The impact of anti-mould prophylaxis on Aspergillus PCR blood testing for the diagnosis of invasive aspergillosis
Abstract Background The performance of the galactomannan enzyme immunoassay (GM-EIA) is impaired in patients receiving mould-active antifungal therapy. The impact of mould-active antifungal therapy on Aspergillus PCR testing needs to be determined. Objectives To determine the influence of anti-mould...
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| Veröffentlicht in: | Journal of antimicrobial chemotherapy 2021-02, Vol.76 (3), p.635-638 |
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| creator | Cruciani, M White, P L Mengoli, C Löffler, J Morton, C O Klingspor, L Buchheidt, D Maertens, J Heinz, W J Rogers, T R Weinbergerova, B Warris, A Lockhart, D E A Jones, B Cordonnier, C Donnelly, J P Barnes, R A |
| description | Abstract
Background
The performance of the galactomannan enzyme immunoassay (GM-EIA) is impaired in patients receiving mould-active antifungal therapy. The impact of mould-active antifungal therapy on Aspergillus PCR testing needs to be determined.
Objectives
To determine the influence of anti-mould prophylaxis (AMP) on the performance of PCR blood testing to aid the diagnosis of proven/probable invasive aspergillosis (IA).
Methods
As part of the systematic review and meta-analysis of 22 cohort studies investigating Aspergillus PCR blood testing in 2912 patients at risk of IA, subgroup analysis was performed to determine the impact of AMP on the accuracy of Aspergillus PCR. The incidence of IA was calculated in patients receiving and not receiving AMP. The impact of two different positivity thresholds (requiring either a single PCR positive test result or ≥2 consecutive PCR positive test results) on accuracy was evaluated. Meta-analytical pooling of sensitivity and specificity was performed by logistic mixed-model regression.
Results
In total, 1661 (57%) patients received prophylaxis. The incidence of IA was 14.2%, significantly lower in the prophylaxis group (11%–12%) compared with the non-prophylaxis group (18%–19%) (P |
| doi_str_mv | 10.1093/jac/dkaa498 |
| format | Article |
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Background
The performance of the galactomannan enzyme immunoassay (GM-EIA) is impaired in patients receiving mould-active antifungal therapy. The impact of mould-active antifungal therapy on Aspergillus PCR testing needs to be determined.
Objectives
To determine the influence of anti-mould prophylaxis (AMP) on the performance of PCR blood testing to aid the diagnosis of proven/probable invasive aspergillosis (IA).
Methods
As part of the systematic review and meta-analysis of 22 cohort studies investigating Aspergillus PCR blood testing in 2912 patients at risk of IA, subgroup analysis was performed to determine the impact of AMP on the accuracy of Aspergillus PCR. The incidence of IA was calculated in patients receiving and not receiving AMP. The impact of two different positivity thresholds (requiring either a single PCR positive test result or ≥2 consecutive PCR positive test results) on accuracy was evaluated. Meta-analytical pooling of sensitivity and specificity was performed by logistic mixed-model regression.
Results
In total, 1661 (57%) patients received prophylaxis. The incidence of IA was 14.2%, significantly lower in the prophylaxis group (11%–12%) compared with the non-prophylaxis group (18%–19%) (P < 0.001). The use of AMP did not affect sensitivity, but significantly decreased specificity [single PCR positive result threshold: 26% reduction (P = 0.005); ≥2 consecutive PCR positive results threshold: 12% reduction (P = 0.019)].
