Variable Correlation between Bronchoalveolar Lavage Fluid Fungal Load and Serum-(1,3)-β-d-Glucan in Patients with Pneumocystosis—A Multicenter ECMM Excellence Center Study

Mercier, Toine; Aissaoui, Nesrine; Gits-Muselli, Maud; Hamane, Samia; Prattes, Juergen; Kessler, Harald H.; Mareković, Ivana; Pleško, Sanja; Steinmann, Jörg; Scharmann, Ulrike; Maertens, Johan; Lagrou, Katrien; Denis, Blandine; Bretagne, Stéphane; Alanio, Alexandre

doi:10.3390/jof6040327

Cited by 17 publications

(14 citation statements)

References 24 publications

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“…Thus, our findings support the EORTC/MSGERC recommendations that require ≥2 consecutive serum samples to be BDG positive to diagnose probable PCP if other etiologies have been ruled out [11]. Conversely, a negative BDG result-that may be potentially false negative because of a low PJ load and low BDG release [16]-strongly suggested the absence of PCP in our patients, which was supported by either the BAL fluid sample PCR negativity or the determination of alternative etiologies (Table 1).…”

Section: Discussionsupporting

confidence: 78%

“…According to positive IFA or PJ -PCR results, the revised/updated EORTC/MSGERC 2008 consensus definitions of invasive fungal disease [ 11 ] allowed one to classify pneumonia episodes as proven (both IFA and PJ -PCR positive) or probable (only PJ -PCR positive) PCP episodes, respectively. In view of conflicting opinions about the role of BDG in the PCP diagnosis [ 4 , 16 , 17 ], we only used BDG results to corroborate the results obtained with the PJ -PCR assay. Furthermore, microbiological standard-of-care testing results allowed one to classify non-PCP episodes as bacterial, viral, or (outside PCP) fungal pneumonia episodes, respectively.…”

Section: Methodsmentioning

confidence: 99%

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A New PCR-Based Assay for Testing Bronchoalveolar Lavage Fluid Samples from Patients with Suspected Pneumocystis jirovecii Pneumonia

Liotti

Posteraro

Angelis

et al. 2021

JoF

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To support the clinical laboratory diagnosis of Pneumocystis jirovecii (PJ) pneumonia (PCP), an invasive fungal infection mainly occurring in HIV-negative patients, in-house or commercial PJ-specific real-time quantitative PCR (qPCR) assays are todays’ reliable options. The performance of these assays depends on the type of PJ gene (multi-copy mitochondrial versus single-copy nuclear) targeted by the assay. We described the development of a PJ-PCR assay targeting the dihydrofolate reductase (DHFR)-encoding gene. After delineating its analytical performance, the PJ-PCR assay was used to test bronchoalveolar lavage (BAL) fluid samples from 200 patients (only seven were HIV positive) with suspected PCP. Of 211 BAL fluid samples, 18 (8.5%) were positive and 193 (91.5%) were negative by PJ-PCR. Of 18 PJ-PCR-positive samples, 11 (61.1%) tested positive and seven (38.9%) tested negative with the immunofluorescence assay (IFA). All (100%) of the 193 PJ-PCR-negative samples were IFA negative. Based on IFA/PCR results, patients were, respectively, classified as having (n = 18) and not having (n = 182) proven (PJ-PCR+/IFA+) or probable (PJ-PCR+/IFA−) PCP. For 182 patients without PCP, alternative infectious or non-infectious etiologies were identified. Our PJ-PCR assay was at least equivalent to IFA, fostering studies aimed at defining a qPCR-based standard for PCP diagnosis in the future.

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Section: Discussionsupporting

confidence: 78%

Section: Methodsmentioning

confidence: 99%

A New PCR-Based Assay for Testing Bronchoalveolar Lavage Fluid Samples from Patients with Suspected Pneumocystis jirovecii Pneumonia

Liotti

Posteraro

Angelis

et al. 2021

JoF

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“…The significance of detected Pneumocystis DNA using PCR alone remains uncertain, and can be due to colonization of the respiratory tract [ 37 ]. Real-time quantitative (RTqPCR) assays are the only PCR method recommended for diagnosis [ 38 ]. A study conducted in 108 critical patients with COVID-19 from the intensive care unit showed that 9.3% had positive Pneumocystis RTqPCR tests from bronchoalveolar lavage/tracheal aspirate/sputum samples [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

“…Serological tests for detection of anti- Pneumocystis antibodies have not proven clinically useful for establishing a diagnosis of pneumonia [ 35 , 39 ]. β-1,3-glucan is sensitive, but not specific [ 38 , 40 ]. The identification of specific biomarkers would be particularly useful, especially in patients where manipulation of the airway is limited and therefore the collection of respiratory samples is difficult.…”

Section: Discussionmentioning

confidence: 99%

COVID-19 and Pneumocystis jirovecii Pulmonary Coinfection—The First Case Confirmed through Autopsy

