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Breakthrough Invasive Mould Infections Under Posaconazole Prophylaxis in Patients With Haematologic Malignancies: A Case–Control Study

Summary

This study examined cases where patients receiving posaconazole to prevent fungal infections still developed serious mould infections despite the medication. Researchers compared 29 patients who developed these breakthrough infections with 46 control patients who did not. They found that over half of patients with breakthrough infections died, compared to only 20% of controls, and that surgical treatment significantly improved survival for certain types of fungal infections.

Background

Posaconazole (POS) prophylaxis is recommended for preventing invasive mould infections in haematologic cancer patients with prolonged neutropenia or following allogeneic haematopoietic cell transplantation. Breakthrough invasive mould infections (bIMI) under POS prophylaxis are rare but associated with high mortality rates.

Objective

To assess the epidemiology, causes, and outcomes of breakthrough invasive mould infections occurring under posaconazole prophylaxis in patients with haematologic malignancies.

Results

Invasive aspergillosis was most frequent (52%), followed by invasive mucormycosis (31%). POS non-susceptible pathogens caused 14% of bIMI cases. While 39% of bIMI cases had insufficient POS exposure, this proportion was similar in controls. Overall mortality was significantly higher in bIMI cases (52%) versus controls (20%), with surgery significantly associated with improved survival.

Conclusion

Breakthrough invasive mould infections are associated with significant mortality impact. Most cases involved presumably POS-susceptible pathogens without clear association with underexposure, suggesting multifactorial causes. Surgery is crucial for non-Aspergillus infections, and prospective studies with standardized procedures are needed.
  • Published in:Mycoses,
  • Study Type:Case-Control Study,
  • Source: PMID: 41090805, DOI: 10.1111/myc.70123
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