Abstract

BackgroundThe gene for New Delhi metallo-β-lactamase 1 (NDM-1) has been reported to be transmitted via plasmids which are easily transferable and capable of wide distribution. We report the isolation of two NDM-1 producing strains and possible in vivo transfer of bla NDM-1 in a patient.MethodsClinical samples were collected for bacterial culture and antibiotic susceptibility testing from a patient during a 34-day hospitalization. The presence of bla NDM-1 was detected by PCR and sequencing. Plasmids of interest were sequenced. Medical records were reviewed for evidence of association between the administration of antibiotics and the acquisition of the NDM-1 resistance.ResultsA NDM-1 positive Raoultella planticola was isolated from blood on the ninth day of hospitalization without administration of any carbapenem antibiotics and a NDM-1 positive Escherichia coli was isolated from feces on the 29th day of hospitalization and eight days after imipenem administration. The bla NDM-1 was carried by a 280 kb plasmid pRpNDM1-1 in R. planticola and a 58 kb plasmid pEcNDM1-4 in E. coli. The two plasmids shared a 4812 bp NDM-1-ISCR1 element which was found to be excisable from the plasmid as a free form and transferrable in vitro to a NDM-1 negative plasmid from E. coli.Conclusion bla NDM-1 was embedded in an ISCR1 complex class 1 integron as a novel 4812 bp NDM-1-ISCR1 element. The element was found to be able to self excise to become a free form, which may provide a new vehicle for NDM-1 dissemination. This mechanism could greatly accelerate the spread of NDM-1 mediated broad spectrum β-lactam resistance.

Highlights

  • Carbapenems often represent last-resource drugs for Gram negative bacterial infections

  • The blaNDM-1 was embedded in an insertion sequence common region 1 (ISCR1) complex class 1 integron, which is most likely responsible for blaNDM-1 transfer between R. planticola and E. coli in the patient in vivo

  • Isolation of New Delhi metallo-b-lactamase 1 (NDM-1) positive R. planticola and E. coli Bacterial culture was attempted on four occasions to guide clinical care of the patient during hospitalization

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Summary

Introduction

Carbapenems often represent last-resource drugs for Gram negative bacterial infections. The most common mechanism of carbapenem resistance in Gram negative bacteria is the production of carbapenemases, including metallo-b-lactamases (MBLs). The New Delhi metallo-beta-lactamase (NDM-1), a recently identified novel type of MBL can hydrolyze virtually all b-lactams, adding further burden to an already high level of antibiotic resistance. The gene blaNDM-1 encoding NDM-1 has been mostly reported to be on plasmids, which could rapidly disseminate and spread between different bacterial species by cell-to-cell transfer of the plasmids. The plasmids carrying blaNDM-1 are different in sizes, ranging from 40 kb to 400 kb [9], suggesting that direct transfer by plasmid is only one means of NDM-1 dissemination. The gene for New Delhi metallo-b-lactamase 1 (NDM-1) has been reported to be transmitted via plasmids which are transferable and capable of wide distribution. We report the isolation of two NDM-1 producing strains and possible in vivo transfer of blaNDM-1 in a patient

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