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P3.134 Modelling the dynamics of antibiotic resistance in gonorrhoea to determine fitness benefits and costs
  1. Lilith K Whittles1,
  2. Peter J White2,
  3. Xavier Didelot1
  1. 1NIHR Health Protection Research Unit In Modelling Methodology, Imperial College London, London, UK
  2. 2NIHR HPRU In Modelling Methodology, Imperial College London; National Infection Service, Phe, London, UK

Abstract

Introduction Gonorrhoea is one of the most common bacterial STI in the UK. Incidence has increased since 2008 culminating in over 41 000 cases in 2015, over 50% of which are among men who have sex with men (MSM). The bacterium has developed resistance to each frontline antibiotic in turn. Resistance to cefixime grew rapidly between its recommendation as a single-dose treatment in 2005 and removal in 2010, reaching 33% among MSM. Since prescribing has fallen, however, so has resistance. We hypothesise there is a net fitness-benefit to resistance when cefixime is widely prescribed but a net fitness-cost when prescriptions decline.

Methods A compartmental stochastic model incorporating latent, asymptomatic and symptomatic infection, with both cefixime-susceptible and resistant strains, was fitted to UK MSM incidence and prescription data over 2008–15 using particle Markov Chain Monte Carlo (pMCMC) methods. The fitness-cost of resistance was modelled as an increased natural-recovery rate from asymptomatic resistant infection; the fitness-benefit was conferred when a proportion of treatment-failures are undetected and become asymptomatic. The hypothesis was tested via 99% credible intervals and posterior-predictive testing.

Results We were able to replicate the data using model parameters based on literature-review. Our model suggests that natural-recovery from resistant gonorrhoea occurs 1.75x (99% CI: 1.57–1.87) faster than from cefixime-susceptible infection, giving resistance a fitness-cost; and 91% (99% CI: 65%–100%) of treatments of resistant cases with cefixime fail, conferring a fitness-benefit when cefixime is highly-prescribed.

Conclusion The use of state-of-the-art pMCMC methods provided significant evidence in favour of our hypothesis and insights into the dynamics of cefixime-resistance in gonorrhoea. Our findings have important implications for antibiotic stewardship and public health policies, such as targeted prescriptions and combination therapy; as well as emerging resistance through similar mechanisms to the current frontline treatment, ceftriaxone.

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