Skip to main content


Halting NDM-producing enterobacteriaceae spread with the reactive infection control strategy: a real-world experience analyzed using a novel spatiotemporal epidemiologic risk measure (Epi-score) and whole-genome sequencing (WGS)

Article metrics

  • 381 Accesses


Guidelines recommend screening of epidemiologically linked patients to contain the spread of NDM-producing enterobacteriaceae (NDM-EB).


We assessed the effectiveness of this strategy in controlling the spread of NDM-EB using Epi-score and whole-genome sequencing (WGS).


This study was conducted at Tan Tock Seng Hospital (TTSH) between September 2010 and December 2011. TTSH implemented a reactive infection control strategy which constituted pre-emptive cohorting and rectal surveillance of patients with epidemiological linkage (contacts) to patients with NDM-EB isolated from clinical cultures (index). A clinical transmission model was produced for NDM-EB patients both from clinical and surveillance cultures based on epidemiological relatedness. The Epi-score graded epidemiologic-relatedness from 0 (unrelated) to 4 (very related), based on spatiotemporal ward overlap (2 points), shared medical teams (1 point), and shared medical department (1 point). This was the compared with a molecular transmission model which was produced using WGS of all NDM-EB isolates with core-genome single-nucleotide polymorphism analysis after excluding recombinant sites.


A total of six index clinical NDM-EB were detected (patients 1-3,5,7-8) (5 urine and 1 bile). Contact screening as part of reactive strategy involved 436 patients, of which 2 (patients 4, 6) were newly-detected NDM-EB carriers. Epi-score distributions: 3 points (patients 1-4,2-3,5-6); 2 points (patients 1-5,4-5), 1 point (patients 1-7,5-8,6-8). Of the 3 point pairs, one (5-6) was confirmed direct transmission by whole-genome phylogenetic analysis (4 SNVs). None of the other patients were identified by WGS as direct transmission. In six (75%) isolates, NDM was carried on plasmid pTR3 which is unique to Singapore.


Only one direct ward transmission pair (confirmed by whole-genome-sequencing) was detected by the reactive strategy. The Epi-score performed well in classifying the direct ward transmission pair in the highest relatedness category. Most (75%) NDM-producing EB originated in Singapore, with possibly 25% of NDM-producing EB from overseas.

Disclosure of interest

None declared.

Author information

Correspondence to K Marimuthu.

Rights and permissions

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark


  • Risk Measure
  • Reactive Strategy
  • Direct Transmission
  • Transmission Model
  • Point Pair