Conclusions
Contrary to its influence on GM-EIA, AMP significantly decreases Aspergillus PCR specificity, without affecting sensitivity, possibly as a consequence of AMP limiting the clinical progression of IA and/or leading to false-negative GM-EIA results, preventing the classification of probable IA using the EORTC/MSGERC definitions.</description><identifier>ISSN: 0305-7453</identifier><identifier>EISSN: 1460-2091</identifier><identifier>DOI: 10.1093/jac/dkaa498</identifier><identifier>PMID: 33374010</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Aspergillosis - diagnosis ; Aspergillosis - prevention & control ; Aspergillus - genetics ; Humans ; Invasive Fungal Infections ; Mannans ; Meta-Analysis as Topic ; Polymerase Chain Reaction ; Sensitivity and Specificity</subject><ispartof>Journal of antimicrobial chemotherapy, 2021-02, Vol.76 (3), p.635-638</ispartof><rights>The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com. 2021</rights><rights>The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c358t-46630149a0a92932fe174d1248b3494fd30e05517d3d0d10fecab6b2202b78823</citedby><cites>FETCH-LOGICAL-c358t-46630149a0a92932fe174d1248b3494fd30e05517d3d0d10fecab6b2202b78823</cites><orcidid>0000-0002-8521-335X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,550,776,780,881,1578,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33374010$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:146082982$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Cruciani, M</creatorcontrib><creatorcontrib>White, P L</creatorcontrib><creatorcontrib>Mengoli, C</creatorcontrib><creatorcontrib>Löffler, J</creatorcontrib><creatorcontrib>Morton, C O</creatorcontrib><creatorcontrib>Klingspor, L</creatorcontrib><creatorcontrib>Buchheidt, D</creatorcontrib><creatorcontrib>Maertens, J</creatorcontrib><creatorcontrib>Heinz, W J</creatorcontrib><creatorcontrib>Rogers, T R</creatorcontrib><creatorcontrib>Weinbergerova, B</creatorcontrib><creatorcontrib>Warris, A</creatorcontrib><creatorcontrib>Lockhart, D E A</creatorcontrib><creatorcontrib>Jones, B</creatorcontrib><creatorcontrib>Cordonnier, C</creatorcontrib><creatorcontrib>Donnelly, J P</creatorcontrib><creatorcontrib>Barnes, R A</creatorcontrib><creatorcontrib>Fungal PCR Initiative</creatorcontrib><creatorcontrib>the Fungal PCR Initiative</creatorcontrib><title>The impact of anti-mould prophylaxis on Aspergillus PCR blood testing for the diagnosis of invasive aspergillosis</title><title>Journal of antimicrobial chemotherapy</title><addtitle>J Antimicrob Chemother</addtitle><description>Abstract
Background
The performance of the galactomannan enzyme immunoassay (GM-EIA) is impaired in patients receiving mould-active antifungal therapy. The impact of mould-active antifungal therapy on Aspergillus PCR testing needs to be determined.
Objectives
To determine the influence of anti-mould prophylaxis (AMP) on the performance of PCR blood testing to aid the diagnosis of proven/probable invasive aspergillosis (IA).
Methods
As part of the systematic review and meta-analysis of 22 cohort studies investigating Aspergillus PCR blood testing in 2912 patients at risk of IA, subgroup analysis was performed to determine the impact of AMP on the accuracy of Aspergillus PCR. The incidence of IA was calculated in patients receiving and not receiving AMP. The impact of two different positivity thresholds (requiring either a single PCR positive test result or ≥2 consecutive PCR positive test results) on accuracy was evaluated. Meta-analytical pooling of sensitivity and specificity was performed by logistic mixed-model regression.
Results
In total, 1661 (57%) patients received prophylaxis. The incidence of IA was 14.2%, significantly lower in the prophylaxis group (11%–12%) compared with the non-prophylaxis group (18%–19%) (P < 0.001). The use of AMP did not affect sensitivity, but significantly decreased specificity [single PCR positive result threshold: 26% reduction (P = 0.005); ≥2 consecutive PCR positive results threshold: 12% reduction (P = 0.019)].
