Prattes Juergen, Giacobbe Daniele R, Marelli Cristina, Signori Alessio, Dettori Silvia, Cattardico Greta, Hatzl Stefan, Reisinger Alexander C, Eller Philipp, Krause Robert, Reizine Florian, Bassetti Matteo, Gangneux Jean-Pierre, Hoenigl Martin
Division of Infectious Diseases, Department of Internal Medicine, Excellence Center for Medical Mycology (ECMM), Medical University of Graz, Graz, Austria.
BioTechMed Graz, Graz, Austria.
Mycoses. 2025 Jan;68(1):e70023. doi: 10.1111/myc.70023.
This study investigated the impact of posaconazole (POSA) prophylaxis in COVID-19 patients with acute respiratory failure receiving systemic corticosteroids on the risk for the development of COVID-19-associated pulmonary aspergillosis (CAPA).
The primary aim of this prospective, multicentre, case-control study was to assess whether application of POSA prophylaxis in mechanically ventilated COVID-19 patients reduces the risk for CAPA development. All consecutive patients from centre 1 (cases) who received POSA prophylaxis as standard-of-care were matched to one subject from centre 2 and centre 3 who did not receive any antifungal prophylaxis, using propensity score matching for the following variables: (i) age, (ii) sex, (iii) treatment with tocilizumab and (iv) time at risk.
Eighty-three consecutive patients receiving POSA prophylaxis were identified at centre 1 and matched to 166 controls. In the matched cohort, incidence rates of CAPA were 1.69 (centre 1), 0.84 (centre 2) and 7.18 (centre 3) events per 1000 ICU days. In multivariable logistic regression analysis, the presence of an EORTC/MSGERC risk factor at ICU admission (OR 4.35) and centre 3 versus centre 1 (OR 6.07; 95% CI 1.76-20.91; p = 0.004) were associated with an increased risk of CAPA. No increased risk of CAPA was registered for centre 2 versus centre 1.
The impact of POSA prophylaxis depends on the baseline CAPA incidence rate, which varies widely between centres. Future trials should therefore investigate targeted antifungal prophylaxis (e.g., stratified for high-prevalence centres or high-risk patients) in COVID-19 patients.
NCT05065658.
本研究调查了泊沙康唑（POSA）预防对接受全身糖皮质激素治疗的急性呼吸衰竭COVID-19患者发生COVID-19相关肺曲霉病（CAPA）风险的影响。
这项前瞻性、多中心、病例对照研究的主要目的是评估在机械通气的COVID-19患者中应用POSA预防是否能降低CAPA发生风险。中心1所有接受POSA预防作为标准治疗的连续患者，与中心2和中心3未接受任何抗真菌预防的一名受试者进行匹配，使用倾向评分匹配以下变量：（i）年龄，（ii）性别，（iii）托珠单抗治疗，（iv）风险时间。
中心1确定了83例连续接受POSA预防的患者，并与166例对照匹配。在匹配队列中，每1000个ICU日的CAPA发生率分别为中心1为1.69、中心2为0.84、中心3为7.18。在多变量逻辑回归分析中，ICU入院时存在欧洲癌症研究与治疗组织/欧洲医学真菌学联合会（EORTC/MSGERC）风险因素（比值比[OR]4.35）以及中心3与中心1相比（OR 6.07；95%置信区间[CI]1.76 - 20.91；p = 0.004）与CAPA风险增加相关。中心2与中心1相比未发现CAPA风险增加。
POSA预防的影响取决于基线CAPA发生率，各中心之间差异很大。因此，未来试验应研究针对COVID-19患者的靶向抗真菌预防（例如，按高流行中心或高危患者分层）。
NCT05065658。
