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Using rapid point-of-care tests to inform antibiotic choice to mitigate drug resistance in gonorrhoea

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Vegvari, Carolin, Grad, Yonatan H., White, Peter J., Didelot, Xavier, Whittles, Lilith K., Scangarella-Oman, Nicole E., Mitrani-Gold, Fanny S., Dumont, Etienne, Perry, Caroline R., Gilchrist, Kim, Hossain, Mohammad, Mortimer, Tatum D., Anderson, Roy M. and Gardiner, David (2020) Using rapid point-of-care tests to inform antibiotic choice to mitigate drug resistance in gonorrhoea. Eurosurveillance, 25 (43). doi:10.2807/1560-7917.ES.2020.25.43.1900210

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Official URL: http://dx.doi.org/10.2807/1560-7917.ES.2020.25.43....

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Abstract

Background:
The first cases of extensively drug resistant gonorrhoea were recorded in the United Kingdom in 2018. There is a public health need for strategies on how to deploy existing and novel antibiotics to minimise the risk of resistance development. As rapid point-of-care tests (POCTs) to predict susceptibility are coming to clinical use, coupling the introduction of an antibiotic with diagnostics that can slow resistance emergence may offer a novel paradigm for maximising antibiotic benefits. Gepotidacin is a novel antibiotic with known resistance and resistance-predisposing mutations. In particular, a mutation that confers resistance to ciprofloxacin acts as the ‘stepping-stone’ mutation to gepotidacin resistance.

Aim:
To investigate how POCTs detecting Neisseria gonorrhoeae resistance mutations for ciprofloxacin and gepotidacin can be used to minimise the risk of resistance development to gepotidacin.

Methods:
We use individual-based stochastic simulations to formally investigate the aim.

Results:
The level of testing needed to reduce the risk of resistance development depends on the mutation rate under treatment and the prevalence of stepping-stone mutations. A POCT is most effective if the mutation rate under antibiotic treatment is no more than two orders of magnitude above the mutation rate without treatment and the prevalence of stepping-stone mutations is 1–13%.

Conclusion:
Mutation frequencies and rates should be considered when estimating the POCT usage required to reduce the risk of resistance development in a given population. Molecular POCTs for resistance mutations and stepping-stone mutations to resistance are likely to become important tools in antibiotic stewardship.

Item Type: Journal Article
Subjects: Q Science > QR Microbiology
R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculty of Science > Life Sciences (2010- )
Faculty of Science > Statistics
Library of Congress Subject Headings (LCSH): Neisseria gonorrhoeae , Ciprofloxacin, Gonorrhea, Drug resistance in microorganisms, Antibiotics
Journal or Publication Title: Eurosurveillance
Publisher: Centre European pour la Surveillance Epidemiologique du SIDA
ISSN: 1560-7917
Official Date: 29 October 2020
Dates:
DateEvent
29 October 2020Published
1 May 2020Accepted
Volume: 25
Number: 43
DOI: 10.2807/1560-7917.ES.2020.25.43.1900210
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
HHSO100201300011CBiomedical Advanced Research and Development Authorityhttp://dx.doi.org/10.13039/100012399
UNSPECIFIEDGlaxoSmithKlinehttp://dx.doi.org/10.13039/100004330
HPRU-2012-10080[NIHR] National Institute for Health Researchhttp://dx.doi.org/10.13039/501100000272
MR/R015600/1[MRC] Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
F32AI145157Richard and Susan Smith Family Foundationhttp://dx.doi.org/10.13039/100001341

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