

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.


Subject(s)
Amphotericin B , Antifungal Agents , Drug Resistance, Fungal , Myelodysplastic Syndromes , Triazoles , Humans , Myelodysplastic Syndromes/drug therapy , Myelodysplastic Syndromes/complications , Antifungal Agents/therapeutic use , Triazoles/therapeutic use , Triazoles/administration & dosage , Amphotericin B/therapeutic use , Candida tropicalis/drug effects , Male , Invasive Fungal Infections/drug therapy , Invasive Fungal Infections/diagnosis , Invasive Fungal Infections/microbiology , Micafungin/therapeutic use , Micafungin/administration & dosage , Aged , Middle Aged , Treatment Outcome
7.
Lakartidningen ; 1212024 Jun 03.
Article in Swedish | MEDLINE | ID: mdl-38828641

ABSTRACT

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.


Subject(s)
Amphotericin B , Antifungal Agents , Immunocompetence , Humans , Female , Antifungal Agents/therapeutic use , Amphotericin B/therapeutic use , Accidents, Traffic , Mucormycosis/diagnosis , Mucormycosis/drug therapy , Soft Tissue Infections/microbiology , Soft Tissue Infections/drug therapy , Soft Tissue Infections/diagnosis , Invasive Fungal Infections/drug therapy , Invasive Fungal Infections/diagnosis , Adult , Mucorales/isolation & purification
8.
Front Cell Infect Microbiol ; 14: 1368165, 2024.
Article in English | MEDLINE | ID: mdl-38915923

ABSTRACT

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.


Subject(s)
High-Throughput Nucleotide Sequencing , Metagenomics , Mucormycosis , Humans , Mucormycosis/diagnosis , Mucormycosis/microbiology , High-Throughput Nucleotide Sequencing/methods , Male , Female , Child , Child, Preschool , Metagenomics/methods , Retrospective Studies , Infant , Adolescent , Invasive Fungal Infections/diagnosis , Invasive Fungal Infections/microbiology , China
9.
Mycopathologia ; 189(3): 41, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38704761

ABSTRACT

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.


Subject(s)
Antifungal Agents , Intensive Care Units , Invasive Fungal Infections , Humans , Invasive Fungal Infections/drug therapy , Invasive Fungal Infections/diagnosis , Antifungal Agents/therapeutic use , Europe , Surveys and Questionnaires , Consensus , Disease Management
10.
J Clin Microbiol ; 62(6): e0147623, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38695528

ABSTRACT

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.


Subject(s)
Fungi , Lung Diseases, Fungal , Sensitivity and Specificity , Humans , Lung Diseases, Fungal/diagnosis , Lung Diseases, Fungal/microbiology , Fungi/genetics , Fungi/isolation & purification , Fungi/classification , Molecular Diagnostic Techniques/methods , Transition Temperature , Bronchoalveolar Lavage Fluid/microbiology , Machine Learning , Invasive Fungal Infections/diagnosis , Invasive Fungal Infections/microbiology
11.
J Infect Dev Ctries ; 18(4): 636-639, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38728631

ABSTRACT

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.


Subject(s)
Antifungal Agents , Immunocompromised Host , Saccharomycetales , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Humans , Antifungal Agents/therapeutic use , Antifungal Agents/pharmacology , Male , Saccharomycetales/isolation & purification , Saccharomycetales/drug effects , Female , Middle Aged , Aged , Invasive Fungal Infections/drug therapy , Invasive Fungal Infections/diagnosis , Invasive Fungal Infections/microbiology , Microbiological Techniques
12.
Arch Microbiol ; 206(5): 237, 2024 Apr 28.
Article in English | MEDLINE | ID: mdl-38678508

ABSTRACT

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.


Subject(s)
Hematopoietic Stem Cell Transplantation , Invasive Fungal Infections , Humans , Hematopoietic Stem Cell Transplantation/adverse effects , Invasive Fungal Infections/diagnosis , Fluorescence Resonance Energy Transfer , High-Throughput Nucleotide Sequencing , Biosensing Techniques/methods
13.
J Clin Microbiol ; 62(5): e0039424, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38602412

ABSTRACT

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.


Subject(s)
Cell-Free Nucleic Acids , DNA, Fungal , Invasive Fungal Infections , Mucormycosis , Polymerase Chain Reaction , Humans , Mucormycosis/diagnosis , Mucormycosis/mortality , Mucormycosis/blood , Mucormycosis/microbiology , Male , Female , Middle Aged , Prognosis , Aged , Cell-Free Nucleic Acids/blood , Polymerase Chain Reaction/methods , Adult , DNA, Fungal/genetics , DNA, Fungal/blood , Invasive Fungal Infections/diagnosis , Invasive Fungal Infections/mortality , Invasive Fungal Infections/microbiology , Aspergillus/genetics , Aspergillus/isolation & purification , Aspergillosis/diagnosis , Aspergillosis/mortality , Aspergillosis/microbiology , Mucorales/genetics , Mucorales/isolation & purification , Biomarkers/blood , Aged, 80 and over , Prospective Studies
16.
Eur J Haematol ; 113(1): 90-98, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38558136

ABSTRACT

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.


Subject(s)
Hematologic Neoplasms , Invasive Fungal Infections , Humans , Child , Adolescent , Male , Female , Invasive Fungal Infections/diagnosis , Invasive Fungal Infections/surgery , Invasive Fungal Infections/mortality , Invasive Fungal Infections/etiology , Invasive Fungal Infections/drug therapy , Child, Preschool , Retrospective Studies , Infant , Young Adult , Hematologic Neoplasms/complications , Hematologic Neoplasms/therapy , Treatment Outcome , Disease Management
17.
Int J Infect Dis ; 144: 107054, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38614232

ABSTRACT

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.


Subject(s)
COVID-19 , SARS-CoV-2 , Sinusitis , Humans , COVID-19/complications , COVID-19/epidemiology , COVID-19/diagnosis , Risk Factors , Sinusitis/microbiology , Sinusitis/epidemiology , Male , Female , Middle Aged , Invasive Fungal Infections/epidemiology , Invasive Fungal Infections/diagnosis , Invasive Fungal Infections/drug therapy , Diabetes Mellitus/epidemiology
18.
Front Cell Infect Microbiol ; 14: 1210857, 2024.
Article in English | MEDLINE | ID: mdl-38590441

ABSTRACT

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.


Subject(s)
Hematopoietic Stem Cell Transplantation , Invasive Fungal Infections , Mycoses , Humans , Antifungal Agents/therapeutic use , Hematopoietic Stem Cell Transplantation/adverse effects , Retrospective Studies , Transplantation, Homologous/adverse effects , Mycoses/drug therapy , Invasive Fungal Infections/diagnosis , Invasive Fungal Infections/drug therapy , High-Throughput Nucleotide Sequencing , Sulfonamides/therapeutic use
20.
Dtsch Med Wochenschr ; 149(10): 551-559, 2024 May.
Article in German | MEDLINE | ID: mdl-38657594

ABSTRACT

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.


Subject(s)
Invasive Fungal Infections , Humans , Invasive Fungal Infections/diagnosis
SELECTION OF CITATIONS
SEARCH DETAIL
...