2025/11/15 by Stefan Hatzl, Christina Geiger, Lisa Kriegl +7 · 1 voice
Medicine · #Antifungal resistance and susceptibility #Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis #Peptidase Inhibition and Analysis
paper · pdf · doi:10.1093/ofid/ofaf709
openalex publication_date 2025/11/15 · openalex created_date 2025/11/19 · openalex updated_date 2026/07/31
Abstract Background Triazoles (eg, isavuconazole, posaconazole, voriconazole) are the first-line treatment for invasive pulmonary aspergillosis (IPA), but their use can be limited by drug interactions, hepatotoxicity, and emerging azole resistance. Recent guidelines recommend echinocandins as a safe and well-tolerated first-line alternative. Methods In this multicenter observational study across 9 treatment centers, we included all consecutive patients with IPA from 1 January 2014 to 1 June 2024. We compared 30-day overall survival (OS) as the primary outcome and 90-day OS as the secondary outcome between patients receiving triazoles versus echinocandins as first-line therapy. Propensity score adjustment was applied to address baseline characteristic imbalances. Results We included 177 patients, of whom 153 (86%) received triazoles as first-line therapy (69 voriconazole, 54 isavuconazole, 30 posaconazole). Before propensity score adjustment, patients treated with echinocandins were significantly sicker, with higher rates of intensive care treatment (95% vs 75%, P = .002). In both crude and propensity score–adjusted analyses, 30-day mortality was significantly higher in the echinocandin group compared to the triazole group (63% [95% CI 55–70] vs 30% [95% CI 13–50], P < .001). Even switching from echinocandins after initial treatment failure to salvage therapy did not mitigate the negative impact on OS. Switching from triazoles (28/153 cases) was mainly due to tolerability concerns, while echinocandins (12 cases) were switched for treatment failure. Conclusions Using echinocandins as alternative first-line treatment for IPA may result in poorer survival outcomes and should be approached with caution until further trials confirm our findings.