Conclusions
Contrary to its influence on GM-EIA, AMP significantly decreases Aspergillus PCR specificity, without affecting sensitivity, possibly as a consequence of AMP limiting the clinical progression of IA and/or leading to false-negative GM-EIA results, preventing the classification of probable IA using the EORTC/MSGERC definitions.</description><subject>Aspergillosis - diagnosis</subject><subject>Aspergillosis - prevention & control</subject><subject>Aspergillus - genetics</subject><subject>Humans</subject><subject>Invasive Fungal Infections</subject><subject>Mannans</subject><subject>Meta-Analysis as Topic</subject><subject>Polymerase Chain Reaction</subject><subject>Sensitivity and Specificity</subject><issn>0305-7453</issn><issn>1460-2091</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>D8T</sourceid><recordid>eNp9kU1LxDAQhoMouq6evEtOIkjdyVebHmXxCwRF1nNIm3SNtk1t2lX_vVl29egpQ-aZB2ZehE4IXBLI2exNlzPzrjXP5Q6aEJ5CQiEnu2gCDESSccEO0GEIbwCQilTuowPGWMaBwAR9LF4tdk2nywH7Cut2cEnjx9rgrvfd63etv1zAvsVXobP90tX1GPDT_BkXtfcGDzYMrl3iyvd4iCbj9LL1YT1SYdeudHAri_Xv7LpzhPYqXQd7vH2n6OXmejG_Sx4eb-_nVw9JyYQcEp6mDAjPNeic5oxWlmTcEMplwXjOK8PAghAkM8yAIVDZUhdpQSnQIpOSsilKNt7wabuxUF3vGt1_K6-d2n69x8oqngoRbzRF5xs-Lv4xxr1U40Jp61q31o9BUZ4xmUspZEQvNmjZ-xB6W_3JCah1JipmoraZRPp0Kx6Lxpo_9jeECJxtAD92_5p-AI5GlpU</recordid><startdate>20210211</startdate><enddate>20210211</enddate><creator>Cruciani, M</creator><creator>White, P L</creator><creator>Mengoli, C</creator><creator>Löffler, J</creator><creator>Morton, C O</creator><creator>Klingspor, L</creator><creator>Buchheidt, D</creator><creator>Maertens, J</creator><creator>Heinz, W J</creator><creator>Rogers, T R</creator><creator>Weinbergerova, B</creator><creator>Warris, A</creator><creator>Lockhart, D E A</creator><creator>Jones, B</creator><creator>Cordonnier, C</creator><creator>Donnelly, J P</creator><creator>Barnes, R A</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope><orcidid>https://orcid.org/0000-0002-8521-335X</orcidid></search><sort><creationdate>20210211</creationdate><title>The impact of anti-mould prophylaxis on Aspergillus PCR blood testing for the diagnosis of invasive aspergillosis</title><author>Cruciani, M ; White, P L ; Mengoli, C ; Löffler, J ; Morton, C O ; Klingspor, L ; Buchheidt, D ; Maertens, J ; Heinz, W J ; Rogers, T R ; Weinbergerova, B ; Warris, A ; Lockhart, D E A ; Jones, B ; Cordonnier, C ; Donnelly, J P ; Barnes, R A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c358t-46630149a0a92932fe174d1248b3494fd30e05517d3d0d10fecab6b2202b78823</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Aspergillosis - diagnosis</topic><topic>Aspergillosis - prevention & control</topic><topic>Aspergillus - genetics</topic><topic>Humans</topic><topic>Invasive Fungal Infections</topic><topic>Mannans</topic><topic>Meta-Analysis as Topic</topic><topic>Polymerase Chain Reaction</topic><topic>Sensitivity and Specificity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cruciani, M</creatorcontrib><creatorcontrib>White, P L</creatorcontrib><creatorcontrib>Mengoli, C</creatorcontrib><creatorcontrib>Löffler, J</creatorcontrib><creatorcontrib>Morton, C O</creatorcontrib><creatorcontrib>Klingspor, L</creatorcontrib><creatorcontrib>Buchheidt, D</creatorcontrib><creatorcontrib>Maertens, J</creatorcontrib><creatorcontrib>Heinz, W J</creatorcontrib><creatorcontrib>Rogers, T R</creatorcontrib><creatorcontrib>Weinbergerova, B</creatorcontrib><creatorcontrib>Warris, A</creatorcontrib><creatorcontrib>Lockhart, D E A</creatorcontrib><creatorcontrib>Jones, B</creatorcontrib><creatorcontrib>Cordonnier, C</creatorcontrib><creatorcontrib>Donnelly, J