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Randomized Controlled Trial
. 2023 Apr 27:13:1165236.
doi: 10.3389/fcimb.2023.1165236. eCollection 2023.

Antifungal prophylaxis with nebulized amphotericin-B in solid-organ transplant recipients with severe COVID-19: a retrospective observational study

Alexander Rombauts  1 , Marta Bodro  2 , Victor Daniel Gumucio  3 , Irene Carbonell  2 , Àlex Favà  4 , Laura Lladó  5 , José González-Costello  6 , Federico Oppenheimer  7 , María Ángeles Castel-Lavilla  8 , Oscar Len  9   10   11 , Ester Marquez-Algaba  9   10 , Xavier Nuvials-Casals  12 , Daniel Martínez González  12 , Judith Sacanell Lacasa  12 , Jordi Carratalà  1   11   13 , Nuría Sabé  1   11
Affiliations
Randomized Controlled Trial

Antifungal prophylaxis with nebulized amphotericin-B in solid-organ transplant recipients with severe COVID-19: a retrospective observational study

Alexander Rombauts et al. Front Cell Infect Microbiol. .

Abstract

COVID-19-associated pulmonary aspergillosis (CAPA) has emerged as a frequent complication in the intensive care unit (ICU). However, little is known about this life-threatening fungal superinfection in solid organ transplant recipients (SOTRs), including whether targeted anti-mold prophylaxis might be justified in this immunosuppressed population. We performed a multicentric observational retrospective study of all consecutive ICU-admitted COVID-19 SOTRs between August 1, 2020 and December 31, 2021. SOTRs receiving antifungal prophylaxis with nebulized amphotericin-B were compared with those without prophylaxis. CAPA was defined according the ECMM/ISHAM criteria. Sixty-four SOTRs were admitted to ICU for COVID-19 during the study period. One patient received antifungal prophylaxis with isavuconazole and was excluded from the analysis. Of the remaining 63 SOTRs, nineteen (30.2%) received anti-mold prophylaxis with nebulized amphotericin-B. Ten SOTRs who did not receive prophylaxis developed pulmonary mold infections (nine CAPA and one mucormycosis) compared with one who received nebulized amphotericin-B (22.7% vs 5.3%; risk ratio 0.23; 95%CI 0.032-1.68), but with no differences in survival. No severe adverse events related to nebulized amphotericin-B were recorded. SOTRs admitted to ICU with COVID-19 are at high risk for CAPA. However, nebulized amphotericin-B is safe and might reduce the incidence of CAPA in this high-risk population. A randomized clinical trial to confirm these findings is warranted.

Keywords: Aspergillosis; Aspergillus spp.; CAPA; COVID-19; SARS-CoV-2; amphotericin-B; prophylaxis; solid-organ transplant recipients.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Grants and funding

AR received a predoctoral research grant from the Instituto de Salud Carlos III, Spanish Ministry of Science, Innovation and Universities, (PFIS grant FI18/00183). This work was supported by the Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain. We thank CERCA Programme/Generalitat de Catalunya for institutional support.