Clinical characteristics and treatment of IMP-type carbapenemase-producing Enterobacteriaceae bacteremia: Case series and literature review

Published:September 21, 2022DOI:



      Several carbapenemases have been identified globally in Enterobacteriaceae. In Japan, IMP-type carbapenemase is the most prevalent, although cases of carbapenemase-producing Enterobacteriaceae (CPE) bacteremia are still scarce. The present case series and literature review aimed to elucidate the clinical characteristics and treatment strategies for IMP-type CPE bacteremia.


      Clinical data on pediatric cases of IMP-type CPE bacteremia at the Tokyo Metropolitan Children's Medical Center between 2010 and 2020 were collected, and a review of past studies of IMP-type CPE bacteremia has been provided.


      Five pediatric episodes of IMP-type CPE bacteremia were identified. Our review of previous literature on IMP-type CPE bacteremia revealed 24 adult patients, but no pediatric patients. All 29 cases had underlying diseases, and 23 (79%) received combination therapy. The median duration of antibiotic therapy was 14 days (interquartile range: 9–14 days). The overall mortality rate was 38% (11/29). The mortality rates associated with monotherapy and combination therapy were 67% (4/6) and 30% (7/23), respectively.


      We report the first case series of IMP-type CPE bacteremia in children. Our review of past studies suggests that combination therapy might lead to better survival outcomes in patients with IMP-type CPE bacteremia. Further research is needed to establish an optimal treatment strategy for IMP-type CPE bacteremia.


