Impact of Azithromycin on Neutrophil-Mediated Immune Responses Against Aspergillus Fumigatus

Presenter: Romain Manchon

This ex vivo study evaluated the effect of azithromycin (AZM) on neutrophil antifungal activity against Aspergillus fumigatus. Neutrophils from healthy donors were pre-exposed to AZM (1–100 µg/mL) and stimulated with A. fumigatus conidia to assess fungal growth inhibition, reactive oxygen species (ROS) production, and phagocytosis. AZM exposure led to a dose-dependent increase in fungal burden, with a significant reduction in the metabolic inhibition ratio by 20% [IQR, 33–13] (p=0.01) at 50 µg/mL and 34% [40–20] (p<0.01) at 100 µg/mL. ROS production was markedly reduced, decreasing by 63% [73–52] (p<0.01) at 50 µg/mL and 67% [75–57] (p<0.01) at 100 µg/mL.

Phagocytic activity was also significantly impaired, declining by 21% [30–15] (p<0.01) at 50 µg/mL and 53% [70–41] (p<0.01) at 100 µg/mL compared to vehicle controls.

Overall, AZM significantly impaired key neutrophil antifungal functions, including fungal growth inhibition, ROS production, and phagocytosis, supporting its potential role as a modifiable risk factor for A. fumigatus infection.

Clinical, Laboratory and Financial Evaluation of Diagnostic Testing for Invasive Aspergillus Infections in Haemato-Oncology Patients with Neutropenic Fever in A Large U.K. Teaching Hospital

Presenter: James Moore

This single-centre study evaluated the diagnostic performance and cost-benefit of serum Aspergillus galactomannan (AGM) and respiratory Aspergillus PCR in neutropenic haemato-oncology patients. A total of 1,187 AGM samples from 733 patients were analysed. Overall positivity was 3.1% (37/1187). Of these, 860 (73%) were serum samples and 327 (28%) bronchoalveolar lavage fluid (BALF). Positivity rates were 1.0% for serum and 8.6% for BALF. Among haemato-oncology patients, 432 samples (36%) were tested, with serum AGM positivity <0.5%.

In patients with positive serum AGM, clinical assessment and CT findings were sufficient to guide treatment. In patients with negative serum AGM (n=50), results had minimal impact on clinical decision-making. PCR detected A. fumigatus at very low concentrations (down to 10⁻⁸ dilution) and identified A. terreus. It was positive in 12/13 BALF samples with confirmed Aspergillus infection.

Reducing serum AGM testing by 20% would offset the cost of implementing BALF PCR. Overall, BALF PCR combined with AGM showed better diagnostic performance, while serum AGM alone had limited utility.

Diagnostic Value of Galactomannan in Tracheobronchial Aspirate for Aspergillus Infection in Lung Transplant Recipients (The GALACTBAS Study)

Presenter: Arnau Monforte Pallares

This retrospective single-centre study evaluated the diagnostic performance of tracheobronchial aspirate (TBA) galactomannan (GM) compared with bronchoalveolar lavage fluid (BALF) GM in lung transplant recipients. A total of 545 paired TBA–BALF samples from 282 patients were analysed. Proven or probable Aspergillus infection was identified in 22 samples (4%).

Diagnostic performance:

• TBA GM (cut-off ≥0.54 ODI): sensitivity 95.2%, specificity 92%, AUC 0.97 (95% CI 0.95–0.99)
• BALF GM (cut-off ≥1.0 ODI): sensitivity 33.3%, specificity 99.6%, AUC 0.88 (95% CI 0.80–0.95)

TBA cultures were more frequently positive than BALF (24% vs 9.9%). TBA and BALF GM values showed moderate correlation (r = 0.54). Combined testing with concordant results improved diagnostic accuracy to 99.6%.

Overall, TBA GM showed higher sensitivity than BALF GM while maintaining high specificity.

Fungal Diagnostic Approach Among Hospitalised Patients Receiving Polyene vs Azole in US, 2021-2024

Presenter: Emma Harvey

This multicentre retrospective cohort study assessed the use of diagnostic tests for identifying fungal pathogens in hospitalized patients treated with polyenes or azoles.

A total of 12,456 patients received polyenes (96.4% liposomal amphotericin B) and 18,741 received azoles (78.0% voriconazole) across ~900 hospitals. Polyene-treated patients were younger (median 55 vs 62 years), more often male (63.5% vs 57.6%), Hispanic (17.2% vs 14.6%), and had higher HIV/AIDS prevalence (14.6% vs 2.2%). Azole-treated patients more frequently had hematologic (24.8% vs 15.5%) and solid organ malignancies (9.2% vs 6.3%). Community-acquired infections were more common with polyenes (41.4% vs 29.7%).

Among ~300 hospitals with microbiology data, 57.5% (2,158/3,755) of polyene and 59.8% (3,450/5,770) of azole patients underwent culture testing. A fungal pathogen was identified in 506 polyene and 709 azole patients. Common sources were blood and cerebrospinal fluid (polyenes) and lung and blood (azoles). Aspergillus spp. were most frequent, followed by Cryptococcus neoformans and Histoplasma capsulatum.

Biomarker testing showed that galactomannan was used more often in azole-treated patients, while beta-D-glucan and PCR were less commonly used overall. Overall, fungal pathogens were infrequently identified despite antifungal use, and advanced diagnostics remained underutilized.

Steroid-Linked Invasive Fungal Infections After CAR-T: Insights from a National Australian Cohort

Presenter: Gemma Reynolds

This national, multicentre cohort study evaluated the incidence and risk factors for invasive fungal infections (IFI) in adults receiving CD19-directed CAR-T therapy for aggressive lymphoma (2019–2023; follow-up to March 2025). A total of 291 patients (median age 64 years) were included. Seventeen IFIs occurred in 17 patients (5.8% of the cohort; 11% of microbiologically confirmed infections). IFIs developed at a median of 122 days post-infusion (IQR: 25–263), with 29% occurring ≥6 months. Infection rates were significantly higher within the first 30 days compared to later periods (0.14 vs 0.007 per 100 patient-days; IRR=0.05, p=0.003). Common pathogens included pulmonary aspergillosis (47%), Candida bloodstream infections (35%), and Pneumocystis jirovecii (6%). IFIs occurred despite antifungal prophylaxis in 29% of cases, and all were grade ≥3, with three fatalities.

In multivariable competing-risk Cox regression, higher cumulative dexamethasone exposure within 30 days post-infusion was independently associated with IFI risk (HR 1.003, 95% CI: 1.002–1.004; p<0.001). A threshold of 56 mg dexamethasone-equivalent predicted IFI (HR 6.6, 95% CI: 1.6–27.1; AUC 0.71; p=0.015).

Overall, IFIs were infrequent but clinically significant, with early steroid exposure identifying a high-risk subgroup.

ESCMID 2026, 17-21 April, Munich, Germany.