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Erschienen in: Infection 2/2016

16.10.2015 | Original Paper

Evaluation of serum (1 → 3)-β-d-glucan clinical performance: kinetic assessment, comparison with galactomannan and evaluation of confounding factors

verfasst von: P. Pini, C. Bettua, C. F. Orsi, C. Venturelli, F. Forghieri, S. Bigliardi, L. Faglioni, F. Luppi, L. Serio, M. Codeluppi, M. Luppi, C. Mussini, M. Girardis, Elisabetta Blasi

Erschienen in: Infection | Ausgabe 2/2016

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Abstract

Purpose

We investigated the clinical performance of (1 → 3)-β-d-glucan (BG), as an early marker of invasive fungal infections (IFI), in different clinical settings.

Methods

BG serum levels were assessed by Fungitell (Associates of Cape Cod, Inc), in parallel with galactomannan (GM) when requested by clinicians. By a prospective monocentric study, 270 episodes at risk or with suspect of IFI were enrolled, namely 58 proven-probable invasive aspergillosis (IA), 27 proven invasive candidiasis (IC), 11 possible IC, 16 P.jirovecii pneumonia (PJP), 4 episodes of other IFI and 154 non-IFI controls.

Results

We found that (a) the BG overall sensitivity, specificity, positive predictive value and negative predictive value (NPV) were 87.9, 80.5, 76.7 and 89.9 %, respectively; (b) the highest sensitivity was found in the IC groups, followed by PJP, IA and other IFI groups; (c) an association was observed between BG kinetics and patients outcome; (d) in the IA episodes, the combination of BG or GM vs GM alone increased sensitivity from 60.0 to 83.3 % in the haematological patients; (e) false-positive BG results were related to Gram-negative infections or infusion of polyclonal IgM-enriched immunoglobulins, where high levels of BG were indeed detected.

