Triazoles vs Liposomal Amphotericin B Show Similar Survival in Invasive Aspergillosis Study

Invasive aspergillosis (IA) remains a serious and often fatal infection despite advances in diagnostics and antifungal therapy. Although mold-active triazoles have long been recommended as first-line therapy, liposomal amphotericin B continues to be used in selected patients because of drug interactions, toxicity concerns, and rising azole resistance. A new multicenter retrospective study published in Open Forum Infectious Diseases provides updated real-world data comparing these 2 approaches as primary therapy.

“Over the past decade, described risk factors for IA have broadened beyond classical disease states such as hematologic malignancies and solid organ transplantation to include patients with chronic pulmonary diseases, chronic steroid treatment, and prolonged [intensive care unit] hospitalization,” the authors wrote.

The study evaluated adult patients with proven or probable IA treated at 2 tertiary academic hospitals in northern Italy over a 10-year period from January 2013 through December 2022. Investigators compared outcomes among patients who received either liposomal amphotericin B or mold-active triazoles as initial antifungal therapy, focusing on all-cause 90-day mortality from diagnosis.

A total of 401 patients met the inclusion criteria. The median age was 65 years (interquartile range, 56-74 years), and 60.8% of patients were male. Most cases were classified as probable IA (96.0%), with proven disease accounting for 4.0%. The most common predisposing condition was hematologic malignancy in 151 patients or 37.7%, followed by viral-associated pulmonary aspergillosis in 120 patients or 29.9%. Chronic steroid treatment and chronic pulmonary disease were each present in 64 patients, or 16%.

Initial antifungal therapy consisted of mold-active triazoles in 296 patients (73.8%), whereas 105 patients (26.2%) received liposomal amphotericin B. Among those treated with triazoles, voriconazole was used in 272 patients (91.9%), and isavuconazole in 24 patients (8.1%). No patients received posaconazole as primary therapy. Combination antifungal therapy was uncommon overall, occurring in 18 patients (4.5%), but was more frequent in the liposomal amphotericin B group than in the triazole group (9.5% vs. 2.7%).

Treatment modification was significantly more common among patients who initially received liposomal amphotericin B. In this group, 66 patients (62.9%) switched therapy at a median of 10 days after diagnosis. The most common reason for switching was transition to oral triazoles, which occurred in 71.6% of those who changed therapy. In contrast, only 46 patients (15.5%) in the triazole group required treatment modification at a median of 13 days, most often due to adverse events (45.1%).

Despite differences in treatment durability and switching patterns, survival outcomes were similar between groups. The overall 90-day survival rate was 58.8% for patients treated with triazoles and 53.3% for those treated with liposomal amphotericin B. Using a landmark analysis beginning at day 7 postdiagnosis and inverse probability of treatment weighting to address confounding by indication, investigators found no statistically significant difference in mortality. The adjusted hazard ratio for death was 1.43 (95% confidence interval, 0.87-2.33).

For infection prevention personnel, these findings reinforce several important points. First, IA continues to affect a broad population beyond traditional hematologic malignancy patients, including those with severe viral respiratory infections and chronic steroid exposure. Second, primary therapy with liposomal amphotericin B was well tolerated and associated with outcomes comparable to triazoles in this real-world cohort. Finally, the high rates of treatment switching highlight the importance of antifungal stewardship, monitoring for adverse events, and early reassessment of therapy.

The authors conclude that, although triazoles remain the standard first-line therapy, liposomal amphotericin B is a viable alternative for selected patients. Further studies are needed to better define which patients may benefit most from primary liposomal amphotericin B therapy and how treatment choice impacts outcomes across evolving IA risk groups.