Triazoles versus Echinocandins for the first-line treatment of invasive pulmonary aspergillosis – A propensity score weighted multicenter study

Background Triazoles (e.g., 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 azol-resistance. Recent guidelines recommend echinocandins as a safe and well-tolerated first-line alternative. Methods In this multicenter observational study across nine treatment centers, we included all consecutive patients with invasive pulmonary aspergillosis (IPA) from January 1, 2014, to June 1, 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 = 0.002). 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 < 0.001). Even switching from echinocandins after initial treatment failure to salvage therapy did not mitigate the negative impact on overall survival. Switching from triazoles (28/153 cases) was mainly due to tolerability concerns, while echinocandins (12 cases) were switched for treatment failure. Conclusion 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.