Antimicrobial susceptibility characterisation of legionella in patients and the environment

Portal, Edward 2022. Antimicrobial susceptibility characterisation of legionella in patients and the environment. PhD Thesis, Cardiff University. Item availability restricted.

Preview	PDF (PhD Thesis) - Accepted Post-Print Version Download (15MB) | Preview
	PDF (Cardiff University Electronic Publication Form) - Supplemental Material Restricted to Repository staff only Download (1MB)

Abstract

Legionella causing legionnaires disease is a global health concern affecting thousands of people every year and the treatment requires antibiotics, usually fluoroquinolones or macrolides. As we approach a post antibiotic era, in which common infection treatments and prevention are rendered ineffective, a detailed investigation into the Legionella with regard to their susceptibility was lacking. Investigative MIC in Legionella required development of a novel media, due to the unsuitability and lack of concordance between currently available media. During this project, LASARUS (Legionella Antimicrobial Susceptibility and Universal Screening) media was developed, a clear solid agar lacking the chelating effects of prior solid media. This media was subsequently patented, validated against other MIC methods and published. Using LASARUS, 2,100 isolates from the UKHSA archive were screened for susceptibility against a panel of eight antibiotics, with a wide range of modes of action, to determine a baseline of susceptibility from which ECOFF (Epidemiological Cut Off) values could be determined. Once a base line of susceptibility was available it then became possible to select for resistant isolates and the mechanism of resistance. This screening found very few cases of resistance and where it was present, usually to a macrolide, mediated by lpeAB an efflux pump. A dual beta-lactamase (loxA and blaoxa29) that in combination counter-intuitively reduced resistance to ampicillin, was also found. This project led to the publication of an international position paper, which delineates for the first time the guidance for antimicrobial susceptibility testing in Legionella spp. with a specific focus on normalising the methodologies to correlate to the gold standard of broth microdilution (BMD) and for cessation of use of methods, which fail to correlate with BMD.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Medicine
Date of First Compliant Deposit:	20 May 2022
Last Modified:	17 May 2023 01:30
URI:	https://orca.cardiff.ac.uk/id/eprint/149819

Actions (repository staff only)

Edit Item