Conclusion

Besides strengthening its overall good clinical performance, we provide evidence that serum BG correlates with clinical outcome and that, once used in combination with GM, BG allows to enhance IFI diagnosis rate. The high sensitivity and NPV, observed in the Intensive Care Unit setting, open to BG validation as a marker for assessment of antifungal treatment.
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Literatur
1.
Zurück zum Zitat Pittet D, Monod M, Suter PM, et al. Candida colonization and subsequent infections in critically ill surgical patients. Ann Surg. 1994;220:751–8.CrossRefPubMedPubMedCentral Pittet D, Monod M, Suter PM, et al. Candida colonization and subsequent infections in critically ill surgical patients. Ann Surg. 1994;220:751–8.CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat León C, Ruiz-Santana S, Saavedra P, et al. Usefulness of the “Candida score” for discriminating between Candida colonization and invasive candidiasis in non-neutropenic critically ill patients: a prospective multicenter study. Crit Care Med. 2009;37:1624–33. doi:10.1097/CCM.0b013e31819daa14.CrossRefPubMed León C, Ruiz-Santana S, Saavedra P, et al. Usefulness of the “Candida score” for discriminating between Candida colonization and invasive candidiasis in non-neutropenic critically ill patients: a prospective multicenter study. Crit Care Med. 2009;37:1624–33. doi:10.​1097/​CCM.​0b013e31819daa14​.CrossRefPubMed
3.
Zurück zum Zitat Pini P, Bettua C, Orsi CF, et al. Clinical performance of a commercial real-time PCR assay for Aspergillus DNA detection in serum samples from high-risk patients: comparison with a galactomannan enzyme immunoassay. Eur J Clin Microbiol Infect Dis. 2015;34:131–6. doi:10.1007/s10096-014-2211-y.CrossRefPubMed Pini P, Bettua C, Orsi CF, et al. Clinical performance of a commercial real-time PCR assay for Aspergillus DNA detection in serum samples from high-risk patients: comparison with a galactomannan enzyme immunoassay. Eur J Clin Microbiol Infect Dis. 2015;34:131–6. doi:10.​1007/​s10096-014-2211-y.CrossRefPubMed
4.
Zurück zum Zitat Orsi CF, Gennari W, Venturelli C, et al. Performance of 2 commercial real-time polymerase chain reaction assays for the detection of Aspergillus and Pneumocystis DNA in bronchoalveolar lavage fluid samples from critical care patients. Diagn Microbiol Infect Dis. 2012. doi:10.1016/j.diagmicrobio.2012.03.001.PubMed Orsi CF, Gennari W, Venturelli C, et al. Performance of 2 commercial real-time polymerase chain reaction assays for the detection of Aspergillus and Pneumocystis DNA in bronchoalveolar lavage fluid samples from critical care patients. Diagn Microbiol Infect Dis. 2012. doi:10.​1016/​j.​diagmicrobio.​2012.​03.​001.PubMed
6.
Zurück zum Zitat Mikulska M, Calandra T, Sanguinetti M, et al. The use of mannan antigen and anti-mannan antibodies in the diagnosis of invasive candidiasis: recommendations from the Third European Conference on Infections in Leukemia. Crit Care. 2010;14:222. doi:10.1186/cc9365.CrossRef Mikulska M, Calandra T, Sanguinetti M, et al. The use of mannan antigen and anti-mannan antibodies in the diagnosis of invasive candidiasis: recommendations from the Third European Conference on Infections in Leukemia. Crit Care. 2010;14:222. doi:10.​1186/​cc9365.CrossRef
7.
Zurück zum Zitat Ardizzoni A, Posteraro B, Baschieri MC, et al. An antibody reactivity-based assay for diagnosis of invasive candidiasis using protein array. Int J Immunopathol Pharmacol. 2014;27:403–12.PubMed Ardizzoni A, Posteraro B, Baschieri MC, et al. An antibody reactivity-based assay for diagnosis of invasive candidiasis using protein array. Int J Immunopathol Pharmacol. 2014;27:403–12.PubMed
9.
