Exploring Epidemiological and Genetic Links between Biocides and Spread of Multidrug Resistant Staphylococci

Supervisors: Dr Karolin Hijazi, Dr Charis Marwick, Dr Ian M Gould, Dr Ian F Laurenson

Project Description:

Antimicrobial resistance is a major health problem worldwide. UK institutions have committed to a multi-disciplinary strategy that will limit the risk of antimicrobial resistance and minimise its impact for health1. In keeping with such commitment, this project stems from our efforts of bringing together clinicians and scientists with synergistic expertise to investigate the effect of current infection control practices in intensive care units on the selection pressures for antimicrobial resistance. The candidate will investigate the role of biocides in emergence and spread of multidrug resistant Staphylococci in intensive care units.

Intensive use of biocides in hospitals, primarily chlorhexidine and mupirocin, has led to remarkable success in containment of the MRSA epidemic in the early 2000s, but their long-term use has been implicated in increased frequencies of multidrug resistant bacteria responsible for healthcare-associated infections. Concerns have intensified following recent evidence of chlorhexidine being associated with resistance to a last resort antibiotic2. Findings from our research showed that the majority of Staphylococcus epidermidis isolates from bloodstream infections in an intensive therapy unit carried genes for chlorhexidine resistance and belonged to a single multidrug resistant clone.  We have also shown that chlorhexidine resistance genes were co-present on a variant of a transmissible MRSA plasmid carrying genes for resistance to other biocides (triclosan and mupirocin) and a range of antibiotics3.

These findings raise concerns in relation to

  • Selection of multidrug resistant Staphylococci by chlorhexidine
  • Horizontal transfer of multidrug resistance genes between coagulase-negative Staphylococci and S. aureus.

To further address these concerns this project aims to investigate Staphylococcus isolates collected from multiple intensive therapy units in Scotland as described below. The work will involve analyses of bacteraemia isolates as well as screening samples from skin/mucosa. The specific objectives of the project will be as follows:

  1. To analyse the genotypic and phenotypic resistance profiles to antibiotics and biocides and conduct clonal structure analyses of multidrug resistant isolates by whole genome sequencing.
  2. To conduct epidemiological analyses by statistical modelling to correlate decolonisation practices with antimicrobial resistance and clonal structure profiles.
  3. To characterise the mobile genetic elements carrying genes for biocide and antibiotic resistance.
  4. To assess inter-species horizontal transmission of the mobile genetic elements.

Findings of objectives 1-2 will contribute to the development of infection control strategies in the context of considering their effect on antimicrobial resistance in intensive care units. Findings of objectives 3-4 will make a major contribution to characterisation of mobile genetic elements, which are a primary vehicle for spread of antimicrobial resistance.

Breadth of training - The programme will provide training in a range of transferable skills and experience that can be taken forward into several career paths. The candidate will receive exposure to the clinical setting (e.g. wards and medical microbiology diagnostic laboratories in Aberdeen, Dundee and Edinburgh). They will receive training in relevant aspects of bacteriology, molecular microbiology, statistics, bacterial genetics techniques as well as next-generation sequencing and bioinformatics. The amount of time spent outside Aberdeen will depend on the candidate’s individual circumstances.

References:

1 Review on Antimicrobial Resistance, May 2016, Chaired by Jim O’Neill, sponsored by Department of Health and Wellcome Trust. https://amr-review.org/

2 Wand ME, Bock LJ, Bonney LC, Sutton JM. Mechanisms of Increased Resistance to Chlorhexidine and Cross-Resistance to Colistin following Exposure of Klebsiella pneumoniae Clinical Isolates to Chlorhexidine. Antimicrob Agents Chemother. 2016 Dec 27;61(1).

3 Hijazi K, Mukhopadhya I, Abbott F, Milne K, Al-Jabri ZJ, Oggioni MR, Gould IM. Susceptibility to chlorhexidine amongst multidrug-resistant clinical isolates of Staphylococcus epidermidis from bloodstream infections. (2016)  Int J Antimicrob Agents. 48(1):86-90.

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