Empirical antifungal treatment for diagnosed and undiagnosed invasive fungal disease in patients with hematologic malignancies

Abstract

Background: Empirical antifungal therapy is effective in some patients with risk factors for invasive fungal disease (IFD) who do not qualify for the EORTC/MSG criteria for IFD, but who fail to respond to anti-bacterial and anti-viral therapy.

Objective: This retrospective single-center study investigated the epidemiology of IFD and empirical antifungal therapy in patients with hematological malignancies.

Methods: This study recruited 893 patients with hematologic malignancies who had failed to respond to anti-bacterial and anti-viral treatment and received antifungal therapy, but not for antifungal prophylaxis. Antifungal therapy regimens included amphotericin B, voriconazole, itraconazole and caspofungin. A total of 689 patients were diagnosed with proven, probable, or possible IFD, while 159 patients did not meet the EORTC/MSG criteria for IFD diagnosis but recovered with antifungal treatment, and 45 were excluded from having IFD. Effective treatment was defined as the disappearance or resolution of clinical symptoms of IFD.

Results: Patients diagnosed with IFD underwent chemotherapy at a higher proportion, and had significantly higher neutrophil counts compared to those who did not qualify for the EORTC/MSG criteria for IFD but responded to antifungals. The mortality due to all causes within 3 months was significantly higher for patients diagnosed with proven IFD, compared with those who did not qualify for the EORTC/MSG criteria for IFD. There was no discontinuation reported due to adverse events of caspofungin.

Conclusion: Empirical antifungal treatment could help save the lives of some patients with severe infections who are strongly suspected of having IFD.

Keywords:

• Invasive fungal disease
• hematology
• epidemiology
• risk factors
• antifungal treatment

Transparency

Declaration of funding

This study was supported by grants from the Tianjin Municipal Health Bureau of Science and Technology Fund 2015 Project (No. 15KG135). The project title is: The establishment of the individualized programs to prevent invasive fungal disease in acute leukemia. The sponsor had no such involvement in this study.

Author contributions: Q.D.: conceived, designed, or planned the study; wrote sections of the initial draft; provided substantive suggestions for revision or critically reviewed subsequent iterations of the manuscript; reviewed and approved the final version of the paper. For all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved; provision of study materials or patients; obtaining of funding; administrative, technical, or logistic support. Co-authors: collected or assembled the data; provided substantive suggestions for revision or critically reviewed subsequent iterations of the manuscript; reviewed and approved final version of the paper; for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Declaration of financial/other relationships

Q.D., H.L., X.L., M.Z., L.G. and Y.L. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgements

This study was designed, conducted and analyzed by the authors. Medical writing and editorial assistance was funded by MSD China and provided by Dr. Padma Sridhar at MedCom Asia.

Notice of correction

Table 1 has been edited since the article was first published online (27 October 2017).