Impact of commonly used antimicrobial biocides on resistance and cross-resistance in carbapenemase-producing Enterobacteriaceae

Herault, Helene Sandra Sophie 2019. Impact of commonly used antimicrobial biocides on resistance and cross-resistance in carbapenemase-producing Enterobacteriaceae. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Infections due to multi-drug resistant organisms (MDROs) are a major concern worldwide. With very few new antibiotics on the market, infection prevention and control measures, including the use of biocides, are paramount to limit the spread of MDROs. Little is known about the impact of biocide overuse and the selective pressure they exert on adaptive mechanisms (co-selection) within bacteria. This study evaluated the effects of biocides commonly used in the UK on antibiotic susceptibility and on the mechanisms they might trigger within carbapenemase-producing Enterobacteriaceae (CPE). The minimum inhibitory concentrations (MICs) of a wide range of antibiotics and four biocides (benzalkonium chloride, chlorhexidine digluconate [CHX], copper sulphate and silver nitrate) were determined for multi-drug resistant, carbapenemase-producing Escherichia coli and Klebsiella pneumoniae isolates collected from UK hospitals. Regarding biocides, MICs were found to be much lower than in-use concentrations found in most commercial products (e.g. CHX MICs: 0.5-16 μg/mL; CHX concentration in a skin decontamination product: 40,000 μg/mL). Correlation were detected between antibiotic and biocide MICs, especially between CHX and carbapenems, cephalosporins, ciprofloxacin and tetracycline in K. pneumoniae. Exposure to CHX for 50 strains led to increased lag phase duration and changes in growth rate. Addition of efflux-pump inhibitor reduced the CHX MICs. These findings seemed to indicate the involvement of efflux in reduced susceptibility to CHX and antibiotics. Overexpression of efflux-related genes (acrB, extruding a wide range of antibiotics; smvA, for cationic compounds) was observed following exposure to sub-MIC CHX concentrations for two K. pneumoniae isolates. However, the molecular changes did not necessarily translate at the phenotypical level, with unchanged susceptibility towards CHX and several antibiotics. This work highlighted the involvement of efflux pumps following CHX exposure in CPE; while it did not result in reduced susceptibility to antimicrobials, precautions should still be taken, considering the extensive use of biocides.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Pharmacy
Subjects:	Q Science > Q Science (General)
Date of First Compliant Deposit:	21 April 2020
Last Modified:	06 Jan 2021 02:25
URI:	https://orca.cardiff.ac.uk/id/eprint/131107

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