The diagnosis and treatment of invasive aspergillosis in Dutch haematology units facing a rapidly increasing prevalence of azole‐resistance. A nationwide survey and rationale for the DB‐MSG 002 study protocol

Abstract

Patients with haematological malignancies are at risk for invasive fungal diseases (IFD). A survey was conducted in all Dutch academic haematology centres on their current diagnostic, prophylactic and therapeutic approach towards IFD in the context of azole-resistance. In all 8 centres, a haematologist and microbiologist filled in the questionnaire that focused on different subgroups of haematology patients. Fungal prophylaxis during neutropaenia was directed against Candida and consisted of fluconazole and/or amphotericin B suspension. Mould-active prophylaxis was given to acute myeloid leukaemia patients during chemotherapy in 2 of 8 centres. All centres used azole prophylaxis in a subset of patients with graft-versus-host disease. A uniform approach towards the diagnosis and treatment of IFD and in particular azole-resistant Aspergillus fumigatus was lacking. In 2017, all centres agreed to implement a uniform diagnostic and treatment algorithm regarding invasive aspergillosis with a central role for comprehensive diagnostics and PCR-based detection of azole-resistance. This study (DB-MSG 002) will re-evaluate this algorithm when 280 patients have been treated. A heterogeneous approach towards antifungal prophylaxis, diagnosis and treatment was apparent in the Netherlands. Facing triazole-resistance, consensus was reached on the implementation of a uniform diagnostic approach in all 8 centres.

Prevalence of voriconazole-resistant invasive aspergillosis and its impact on mortality in haematology patients

“…Therefore, another approach that has been advocated is the one in which a triazole constitutes part of the initial antifungal therapy until resistance is adequately documented by culture (or PCR). 26,27 To assess the prevalence and mortality of voriconazole-resistant A. fumigatus IA, we performed a retrospective multicentre study in a large cohort of haematology patients with IA.…”

Immune Parameters for Diagnosis and Treatment Monitoring in Invasive Mold Infection

“…Invasive mold infections (IMI) continue to be associated with significant morbidity and high mortality rates globally, particularly in immunocompromised individuals [1][2][3][4]. Early diagnosis and appropriate treatment remain the most important predictors of survival [5], although early diagnosis remains difficult to establish, particularly at the initial stages of infection [6,7], and treatment is becoming increasingly complicated due to antifungal resistance [8,9].…”

(New) Methods for Detection of Aspergillus fumigatus Resistance in Clinical Samples

“…Early and reliable diagnosis of invasive aspergillosis (IA) and subsequent rapid initiation of appropriate antifungal therapy has been shown to improve survival significantly [4, 5•]. However, IA progresses rapidly and is difficult to diagnose at early stages [6, 7•], and once diagnosed, emergence of triazole resistance complicates selection of appropriate antifungal treatment [8, 9, 10••].…”