NDM carbapenemases in the United Kingdom: an analysis of the first 250 cases

J Antimicrob Chemother. 2014 Jul;69(7):1777-84. doi: 10.1093/jac/dku084. Epub 2014 Apr 25.

Abstract

Objectives: Gram-negative bacteria with diverse carbapenemases, including New Delhi metallo-β-lactamase (NDM) enzymes, have been increasingly recorded in the UK since 2007. We analysed patient data for NDM-positive isolates confirmed by the national reference laboratory from UK laboratories from February 2008 to July 2013.

Methods: Isolates resistant to carbapenems and with imipenem MICs reduced ≥8-fold by EDTA were tested by PCR for genes encoding acquired class B carbapenemases. MICs were determined by BSAC agar dilution methodology. When requested by the sender, or when they were members of apparent clusters, NDM-positive isolates were typed by variable number tandem repeat (VNTR) analysis or PFGE. Data provided by the sending laboratories were collated and reviewed.

Results: From February 2008 to July 2013 the reference laboratory confirmed 326 NDM-positive isolates from 250 patients, submitted by 83 laboratories. Most (85%, 213/250) patients were already hospitalized when the NDM-positive bacteria were detected, were male (61%, 152/250) and were aged >60 years (58%, 145/250). Travel history was available for only 40% of patients, but 52% (53/101) of these had documented healthcare contact within or travel to the Indian subcontinent. Most NDM-positive isolates (94%, 306/326) were Enterobacteriaceae with just 6% (20/326) non-fermenters; the predominant hosts were Klebsiella spp. (55%, 180/326) and Escherichia coli (25%, 80/326). Almost all NDM-positive isolates were resistant to multiple antibiotic classes, but 90% remained susceptible to colistin.

Conclusions: Gram-negative bacteria with NDM carbapenemases are a growing challenge, especially for elderly hospitalized patients, including those with healthcare contact in the Indian subcontinent, and leave few therapeutic options. UK outbreaks remain rare and contained.

Keywords: Acinetobacter; Enterobacteriaceae; MBLs; Pseudomonas; meropenem.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism*
  • Carbapenems / pharmacology*
  • Female
  • Gram-Negative Bacteria / classification
  • Gram-Negative Bacteria / drug effects*
  • Gram-Negative Bacteria / enzymology*
  • Gram-Negative Bacteria / isolation & purification
  • Gram-Negative Bacterial Infections / microbiology
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • United Kingdom
  • beta-Lactam Resistance*
  • beta-Lactamases / genetics*
  • beta-Lactamases / metabolism*

Substances

  • Bacterial Proteins
  • Carbapenems
  • beta-Lactamases
  • carbapenemase