Does galactomannan testing increase diagnostic accuracy for IPA in the ICU? A prospective observational study

Maria Schroeder, Marcel Simon, Juri Katchanov, Charles Wijaya, Holger Rohde, Martin Christner, Azien Laqmani, Dominic Wichmann, Valentin Fuhrmann, Stefan Kluge, Maria Schroeder, Marcel Simon, Juri Katchanov, Charles Wijaya, Holger Rohde, Martin Christner, Azien Laqmani, Dominic Wichmann, Valentin Fuhrmann, Stefan Kluge

Abstract

Background: An algorithm for distinguishing invasive pulmonary aspergillosis (IPA) in critically ill patients (AspICU) has been proposed but not tested.

Methods: This was a prospective observational study applying the AspICU protocol to patients with positive Aspergillus culture (PAC group) and those with negative aspergillus culture but positive galactomannan test in respiratory tract samples (only positive galactomannan (OPG group)). Patients underwent a standardized diagnostic workup with bronchoscopy, computed tomography (CT), and galactomannan determination in serum and bronchoalveolar lavage fluid (BALF).

Results: We included 85 patients in the study. Of these, 43 had positive aspergillus cultures and 42 patients had only a positive galactomannan test. There were no statistically significant differences in baseline characteristics, underlying conditions or ICU scores between the two groups. The galactomannan titre in BALF was significantly higher in the positive aspergillus culture (PAC) group (enzyme immunoassay (EIA) 5.9, IQR 3.2-5.7) than in the OPG group (EIA 1.7, IQR 0.9-4.5) (p < 0.001). Classic features of IPA were detected on CT in 37.5 % and 36.6 % of patients in the PAC and OPG groups, respectively. There were no statistically significant differences between the PAC and the OPG group in relation to AspICU or European Organization for the Research and Treatment of Cancer (EORTC) criteria. A positive aspergillus culture was a stronger trigger for initiating antimycotic treatment than positive BALF galactomannan: 88.4 % of patients in the PAC group were regarded by clinicians as having IPA and received antimycotic treatment as opposed to 59.5 % in the OPG group (p = 0.002). The 180-day mortality was 58.1 % in the PAC group and 59.5 % in the OPG group.

Conclusions: The inclusion of BALF galactomannan as an additional entry criterion for the AspICU clinical algorithm could increase the diagnostic sensitivity for IPA in ICU patients.

Trial registration: The study was registered at ClinicalTrials.gov (registration number NCT01866020 ) on 27 May 2013.

Keywords: Antifungal agents; Aspergillus; Critically ill patients; Galactomannan; Intensive care unit; Invasive pulmonary aspergillosis.

Figures

Fig. 1
Fig. 1
Classification of all patients with positive Aspergillus culture (PAC group) and only positive galactomannan with negative culture (OPG group) according to the Aspergillus algorithm for use in critically ill patients (AspICU) and European Organization for the Research and Treatment of Cancer (EORTC) criteria. IPA invasive pulmonary aspergillosis
Fig. 2
Fig. 2
Outcome of patients with proven and putative invasive pulmonary aspergillosis (IPA) according to the modified Aspergillus algorithm for use in critically ill patients (AspICU). PAC patients with positive Aspergillus culture, OPG patients with only positive galactomannan with negative culture, d day
Fig. 3
Fig. 3
Survival curve of critically ill patients with positive Aspergillus culture in respiratory tract samples (PAC group) and only positive galactomannan test in bronchoalveolar fluid (OPG group). Overall survival was plotted using the Kaplan-Meier method. pos. positive

