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Clinical Therapeutics

A Matched Case-Case-Control Study of the Impact of Clinical Outcomes and Risk Factors of Patients with IMP-Type Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae in Japan

Sho Saito, Kayoko Hayakawa, Shinya Tsuzuki, Masahiro Ishikane, Maki Nagashima, Kazuhisa Mezaki, Yuko Sugiki, Taichi Tajima, Nobuaki Matsunaga, Satoshi Ide, Noriko Kinoshita, Yoshiki Kusama, Yumiko Fujitomo, Takato Nakamoto, Yuta Toda, Mitsuo Kaku, Eiichi N. Kodama, Norio Ohmagari
Sho Saito
aDisease Control and Prevention Center, National Centre for Global Health and Medicine, Tokyo, Japan
bAMR Clinical Reference Center, National Centre for Global Health and Medicine, Tokyo, Japan
cDepartment of Emerging and Reemerging Infectious Diseases, Tohoku University School of Medicine, Sendai, Miyagi, Japan
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  • ORCID record for Sho Saito
Kayoko Hayakawa
aDisease Control and Prevention Center, National Centre for Global Health and Medicine, Tokyo, Japan
bAMR Clinical Reference Center, National Centre for Global Health and Medicine, Tokyo, Japan
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Shinya Tsuzuki
bAMR Clinical Reference Center, National Centre for Global Health and Medicine, Tokyo, Japan
dFaculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
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Masahiro Ishikane
aDisease Control and Prevention Center, National Centre for Global Health and Medicine, Tokyo, Japan
bAMR Clinical Reference Center, National Centre for Global Health and Medicine, Tokyo, Japan
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Maki Nagashima
aDisease Control and Prevention Center, National Centre for Global Health and Medicine, Tokyo, Japan
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Kazuhisa Mezaki
eMicrobiology Laboratory, National Center for Global Health and Medicine, Tokyo, Japan
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Yuko Sugiki
fInfection Control and Prevention, National Center for Global Health and Medicine, Tokyo, Japan
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Taichi Tajima
bAMR Clinical Reference Center, National Centre for Global Health and Medicine, Tokyo, Japan
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Nobuaki Matsunaga
bAMR Clinical Reference Center, National Centre for Global Health and Medicine, Tokyo, Japan
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Satoshi Ide
aDisease Control and Prevention Center, National Centre for Global Health and Medicine, Tokyo, Japan
cDepartment of Emerging and Reemerging Infectious Diseases, Tohoku University School of Medicine, Sendai, Miyagi, Japan
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Noriko Kinoshita
aDisease Control and Prevention Center, National Centre for Global Health and Medicine, Tokyo, Japan
bAMR Clinical Reference Center, National Centre for Global Health and Medicine, Tokyo, Japan
cDepartment of Emerging and Reemerging Infectious Diseases, Tohoku University School of Medicine, Sendai, Miyagi, Japan
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Yoshiki Kusama
bAMR Clinical Reference Center, National Centre for Global Health and Medicine, Tokyo, Japan
cDepartment of Emerging and Reemerging Infectious Diseases, Tohoku University School of Medicine, Sendai, Miyagi, Japan
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Yumiko Fujitomo
bAMR Clinical Reference Center, National Centre for Global Health and Medicine, Tokyo, Japan
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Takato Nakamoto
aDisease Control and Prevention Center, National Centre for Global Health and Medicine, Tokyo, Japan
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Yuta Toda
aDisease Control and Prevention Center, National Centre for Global Health and Medicine, Tokyo, Japan
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Mitsuo Kaku
gDepartment of Infection Control and Laboratory Diagnostics, Tohoku University School of Medicine, Sendai, Miyagi, Japan
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Eiichi N. Kodama
hDivision of Infectious Diseases, School of Medicine, International Research Institute of Disaster Science, and Tohoku Medical Megabank Organization, Tohoku University, Sendai, Miyagi, Japan
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Norio Ohmagari
aDisease Control and Prevention Center, National Centre for Global Health and Medicine, Tokyo, Japan
bAMR Clinical Reference Center, National Centre for Global Health and Medicine, Tokyo, Japan
cDepartment of Emerging and Reemerging Infectious Diseases, Tohoku University School of Medicine, Sendai, Miyagi, Japan
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DOI: 10.1128/AAC.01483-20
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ABSTRACT

