The worldwide emergence of drug-resistant Gram-negative rods

Hisakazu Yano, Yoichi Hirakata, Mitsuo Kaku

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1 Citation (Scopus)


Population mobility due to globalization has caused the world wide spread of drug-resistant bacteria. Recently, the prevalence of drug-resistant Gram-negative rods, such as NDM-1-, KPC-, and extended-spectrum β-lactamases (ESBLs) -producing bacteria, and multidrug-resistant Acinetobacter spp. has been increasing. NDM-1 was first reported in 2009. NDM-1 is a novel type of metallo-β-lactamase, which conferred resistance not only to carbapenems but also to other classes of β-lactam except for monobactams, and was poorly inhibited by β-lactamase inhibitors, such as clavulanic acid. The NDM-1 encoding gene was located on transferable plasmid, and was found frequently in Enterobacteriaceae, especially in Escherichia coli and Klebsiella pneumoniae. The KPC enzyme belongs to the Ambler class A carbapenemase. KPC-producing K. pneumoniae is often judged as susceptible to imipenem with the broth microdilution method. If treatment with imipenem or meropenem was attempted in patients with infection due to K. pneumoniae, which was imipenem-susceptible and was KPC-positive by PCR, clinical failure was frequently observed. The detection of KPC-producing K. pneumoniae still remains a challenging issue. ESBLs, which belong to the Ambler class A, can hydrolyze cephalosporins and monobactams. Recently, the prevalence of ESBLs, especially CTX-M-15, a variant of CTX-M, has been increasing and infections due to ESBL-producers have been emerging causing public-health concerns worldwide. CTX-M-15 was first detected in E. coli isolated from India in 2001, and CTX-M-15-producing E. coli has emerged worldwide, especially since 2003, as an important pathogen causing community-onset and hospital-acquired infections. CTX-M-15-producing E. coli is mainly due to a single clone ST131 O25: H4, and is resistant to aminoglycoside and fluoroquinolone. Multidrug-resistant A. baumannii is also mainly due to a single clone, European clone II. Although the prevalence of these drug-resistant Gram-negative rods is fortunately very low in Japan, it is none-the-less important to develop an effective therapeutic strategy and to prevent the further dissemination of these bacteria.

Original languageEnglish
Pages (from-to)8-16
Number of pages9
JournalJapanese Journal of Chemotherapy
Issue number1
Publication statusPublished - 2011 Jan


  • Acinetobacter spp
  • Extended-spectrum β-lactamases
  • Gram-negative rod
  • KPC
  • NDM-1

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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