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Article

Isavuconazole-Amphotericin B and Isavuconazole-Caspofungin In Vitro Synergic Activity Against Invasive Pulmonary Aspergillosis Molds Isolates

by
Maddalena Calvo
1,
Michelangelo Caruso
2,
Adriana Antonina Tempesta
2 and
Laura Trovato
1,2,*
1
U.O.C. Laboratory Analysis Unit, A.O.U. Policlinico “G. Rodolico-San Marco” Catania, 95123 Catania, Italy
2
Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
*
Author to whom correspondence should be addressed.
Antibiotics 2025, 14(10), 993; https://doi.org/10.3390/antibiotics14100993 (registering DOI)
Submission received: 11 September 2025 / Revised: 29 September 2025 / Accepted: 3 October 2025 / Published: 4 October 2025

Abstract

Background/Objectives: Invasive pulmonary aspergillosis (IPA) represents a critical respiratory condition mainly caused by Aspergillus fumigatus and other ubiquitous species such as Aspergillus flavus, Aspergillus niger, and Aspergillus terreus. IPA clinical management has been complicated by diagnostic challenges and therapeutic difficulties due to antifungal intrinsic or secondary resistance episodes. Despite this assumption, few scientific data have been reported about possible antifungal drug combinations. Herein, we propose an experimental evaluation using isavuconazole/amphotericin B and isavuconazole/caspofungin in vitro synergy assays to investigate their combined activity on Aspergillus spp. IPA clinical isolates. Methods: We globally analyzed 55 Aspergillus spp. isolates, practicing the gradient test methods with single and combined antifungal drugs through the MIC Strip test (Liofilchem, Roseto degli Abruzzi, Italy). The collected MIC values were interpreted according to the EUCAST guidelines and classified as synergy, additivity, indifference, and antagonism cases through a FIC index calculation. A statistical analysis on species’ correlation with particular synergy testing results was finally provided. Results: Despite an interesting activity against A. fumigatus, isavuconazole/amphotericin B did not report statistical significance, obtaining a consistent antagonism percentage (43.6%). On the other hand, isavuconazole/caspofungin showed a promising in vitro synergic activity, except for A. flavus isolates. Conclusions: Synergy testing demonstrated a significant species-specific trend. Future studies should be focused on Aspergillus spp. isolates and antifungal in vitro synergy testing, aiming to discourage or recommend any specific antifungal combinations, depending on the isolated species.
Keywords: invasive pulmonary aspergillosis; isavuconazole; caspofungin; amphotericin B; Aspergillus spp.; synergy testing invasive pulmonary aspergillosis; isavuconazole; caspofungin; amphotericin B; Aspergillus spp.; synergy testing

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MDPI and ACS Style

Calvo, M.; Caruso, M.; Tempesta, A.A.; Trovato, L. Isavuconazole-Amphotericin B and Isavuconazole-Caspofungin In Vitro Synergic Activity Against Invasive Pulmonary Aspergillosis Molds Isolates. Antibiotics 2025, 14, 993. https://doi.org/10.3390/antibiotics14100993

AMA Style

Calvo M, Caruso M, Tempesta AA, Trovato L. Isavuconazole-Amphotericin B and Isavuconazole-Caspofungin In Vitro Synergic Activity Against Invasive Pulmonary Aspergillosis Molds Isolates. Antibiotics. 2025; 14(10):993. https://doi.org/10.3390/antibiotics14100993

Chicago/Turabian Style

Calvo, Maddalena, Michelangelo Caruso, Adriana Antonina Tempesta, and Laura Trovato. 2025. "Isavuconazole-Amphotericin B and Isavuconazole-Caspofungin In Vitro Synergic Activity Against Invasive Pulmonary Aspergillosis Molds Isolates" Antibiotics 14, no. 10: 993. https://doi.org/10.3390/antibiotics14100993

APA Style

Calvo, M., Caruso, M., Tempesta, A. A., & Trovato, L. (2025). Isavuconazole-Amphotericin B and Isavuconazole-Caspofungin In Vitro Synergic Activity Against Invasive Pulmonary Aspergillosis Molds Isolates. Antibiotics, 14(10), 993. https://doi.org/10.3390/antibiotics14100993

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