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. 2025 Jan 17;12(2):ofaf025.
doi: 10.1093/ofid/ofaf025. eCollection 2025 Feb.

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

Isabel Rodríguez-Goncer  1   2   3 , Jorge Boán  1 , Riansares Carrero-Arribas  1 , José María Sanchez-Pina  4 , Manuel Lizasoaín  1   3 , Mario Fernández-Ruiz  1   2   3 , Rafael San-Juan  1   2   3 , Francisco López-Medrano  1   2   3 , Ana Pérez-Ayala  5 , José Manuel Caro-Teller  6 , Joaquín Martínez-López  3   4 , José María Aguado  1   2   3 , María Calbacho  3   4
Affiliations

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

Isabel Rodríguez-Goncer et al. Open Forum Infect Dis. .

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.

Keywords: breakthrough; hematology; invasive fungal infection; mold; prophylaxis.

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Conflict of interest statement

Potential conflict of interest. M. F.-R. and M. L. have received honoraria for talks on behalf of Pfizer Spain and Gilead Sciences. All other authors report no potential conflicts.

Figures

Graphical abstract
Graphical abstract
Figure 1.
Figure 1.
Distribution of causative fungi according to the previous mold-active antifungal agent in episodes of breakthrough invasive mold infection with microbiological documentation (n = 14). Abbreviations: ISA, isavuconazole; POS, posaconazole; VCZ, voriconazole.
Figure 2.
Figure 2.
Sankey diagram depicting sequential modifications in antifungal therapy once bIMI was diagnosed according to the previous mold-active antifungal agent. Abbreviations: bIMI, breakthrough invasive mold infection; ISA, isavuconazole; L-AmB, liposomal amphotericin B; POS, posaconazole; VCZ, voriconazole.
Figure 3.
Figure 3.
Kaplan-Meier curves for 30-day mortality attributable to breakthrough invasive mold infection according to the Charlson Comorbidity Index (CCI; log-rank test P = .004).
See this image and copyright information in PMC

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