LAUSR

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.