Difficult-to-treat resistance (DTR), treatment, and outcomes of carbapenem-resistant Enterobacterales infections in the setting of IMP-type carbapenemase predominance in Japan

= 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.IMPORTANCEDifficult-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.

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Publication Details

Journal
Microbiology Spectrum
Published
2026-04-27
DOI
https://doi.org/10.1128/spectrum.01007-26
Primary Topic
Antibiotic Resistance in Bacteria
Type
article
Field-Weighted Citation Impact
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article

Difficult-to-treat resistance (DTR), treatment, and outcomes of carbapenem-resistant Enterobacterales infections in the setting of IMP-type carbapenemase predominance in Japan

Kayoko Hayakawa, Momoko Mawatari, Yohei Doi, Kohei Uemura et al.
Microbiology Spectrum
Antibiotic Resistance in Bacteria
article

Difficult-to-treat resistance (DTR), treatment, and outcomes of carbapenem-resistant Enterobacterales infections in the setting of IMP-type carbapenemase predominance in Japan

Kayoko Hayakawa, Momoko Mawatari, Yohei Doi, Kohei Uemura, Giichi Yamamoto, Yasufumi Matsumura, Sho Saito, Masahiro Suzuki, Naoya Itoh, Tetsuya Suzuki, Takashi Matono, Koji Ohyama, Ryota Hase, Yusuke Asai, Norio Ohmagari, Takeya Tsutsumi, Aki Sakurai, Hideaki Kato, Takuya Hosoda, Takehiro Hashimoto, David van Duin, Shinya Tsuzuki
article en

Abstract

= 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.IMPORTANCEDifficult-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.

Microbiology Spectrum
Fujita Health University (JP), University of Antwerp (BE), University of Pittsburgh (US), Saga University (JP), Kyoto University (JP), Nagoya City University (JP), Department of Disease Control (TH), National Center for Global Health and Medicine (JP), Yokohama City University Hospital (JP), Japanese Red Cross Medical Center (JP), University of Tokyo Hospital (JP), University of Yamanashi Hospital (JP), Center for Global Health (US), Japanese Red Cross Narita Hospital (JP), Institute of Bioinformatics (IN), Oita University Hospital (JP), Osaka University Hospital (JP), Yokohama City University (JP)
Shionogi, Japan Society for the Promotion of Science
Good health and well-being
Openalex Percentile: Top 9%
Antibiotic Resistance in Bacteria
DOIOpen Access PDFOpenAlex
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