Jeican

Inișca²,

Gheban

et al. 2021

Medicina

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Background: Establishing the diagnosis of COVID-19 and Pneumocystis jirovecii pulmonary coinfection is difficult due to clinical and radiological similarities that exist between the two disorders. For the moment, fungal coinfections are underestimated in COVID-19 patients. Case presentation: We report the case of a 52-year-old male patient, who presented to the emergency department for severe dyspnea and died 17 h later. The RT-PCR test performed at his admission was negative for SARS-CoV-2. Retesting of lung fragments collected during autopsy revealed a positive result for SARS-CoV-2. Histopathological examination showed preexisting lesions, due to comorbidities, as well as recent lesions: massive lung thromboses, alveolar exudate rich in foam cells, suprapleural and intra-alveolar Pneumocystis jirovecii cystic forms, and bilateral adrenal hemorrhage. The existing coinfection was identified after the autopsy. Establishing the diagnosis of this coinfection is difficult due to clinical and radiological similarities that exist between the two disorders. For the moment, fungal coinfections are underestimated in COVID-19 patients. Conclusion: COVID-19 and P. jirovecii coinfection should be considered, particularly in critically ill patients, and we recommend the systematic search for P. jirovecii in respiratory samples.

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“…In this context, it was suggested that a negative BG result could accurately exclude a PCP diagnosis (Held et al, 2011;Onishi et al, 2012;Alanio et al, 2016;Lahmer et al, 2017;Morjaria et al, 2019;Ideguchi et al, 2020;Szvalb et al, 2020). In contrast, other reports describe a suboptimal sensitivity of this assay, especially in HIV-negative patients (Nakamura et al, 2009;Li et al, 2015;Engsbro et al, 2019;Kato et al, 2019;Del Corpo et al, 2020;Mercier et al, 2020;Rogina and Skvarc, 2020). These discrepant results regarding the usefulness of serum BG assay in HIV-negative PCP patients could be related to the underlying condition that exposes to PCP risk.…”

Section: Introductionmentioning

confidence: 99%

A Negative (1,3)-β-D-Glucan Result Alone Is Not Sufficient to Rule Out a Diagnosis of Pneumocystis Pneumonia in Patients With Hematological Malignancies

et al. 2021

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Background: Serum (1,3)-β-D-glucan (BG) testing is increasingly being used in the diagnostic armamentarium for invasive fungal diseases. Given its high sensitivity, some studies suggest that a negative BG result contributes to rule out a diagnosis of Pneumocystis pneumonia (PCP). However, recent reports described a suboptimal sensitivity in HIV-negative immunocompromised patients. In this study, we evaluated the performance of BG assay for PCP diagnosis in HIV-negative patients with diverse PCP risk factors. We also assessed the correlation between Pneumocystis jirovecii load in pulmonary samples and serum BG levels.Methods: We retrospectively included HIV-negative patients with microscopically proven PCP and for whom a BG result was available. We also enrolled patients colonized by Pneumocystis as control group. Colonized patients were matched with PCP patients based on their underlying condition that exposed to PCP. Pulmonary fungal loads were determined by an in-house real-time PCR, and BG levels were measured by using the Fungitell® kit (Associates of Cape Cod, Inc.).Results: Thirty-nine patients were included in each of the two groups. Thirty-four of 39 PCP patients and one of 39 colonized patient had a positive BG test, resulting in a sensitivity of 0.87 (95% CI: 0.73–0.94), a specificity of 0.97 (95% CI: 0.87–0.99), a positive predictive value of 0.97 (95% CI: 0.85–0.99), and a negative predictive value of 0.88 (95% CI: 0.75–0.95) for BG assay. Nonetheless, median BG level differed according to the underlying condition. Among the PCP group, the lowest median level of 211 pg/ml was observed in patients with hematological malignancy (HM) and differed significantly from that observed either in solid organ transplants (3,473 pg/ml) or in patients with autoimmune or inflammatory disorder (3,480 pg/ml). Indeed, the sensitivity of BG assay was estimated at 0.64 (95% CI: 0.35–0.85) in HM patients and was lower than the one observed in the whole PCP group. Furthermore, BG level and fungal burden correlated poorly among all PCP patients.Conclusion: BG is not a reliable biomarker for ruling out PCP in HIV-negative patients with HM. Interpretation of a negative BG result should take into account, but not be limited to, the underlying condition predisposing to PCP.

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Variable Correlation between Bronchoalveolar Lavage Fluid Fungal Load and Serum-(1,3)-β-d-Glucan in Patients with Pneumocystosis—A Multicenter ECMM Excellence Center Study

Cited by 17 publications

References 24 publications

A New PCR-Based Assay for Testing Bronchoalveolar Lavage Fluid Samples from Patients with Suspected Pneumocystis jirovecii Pneumonia

A New PCR-Based Assay for Testing Bronchoalveolar Lavage Fluid Samples from Patients with Suspected Pneumocystis jirovecii Pneumonia

COVID-19 and Pneumocystis jirovecii Pulmonary Coinfection—The First Case Confirmed through Autopsy

A Negative (1,3)-β-D-Glucan Result Alone Is Not Sufficient to Rule Out a Diagnosis of Pneumocystis Pneumonia in Patients With Hematological Malignancies

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