P</creatorcontrib><creatorcontrib>Barnes, R A</creatorcontrib><creatorcontrib>Fungal PCR Initiative</creatorcontrib><creatorcontrib>the Fungal PCR Initiative</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>Journal of antimicrobial chemotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cruciani, M</au><au>White, P L</au><au>Mengoli, C</au><au>Löffler, J</au><au>Morton, C O</au><au>Klingspor, L</au><au>Buchheidt, D</au><au>Maertens, J</au><au>Heinz, W J</au><au>Rogers, T R</au><au>Weinbergerova, B</au><au>Warris, A</au><au>Lockhart, D E A</au><au>Jones, B</au><au>Cordonnier, C</au><au>Donnelly, J P</au><au>Barnes, R A</au><aucorp>Fungal PCR Initiative</aucorp><aucorp>the Fungal PCR Initiative</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The impact of anti-mould prophylaxis on Aspergillus PCR blood testing for the diagnosis of invasive aspergillosis</atitle><jtitle>Journal of antimicrobial chemotherapy</jtitle><addtitle>J Antimicrob Chemother</addtitle><date>2021-02-11</date><risdate>2021</risdate><volume>76</volume><issue>3</issue><spage>635</spage><epage>638</epage><pages>635-638</pages><issn>0305-7453</issn><eissn>1460-2091</eissn><abstract>Abstract
Background
The performance of the galactomannan enzyme immunoassay (GM-EIA) is impaired in patients receiving mould-active antifungal therapy. The impact of mould-active antifungal therapy on Aspergillus PCR testing needs to be determined.
Objectives
To determine the influence of anti-mould prophylaxis (AMP) on the performance of PCR blood testing to aid the diagnosis of proven/probable invasive aspergillosis (IA).
Methods
As part of the systematic review and meta-analysis of 22 cohort studies investigating Aspergillus PCR blood testing in 2912 patients at risk of IA, subgroup analysis was performed to determine the impact of AMP on the accuracy of Aspergillus PCR. The incidence of IA was calculated in patients receiving and not receiving AMP. The impact of two different positivity thresholds (requiring either a single PCR positive test result or ≥2 consecutive PCR positive test results) on accuracy was evaluated. Meta-analytical pooling of sensitivity and specificity was performed by logistic mixed-model regression.
Results
In total, 1661 (57%) patients received prophylaxis. The incidence of IA was 14.2%, significantly lower in the prophylaxis group (11%–12%) compared with the non-prophylaxis group (18%–19%) (P < 0.001). The use of AMP did not affect sensitivity, but significantly decreased specificity [single PCR positive result threshold: 26% reduction (P = 0.005); ≥2 consecutive PCR positive results threshold: 12% reduction (P = 0.019)].
Conclusions
Contrary to its influence on GM-EIA, AMP significantly decreases Aspergillus PCR specificity, without affecting sensitivity, possibly as a consequence of AMP limiting the clinical progression of IA and/or leading to false-negative GM-EIA results, preventing the classification of probable IA using the EORTC/MSGERC definitions.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>33374010</pmid><doi>10.1093/jac/dkaa498</doi><tpages>4</tpages><orcidid>https://orcid.org/0000-0002-8521-335X</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection; SWEPUB Freely available online; Free Full-Text Journals in Chemistry |
| subjects | Aspergillosis - diagnosis Aspergillosis - prevention & control Aspergillus - genetics Humans Invasive Fungal Infections Mannans Meta-Analysis as Topic Polymerase Chain Reaction Sensitivity and Specificity |
| title | The impact of anti-mould prophylaxis on Aspergillus PCR blood testing for the diagnosis of invasive aspergillosis |
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