Effect of BALF-based mNGS on clinical outcomes of immunocompromised subjects with opportunistic pulmonary infections: a multicenter propensity score-matched study.

Background: Metagenomic next-generation sequencing (mNGS) is a promising tool for pathogen detection. However, its clinical utility in detecting opportunistic pulmonary infections of immunocompromised patients remains controversial. Methods: This multicenter retrospective study involving 162 immunocompromised patients with opportunistic pulmonary infections was conducted across four respiratory centers. The enrolled patients were divided into the conventional microbiological tests (CMT) group and the mNGS group based on whether mNGS of BALF was performed after admission. Propensity score-matching (PSM) was adopted to minimize selection bias, and sensitivity analysis confirmed the robustness. The primary outcomes were >30% improvement in oxygenation index (OI) at 7 days post-admission and clinical improvement by day 14 as assessed with the WHO 7-category ordinal scale. Secondary outcomes included 21-day mortality, incidence of septic shock during hospitalization, and pathogen detection rate. Results: Among the 110 patients who underwent mNGS, the results prompted modifications to the antibiotic therapy in 89 patients (80.9%), encompassing both escalation and de-escalation of therapy. The remaining 52 patients received only CMT. After the PSM, 41 matched pairs were further analyzed. Compared to the CMT group, OI improvement >30% on day 7 was more frequent in the mNGS group (41.5% vs. 9.8%, P = 0.001). Clinical improvement on day 14 in the mNGS group was higher than in the CMT group (36.6% vs. 9.8%, P = 0.004). Additionally, BALF mNGS was associated with decreased 21-day mortality (7.3% vs. 34.1%; P = 0.003) in patients with opportunistic pulmonary infections, while showing no significant association with reduced incidence of septic shock during hospitalization. Moreover, the causative pathogen detection rate was significantly higher in the mNGS group compared to the CMT group (97.6% vs. 22.0%, P<0.001), demonstrating the superior diagnostic yield of mNGS. Conclusion: Our study indicated that early BALF mNGS testing upon admission was associated with improved OI up to day 7, clinical improvement on day 14, and decreased 21-day mortality. These benefits are likely facilitated by the higher diagnostic yield of mNGS and its direct impact on guiding targeted antibiotic therapy.