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        • Overturf G.D.
        Carbapenemases: a brief review for pediatric infectious disease specialists.
        Pediatr Infect Dis J. 2010; 29: 68-70
        • Boyd S.E.
        • Livermore D.M.
        • Hooper D.C.
        • Hope W.W.
        Metallo-β-Lactamases: structure, function, epidemiology, treatment options, and the development pipeline.
        Antimicrob Agents Chemother. 2020; 64e00397-20
        • Walsh T.R.
        • Weeks J.
        • Livermore D.M.
        • Toleman M.A.
        Dissemination of NDM-1 positive bacteria in the New Delhi environment and its implications for human health: an environmental point prevalence study.
        Lancet Infect Dis. 2011; 11: 355-362
        • van Duin D.
        • Doi Y.
        The global epidemiology of carbapenemase-producing Enterobacteriaceae.
        Virulence. 2017; 8: 460-469
        • Matsumura Y.
        • Peirano G.
        • Motyl M.R.
        • Adams M.D.
        • Chen L.
        • Kreiswirth B.
        • et al.
        Global molecular epidemiology of IMP-producing enterobacteriaceae.
        Antimicrob Agents Chemother. 2017; 61e02729-16
        • Japan Nosocomial Infections Surveillance (Janis)
        Annual open report 2021 (all facilities) number of patients and isolation rate of specific AMR bacteria.
        (Available at: [Accessed 26th July 2022])
        • National Institute of Infectious Diseases J
        Carbapenemresistant enterobacteriaceae infection in 2019.
        (Japan, Available at:)
        Date: June 29, 2021
        Date accessed: February 1, 2022
        • Arakawa Y.
        • Shibata N.
        • Shibayama K.
        • Kurokawa H.
        • Yagi T.
        • Fujiwara H.
        • et al.
        Convenient test for screening metallo-beta-lactamase-producing gram-negative bacteria by using thiol compounds.
        J Clin Microbiol. 2000; 38: 40-43
        • Tumbarello M.
        • Viale P.
        • Viscoli C.
        • Trecarichi E.M.
        • Tumietto F.
        • Marchese A.
        • et al.
        Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae: importance of combination therapy.
        Clin Infect Dis. 2012; 55: 943-950
        • Tzouvelekis L.S.
        • Markogiannakis A.
        • Piperaki E.
        • Souli M.
        • Daikos G.L.
        Treating infections caused by carbapenemase-producing Enterobacteriaceae.
        Clin Microbiol Infect. 2014; 20: 862-872
        • Qureshi Z.A.
        • Paterson D.L.
        • Potoski B.A.
        • Kilayko M.C.
        • Sandovsky G.
        • Sordillo E.
        • et al.
        Treatment outcome of bacteremia due to KPC-producing Klebsiella pneumoniae: superiority of combination antimicrobial regimens.
        Antimicrob Agents Chemother. 2012; 56: 2108-2113
        • Zarkotou O.
        • Pournaras S.
        • Tselioti P.
        • Dragoumanos V.
        • Pitiriga V.
        • Ranellou K.
        • et al.
        Predictors of mortality in patients with bloodstream infections caused by KPC-producing Klebsiella pneumoniae and impact of appropriate antimicrobial treatment.
        Clin Microbiol Infect. 2011; 17: 1798-1803
        • Tumbarello M.
        • Trecarichi E.M.
        • De Rosa F.G.
        • Giannella M.
        • Giacobbe D.R.
        • Bassetti M.
        • et al.
        Infections caused by KPC-producing Klebsiella pneumoniae: differences in therapy and mortality in a multicentre study.
        J Antimicrob Chemother. 2015; 70: 2133-2143
        • Tzouvelekis L.S.
        • Markogiannakis A.
        • Psichogiou M.
        • Tassios P.T.
        • Daikos G.L.
        Carbapenemases in Klebsiella pneumoniae and other Enterobacteriaceae: an evolving crisis of global dimensions.
        Clin Microbiol Rev. 2012; 25: 682-707
        • Ho V.P.
        • Jenkins S.G.
        • Afaneh C.I.
        • Turbendian H.K.
        • Nicolau D.P.
        • Barie P.S.
        Use of meropenem by continuous infusion to treat a patient with a Bla(kpc-2)-positive Klebsiella pneumoniae blood stream infection.
        Surg Infect. 2011; 12: 325-327
        • Castanheira M.
        • Sader H.S.
        • Jones R.N.
        Antimicrobial susceptibility patterns of KPC-producing or CTX-M-producing Enterobacteriaceae.
        Microb Drug Resist. 2010; 16: 61-65
        • Kumarasamy K.K.
        • Toleman M.A.
        • Walsh T.R.
        • BagariaJ
        • Butt F.
        • Balakrishnan R.
        • et al.
        Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study.
        Lancet Infect Dis. 2010; 10: 597-602
        • Yamamoto N.
        • Asada R.
        • Kawahara R.
        • Hagiya H.
        • Akeda Y.
        • Shanmugakani R.K.
        • et al.
        Prevalence of, and risk factors for, carriage of carbapenem-resistant Enterobacteriaceae among hospitalized patients in Japan.