IMP-type carbapenemase, found in various Gram-negative bacteria, has been increasingly detected worldwide. We aimed to study the outcomes and risk factors for acquisition of IMP-type carbapenemase-producing carbapenem-resistant Enterobacteriaceae (IMP-CRE), as this has not been evaluated in detail. We conducted a matched case-case-control study of patients from whom IMP-CRE isolates were obtained. All patients who tested positive for IMP-CRE were included; they were matched with patients with carbapenem-susceptible Enterobacteriaceae (CSE) and with controls at a ratio of 1:1:2. The risk factors for acquisition for the CRE and CSE groups and mortality rates, which were calculated using multivariate logistic regression models with weighting according to the inverse probability of propensity scores, were compared. In total, 192 patients (96 patients each in the CRE and CSE groups, with 130 Enterobacter cloacae isolates and 62 Klebsiella sp. isolates) were included. The IMP-11 type was present in 43 patients, IMP-1 in 33, and IMP-60 and IMP-66 in 1 each; 31 patients with CRE (32.3%) and 34 with CSE (35.4%) developed infections. Multivariate analysis identified the following independent risk factors: gastrostomy, history of intravenous therapy or hemodialysis, and previous exposure to broad-spectrum β-lactam antibiotics, including penicillin with β-lactamase inhibitors, cephalosporins, and carbapenems. In propensity score-adjusted analysis, mortality rates for the CRE and CSE groups were similar (15.0% and 19.5%, respectively). We found that IMP-CRE may not contribute to worsened clinical outcomes, compared to CSE, and gastrostomy, previous intravenous therapy, hemodialysis, and broad-spectrum antimicrobial exposure were identified as risk factors for CRE isolation. Fluoroquinolone and aminoglycosides are potentially useful antibiotics for IMP-CRE infections.

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A Matched Case-Case-Control Study of the Impact of Clinical Outcomes and Risk Factors of Patients with IMP-Type Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae in Japan
Sho Saito, Kayoko Hayakawa, Shinya Tsuzuki, Masahiro Ishikane, Maki Nagashima, Kazuhisa Mezaki, Yuko Sugiki, Taichi Tajima, Nobuaki Matsunaga, Satoshi Ide, Noriko Kinoshita, Yoshiki Kusama, Yumiko Fujitomo, Takato Nakamoto, Yuta Toda, Mitsuo Kaku, Eiichi N. Kodama, Norio Ohmagari
Antimicrobial Agents and Chemotherapy Feb 2021, 65 (3) e01483-20; DOI: 10.1128/AAC.01483-20

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A Matched Case-Case-Control Study of the Impact of Clinical Outcomes and Risk Factors of Patients with IMP-Type Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae in Japan
Sho Saito, Kayoko Hayakawa, Shinya Tsuzuki, Masahiro Ishikane, Maki Nagashima, Kazuhisa Mezaki, Yuko Sugiki, Taichi Tajima, Nobuaki Matsunaga, Satoshi Ide, Noriko Kinoshita, Yoshiki Kusama, Yumiko Fujitomo, Takato Nakamoto, Yuta Toda, Mitsuo Kaku, Eiichi N. Kodama, Norio Ohmagari
Antimicrobial Agents and Chemotherapy Feb 2021, 65 (3) e01483-20; DOI: 10.1128/AAC.01483-20
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KEYWORDS

carbapenem resistance
IMP
Enterobacteriaceae
clinical outcomes
propensity score

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