Beyond Pathogen Identity: Host-Specific Prognostic Markers and mNGS Insights in ICU MDRO Infections

Background: Multidrug-resistant organism (MDRO) infections in the intensive care unit (ICU) pose a significant threat to global public health, leading to high mortality rates. However, the comprehensive analysis integrating clinical outcomes with the concordance between genotypic resistance (by metagenomic next-generation sequencing, mNGS) and phenotypic resistance (by antimicrobial susceptibility testing, AST) remains limited. This study aimed to investigate the incidence, distribution, risk factors for adverse outcomes, and the genotypic-phenotypic discordance in ICU patients with MDRO infections.Methods: We conducted a retrospective observational study of 190 patients with MDRO infections in the ICU/Neurological ICU of a university-affiliated hospital from January 2023 to August 2024. Patients were stratified into survival (n=92) and non-survival (n=98) groups based on 28-day prognosis. Logistic regression was employed to identify independent risk factors for mortality. Furthermore, we utilized mNGS to profile resistance genes in predominant MDROs and compared these profiles with conventional AST results.Results: The overall mortality rate was 51.6%. mNGS revealed distinct resistance gene profiles: In MDR-Acinetobacter baumannii (MDR-AB), adeIJK (79.2%), OXA-23 (45.8%), and OXA-51 (37.5%) were predominant. Strains co-harboring all three genes exhibited 100% phenotypic resistance, whereas those with OXA-23/OXA-51 alone were susceptible. Complex genotypic-phenotypic discordances were also observed in other MDROs like Stenotrophomonas maltophilia and Carbapenem-resistant Klebsiella pneumoniae (CRKP). Multivariate analysis identified elevated neutrophil count (OR=1.120, 95% CI: 1.04–1.21, P=0.004), decreased prealbumin level (OR=0.99, 95% CI: 0.98–0.99, P=0.032), and surprisingly, non-infection with MRSA (OR=0.38, 95% CI: 0.14–0.99, P=0.048) as independent risk factors for poor prognosis.Conclusion: Elevated neutrophils and decreased prealbumin are robust prognostic markers in ICU patients with MDRO infections. The paradoxical protective effect of MRSA infection warrants further investigation. Our study underscores the value of mNGS in revealing the complex landscape of resistance genes, while highlighting that their expression is not always straightforward, necessitating a combined interpretation with AST for effective clinical decision-making.