Breakthrough Invasive Mold Infections in Hematologic Cases: Relevance of the Host's Factors

Abstract

Background: Breakthrough invasive mold infections (bIMIs) are life-threatening complications in hematologic cases. Most previous studies in this field covered the whole spectrum of fungal pathogens, including yeasts, and antifungal agents. Methods: We conducted a retrospective study including all hematologic cases of patients diagnosed with a bIMI while receiving a mold-active antifungal agent at our center between January 2017 and June 2022. Results: Overall 37 patients were diagnosed with bIMI: 6 (16.2%) proven, 18 (48.6%) probable, and 13 (35.1%) possible. The highest incidence rate was found for micafungin (1.31 bIMI episodes per 1000 treatment-days), although with no significant differences across antifungal agents. Most patients (90.9%) for whom therapeutic drug monitoring was performed exhibited adequate through levels. Ten (27.0%) patients had undergone allogeneic hematopoietic stem cell transplantation. Aspergillus species was the most common pathogen in cases with microbiological identification. Regarding risk factors, 67.6% had severe neutropenia at diagnosis and 40.5% had received high-intensity chemotherapy. Rates of clinical response and attributable mortality by day +30 were 64.9% and 23.3%, respectively. Poorer performance status, higher Charlson Comorbidity index, older age, and higher C-reactive protein by day +7 were associated with 30-day attributable mortality. Conclusions: Aspergillus was the predominant pathogen in our cohort of bIMIs, with a significant proportion of episodes occurring despite adequate triazole levels. Thirty-day attributable mortality was lower than previously reported. Poorer performance status, higher comorbidity burden, and older age had a relevant role in the outcome of bIMI.