Using (1,3)‐β‐D‐glucan concentrations in serum to monitor the response of azole therapy in patients with eumycetoma caused by Madurella mycetomatis

Author:

Nyuykonge Bertrand1ORCID,Siddig Emmanuel E.2ORCID,Nyaoke Borna A.3ORCID,Zijlstra Eduard E.3,Verbon Annelies1ORCID,Bakhiet Sahar M.2,Fahal Ahmed H.2ORCID,van de Sande Wendy W. J.1ORCID

Affiliation:

1. Department of Medical Microbiology and Infectious Diseases Erasmus MC, University Medical Centre Rotterdam Rotterdam Netherlands

2. Mycetoma Research Centre University of Khartoum Khartoum Sudan

3. Drugs for Neglected Diseases initiative (DNDi) Geneva Switzerland

Abstract

AbstractIntroduction(1,3)‐β‐D‐glucan is a panfungal biomarker secreted by many fungi, including Madurella mycetomatis, the main causative agent of eumycetoma. Previously we demonstrated that (1,3)‐β‐D‐glucan was present in serum of patients with eumycetoma. However, the use of (1,3)‐β‐D‐glucan to monitor treatment responses in patients with eumycetoma has not been evaluated.Materials and MethodsIn this study, we measured (1,3)‐β‐D‐glucan concentrations in serum with the WAKO (1,3)‐β‐D‐glucan assay in 104 patients with eumycetoma treated with either 400 mg itraconazole daily, or 200 mg or 300 mg fosravuconazole weekly. Serial serum (1,3)‐β‐D‐glucan concentrations were measured at seven different timepoints. Any correlation between initial and final (1,3)‐β‐D‐glucan concentrations and clinical outcome was evaluated.ResultsThe concentration of (1,3)‐β‐D‐glucan was obtained in a total of 654 serum samples. Before treatment, the average (1,3)‐β‐D‐glucan concentration was 22.86 pg/mL. During the first 6 months of treatment, this concentration remained stable. (1,3)‐β‐D‐glucan concentrations significantly dropped after surgery to 8.56 pg/mL. After treatment was stopped, there was clinical evidence of recurrence in 18 patients. Seven of these 18 patients had a (1,3)‐β‐D‐glucan concentration above the 5.5 pg/mL cut‐off value for positivity, while in the remaining 11 patients, (1,3)‐β‐D‐glucan concentrations were below the cut‐off value. This resulted in a sensitivity of 38.9% and specificity of 75.0%. A correlation between lesion size and (1,3)‐β‐D‐glucan concentration was noted.ConclusionAlthough in general (1,3)‐β‐D‐glucan concentrations can be measured in the serum of patients with eumycetoma during treatment, a sharp decrease in β‐glucan concentration was only noted after surgery and not during or after antimicrobial treatment. (1,3)‐β‐D‐glucan concentrations were not predictive for recurrence and seem to have no value in determining treatment response to azoles in patients with eumycetoma.

Funder

Drugs for Neglected Diseases initiative

Global Health Innovative Technology Fund

Médecins Sans Frontières

Ministerie van Buitenlandse Zaken

Publisher

Wiley

Subject

Infectious Diseases,Dermatology,General Medicine

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