Carbapenem-resistant Gram-negative bacilli (CR-GNB) are a major public health threat, traditionally linked to hospital settings. However, infections are increasingly reported in the community, and the clinical distinctions between community-associated (CA) and healthcare-associated (HA) infections remain unclear.MethodsWe conducted a prospective multicenter study of hospitalized patients with CR-GNB infections across 13 Japanese tertiary hospitals between April 2019 and March 2024. Infections were categorized as CA, HA, or hospital-onset (HO) using standardized criteria. We compared patient demographics, microbiological findings, infection sites, and clinical outcomes based on the setting of onset.ResultsAmong 425 patients, 43 had CA, 59 HA, and 323 HO infections. Pseudomonas aeruginosa was the predominant pathogen in all groups. Aeromonas species were more frequently associated with CA than HO cases (23.3% of CA vs 2.2% of HO cases), whereas Stenotrophomonas maltophilia was detected almost exclusively among HO cases. Hospital-onset infections were associated with longer median hospital stays compared with CA infections (68 vs 17 days) and a trend toward higher 30-day mortality (23.9% vs 9.5%). In contrast, HA infections demonstrated no significant differences from CA infections in either hospital length of stay (23 vs 17 days) or 30-day mortality rate (10.3% vs 9.5%).ConclusionsCommunity-associated CR-GNB infections are an emerging concern in Japan, showing distinct pathogen profiles and infection sites compared to HO cases. Importantly, HA infections resembled CA infections in terms of clinical characteristics and outcomes, suggesting a need to reexamine the clinical relevance of current HA classification criteria for guiding therapy and risk stratification.