Zurück zum Zitat De Pauw B, Walsh TJ, Donnelly JP, et al. Revised definitions of invasive fungal disease from 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 (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008;46:1813–21. doi:10.1086/588660.CrossRefPubMedPubMedCentral De Pauw B, Walsh TJ, Donnelly JP, et al. Revised definitions of invasive fungal disease from 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 (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008;46:1813–21. doi:10.​1086/​588660.CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Marchetti O, Lamoth F, Mikulska M, et al. ECIL recommendations for the use of biological markers for the diagnosis of invasive fungal diseases in leukemic patients and hematopoietic SCT recipients. Bone Marrow Transplant. 2012;47:846–54. doi:10.1038/bmt.2011.178.CrossRefPubMed Marchetti O, Lamoth F, Mikulska M, et al. ECIL recommendations for the use of biological markers for the diagnosis of invasive fungal diseases in leukemic patients and hematopoietic SCT recipients. Bone Marrow Transplant. 2012;47:846–54. doi:10.​1038/​bmt.​2011.​178.CrossRefPubMed
12.
14.
Zurück zum Zitat Meersseman W, Lagrou K, Maertens J, Van Wijngaerden E. Invasive Aspergillosis in the intensive care unit. Clin Infect Dis Off Publ Infect Dis Soc Am. 2007;45:205–16. doi:10.1086/518852.CrossRef Meersseman W, Lagrou K, Maertens J, Van Wijngaerden E. Invasive Aspergillosis in the intensive care unit. Clin Infect Dis Off Publ Infect Dis Soc Am. 2007;45:205–16. doi:10.​1086/​518852.CrossRef
15.
Zurück zum Zitat Torelli R, Sanguinetti M, Moody A, et al. Diagnosis of invasive aspergillosis by a commercial real-time PCR assay for Aspergillus DNA in bronchoalveolar lavage fluid samples from high-risk patients compared to a galactomannan enzyme immunoassay. J Clin Microbiol. 2011;49:4273–8. doi:10.1128/JCM.05026-11.CrossRefPubMedPubMedCentral Torelli R, Sanguinetti M, Moody A, et al. Diagnosis of invasive aspergillosis by a commercial real-time PCR assay for Aspergillus DNA in bronchoalveolar lavage fluid samples from high-risk patients compared to a galactomannan enzyme immunoassay. J Clin Microbiol. 2011;49:4273–8. doi:10.​1128/​JCM.​05026-11.CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Orsi CF, Bettua C, Pini P, et al. Detection of Pneumocystis jirovecii and Aspergillus spp. DNA in bronchoalveolar lavage fluids by commercial real-time PCR assays: comparison with conventional diagnostic tests. New Microbiol. 2015;38:75–84.PubMed Orsi CF, Bettua C, Pini P, et al. Detection of Pneumocystis jirovecii and Aspergillus spp. DNA in bronchoalveolar lavage fluids by commercial real-time PCR assays: comparison with conventional diagnostic tests. New Microbiol. 2015;38:75–84.PubMed
17.
Zurück zum Zitat Obayashi T, Negishi K, Suzuki T, Funata N. Reappraisal of the serum (1 → 3)-β-d-glucan assay for the diagnosis of invasive fungal infections—a study based on autopsy cases from 6 years. Clin Infect Dis. 2008;46:1864–70. doi:10.1086/588295.CrossRefPubMed Obayashi T, Negishi K, Suzuki T, Funata N. Reappraisal of the serum (1 → 3)-β-d-glucan assay for the diagnosis of invasive fungal infections—a study based on autopsy cases from 6 years. Clin Infect Dis. 2008;46:1864–70. doi:10.​1086/​588295.CrossRefPubMed
20.
Zurück zum Zitat Hauser PM, Bille J, Lass-Florl C, et al. Multicenter, prospective clinical evaluation of respiratory samples from subjects at risk for Pneumocystis jirovecii infection by use of a commercial real-time PCR assay. J Clin Microbiol. 2011;49:1872–8. doi:10.1128/JCM.02390-10.CrossRefPubMedPubMedCentral Hauser PM, Bille J, Lass-Florl C, et al. Multicenter, prospective clinical evaluation of respiratory samples from subjects at risk for Pneumocystis jirovecii infection by use of a commercial real-time PCR assay. J Clin Microbiol. 2011;49:1872–8. doi:10.​1128/​JCM.​02390-10.CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Onishi A, Sugiyama D, Kogata Y, et al. Diagnostic accuracy of serum 1,3-β-d-glucan for Pneumocystis jiroveci pneumonia, invasive candidiasis, and invasive aspergillosis: systematic review and meta-analysis. J Clin Microbiol. 2012;50:7–15. doi:10.1128/JCM.05267-11.CrossRefPubMedPubMedCentral Onishi A, Sugiyama D, Kogata Y, et al. Diagnostic accuracy of serum 1,3-β-d-glucan for Pneumocystis jiroveci pneumonia, invasive candidiasis, and invasive aspergillosis: systematic review and meta-analysis. J Clin Microbiol. 2012;50:7–15. doi:10.​1128/​JCM.​05267-11.CrossRefPubMedPubMedCentral
22.
23.
