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. 2025 Sep 29;12(10):ofaf585.
doi: 10.1093/ofid/ofaf585. eCollection 2025 Oct.

Features of Carbapenem-resistant Gram-negative Bacterial Infections in Japan Based on the Setting of Onset

Yuya Kawamoto  1   2 , Yusuke Asai  3   4 , Aki Sakurai  5 , Yasufumi Matsumura  6 , Ryota Hase  7 , Hideaki Kato  8 , Takashi Matono  9   10 , Naoya Itoh  11   12   13 , Takehiro Hashimoto  14 , Go Yamamoto  15 , Momoko Mawatari  16 , Takeya Tsutsumi  17 , Tetsuya Suzuki  18 , Shinya Tsuzuki  3   5 , Koji Ohyama  2 , Masahiro Suzuki  2 , Kayoko Hayakawa  3   5 , Kohei Uemura  19 , David van Duin  20 , Norio Ohmagari  3   5 , Yohei Doi  1   2   21 , Sho Saito  5
Affiliations

Features of Carbapenem-resistant Gram-negative Bacterial Infections in Japan Based on the Setting of Onset

Yuya Kawamoto et al. Open Forum Infect Dis. .

Abstract

Background: 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.

Methods: We 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.

Results: Among 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%).

Conclusions: Community-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.

Keywords: carbapenem-resistant Gram-negative bacilli; clinical outcomes; community-associated infection; healthcare-associated infection; hospital-onset infection.

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Conflict of interest statement

Potential conflicts of interest. The study was supported by Shionogi & Co., Ltd. Y.D. has received honorarium from Gilead, Shionogi, BD, Chugai, and has served as advisors for Shionogi, GSK, and Meiji Seika Pharma for work unrelated to this manuscript. S.S. received a research grant from Shionogi. T.M. has received speaker honoraria from MSD, Pfizer, Meiji Seika Pharma, and Daiichi Sankyo. D.v.D. reports grants and contracts from the NIH, Merck, and Shinogi, paid to his institution, outside of the published work; consultancy for Actavis, Tetraphase, Sanofi-Pasteur, MedImmune, Astellas, Merck, Allergan, T2Biosystems, Roche, Achaogen, Neumedicine, Shionogi, Pfizer, Entasis, Qpex, Wellspring, Karius, and Utility paid directly to him; honoraria from Pfizer; and an editor's stipend from the British Society for Antimicrobial Chemotherapy (BSAC). All other authors declare no competing interests.

Figures

Graphical Abstract
Graphical Abstract
Figure 1.
Figure 1.
Kaplan–Meier survival curves showing patient days from the first positive culture to death for patients with community-associated, healthcare-associated, and hospital-onset CR-GNB infections. (a) comparison between community-associated and healthcare-associated infections; (b) comparison between community-associated and hospital-onset infections. For multiple comparisons, a Bonferroni-corrected threshold of P < .025 was considered statistically significant. Patients with unknown 30-day survival status who were discharged alive were censored at the date of discharge (n = 7). CR-GNB, carbapenem-resistant Gram-negative bacilli.
See this image and copyright information in PMC

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