References

    1. Limper AH, Knox KS, Sarosi GA, Ampel NM, Bennett JE, Catanzaro A, et al. An official American Thoracic Society statement: treatment of fungal infections in adult pulmonary and critical care patients. Am J Respir Crit Care Med. 2011;183(1):96–128. doi: 10.1164/rccm.2008-740ST.
    1. Segal BH. Aspergillosis. N Engl J Med. 2009;360(18):1870–84. doi: 10.1056/NEJMra0808853.
    1. Baddley JW, Stephens JM, Ji X, Gao X, Schlamm HT, Tarallo M. Aspergillosis in Intensive Care Unit (ICU) patients: epidemiology and economic outcomes. BMC Infect Dis. 2013;13:29. doi: 10.1186/1471-2334-13-29.
    1. Meersseman W, Vandecasteele SJ, Wilmer A, Verbeken E, Peetermans WE, Van Wijngaerden E. Invasive aspergillosis in critically ill patients without malignancy. Am J Respir Crit Care Med. 2004;170(6):621–5. doi: 10.1164/rccm.200401-093OC.
    1. Dimopoulos G, Frantzeskaki F, Poulakou G, Armaganidis A. Invasive aspergillosis in the intensive care unit. Ann NY Acad Sci. 2012;1272:31–9. doi: 10.1111/j.1749-6632.2012.06805.x.
    1. Garnacho-Montero J, Olaechea P, Alvarez-Lerma F, Alvarez-Rocha L, Blanquer J, Galvan B, et al. Epidemiology, diagnosis and treatment of fungal respiratory infections in the critically ill patient. Rev Esp Quimioter. 2013;26(2):173–88.
    1. Bulpa P, Dive A, Sibille Y. Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease. Eur Respir J. 2007;30(4):782–800. doi: 10.1183/09031936.00062206.
    1. Vandewoude KH, Vogelaers D, Blot SI. Aspergillosis in the ICU – the new 21st century problem? Med Mycol. 2006;44(s1):71–6. doi: 10.1080/13693780600919262.
    1. Vandewoude K, Blot S, Benoit D, Depuydt P, Vogelaers D, Colardyn F. Invasive aspergillosis in critically ill patients: analysis of risk factors for acquisition and mortality. Acta Clin Belg. 2004;59(5):251–7. doi: 10.1179/acb.2004.037.
    1. Blot SI, Taccone FS, Van den Abeele AM, Bulpa P, Meersseman W, Brusselaers N, et al. A clinical algorithm to diagnose invasive pulmonary aspergillosis in critically ill patients. Am J Respir Crit Care Med. 2012;186(1):56–64. doi: 10.1164/rccm.201111-1978OC.
    1. Vandewoude KH, Blot SI, Depuydt P, Benoit D, Temmerman W, Colardyn F, et al. Clinical relevance of Aspergillus isolation from respiratory tract samples in critically ill patients. Crit Care. 2006;10(1):R31. doi: 10.1186/cc4823.
    1. McNeil MM, Nash SL, Hajjeh RA, Phelan MA, Conn LA, Plikaytis BD, et al. Trends in mortality due to invasive mycotic diseases in the United States, 1980–1997. Clin Infect Dis. 2001;33(5):641–7. doi: 10.1086/322606.
    1. Khasawneh F, Mohamad T, Moughrabieh MK, Lai Z, Ager J, Soubani AO. Isolation of Aspergillus in critically ill patients: a potential marker of poor outcome. J Crit Care. 2006;21(4):322–7. doi: 10.1016/j.jcrc.2006.03.006.
    1. Taccone FS, Van den Abeele AM, Bulpa P, Misset B, Meersseman W, Cardoso T, et al. Epidemiology of invasive aspergillosis in critically ill patients: clinical presentation, underlying conditions, and outcomes. Crit Care. 2015;19:7. doi: 10.1186/s13054-014-0722-7.
    1. Meersseman W, Lagrou K, Maertens J, Van Wijngaerden E. Invasive aspergillosis in the intensive care unit. Clin Infect Dis. 2007;45(2):205–16. doi: 10.1086/518852.
    1. Egerer G, Schmitt T. Fungal infections in hematology patients and after blood stem cell transplantation: prophylaxis and treatment. Med Klin Intensivmed Notfmed. 2014;109(7):526–30. doi: 10.1007/s00063-013-0238-y.
    1. De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, 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(12):1813–21. doi: 10.1086/588660.
    1. Donnelly P. Trends in medical mycology 2015, Oral presentation, Symposium 14. Scientific Programme. Mycoses 2015;58:3-9.
    1. Aliaga M, Forel JM, De Bourmont S, Jung B, Thomas G, Mahul M, et al. Diagnostic yield and safety of CT scans in ICU. Intensive Care Med. 2015;41(3):436–43. doi: 10.1007/s00134-014-3592-1.
    1. Morrissey CO, Chen SC, Sorrell TC, Milliken S, Bardy PG, Bradstock KF, et al. 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. Lancet Infect Dis. 2013;13:519–28. doi: 10.1016/S1473-3099(13)70076-8.
    1. Meersseman W, Lagrou K, Maertens J, Wilmer A, Hermans G, Vanderschueren S, et al. Galactomannan in bronchoalveolar lavage fluid: a tool for diagnosing aspergillosis in intensive care unit patients. Am J Respir Crit Care Med. 2008;177(1):27–34. doi: 10.1164/rccm.200704-606OC.
    1. Meersseman W, Van Wijngaerden E. Invasive aspergillosis in the ICU: an emerging disease. Intensive Care Med. 2007;33(10):1679–81. doi: 10.1007/s00134-007-0792-y.
    1. Soeffker G, Wichmann D, Loderstaedt U, Sobottka I, Deuse T, Kluge S. Aspergillus galactomannan antigen for diagnosis and treatment monitoring in cerebral aspergillosis. Prog Transplant. 2013;23(1):71–4. doi: 10.7182/pit2013386.
    1. Bergeron A, Porcher R, Menotti J, Poirot JL, Chagnon K, Vekhoff A, et al. Prospective evaluation of clinical and biological markers to predict the outcome of invasive pulmonary aspergillosis in hematological patients. J Clin Microbiol. 2012;50(3):823–30. doi: 10.1128/JCM.00750-11.
    1. Chai LY, Kullberg BJ, Earnest A, Johnson EM, Teerenstra S, Vonk AG, et al. Voriconazole or amphotericin B as primary therapy yields distinct early serum galactomannan trends related to outcomes in invasive aspergillosis. PLoS One. 2014;9(2):e90176. doi: 10.1371/journal.pone.0090176.
    1. He H, Ding L, Sun B, Li F, Zhan Q. Role of galactomannan determinations in bronchoalveolar lavage fluid samples from critically ill patients with chronic obstructive pulmonary disease for the diagnosis of invasive pulmonary aspergillosis: a prospective study. Crit Care. 2012;16(4):R138. doi: 10.1186/cc11443.
    1. Azoulay E, Afessa B. Diagnostic criteria for invasive pulmonary aspergillosis in critically ill patients. Am J Respir Crit Care Med. 2012;186(1):8–10. doi: 10.1164/rccm.201204-0761ED.

Source: PubMed

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