Evaluation of PCR on Bronchoalveolar Lavage Fluid for Diagnosis of Invasive Aspergillosis: A Bivariate Metaanalysis and Systematic Review

Sun, Wenmin; Wang, Ke; Gao, Wei; Su, Xin; Qian, Qian; Lü, Xin; Song, Yong; Guo, Yaling; Shi, Yi

doi:10.1371/journal.pone.0028467

Cited by 73 publications

(42 citation statements)

References 49 publications

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“…The sensitivity of broad-range PCR in our data set was 95.6%, and the specificity was 96.4%. A recent metaanalysis reported similar data: sensitivity and specificity were 91% and 92%, respectively, by BAL fluid PCR assays for proven and probable IA (22). A subgroup analysis showed that the performance of the PCR assay was influenced by the PCR assay methodology, primer design, and the methods used for cell wall disruption and DNA extraction.…”

Section: Discussionmentioning

confidence: 78%

Utility of PCR in Diagnosis of Invasive Fungal Infections: Real-Life Data from a Multicenter Study

et al. 2013

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Prospective studies addressing the clinical value of broad-range PCR using the internal transcribed spacer region (ITS) for diagnosis of microscopy-negative fungal infections in nonselected patient populations are lacking. We first assessed the diagnostic performance of ITS rRNA gene PCR compared with that of routine microscopic immunofluorescence examination. Second, we addressed prospectively the impact and clinical value of broad-range PCR for the diagnosis of infections using samples that tested negative by routine microscopy; the corresponding patients' data were evaluated by detailed medical record reviews. Results from 371 specimens showed a high concordance of >80% for broad-range PCR and routine conventional methods, indicating that the diagnostic performance of PCR for fungal infections is comparable to that of microscopy, which is currently considered part of the "gold standard." In this prospective study, 206 specimens with a negative result on routine microscopy were analyzed with PCR, and patients' clinical data were reviewed according to the criteria of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group. We found that broad-range PCR showed a sensitivity, specificity, positive predictive value, and negative predictive value of 57.1%, 97.0%, 80%, and 91.7%, respectively, for microscopy-negative fungal infections. This study defines a possible helpful role of broad-range PCR for diagnosis of microscopy-negative fungal infections in conjunction with other tests.

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Section: Discussionmentioning

confidence: 78%

Utility of PCR in Diagnosis of Invasive Fungal Infections: Real-Life Data from a Multicenter Study

et al. 2013

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“…PCR assays of bronchoalveolar lavage fluid have been previously performed, with very promising findings (70). However, despite the large number of new studies on the issue, to our knowledge, there is only one meta-analysis of whole-blood and serum PCR performance to date.…”

Section: Discussionmentioning

confidence: 99%

PCR in Diagnosis of Invasive Aspergillosis: a Meta-Analysis of Diagnostic Performance

et al. 2014

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Invasive aspergillosis is a difficult-to-diagnose infection with a high mortality rate that affects high-risk groups such as patients with neutropenia and hematologic malignancies. We performed a bivariate meta-analysis of diagnostic data for an Aspergillus sp. PCR assay with blood specimens from high-risk hematology patients. We included all studies involving human subjects that assessed the performance of any PCR assay for invasive aspergillosis in whole blood or serum and that used the European Organization for the treatment of Cancer/Mycoses Study Group criteria as a reference standard. Three investigators independently searched the literature for eligible studies and extracted the data. Out of a total of 37 studies, 25 met strict quality criteria and were included in our evidence synthesis. Twenty-five studies with 2,595 patients were analyzed. The pooled diagnostic performance of whole-blood and serum PCR assays was moderate, with a sensitivity and specificity of 84% (95% confidence interval [CI], 75 to 91%) and 76% (95% CI, 65 to 84%), respectively, suggesting that a positive or negative result is unable, on its own, to confirm or exclude a suspected infection. The performance of a PCR assay of serum was not significantly different from that of whole blood. Notably, at least two positive PCR test results were found to have a specificity of 95% and a sensitivity of 64% for invasive infection, achieving a high positive likelihood ratio of 12.8. Importantly, the European Aspergillus PCR Initiative (EAP-CRI) recommendations improved the performance of the PCR even further when at least two positive specimens were used to define PCR positivity. In conclusion, two positive PCR results should be considered highly indicative of an active Aspergillus sp. infection. Use of the EAPCRI recommendations by clinical laboratories can further enhance PCR performance. D espite advances in treatment and supportive care, invasive aspergillosis (IA) is associated with significant morbidity and mortality rates, especially among patients with hematologic malignancies and hematopoietic stem cell transplant (HSCT) recipients (1, 2). Systemic antifungal prophylaxis is widely used in this patient population (3, 4), and patients with recurrent or persistent fever and prolonged neutropenia frequently require empirical coverage with antifungal agents (5). Timely and accurate diagnosis of an active infection is needed in order to initiate targeted antifungal therapy and avoid unnecessary antifungal treatment, which is often accompanied by a multitude of side effects and the cumulative risk of resistance.There is a need for the development of newer diagnostic techniques that would ideally be able to identify IA rapidly, noninvasively, and at an early stage. To aid in this endeavor, the European Organization for the treatment of Cancer/Mycoses Study Group (EORTC/MSG) developed specific criteria for the diagnosis of IA in 2002 (6), which were later revised in 2008 (7), in an attempt to provide the elusive "gold standard" to which any newe...

