Recent developments in the management of invasive fungal infections in patients with oncohematological diseases

Ruhnke, Markus; Schwartz, Stefan

doi:10.1177/2040620716656381

Cited by 30 publications

(18 citation statements)

References 117 publications

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“…Ultimately, proving a diagnosis of IFD is difficult and routine practice promotes initiation of therapy based on concerning clinical or imaging findings, especially in high‐risk neutropenic patients with persistent or recurrent fevers despite broad‐spectrum antibiotics . In accordance with this practice, 21 of 28 (75%) of enrolled patients at risk for IFD due to prolonged or recrudescent FN were placed on >1 week of treatment dosing antifungal therapy by their primary providers.…”

Section: Discussionmentioning

confidence: 99%

Cell‐free DNA next‐generation sequencing successfully detects infectious pathogens in pediatric oncology and hematopoietic stem cell transplant patients at risk for invasive fungal disease

Armstrong

Rossoff

Hollemon³

et al. 2019

Pediatric Blood & Cancer

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Background We sought to determine if next‐generation sequencing (NGS) of microbial cell‐free DNA (cfDNA) in plasma would detect pathogens in pediatric patients at risk for invasive fungal disease (IFD). Procedures Pediatric hematology, oncology, and stem cell transplant patients deemed at risk for new IFD had blood samples drawn at three time‐points separated by 1‐month intervals. The primary outcome measure was detection of fungal pathogens compared to standard clinical testing. Secondary outcomes included identification of other infectious pathogens, relationship to European Organization for Research and Treatment of Cancer's Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases’ Mycoses Study Group (EORTC/MSG) guidelines, and assessment of antifungal therapy. Results NGS identified fungal pathogens in seven of 40 at‐risk patients for IFD and results were identical in four of six proven cases, including Aspergillus fumigatus by lung biopsy, Candida albicans by blood or pancreatic pseudocyst cultures, and Rhizopus delemar by skin biopsy. Rhizopus oryzae identified on skin biopsy and A. fumigatus isolated on day 27 of 28 of culture from lung biopsy were not detected by cfDNA NGS, possibly due to lack of bloodstream penetration and questionable pathogenicity, respectively. Numerous DNA viruses were detected in patients with prolonged febrile neutropenia or abnormal imaging. Extended antifungal therapy was used in 73% of patients. Follow‐up cfDNA sequencing in patients who were positive at enrollment was negative at 1 and 2 months. Conclusions cfDNA NGS detected fungal pathogens from blood confirming its potential to guide treatment decisions in pediatric patients at risk for IFD and limit excessive empiric antifungal use. Future studies are needed to better understand the sensitivity and specificity of this approach.

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Section: Discussionmentioning

confidence: 99%

Cell‐free DNA next‐generation sequencing successfully detects infectious pathogens in pediatric oncology and hematopoietic stem cell transplant patients at risk for invasive fungal disease

Armstrong

Rossoff

Hollemon³

et al. 2019

Pediatric Blood & Cancer

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“…However, the overall sensitivity of culture for the diagnosis of IFI is low. 15,16 The clinical manifestations and imaging features of IFI vary, and their associated hematological and pathological tests are often time-consuming or lacking sensitivity. Therefore, we sought to review the clinical features, diagnosis criteria, and outcomes of emerging IFIs in adult patients in a tertiary hospital setting in China to put forward possible strategies to improve the therapeutic.…”

Section: Introductionmentioning

confidence: 99%

<p>Emerging Invasive Fungal Infections: Clinical Features and Controversies in Diagnosis and Treatment Processes</p>

Zhang¹,

Zhu²

2020

IDR

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Background: The diagnosis and treatment of invasive fungal infection (IFI) are still challenging due to its complexity and non-specificity. This study was aimed to investigate the clinical features, diagnosis process, and outcomes of patients with emerging IFIs. Methods: A retrospective review of emerging IFIs in adult patients at a university hospital in China was conducted; diagnoses were based on the criteria of EORTC/MSG 2008. Results: 145 IFI patients (pulmonary, intestinal and urinary) were enrolled in this study, including 80 proven (55.2%), 59 probable (40.7%), or 6 possible IFIs (4.1%). Among the 126 pulmonary IFIs, the positivity rate for sputum microscopy, sputum culture, and 1.3-ß-D-glucan (BG) test was 54.0%, 44.4%, and 37.3%, respectively. Among the 19 intestinal and urinary IFIs, routine examination of stool or urine and their culture were the main methods of detection. Positive results of 75 detected fungal strains from the samples showed that 30 cases were complicated with one or more bacterial infections. The average length of hospital stay of IFI patients was 14.0 (10.0, 20.0) days. The time from admission to antifungal therapy initiation (P<0.001), liver cirrhosis (P<0.001), hematological tumor (P<0.001), coinfection (P=0.019) and immune diseases (P=0.025) were independent predictors of prolonged hospitalization. Conclusion: Delayed time was the primary predictor of prolonged hospitalization. This prediction is suggested to improve IFI diagnostic and therapeutic process of IFI to promote prognosis.

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“…An early diagnosis and prompt initiation of appropriate antifungal therapy are imperative and essential for a favorable clinical outcome [12]. Thus, the reduction of mortality among patients with IA must be accompanied by research that allows earlier diagnosis by traditional and non-cultural-based molecular tests as well as the development of new strategies for the detection of antifungal resistance.…”

Section: Introductionmentioning

confidence: 99%

Molecular Detection of Aspergillus: Application of a Real-Time PCR Multiplex Assay in Tissue Samples

Sabino

Simões

Veríssimo

2020

JoF

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Diagnosis of invasive fungal infections is complex, and the lack of standardization of molecular methods is still a challenge. Several methods are available for the diagnosis of invasive aspergillosis, but their effectiveness will depend on the studied population, the patients’ comorbidities, and the use of mold active prophylaxis, among others. The ability to determine the identity of the infecting Aspergillus species, and to detect mutations conferring specific resistance patterns directly from DNA extracted from the biological product, is an advantage of nucleic acid testing compared with antigen-based assays. In this study, we present laboratory cases where the diagnosis of aspergillosis was performed using a real-time multiplex PCR for the detection of Aspergillus DNA in tissue samples, showing its usefulness as one more tool in the diagnosis of aspergillosis in tissue samples. Aspergillus real-time multiplex PCR was also used to detect azole-resistance in some cases. In the majority of the PCR positive cases, cultures remained negative after 60 days. The PCR assay directed to Aspergillus gave positive signals for Aspergillus fumigatus sensu stricto. Results were confirmed by panfungal PCR, followed by sequencing, revealing 100% homology with Aspergillus fumigatus sensu stricto. Mutations conferring azole resistance were not detected.

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Recent developments in the management of invasive fungal infections in patients with oncohematological diseases

Cited by 30 publications

References 117 publications

Cell‐free DNA next‐generation sequencing successfully detects infectious pathogens in pediatric oncology and hematopoietic stem cell transplant patients at risk for invasive fungal disease

Cell‐free DNA next‐generation sequencing successfully detects infectious pathogens in pediatric oncology and hematopoietic stem cell transplant patients at risk for invasive fungal disease

<p>Emerging Invasive Fungal Infections: Clinical Features and Controversies in Diagnosis and Treatment Processes</p>

Molecular Detection of Aspergillus: Application of a Real-Time PCR Multiplex Assay in Tissue Samples

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