Zurück zum Zitat He S, Hang J-P, Zhang L, et al. A systematic review and meta-analysis of diagnostic accuracy of serum 1, 3-β-d-glucan for invasive fungal infection: focus on cutoff levels. J Microbiol Immunol Infect. 2014. doi:10.1016/j.jmii.2014.06.009. He S, Hang J-P, Zhang L, et al. A systematic review and meta-analysis of diagnostic accuracy of serum 1, 3-β-d-glucan for invasive fungal infection: focus on cutoff levels. J Microbiol Immunol Infect. 2014. doi:10.​1016/​j.​jmii.​2014.​06.​009.
24.
Zurück zum Zitat Lamoth F, Cruciani M, Mengoli C, et al. β-glucan antigenemia assay for the diagnosis of invasive fungal infections in patients with hematological malignancies: a systematic review and meta-analysis of Cohort Studies From the Third European Conference on Infections in Leukemia (ECIL-3). Clin Infect Dis. 2012;54:633–43. doi:10.1093/cid/cir89.CrossRefPubMed Lamoth F, Cruciani M, Mengoli C, et al. β-glucan antigenemia assay for the diagnosis of invasive fungal infections in patients with hematological malignancies: a systematic review and meta-analysis of Cohort Studies From the Third European Conference on Infections in Leukemia (ECIL-3). Clin Infect Dis. 2012;54:633–43. doi:10.​1093/​cid/​cir89.CrossRefPubMed
25.
Zurück zum Zitat Sulahian A, Porcher R, Bergeron A, et al. Use and limits of (1 → 3)-β-d-glucan assay (fungitell), compared to galactomannan determination (platelia Aspergillus), for diagnosis of invasive Aspergillosis. J Clin Microbiol. 2014;52:2328–33. doi:10.1128/JCM.03567-13.CrossRefPubMedPubMedCentral Sulahian A, Porcher R, Bergeron A, et al. Use and limits of (1 → 3)-β-d-glucan assay (fungitell), compared to galactomannan determination (platelia Aspergillus), for diagnosis of invasive Aspergillosis. J Clin Microbiol. 2014;52:2328–33. doi:10.​1128/​JCM.​03567-13.CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Hachem RY, Kontoyiannis DP, Chemaly RF, et al. Utility of galactomannan enzyme immunoassay and (1,3) β-d-glucan in diagnosis of invasive fungal infections: low sensitivity for Aspergillus fumigatus infection in hematologic malignancy patients. J ClinMicrobiol. 2009;47:129–33. doi:10.1128/JCM.00506-08. Hachem RY, Kontoyiannis DP, Chemaly RF, et al. Utility of galactomannan enzyme immunoassay and (1,3) β-d-glucan in diagnosis of invasive fungal infections: low sensitivity for Aspergillus fumigatus infection in hematologic malignancy patients. J ClinMicrobiol. 2009;47:129–33. doi:10.​1128/​JCM.​00506-08.
27.
Zurück zum Zitat Persat F, Ranque S, Derouin F, et al. Contribution of the (1 → 3)-β-d-glucan assay for diagnosis of invasive fungal infections. J ClinMicrobiol. 2008;46:1009–13. doi:10.1128/JCM.02091-07. Persat F, Ranque S, Derouin F, et al. Contribution of the (1 → 3)-β-d-glucan assay for diagnosis of invasive fungal infections. J ClinMicrobiol. 2008;46:1009–13. doi:10.​1128/​JCM.​02091-07.
28.
Zurück zum Zitat Pazos C, Ponton J, Palacio AD. Contribution of (1 → 3)-β-d-glucan chromogenic assay to diagnosis and therapeutic monitoring of invasive aspergillosis in neutropenic adult patients: a comparison with serial screening for circulating galactomannan. J Clin Microbiol. 2005;43:299–305. doi:10.1128/JCM.43.1.299-305.2005.CrossRefPubMedPubMedCentral Pazos C, Ponton J, Palacio AD. Contribution of (1 → 3)-β-d-glucan chromogenic assay to diagnosis and therapeutic monitoring of invasive aspergillosis in neutropenic adult patients: a comparison with serial screening for circulating galactomannan. J Clin Microbiol. 2005;43:299–305. doi:10.​1128/​JCM.​43.​1.​299-305.​2005.CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Farina C, Lombardi G, Andreoni S, et al. Routine use of a protease zymogen-based colorimetric assay for the detection of β-glucan and its role in clinical practice. Int J Immunopathol Pharmacol. 2014;27:661–8.PubMed Farina C, Lombardi G, Andreoni S, et al. Routine use of a protease zymogen-based colorimetric assay for the detection of β-glucan and its role in clinical practice. Int J Immunopathol Pharmacol. 2014;27:661–8.PubMed
30.
Zurück zum Zitat Clancy CJ, Nguyen MH. Finding the “missing 50 %” of invasive candidiasis: how nonculture diagnostics will improve understanding of disease spectrum and transform patient care. Clin Infect Dis. 2013;56:1284–92. doi:10.1093/cid/cit006.CrossRefPubMed Clancy CJ, Nguyen MH. Finding the “missing 50 %” of invasive candidiasis: how nonculture diagnostics will improve understanding of disease spectrum and transform patient care. Clin Infect Dis. 2013;56:1284–92. doi:10.​1093/​cid/​cit006.CrossRefPubMed
