Clinical Characteristics, Prognosis Factors and Metagenomic Next-Generation Sequencing Diagnosis of Mucormycosis in Patients with Hematologic Diseases: A Single-Center Retrospective Study

Abstract

Mucormycosis is a serious disorder with severe inflammatory response and tissue damage caused by the infection of Mucorales. Mucormycosis usually occurs in immunocompromised population, high mortality of mucormycosis is one of the challenges facing in patients with hematologic diseases. New diagnostic methods and antifungal strategies may improve prognosis of mucormycosis. The aim of our study was to describe the diagnostic value of metagenomic next⁃generation sequencing (mNGS) and identify the prognostic factors of mucormycosis. We conducted a retrospective study of hematologic patients suffered from mucormycosis and treated with monotherapy [amphotericin B (AmB) or posaconazole] or combination therapy (AmB and posaconazole). All the patients were diagnosed as mucormycosis by the 2019 EORTC/MSG criteria from March 2012 to September 2022. The primary outcome was 84-day all-cause mortality after diagnosis. Multivariate cox regression analysis was performed. We described the prognostic factors of mucormycosis in multivariate survival analysis, and investigated the application of different diagnostic methods. Ninety-five patients were included, with “proven” ( n=27), “probable” ( n=16) mucormycosis confirmed by traditional diagnostic methods, and “possible” ( n=52) mucormycosis with positive mNGS results. The median age was 44 (1-68) years. The most common primary diseases was acute leukemia (69.5%, n=66), and 32.6% of patients ( n=31) received hematopoietic stem cell transplantation. The most common pathogen species was Rhizopus spp (34.7%, n=33). The most common infection type was pulmonary infection (84.2%, n=80), followed by disseminated infection (8.4%, n=8) and rhino-orbito-cerebral infection (4.2%, n=4). Breakthrough infection occurred in 47 patients (49.5%). There were 13 patients (13.7%) receiving amphotericin B (AmB), 22 patients (23.2%) receiving posaconazole (Pos), and 60 patients (63.2%) receiving AmB plus Pos. A total of 9 patients (9.5%) underwent surgical treatment. With a median follow up of 79 (1-1015) days, the overall mortality rate at 42 days and 84 days was 33.7% and 44.2%, respectively. Possible patients and probable patients had similar diagnosis processes, overall survival rates (44.2% vs 50.0%, p=0.685) and overall response rates to effective drugs (44.0% vs 37.5%, p=0.647). Furthermore, the median diagnostic time was shorter in possible patients than proven and probable patients (14 vs 26 days, p<0.001). Combination therapy was associated with better survival compared to monotherapy at six weeks after treatment (78.8% vs 53.1%, p=0.0075). Multivariate analysis showed that combination therapy was the protective factor (HR=0.338, 95% CI: 0.162-0.703, p=0.004), though diabetes (HR=3.864, 95% CI: 1.897-7.874, p<0.001) and hypoxemia (HR=3.536, 95% CI: 1.874-6.673, p<0.001) were risk factors for mortality. Mucormycosis is a life-threatening infection in patients with hematologic diseases. Early management of diabetes and hypoxemia may improve the prognosis. Moreover, mNGS may be valuable evidence for microbiologic diagnosis, and combination of AmB and posaconazole is an effective treatment.