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Background The performance of the galactomannan enzyme immunoassay (GM-EIA) is impaired in patients receiving mould-active antifungal therapy. The impact of mould-active antifungal therapy on Aspergillus PCR testing needs to be determined. Objectives To determine the influence of anti-mould prophylaxis (AMP) on the performance of PCR blood testing to aid the diagnosis of proven/probable invasive aspergillosis (IA). Methods As part of the systematic review and meta-analysis of 22 cohort studies investigating Aspergillus PCR blood testing in 2912 patients at risk of IA, subgroup analysis was performed to determine the impact of AMP on the accuracy of Aspergillus PCR. The incidence of IA was calculated in patients receiving and not receiving AMP. The impact of two different positivity thresholds (requiring either a single PCR positive test result or ≥2 consecutive PCR positive test results) on accuracy was evaluated. Meta-analytical pooling of sensitivity and specificity was performed by logistic mixed-model regression. Results In total, 1661 (57%) patients received prophylaxis. The incidence of IA was 14.2%, significantly lower in the prophylaxis group (11%–12%) compared with the non-prophylaxis group (18%–19%) (P Conclusions Contrary to its influence on GM-EIA, AMP significantly decreases Aspergillus PCR specificity, without affecting sensitivity, possibly as a consequence of AMP limiting the clinical progression of IA and/or leading to false-negative GM-EIA results, preventing the classification of probable IA using the EORTC/MSGERC definitions.

Objectives: “Fungal InfectioN Database” (FIND) represents international database of invasive fungal infections in Czech and Slovak hematooncological departments. FIND - aspergillus covers all case of invasive aspergillosis (IA) in participating centers since 2001. Methods: The goal of our retrospective analysis was to evaluate incidence, early diagnostic procedures and effect of antifungal therapy in proven and probable IA that occurred in 16 institutions participating in FIND database between 2001–2011. Till 2009 we followed EORTC/MSG 2002 and from 2010 EORTC/MSG 2008 criteria in evaluation of IA diagnosis and therapy response. Results: 256 probable and 58 proven IA (91% isolated pulmonary IA, IPA) have been documented. Prolonged and profound neutropenia (61%) and long-term use of corticosteroids (28%) were identified as the major risk factors of IA. 68% pts. had consecutive positivity of serum-galactomannan (S-GM) (OD index >0.5). 83% pts. with IPA and bronchoalveolar lavage (BAL) had positive GM in BAL fluid (OD index >0.5). In pts. with IPA only 7.6% BAL fluids and 8.4% sputum samples had positive microscopic result for filamentous fungi and 2.2% BAL fluids and 1.8% sputum samples had positive culture for Aspergillus spp. The primary antifungal therapy of IA was used in 89% pts. - 41% voriconazole (VORI), 7% echinocandins (ECHINO), 23% VORI+ECHINO, 7% amphotericine B deoxycholate (C-AMB) and 9% lipid- based AMB (LBA). Overall RR to primary therapy of IA was 46% - VORI 55%, VORI+ECHINO 54%, C-AMB 35%, LBA 39%, ECHINO 25%. There was a statistically significant difference in overall RR to targeted therapy in pts. with neutrophil count 1.0x10e9/L at the end of therapy (21% vs. 71%). The overall mortality rate was 61%, with 39% attributable to IA. Conclusion: On the basis of our analysis we confirm typical risk factors for IA and critical role of S-GM and CT for early diagnosis and prompt start of antifungal therapy of IA. A reasonable treatment response was achieved using VORI, VORI+ECHINO or LBA in primary therapy of IA. We have confirmed neutropenia at the end of antifungal therapy as the major predictive factor for therapeutic response. On behalf of CELL - The Czech leukemia study group for life.

Invasive aspergillosis in patients with hematological malignancies in Czech, Slovak and Croatian hematooncological departments: Fungal INfection Database (FIND) analysis (2001-2014) - an update