Digestive enzymes of fungal origin as a relevant cause of false positive Aspergillus antigen testing in intensive care unit patients.
Critical illness
Digestive enzymes of fungal origin
False positive results
Galactomannan antigen assay
Invasive aspergillosis
Nortase
Journal
Infection
ISSN: 1439-0973
Titre abrégé: Infection
Pays: Germany
ID NLM: 0365307
Informations de publication
Date de publication:
Apr 2021
Apr 2021
Historique:
received:
03
07
2020
accepted:
12
08
2020
pubmed:
4
9
2020
medline:
26
11
2021
entrez:
4
9
2020
Statut:
ppublish
Résumé
Galactomannan antigen (GM) testing is widely used in the diagnosis of invasive aspergillosis (IA). Digestive enzymes play an important role in enzyme substitution therapy in exocrine pancreatic insufficiency. As digestive enzymes of fungal origin like Nortase contain enzymes from Aspergillus, a false-positive result of the test might be possible because of cross-reacting antigens of the cell wall of the producing fungi. We, therefore, asked whether the administration of fungal enzymes is a relevant cause of false-positive GM antigen test results. Patients with a positive GM antigen test between January 2016 and April 2020 were included in the evaluation and divided into two groups: group 1-Nortase-therapy, group 2-no Nortase-therapy. In addition, dissolved Nortase samples were analyzed in vitro for GM and β-1,3-D-glucan. For statistical analysis, the chi-squared and Mann‒Whitney U tests were used. Sixty-five patients were included in this evaluation (30 patients receiving Nortase and 35 patients not receiving Nortase). The overall false positivity rate of GM testing was 43.1%. Notably, false-positive results were detected significantly more often in the Nortase group (73.3%) than in the control group (17.1%, p < 0.001). While the positive predictive value of GM testing was 0.83 in the control group, there was a dramatic decline to 0.27 in the Nortase group. In vitro analysis proved that the Nortase enzyme preparation was highly positive for the fungal antigens GM and β-1,3-D-glucan. Our data demonstrate that the administration of digestive enzymes of fungal origin like Nortase leads to a significantly higher rate of false-positive GM test results compared to that in patients without digestive enzyme treatment.
Sections du résumé
BACKGROUND
BACKGROUND
Galactomannan antigen (GM) testing is widely used in the diagnosis of invasive aspergillosis (IA). Digestive enzymes play an important role in enzyme substitution therapy in exocrine pancreatic insufficiency. As digestive enzymes of fungal origin like Nortase contain enzymes from Aspergillus, a false-positive result of the test might be possible because of cross-reacting antigens of the cell wall of the producing fungi. We, therefore, asked whether the administration of fungal enzymes is a relevant cause of false-positive GM antigen test results.
METHODS
METHODS
Patients with a positive GM antigen test between January 2016 and April 2020 were included in the evaluation and divided into two groups: group 1-Nortase-therapy, group 2-no Nortase-therapy. In addition, dissolved Nortase samples were analyzed in vitro for GM and β-1,3-D-glucan. For statistical analysis, the chi-squared and Mann‒Whitney U tests were used.
RESULTS
RESULTS
Sixty-five patients were included in this evaluation (30 patients receiving Nortase and 35 patients not receiving Nortase). The overall false positivity rate of GM testing was 43.1%. Notably, false-positive results were detected significantly more often in the Nortase group (73.3%) than in the control group (17.1%, p < 0.001). While the positive predictive value of GM testing was 0.83 in the control group, there was a dramatic decline to 0.27 in the Nortase group. In vitro analysis proved that the Nortase enzyme preparation was highly positive for the fungal antigens GM and β-1,3-D-glucan.
CONCLUSIONS
CONCLUSIONS
Our data demonstrate that the administration of digestive enzymes of fungal origin like Nortase leads to a significantly higher rate of false-positive GM test results compared to that in patients without digestive enzyme treatment.
Identifiants
pubmed: 32880845
doi: 10.1007/s15010-020-01506-4
pii: 10.1007/s15010-020-01506-4
pmc: PMC7990814
doi:
Substances chimiques
Antigens, Fungal
0
Mannans
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
241-248Références
Cochrane Database Syst Rev. 2015 Dec 30;(12):CD007394
pubmed: 26716951
Am J Respir Crit Care Med. 2012 Jul 1;186(1):56-64
pubmed: 22517788
Transpl Infect Dis. 2010 Aug 1;12(4):309-15
pubmed: 20202177
Lancet Infect Dis. 2004 Jun;4(6):349-57
pubmed: 15172343
Clin Infect Dis. 2016 Aug 15;63(4):433-42
pubmed: 27481947
J Clin Microbiol. 2006 Feb;44(2):389-94
pubmed: 16455889
Med Mycol. 2017 Jul 1;55(5):535-540
pubmed: 27915301
Microorganisms. 2019 Nov 05;7(11):
pubmed: 31694308
Anaesthesiol Intensive Ther. 2014 Jul-Aug;46(3):145-54
pubmed: 25078766
Clin Microbiol Infect. 2017 Dec;23(12):1000.e1-1000.e4
pubmed: 28506782
Mycoses. 2019 Apr;62(4):310-319
pubmed: 30426598
Hepatogastroenterology. 1985 Apr;32(2):97-102
pubmed: 2408983
Clin Infect Dis. 2014 Dec 15;59(12):1696-702
pubmed: 25165088
Clin Microbiol Infect. 2018 May;24 Suppl 1:e1-e38
pubmed: 29544767
Scand J Infect Dis. 2012 Aug;44(8):600-4
pubmed: 22385270
Clin Infect Dis. 2020 Sep 12;71(6):1367-1376
pubmed: 31802125
N Engl J Med. 2003 Dec 11;349(24):2366-7
pubmed: 14668472
Rev Iberoam Micol. 2019 Jan - Mar;36(1):51-52
pubmed: 30704831
Crit Care Clin. 2016 Apr;32(2):203-12
pubmed: 27016162
J Intensive Care. 2019 Mar 20;7:17
pubmed: 30923621
Am J Respir Crit Care Med. 2006 Apr 1;173(7):707-17
pubmed: 16387806
Clin Case Rep. 2016 Apr 12;4(5):505-8
pubmed: 27188260
Adv Respir Med. 2019;87(6):231-243
pubmed: 31970725
Rev Iberoam Micol. 2007 Jun;24(2):106-12
pubmed: 17604427
Clin Gastroenterol Hepatol. 2013 Apr;11(4):333-42; quiz e30-1
pubmed: 23142604