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“…Bu nedenlerden dolayı çalışmamızda, Aspergillus PCR çalışması için serum örnekleri yerine BAL örnekleri tercih edilmiştir. Sun ve arkadaşları 16 tarafından immünosüpresif hastaları kapsayan bir meta-analizde, BAL sıvısında yöntemin duyarlılık ve özgüllüğü sırasıyla %91 ve %92 olarak belirtilmiştir. Reinwald ve arkadaşlarının 31 ça-lışmasında da, immünosüpresif hastalarda duyarlılık ve özgüllük sırasıyla %59 ve %87 olarak saptanmıştır.…”

Section: İstatistiksel Analizunclassified

“…Aspergillus PCR çalışmalarında duyarlılık aralığının değişken olması, yöntemin standardize edilememesinden kaynaklanmaktadır. Ekstraksiyon yöntemi, PCR protokolü, kullanılan primerler ve problardaki farklılıklar nedeniyle sonuçlar değişebil-mektedir 16,31 . Aspergillus PCR çalışmalarının çoğu, hematolojik maligniteli immünosüp-resif hasta grubunda yapılmış olup, YB hastalarında yöntemin tanısal etkinliğine dair veriler yetersizdir.…”

Section: İstatistiksel Analizunclassified

“…Vücut sıvılarında Aspergillus nükleik asidinin polimeraz zincir reaksiyonu (PCR) ile saptanmasının İPA tanısındaki duyarlılığı, standardizasyon sıkıntısı nedeniyle değişkendir ve yöntemin tanı algoritmaları içerisindeki yeri henüz netleşmemiştir 1,16 . İPA tanısı için geliştirilen klinik algoritmalar çoğunlukla immün sistemi baskılanmış hastaları kapsamaktadır 1 .…”

Section: Introductionunclassified

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Evaluation of Risk Factors for Invasive Pulmonary Aspergillosis and Detection of Diagnostic Values of Galactomannan and PCR Methods in Bronchoalveolar Lavage Samples From Non-Neutropenic Intensive Care Unit Patients

Özger¹,

Hızel²,

Kalkancı³

et al. 2015

Mikrobiyol Bul

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ÖZNötropenik olmayan yoğun bakım (YB) hastaları, invazif pulmoner aspergilloz (İPA) gelişimi için artmış risk taşımaktadır. Bu olgularda, tanı için kullanılabilecek radyolojik ve mikrobiyolojik yöntemlerin (direkt mikroskopi, kültür) duyarlılık ve özgüllükleri oldukça düşüktür. Bu çalışmada, nötropenik olmayan YB hastalarında İPA risk faktörlerinin değerlendirilmesi, galaktomannan (GM) antijen ve Aspergillus nükleik asit tespiti yöntemlerinin, İPA için tanısal değerinin belirlenmesi amaçlanmıştır. Çalışmaya, OcakAralık 2013 tarihleri arasında, göğüs hastalıkları YB ünitesinde invazif mekanik ventilasyon (İMV) ile takip edilen ve bronkoskopi uygulanan 44 hasta (13 kadın, 31 erkek; yaş aralığı: 36-96 yıl) dahil edilmiştir. Geliş Tarihi

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Evaluation of PCR on Bronchoalveolar Lavage Fluid for Diagnosis of Invasive Aspergillosis: A Bivariate Metaanalysis and Systematic Review

Cited by 73 publications

References 49 publications

Utility of PCR in Diagnosis of Invasive Fungal Infections: Real-Life Data from a Multicenter Study

Utility of PCR in Diagnosis of Invasive Fungal Infections: Real-Life Data from a Multicenter Study

PCR in Diagnosis of Invasive Aspergillosis: a Meta-Analysis of Diagnostic Performance

Evaluation of Risk Factors for Invasive Pulmonary Aspergillosis and Detection of Diagnostic Values of Galactomannan and PCR Methods in Bronchoalveolar Lavage Samples From Non-Neutropenic Intensive Care Unit Patients

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