Has the mortality from pulmonary mucormycosis changed over time? A systematic review and meta-analysis

Abstract

Objectives: Pulmonary mucormycosis (PM) is increasingly being reported in immunocompromised patients and has a high mortality. Our aim was to assess the mortality of PM and its trend over time. We also evaluated the role of combined medical-surgical therapy in PM.

Methods: We performed a systematic review of Pubmed, Embase, and Cochrane central databases. Studies were eligible if they described at least five confirmed cases of PM and reported mortality. We also assessed the effect of combined medical-surgical therapy versus medical treatment alone on PM mortality. We used a random-effects model to estimate the pooled mortality of PM and compared it across three time periods. The factors influencing mortality were assessed using meta-regression. We evaluated the risk difference (RD) of death in the following: subjects undergoing combined medical-surgical therapy versus medical therapy alone, subjects with isolated PM versus disseminated disease, and PM in diabetes mellitus (DM) versus non-DM as a risk factor.

Results: We included 79 studies (1544 subjects). The pooled mortality of PM was 57.1% (95% confidence interval [CI] 51.7-62.6%). Mortality improved significantly over time (72.1% versus 58.3% versus 49.8% for studies before 2000, 2000-2009, and 2010-2020, respectively, p 0.00001). This improved survival was confirmed in meta-regression after adjusting for the study design, the country's income level, and the sample size. Combined medical-surgical therapy was associated with a significantly lower RD (95%CI) of death: -0.32 (-0.49 to -0.16). The disseminated disease had a higher risk of death than isolated PM, but DM was not associated with a higher risk of death than other risk factors.

Conclusions: While PM is still associated with high mortality, we noted improved survival over time. Combined medical-surgical therapy improved survival compared to medical treatment alone.

Keywords: Fungal pneumonia; Lung surgery; Mucorales; Reversed halo sign; Zygomycosis.