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Diagnostic Failure in Invasive Fungal Infections: Causes, Clinical Consequences, and Mitigation Strategies
Pilar Rivas-Pinedo1, José Millán Oñate Gutiérrez2,3,4
1Medical and Diagnostic Mycology Group, Department of Microbiology, Faculty of Medicine, Universidad Nacional de Colombia, Bogotá 111321, Colombia.
Abstract:
Diagnostic failure in invasive fungal infections (IFIs) remains a relevant and underrecognized cause of mortality, morbidity, delayed therapy, unnecessary antifungal exposure, and pharmacological selective pressure. Although major advances have been achieved in biomarkers, rapid diagnostic tests, molecular methods, imaging studies, and microbiological identification, timely diagnosis continues to be influenced by the interaction among host factors, pathogen-related factors, diagnostic tools, and healthcare system-related factors. This narrative review analyzes diagnostic failure in IFIs as a dynamic process that includes delayed, incorrect, and incomplete diagnosis. It examines its determinants and consequences in high-risk populations-critically ill patients, patients with hematologic diseases or hematopoietic stem cell transplant recipients, and neonates-as well as in invasive candidiasis, aspergillosis, mucormycosis, cryptococcosis, endemic mycoses, and infections caused by rare or emerging fungi. It also reviews how delayed sampling, decontextualized interpretation of biomarkers, incomplete microbiological identification, absence of antifungal susceptibility testing when clinically relevant, and fragmentation between clinical and laboratory teams contribute to adverse outcomes. Finally, it proposes a diagnostic-centered antifungal stewardship framework (AFSP-Dx) based on syndromic bundles, population-specific diagnostic algorithms, 48-72 h reassessment, and auditable indicators intended to support earlier recognition, more precise therapeutic decisions, and rational antifungal use.
Insights
Diagnostic failure in invasive fungal infections (IFIs) leads to poor outcomes. A new framework, AFSP-Dx, aims to improve early recognition and treatment through better diagnostics and stewardship.
Area of Science:
- Medical Mycology
- Infectious Diseases
- Diagnostic Microbiology
Background:
- Diagnostic failure in invasive fungal infections (IFIs) is a significant cause of mortality and morbidity.
- Despite advances in diagnostic tools, timely diagnosis remains challenging due to complex interactions between host, pathogen, and healthcare systems.
Purpose of the Study:
- To analyze diagnostic failure in IFIs as a dynamic process, examining its determinants and consequences.
- To propose a diagnostic-centered antifungal stewardship framework (AFSP-Dx) to improve diagnostic accuracy and therapeutic decisions.
Main Methods:
- Narrative review of diagnostic failure in IFIs across various high-risk populations and fungal pathogens.
- Analysis of factors contributing to diagnostic failure, including delayed sampling and fragmented team communication.
- Development of the AFSP-Dx framework incorporating syndromic bundles and population-specific algorithms.
Main Results:
- Diagnostic failure encompasses delayed, incorrect, and incomplete diagnoses, impacting critically ill patients, transplant recipients, and neonates.
- Specific IFIs like candidiasis, aspergillosis, and mucormycosis are frequently affected by diagnostic delays.
- Incomplete microbiological identification and lack of susceptibility testing exacerbate adverse outcomes.
Conclusions:
- The AFSP-Dx framework offers a structured approach to enhance early recognition and precise treatment of IFIs.
- Implementing auditable indicators and population-specific algorithms can rationalize antifungal use and improve patient care.
- Addressing diagnostic fragmentation and improving laboratory-clinical collaboration are crucial for mitigating IFI-related mortality.
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