Global dissemination of extensively drug-resistant carbapenemase-producing Enterobacteriaceae: clinical perspectives on detection, treatment and infection control

J Intern Med. 2015 May;277(5):501-12. doi: 10.1111/joim.12342. Epub 2015 Jan 27.


The prevalence of carbapenem-resistant Gram-negative bacilli is on the rise worldwide, posing a major public health threat. Previously, this was mostly a problem in Pseudomonas and Acinetobacter, but during the last decade, carbapenem resistance has escalated in medically important species such as Klebsiella pneumoniae and Escherichia coli. In particular, the rising trend in E. coli is of concern, as this may lead to almost untreatable community-acquired infections. Resistance is conferred by carbapenemases, which are beta-lactamases that can breakdown essentially all beta-lactams. Moreover, bacteria carrying these resistance determinants are often resistant to other treatment options, due to the frequent co-acquisition of non-beta-lactam resistance genes located on the same mobile genetic elements. The detection of carbapenemase-producing Enterobacteriaceae (CPE) is a challenge, because some carbapenemases produce relatively discrete levels of carbapenem resistance. Current clinical evidence for treatment guidance is limited and based on retrospective observational studies and case reports. Existing data support the use of combination therapy for treatment of severe infections caused by CPE. Combination regimens including colistin, carbapenems, tigecycline, aminoglycosides and fosfomycin have been used. Randomized controlled studies of combination regimens are ongoing and may help to determine the optimal therapy. Novel beta-lactamase inhibitors may also have a role in future treatment of these infections. Strict infection control measures including isolation or cohort care of affected patients as well as contact tracing and active screening are needed to curb the spread of CPE. In this review, we provide a clinical perspective on the management of patients infected or colonized with CPE.

Keywords: Klebsiella pneumoniae carbapenemase; New Delhi metallo-β-lactamase; carbapenemase; carbapenemase-producing Enterobacteriaceae; colistin; combination therapy.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / therapeutic use
  • Bacterial Proteins / biosynthesis*
  • Carbapenems / therapeutic use
  • Communicable Disease Control / methods
  • Enterobacteriaceae Infections / drug therapy
  • Enterobacteriaceae Infections / enzymology
  • Enterobacteriaceae Infections / prevention & control*
  • Global Health
  • Humans
  • Klebsiella Infections / drug therapy
  • Klebsiella Infections / enzymology
  • Klebsiella Infections / prevention & control
  • Klebsiella pneumoniae
  • beta-Lactam Resistance / drug effects*
  • beta-Lactamases / biosynthesis*


  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Carbapenems
  • beta-Lactamases
  • carbapenemase