Polymerase Chain Reaction for Diagnosing Invasive Aspergillosis: Getting Closer but Still a Ways to Go

Donnelly, J. Peter

doi:10.1086/499818

Cited by 112 publications

(70 citation statements)

References 23 publications

(25 reference statements)

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“…However, there was still a global reduction of antifungal therapy of 38.8% compared to that administered using the standard approach. 5 The development of new diagnostic tests such as b-D-glucan and specific fungal polymerase chain reaction anaysis [26][27][28][29] would improve the specificity of this approach in the future. Finally, our proposed approach requires intensive clinician involvement and diagnostic work-up together with prompt availability of the results of critical diagnostic tests (computed tomography scan, bronchoalveolar lavage and GM).…”

Section: Discussionmentioning

confidence: 99%

Universal antifungal therapy is not needed in persistent febrile neutropenia: a tailored diagnostic and therapeutic approach

Aguilar‐Guisado¹,

Martín-Peña²,

Espigado³

et al. 2011

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundGiving antifungal therapy exclusively to selected patients with persistent febrile neutropenia may avoid over-treatment without increasing mortality. The aim of this study was to validate an innovative diagnostic and therapeutic approach based on assessing patients' risk profile and clinical criteria in order to select those patients requiring antifungal therapy. The efficacy of this approach was compared to that of universal empirical antifungal therapy. Design and MethodsThis was a prospective study which included all consecutive adult hematology patients with neutropenia and fever refractory to 5 days of empirical antibacterial therapy admitted to a teaching hospital in Spain over a 2-year period. A diagnostic and therapeutic approach based on clinical criteria and risk profile was applied in order to select patients for antifungal therapy. The sensitivity, specificity and negative predictive value of this approach and also the overall success rate, according to the same criteria of efficacy described in classical clinical trials, were analyzed. ResultsEighty-five episodes were included, 35 of them (41.2%) in patients at high risk of invasive fungal infections. Antifungal therapy was not indicated in 33 episodes (38.8%). The overall incidence of proven and probable invasive fungal infections was 14.1%, all of which occurred in patients who had received empirical antifungal therapy. The 30-day crude mortality rate was 15.3% and the invasive fungal infection-related mortality rate was 2.8% (2/72). The overall success rate following the diagnostic and therapeutic approach was 36.5% compared with 33.9% and 33.7% obtained in the trial by Walsh et al. The sensitivity, specificity and negative predictive value of the study approach were 100%, 52.4% and 100%, respectively. ConclusionsBased on the high negative predictive value of this diagnostic and therapeutic approach in persistent febrile neutropenia patients with hematologic malignancies or patients who have received a hematopoietic stem cell transplant, the approach is useful for identifying patients who are not likely to develop invasive fungal infection and do not, therefore, require antifungal therapy. The effectiveness of the strategy is similar to that of universal empirical antifungal therapy reported in controlled trials. Haematologica 2012;97(3):464-471. doi:10.3324/haematol.2011

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Section: Discussionmentioning

confidence: 99%

Universal antifungal therapy is not needed in persistent febrile neutropenia: a tailored diagnostic and therapeutic approach

Aguilar‐Guisado¹,

Martín-Peña²,

Espigado³

et al. 2011

Haematologica

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“…A recent meta-analysis reports that bronchoalveolar lavage (BAL) galactomannan testing with an overall sensitivity and specificity of more than 90% for the diagnosis of invasive aspergillosis [59] . In addition, PCR-based methods to diagnose IPA have also been evaluated by detecting Aspergillus DNA in BAL fluid and serum [60] . However, PCR is often associated with false-positive results and is not considered as a routine clinical test.…”

Section: Airway Invasive Aspergillosis Is An Uncommon Invasive Diseasmentioning

confidence: 99%

An update of clinical characteristics and imaging findings of pulmonary aspergillosis

Sah

Liu

Ganganah

et al. 2015

IJDI

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Pulmonary aspergillosis (PA) is a clinical spectrum of rapidly progressive potentially fatal opportunistic mycosis usually caused by Aspergillus organisms. In the recent years, the number of patients with invasive pulmonary aspergillosis (IPA) has increased and it remains a major cause of morbidity and mortality in immunocompromised patients. Chest CT plays an important role in the early diagnosis of IPA and should be included in the investigative protocol. Typical imaging findings of IPA include nodule, consolidation, the halo sign, the hypodense sign and the air crescent sign. CT Angiography (CTA) has a higher sensitivity for detecting angioinvasive aspergillosis. However, the diagnosis of pulmonary aspergillosis remains challenging radiologically in immunocompetent chronic obstructive pulmonary disease (COPD) and critically ill patients in intensive care unit (ICU) because of the non-specific CT findings and further studies are needed to establish the confirm diagnosis.

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“…Crucially, there are no externally validated methods for PCR-based diagnosis, and there is a lack of standardization of protocols, with qPCR assays using disparate chemistries, different targets, there is sample-specific instrument-dependent variability and some assays use contamination-prone nested PCR methods aimed at enhancing analytical sensitivity [154]. This inconsistency is further highlighted by a recent meta-analysis of 16 PCR studies applied to whole blood, serum and plasma, which included three extraction and four disruption methods, three different starting volumes, three different specimen types, three different target genes and four different PCR methods [155].…”

Section: Pcr and Iamentioning

confidence: 99%

Biomarkers for Invasive Aspergillosis: The Challenges Continue

et al. 2014

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The incidence of invasive aspergillosis (IA), an opportunistic infection in immuno compromised individuals, is rising, but its early diagnosis remains challenging and treatment options are limited. Hence there is an urgent need to improve existing diagnostic procedures as well as develop novel approaches. The clinical usefulness of galactomannan and βdglucan, widely used assays detecting cellwall antigens of Aspergillus, is unclear and depends on clinicians' awareness of their practical limitations. This leaves room for new methods that utilize genomic, proteomic and metabolomics approaches as well as novel detection procedures, for example point ofcare lateralflow devices. Each of these strategies has its own limitations and it is likely that a combination of methods will be required to achieve optimal performance for the diagnosis of IA and subsequent appropriate patient management.

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Polymerase Chain Reaction for Diagnosing Invasive Aspergillosis: Getting Closer but Still a Ways to Go

Cited by 112 publications

References 23 publications

Universal antifungal therapy is not needed in persistent febrile neutropenia: a tailored diagnostic and therapeutic approach

Universal antifungal therapy is not needed in persistent febrile neutropenia: a tailored diagnostic and therapeutic approach

An update of clinical characteristics and imaging findings of pulmonary aspergillosis

Biomarkers for Invasive Aspergillosis: The Challenges Continue

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