Efficacy and Safety of Combination Antifungals as Empirical, Preemptive, and Targeted Therapies for Invasive Fungal Infections in Intensive-Care Units

Abstract

Purpose

To determine whether combinations of antifungal drugs are effective and safe for patients in intensive-care units.

Methods

This study compared the efficacy and safety of caspofungin (CAS), voriconazole (VOR), amphotericin B liposome (L-AmB), CAS+VOR, and CAS+L-AmB as empirical, preemptive, and targeted therapies for invasive fungal infection (IFI).

Results

Comparing the CAS, VOR, and CAS+VOR groups revealed that there were no differences in response rates between all therapy types, IFI-associated death within 90 days was less common in the CAS+VOR group (1.8%) than the VOR group (14.3%), and there were more adverse events in the VOR group than in the CAS group (P < 0.05). For empirical or preemptive therapy, the CAS group had a better response rate (80.0%) than the CAS+VOR group (47.1%), and there were more adverse events in the VOR group than in the CAS group (P < 0.05). For targeted therapy, no differences were found for efficacy and safety. There were no differences among the CAS, L-AmB, and CAS+L-AmB groups in efficacy and safety.

Conclusion

Patients who received CAS monotherapy as an empirical or preemptive therapy could achieve good outcomes. Patients who received CAS+VOR or CAS+L-AmB achieved almost the same outcomes when compared with those who received CAS, VOR, and L-AmB monotherapy as targeted therapies, but those who received CAS+VOR had a lower IFI mortality rate than did those who received VOR monotherapy.

Keywords:

• caspofungin
• voriconazole
• amphotericin B liposome
• combination therapy
• invasive fungal infection
• intensive-care units

Abbreviations

IFI, invasive fungal infection; ICUs, intensive-care units; IC, invasive candidiasis; IA, invasive aspergillosis; CAS, Caspofungin; VOR, Voriconazole; L-AmB, Amphotericin B liposome; CAS+VOR, CAS and VOR; CAS+L-AmB, CAS and L-AmB; IDSA, Infectious Diseases Society of America.

Data Sharing Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Ethics Approval and Informed Consent

The Second Affiliated Hospital of Xi’an Jiaotong University Research Ethics Committee approved the study protocol. The consent was waived due to the retrospective nature of the review. We keep the privacy of the participants confidential. We confirm that the data was anonymized and maintained with confidentiality, and the study compliance with the Declaration of Helsinki.

Acknowledgments

The authors sincerely acknowledge the doctors in the ICUs who helped us in this study.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

Authors declare no conflicts of interest.

Additional information

Funding

This work is supported by The National Natural Science Foundation of China (grant number 82003871), The General Project of the Key Research and Development Program of Shaanxi Province (grant number 2022SF-187) and The Specialized Research Fund for Faculty Training of The Second Affiliated Hospital of Xi’an Jiaotong University (grant number RC(XM)202008).