Serum Galactomannan Versus a Combination of Galactomannan and Polymerase Chain Reaction-Based Aspergillus DNA Detection for Early Therapy of Invasive Aspergillosis in High-Risk Hematological Patients: A Randomized Controlled Trial

Aguado, José María; Vázquez, Lourdes; Fernández‐Ruiz, Mario; Villaescusa, Teresa; Ruiz‐Camps, Isabel; Barba, Pere; Silva, Jose T.; Batlle, Montserrat; Solano, Carlos; Gallardo, David; Heras, Inmaculada; Polo, Marta; Varela, Rosario; Vallejo, Carlos; Olavé, Teresa; López‐Jiménez, Javier; Rovira, Montserrat; Parody, Rocío; Cuenca‐Estrella, Manuel; Zarzuela, Marta Polo; González, Francisco Javier Candel; Amador, Paloma Merino; Mediavilla, Joaquín Díaz; Ruiz‐Camps, Isabel; Castillo, Nerea; Martín, María Teresa; Soriano, José; Fernando, Inmaculada Heras; Castilla‐Llorente, Cristina; Cesteros, Rosa; Mondéjar, María Remedios Rodríguez; Caballero, Dolores; García, José Elías; García, Inmaculada García; González, Sara de la Mano; García-Hierro, Jose María Fernandez; Tormo, Mar; Navarro, David; Mollà, M.; González, Ana J.; González, Soledad; González, Ana Pilar; Palomo, P Palomo; Porras, Rocío Parody; Sánchez, Ramón Guardia; Varela, María Rosario; Rubio, María Teresa Olave; Jiménez, Javier López; Tarrats, Montserrat Rovira; Grande, María Suárez-Lledó; Fernández‐Avilés, Francesc; Silva, José Tiago; Buitrago, María J.; Amador, Teresa Merino; Bernal‐Martínez, Leticia

doi:10.1093/cid/ciu833

Cited by 132 publications

(68 citation statements)

References 34 publications

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“…The use of galactomannan and β-d-glucan to assist in the assessment of invasive aspergillus (and a broad range of fungal pathogens) has become well accepted [209,210].…”

Section: We Recommend Daily Assessment For De-escalation Of Antimicromentioning

confidence: 99%

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

et al. 2017

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Objective: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". Design:A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. Methods:The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable.

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“…The use of galactomannan and β-d-glucan to assist in the assessment of invasive aspergillus (and a broad range of fungal pathogens) has become well accepted [209,210].…”

Section: We Recommend Daily Assessment For De-escalation Of Antimicromentioning

confidence: 99%

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

et al. 2017

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“…In one study, combination monitoring led to earlier diagnosis and a lower incidence of IA in high-risk hematology patients receiving fluconazole prophylaxis than did galactomannan surveillance alone (55). Another open-label study of 240 adult hematologic malignancy patients and HSCT recipients randomized subjects to receive preemptive therapy based on Aspergillus PCR plus galactomannan testing or empirical antifungal therapy that was driven by clinical symptoms, culture, and/or histology (56).…”

Section: Surveillance Strategiesmentioning

confidence: 99%

Molecular Diagnostic Testing for Aspergillus

Powers-Fletcher

Hanson

2016

J Clin Microbiol

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The direct detection of Aspergillus nucleic acid in clinical specimens has the potential to improve the diagnosis of aspergillosis by offering more rapid and sensitive identification of invasive infections than is possible with traditional techniques, such as culture or histopathology. Molecular tests for Aspergillus have been limited historically by lack of standardization and variable sensitivities and specificities. Recent efforts have been directed at addressing these limitations and optimizing assay performance using a variety of specimen types. This review provides a summary of standardization efforts and outlines the complexities of molecular testing for Aspergillus in clinical mycology.

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“…It is not yet clear whether confirmatory testing should be in the form of a secondary molecular test or through antigen testing. Recent clinical trials, prospective diagnostic testing, and metaanalysis favor a combined molecular-antigen approach (20,(23)(24)(25). However, methodological differences, including the various sample types used for PCR, and the potential incorporation bias associated with antigen testing need to be considered before finalizing a strategy.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Performance Characteristics of Aspergillus PCR in Testing a Range of Blood-Based Samples in Accordance with International Methodological Recommendations

et al. 2016

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cStandardized methodologies for the molecular detection of invasive aspergillosis (IA) have been established by the European Aspergillus PCR Initiative for the testing of whole blood, serum, and plasma. While some comparison of the performance of Aspergillus PCR when testing these different sample types has been performed, no single study has evaluated all three using the recommended protocols. Standardized Aspergillus PCR was performed on 423 whole-blood pellets (WBP), 583 plasma samples, and 419 serum samples obtained from hematology patients according to the recommendations. This analysis formed a bicenter retrospective anonymous case-control study, with diagnosis according to the revised European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) consensus definitions (11 probable cases and 36 controls). Values for clinical performance using individual and combined samples were calculated. For all samples, PCR positivity was significantly associated with cases of IA (for plasma, P ‫؍‬ 0.0019; for serum, P ‫؍‬ 0.0049; and for WBP, P ‫؍‬ 0.0089). Plasma PCR generated the highest sensitivity (91%); the sensitivities for serum and WBP PCR were 80% and 55%, respectively. The highest specificity was achieved when testing WBP (96%), which was significantly superior to the specificities achieved when testing serum (69%, P ‫؍‬ 0.0238) and plasma (53%, P ‫؍‬ 0.0002). No cases were PCR negative in all specimen types, and no controls were PCR positive in all specimens. This study confirms that Aspergillus PCR testing of plasma provides robust performance while utilizing commercial automated DNA extraction processes. Combining PCR testing of different blood fractions allows IA to be both confidently diagnosed and excluded. A requirement for multiple PCR-positive plasma samples provides similar diagnostic utility and is technically less demanding. Time to diagnosis may be enhanced by testing multiple contemporaneously obtained sample types. Standardized methodologies for the molecular detection of invasive aspergillosis (IA) when testing whole blood (WB), serum, and plasma have been established by the European Aspergillus PCR Initiative (EAPCRI), but direct comparisons of performance for methods compliant with the recommendations are limited (1-8). The published evidence from the data generated is contradictory. Serum was shown to be superior to the cell pellet in one study, only for another to recommend the use of WB over plasma (4,5). A recent study showed no significant difference in PCR performance when testing serum or WB (6). Differences between the methodologies used in the studies, particularly sample volumes and DNA extraction protocols, make comparisons difficult, and if suboptimal methods were used for one particular sample type, the assay performance and conclusions could be biased (1, 2).It is important to compare the different specimen types using optimal methodology and to co...

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Serum Galactomannan Versus a Combination of Galactomannan and Polymerase Chain Reaction-Based Aspergillus DNA Detection for Early Therapy of Invasive Aspergillosis in High-Risk Hematological Patients: A Randomized Controlled Trial

Abstract: A combined monitoring strategy based on serum GM and Aspergillus DNA was associated with an earlier diagnosis and a lower incidence of IA in high-risk hematological patients. Clinical Trials Registration. NCT01742026.

Cited by 132 publications

References 34 publications

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

Molecular Diagnostic Testing for Aspergillus

Comparison of Performance Characteristics of Aspergillus PCR in Testing a Range of Blood-Based Samples in Accordance with International Methodological Recommendations

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