34.
Zurück zum Zitat Posteraro B, De Pascale G, Tumbarello M, et al. Early diagnosis of candidemia in intensive care unit patients with sepsis: a prospective comparison of (1 → 3)-β-d-glucan assay, Candida score, and colonization index. Crit Care Lond Engl. 2011;15:R249. doi:10.1186/cc10507.CrossRef Posteraro B, De Pascale G, Tumbarello M, et al. Early diagnosis of candidemia in intensive care unit patients with sepsis: a prospective comparison of (1 → 3)-β-d-glucan assay, Candida score, and colonization index. Crit Care Lond Engl. 2011;15:R249. doi:10.​1186/​cc10507.CrossRef
36.
Zurück zum Zitat Jaijakul S, Vazquez JA, Swanson RN, Ostrosky-Zeichner L. (1,3)-β-d-glucan as a prognostic marker of treatment response in invasive candidiasis. Clin Infect Dis Off Publ Infect Dis Soc Am. 2012;55:521–6. doi:10.1093/cid/cis456.CrossRef Jaijakul S, Vazquez JA, Swanson RN, Ostrosky-Zeichner L. (1,3)-β-d-glucan as a prognostic marker of treatment response in invasive candidiasis. Clin Infect Dis Off Publ Infect Dis Soc Am. 2012;55:521–6. doi:10.​1093/​cid/​cis456.CrossRef
37.
Zurück zum Zitat Lo Cascio G, Koncan R, Stringari G, et al. Interference of confounding factors on the use of (1,3)-β-d-glucan in the diagnosis of invasive candidiasis in the intensive care unit. Eur J ClinMicrobiol Infect Dis. 2014. doi:10.1007/s10096-014-2239-z. Lo Cascio G, Koncan R, Stringari G, et al. Interference of confounding factors on the use of (1,3)-β-d-glucan in the diagnosis of invasive candidiasis in the intensive care unit. Eur J ClinMicrobiol Infect Dis. 2014. doi:10.​1007/​s10096-014-2239-z.
38.
Zurück zum Zitat Kedzierska A, Kochan P, Pietrzyk A, Kedzierska J. Current status of fungal cell wall components in the immunodiagnostics of invasive fungal infections in humans: galactomannan, mannan and (1 → 3)-β-d-glucan antigens. Eur J Clin Microbiol Infect Dis Off Publ Eur Soc Clin Microbiol. 2007;26:755–66. doi:10.1007/s10096-007-0373-6.CrossRef Kedzierska A, Kochan P, Pietrzyk A, Kedzierska J. Current status of fungal cell wall components in the immunodiagnostics of invasive fungal infections in humans: galactomannan, mannan and (1 → 3)-β-d-glucan antigens. Eur J Clin Microbiol Infect Dis Off Publ Eur Soc Clin Microbiol. 2007;26:755–66. doi:10.​1007/​s10096-007-0373-6.CrossRef
39.
Zurück zum Zitat Duffner U, Abdel-Mageed A, Dahl K, et al. Serum (1 → 3)-β-d-glucan levels (Fungitell assay) is not useful as a screening test for recipients of an allogeneic HSCT while on immunoglobulin replacement. Bone Marrow Transplant. 2012;47:151–2. doi:10.1038/bmt.2011.24.CrossRefPubMed Duffner U, Abdel-Mageed A, Dahl K, et al. Serum (1 → 3)-β-d-glucan levels (Fungitell assay) is not useful as a screening test for recipients of an allogeneic HSCT while on immunoglobulin replacement. Bone Marrow Transplant. 2012;47:151–2. doi:10.​1038/​bmt.​2011.​24.CrossRefPubMed
40.
Zurück zum Zitat Ogawa M, Hori H, Niiguchi S, et al. False-positive plasma (1 → 3)-β-d-d-glucan test following immunoglobulin product replacement in an adult bone marrow recipient. Int J Hematol. 2004;80:97–8. doi:10.1532/IJH97.04030.CrossRefPubMed Ogawa M, Hori H, Niiguchi S, et al. False-positive plasma (1 → 3)-β-d-d-glucan test following immunoglobulin product replacement in an adult bone marrow recipient. Int J Hematol. 2004;80:97–8. doi:10.​1532/​IJH97.​04030.CrossRefPubMed
Metadaten
Titel
Evaluation of serum (1 → 3)-β-d-glucan clinical performance: kinetic assessment, comparison with galactomannan and evaluation of confounding factors
verfasst von
P. Pini
C. Bettua
C. F. Orsi
C. Venturelli
F. Forghieri
S. Bigliardi
L. Faglioni
F. Luppi
L. Serio
M. Codeluppi
M. Luppi
C. Mussini
M. Girardis
Elisabetta Blasi
Publikationsdatum
16.10.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
Infection / Ausgabe 2/2016
Print ISSN: 0300-8126
Elektronische ISSN: 1439-0973
DOI
https://doi.org/10.1007/s15010-015-0849-8

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