Galactomannan and PCR versus culture and histology for directing use of antifungal treatment for invasive aspergillosis in high-risk haematology patients: a randomised controlled trial

Morrissey, Orla; Chen, Sharon C‐A; Sorrell, Tania C.; Milliken, Sam; Bardy, Peter; Bradstock, Kenneth F.; Szer, Jeffrey; Halliday, Catriona; Gilroy, Nicole; Moore, John J.; Schwarer, Anthony P.; Guy, Stephen; Bajel, Ashish; Tramontana, Adrian R; Spelman, Tim; Slavin, Monica A

doi:10.1016/s1473-3099(13)70076-8

Cited by 205 publications

(165 citation statements)

References 33 publications

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“…The combination of histopathological examination and tissue cultures is needed to establish a definitive diagnosis. A proven diagnosis of phaeohyphomycosis infection, with or without molecular identification of the Phaeoacremonium species, was available for 27 patients (67%), which is significantly more than the case for other invasive fungal infections, such as aspergillosis, in immunocompromised subjects, for whom possible and probable diagnoses represent almost all diagnoses (16).…”

Section: Types Of Articlesmentioning

confidence: 99%

Dual Invasive Infection with Phaeoacremonium parasiticum and Paraconiothyrium cyclothyrioides in a Renal Transplant Recipient: Case Report and Comprehensive Review of the Literature of Phaeoacremonium Phaeohyphomycosis

et al. 2015

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e Despite increasing reports of human infection, data about the optimal care of Phaeoacremonium infections are missing. We report a case of an infection due to Phaeoacremonium parasiticum and Paraconiothyrium cyclothyrioides, initially localized to skin and soft tissue, in a kidney transplant patient. Despite surgical drainage and excision of the lesion and combination antifungal therapy with voriconazole and liposomal amphotericin B, a disseminated infection involving the lungs and brain developed and led to death. We performed a systematic literature review to assess the general features and outcome of human infections due to Phaeoacremonium species. Thirty-six articles were selected, and 42 patients, including ours, were reviewed. Thirty-one patients (74%) were immunocompromised because of organ or bone marrow transplantation (n ‫؍‬ 17), diabetes or glucose intolerance (n ‫؍‬ 10), rheumatoid arthritis or Still's disease (n ‫؍‬ 4), chronic hematological diseases (n ‫؍‬ 3), or chronic granulomatous disease (n ‫؍‬ 3). Ten patients (24%) reported initial cutaneous trauma. Skin and soft tissue infections represented 57% of infections (n ‫؍‬ 24), and disseminated infections, all occurring in immunocompromised patients, represented 14% of infections (n ‫؍‬ 6). The main antifungal drugs used were azoles (n ‫؍‬ 41) and amphotericin B (n ‫؍‬ 16). Surgical excision or drainage was performed in 64% of cases (n ‫؍‬ 27). The cure rate was 67% (n ‫؍‬ 28). There were 10% cases of treatment failure or partial response (n ‫؍‬ 4), 19% relapses (n ‫؍‬ 8), and 7% losses to follow-up (n ‫؍‬ 3). The death rate was 19% (n ‫؍‬ 8). Management of Phaeoacremonium infections is complex because of slow laboratory identification and limited clinical data, and treatment relies on a combination of surgery and systemic antifungal therapy. R eports of human diseases related to dark molds are increasing with the expanded spectrum of immunocompromised patients. Phaeohyphomycoses are a heterogenous group of cutaneous, subcutaneous, and systemic infections caused by fungi that are distributed worldwide, with melanized cell walls that develop in the host's tissue as dark-walled septate mycelial elements (1). Phaeoacremonium species, which are found in the environment in soil or in woody plants, as endophytes or as agents of plant disease, particularly in grapevines (2), are included in the phaeohyphomycosis group. Initially described in 1974 as Phialophora parasitica by Ajello et al. (3) and then transferred in 1996 to the new hyphomycete genus Phaeoacremonium by Crous et al., as Phaeoacremonium parasiticum (4), this fungus is a rare cause of human disease, occurring in both immunocompetent and immunosuppressed subjects. Reports of Phaeoacremonium infections are increasing over time, probably because laboratory confirmation of fungal pathogens has improved and because of the increase in immunocompromised conditions in the population. However, clinical and treatment data on Phaeoacremonium infection are scarce.We describe a case of a disseminated in...

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Section: Types Of Articlesmentioning

confidence: 99%

Dual Invasive Infection with Phaeoacremonium parasiticum and Paraconiothyrium cyclothyrioides in a Renal Transplant Recipient: Case Report and Comprehensive Review of the Literature of Phaeoacremonium Phaeohyphomycosis

et al. 2015

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“…Hence, accurate diagnosis continues to rely on complementary diagnostic approaches, as test results must be interpreted in conjunction with a range of clinical indicators of infection [1,9]. Which combination will prove to be the most clinically useful remains a moot point, but one attractive combination is GM testing and PCR analysis [192,193], or a triple test involving GM, the LFD and PCR. For now, clinical decision-making is usually made on intuition and suspicion, rather than on hard evidence.…”

Section: Resultsmentioning

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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“…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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Galactomannan and PCR versus culture and histology for directing use of antifungal treatment for invasive aspergillosis in high-risk haematology patients: a randomised controlled trial

Cited by 205 publications

References 33 publications

Dual Invasive Infection with Phaeoacremonium parasiticum and Paraconiothyrium cyclothyrioides in a Renal Transplant Recipient: Case Report and Comprehensive Review of the Literature of Phaeoacremonium Phaeohyphomycosis

Dual Invasive Infection with Phaeoacremonium parasiticum and Paraconiothyrium cyclothyrioides in a Renal Transplant Recipient: Case Report and Comprehensive Review of the Literature of Phaeoacremonium Phaeohyphomycosis

Biomarkers for Invasive Aspergillosis: The Challenges Continue

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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