Difficult-to-treat resistance (DTR), treatment, and outcomes of carbapenem-resistant Enterobacterales infections in the setting of IMP-type carbapenemase predominance in Japan
Rattachement africain : jp, th, us, be. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
ABSTRACT Carbapenem-resistant Enterobacterales (CRE) pose a global threat due to limited treatment options and high mortality. Difficult-to-treat resistance (DTR), defined as non-susceptibility to all conventional β-lactams and fluoroquinolones, has primarily been applied to Pseudomonas aeruginosa . However, its relevance for Enterobacterales remains unclear, particularly in regions with a distinct carbapenemase landscape, such as Japan where IMP-type metallo-β-lactamases predominate. We analyzed the MultiDrug-Resistant organisms clinical research network (MDRnet) cohort, a multicenter prospective study conducted at 13 Japanese hospitals between April 2019 and March 2024. This analysis included patients with clinically indicated cultures yielding CRE. Clinical characteristics and outcomes assessed using the desirability of outcome ranking (DOOR) framework and genomic epidemiology characterized by whole-genome sequencing were compared between DTR and non-DTR groups. Among 196 CRE cases, 64 (32.7%) represented infections, including 12 DTR cases (18.8%). Carbapenemase genes were detected in 34/64 infections (53.1%), with similar prevalence in the DTR and non-DTR groups (50.0% vs 53.8%). bla IMP-1 was the most frequently identified carbapenemase gene ( n = 28). The overall 30-day mortality rate was 21.9%, with 16.7% (95% confidence interval [CI], 2.1%–48.4%) in the DTR group and 23.1% (95% CI, 12.5%–36.8%) in the non-DTR group. DOOR outcomes were similar between groups. Appropriate empiric and definitive therapy was less frequently administered in the DTR group. In this cohort, where IMP-type carbapenemases and non-DTR CRE are prevalent, DTR classification did not appear to correlate with 30-day mortality or DOOR outcomes. These findings underscore the importance of regional molecular epidemiology when interpreting clinical outcomes of CRE infections. IMPORTANCE Difficult-to-treat resistance (DTR) is increasingly used to assess the clinical impact of antimicrobial resistance, but its significance in carbapenem-resistant Enterobacterales (CRE) may vary across molecular epidemiologic settings. In this prospective multicenter study from Japan, where IMP-type carbapenemases predominated, most CRE infections were classified as non-DTR. Whole-genome sequencing also revealed a distinct local clonal structure. DTR was not associated with 30-day mortality or desirability of outcome ranking despite lower rates of appropriate empiric and definitive therapy. Our study highlights the importance of interpreting DTR in CRE within the context of regional molecular epidemiology and supports the need for continued regional multicenter studies to evaluate its clinical utility.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Difficult-to-treat resistance (DTR), treatment, and outcomes of carbapenem-resistant Enterobacterales infections in the setting of IMP-type carbapenemase predominance in Japan
- Date Crossref
- 02/06/2026
- Éditeur
- American Society for Microbiology
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
-
Fujita Health University Department of Microbiology pays non établi dans la noticeUniversité ou école supérieure
-
Kyoto University Department of Clinical Laboratory Medicine pays non établi dans la noticeUniversité ou école supérieure
-
Japanese Red Cross Narita Hospital Department of Infectious Diseases pays non établi dans la noticeÉtablissement de santé
-
Yokohama City University Hospital Infection Prevention and Control Department pays non établi dans la noticeÉtablissement de santé
-
Yokohama City University pays non établi dans la noticeUniversité ou école supérieure
-
Saga University Division of Infectious Disease and Hospital Epidemiology pays non établi dans la noticeUniversité ou école supérieure
-
Nagoya City University pays non établi dans la noticeUniversité ou école supérieure
-
Oita University Hospital Hospital Infection Control Center pays non établi dans la noticeÉtablissement de santé
-
Department of Disease Control pays non établi dans la noticeOrganisme public
-
Osaka University Hospital Department of Infection Control and Prevention pays non établi dans la noticeÉtablissement de santé
-
Japanese Red Cross Medical Center Department of Infectious Diseases pays non établi dans la noticeÉtablissement de santé
-
University of Tokyo Hospital Department of Infectious Diseases pays non établi dans la noticeÉtablissement de santé
Department of Microbiology — Fujita Health University, Department of Clinical Laboratory Medicine — Kyoto University et Department of Infectious Diseases — Japanese Red Cross Narita Hospital, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.