        J Hosp Infect. 2017; 97: 212-217
        • Carmeli Y.
        • Akova M.
        • Cornaglia G.
        • Daikos G.L.
        • Garau J.
        • Harbarth S.
        • et al.
        Controlling the spread of carbapenemase-producing Gram-negatives: therapeutic approach and infection control.
        Clin Microbiol Infect. 2010; 16: 102-111
        • Zarkotou O.
        • Pournaras S.
        • Tselioti P.
        • Dragoumanos V.
        • Pitiriga V.
        • Ranellou K.
        • et al.
        Predictors of mortality in patients with bloodstream infections caused by KPC-producing Klebsiella pneumoniae and impact of appropriate antimicrobial treatment.
        Clin Microbiol Infect. 2011; 12: 1798-1803
        • Saito S.
        • Hayakawa K.
        • Tsuzuki S.
        • Ishikane M.
        • Nagashima M.
        • Mezaki K.
        • et al.
        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.
        Antimicrob Agents Chemother. 2021; 65e01483-20
        • Infectious Diseases Society of America
        IDSA guidance on the treatment of antimicrobial-resistant gram-negative infections.
        (Available at: [Accessed 26th July 2022])
        • Marshall S.
        • Hujer A.M.
        • Rojas L.
        • Papp-Wallace K.M.
        • Humphries R.M.
        • Spellberg B.
        • et al.
        Can ceftazidime-avibactam and aztreonam overcome β-lactam resistance conferred by metallo-β-lactamases in Enterobacteriaceae?.
        Antimicrob Agents Chemother. 2017; 61e02243-16
        • Falcone M.
        • Daikos G.L.
        • Tiseo G.
        • Bassoulis D.
        • Giordano C.
        • Galfo V.
        • et al.
        Efficacy of ceftazidime-avibactam plus aztreonam in patients with bloodstream infections caused by metallo-beta-lactamase-producing enterobacterales.
        Clin Infect Dis. 2021; 72: 1871-1878
        • Segagni Lusignani L.
        • Presterl E.
        • Zatorska B.
        • Van den Nest M.
        • Diab-Elschahawi M.
        Infection control and risk factors for acquisition of carbapenemase-producing enterobacteriaceae. A 5 year (2011-2016) case-control study.
        Antimicrob Resist Infect Control. 2020; 9: 18
        • Nakakura I.
        • Ogawa Y.
        • Sakakura K.
        • Imanishi K.
        • Hirota K.
        • Shimatani Y.
        • et al.
        IMP-6 carbapenemase-producing enterobacteriaceae bacteremia successfully treated with amikacin-meropenem in two patients.
        Pharmacotherapy. 2017; 37: e96-e102
        • Hayakawa K.
        • Miyoshi-Akiyama T.
        • Kirikae T.
        • Nagamatsu M.
        • Shimada K.
        • Mezaki K.
        • et al.
        Molecular and epidemiological characterization of IMP-type metallo-β-lactamase-producing Enterobacter cloacae in a Large tertiary care hospital in Japan.
        Antimicrob Agents Chemother. 2014; 58: 3441-3450
        • Mori N.
        • Kagawa N.
        • Aoki K.
        • Ishi Y.
        • Tateda K.
        • Aoki Y.
        Clinical and molecular analyses of bloodstream infections caused by IMP metallo-β-lactamase-producing Enterobacteriaceae in a tertiary hospital in Japan.
        J Infect Chemother. 2020; 26: 144-147
        • Hamada Y.
        • Watanabe K.
        • Tada T.
        • Mezaki K.
        • Takeuchi S.
        • Shimizu T.
        • et al.
        Three cases of IMP-type metallo-β-lactamase-producing Enterobacter cloacae bloodstream infection in Japan.
        J Infect Chemother. 2013; 19: 956-958
        • Leung G.H.
        • Gray T.J.
        • Cheong E.Y.
        • Haertsch P.
        • Gottlieb T.
        Persistence of related bla-IMP-4 metallo-beta-lactamase producing Enterobacteriaceae from clinical and environmental specimens within a burns unit in Australia - a six-year retrospective study.
        Antimicrob Resist Infect Control. 2013; 2: 35
        • Yaita K.
        • Gotoh K.
        • Nakano R.
        • Iwahashi J.
        • Sakai Y.
        • Horita R.
        • et al.
        Biofilm-forming by carbapenem resistant enterobacteriaceae may contribute to the blood stream infection.
        Int J Mol Sci. 2019; 20
        • Vergara-López S.
        • Domínguez M.C.
        • Conejo M.C.
        • Pascual Á.
        • Rodríguez-Baño J.
        Prolonged treatment with large doses of fosfomycin plus vancomycin and amikacin in a case of bacteraemia due to methicillin-resistant Staphylococcus epidermidis and IMP-8 metallo-β-lactamase-producing Klebsiella oxytoca.
        J Antimicrob Chemother. 2015; 70: 313-315
        • Tseng S.P.
        • Wang J.T.
        • Liang C.Y.
        • Lee P.S.
        • Chen Y.C.
        • Lu P.L.
        First report of bla(IMP-8) in raoultella planticola.
        Antimicrob Agents Chemother. 2014; 58: 593-595