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. 2020 Oct;25(43):1900210.
doi: 10.2807/1560-7917.ES.2020.25.43.1900210.

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

Carolin Vegvari  1 , Yonatan H Grad  2   3 , Peter J White  1   4   5 , Xavier Didelot  1   4   6 , Lilith K Whittles  1   4 , Nicole E Scangarella-Oman  7 , Fanny S Mitrani-Gold  7 , Etienne Dumont  7 , Caroline R Perry  7 , Kim Gilchrist  7   8 , Mohammad Hossain  7 , Tatum D Mortimer  2 , Roy M Anderson  1 , David Gardiner  7
Affiliations

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

Carolin Vegvari et al. Euro Surveill. 2020 Oct.

Erratum in

  • Erratum for Euro Surveill. 2020;25(43).
    Eurosurveillance editorial team. Eurosurveillance editorial team. Euro Surveill. 2020 Nov;25(45):2011127. doi: 10.2807/1560-7917.ES.2020.25.45.2011127. Euro Surveill. 2020. PMID: 33183409 Free PMC article. No abstract available.

Abstract

BackgroundThe 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.AimTo investigate how POCTs detecting Neisseria gonorrhoeae resistance mutations for ciprofloxacin and gepotidacin can be used to minimise the risk of resistance development to gepotidacin.MethodsWe use individual-based stochastic simulations to formally investigate the aim.ResultsThe 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%.ConclusionMutation 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.

Keywords: antibiotic resistance; antibiotic use; antimicrobial resistance; bacterial infections; epidemiology; gonorrhoea; modelling; molecular methods; multidrug resistance; point-of-care tests; sexually transmitted infections.

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Conflict of interest statement

Conflict of interest: PJW, XD, LKW and TDM have no competing interests and have received no funding from GSK for this work. CV received funding from GSK for this work. NESO, FSMG, ED, CRP, MH, DG are employees of GSK. RMA was a non-executive board member of GSK till June 2018. YHG has consulted for GSK. KG is an employee for Pfizer and was formerly an employee of GSK.

Figures

Figure 1
Figure 1
Two-locus gonorrhoea antibiotic resistance model
Figure 2
Figure 2
Proportion of simulations in which the frequency of gepotidacin-resistant strains reaches 5% with different mutation rates, prevalence of parC D86N and POCT usage levels
See this image and copyright information in PMC

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