Resistance-minimising strategies for introducing a novel antibiotic for gonorrhoea treatment: a mathematical modelling study

• Published in: The Lancet. Microbe 2023-10, Vol.4 (10), p.e781-e789
• Main Authors: Reichert, Emily, Yaesoubi, Reza, Rönn, Minttu M, Gift, Thomas L, Salomon, Joshua A, Grad, Yonatan H
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Ceftriaxone - therapeutic use; Gonorrhea - drug therapy; Gonorrhea - epidemiology; Gonorrhea - prevention & control; Homosexuality, Male; Humans; Male; Sexual and Gender Minorities
• ISSN: 2666-5247; 2666-5247
• DOI: 10.1016/S2666-5247(23)00145-3

Gonorrhoea is a highly prevalent sexually transmitted infection and an urgent public health concern because of increasing antibiotic resistance in Neisseria gonorrhoeae. Only ceftriaxone remains as the recommended treatment in the USA. With the prospect of new anti-gonococcal antibiotics being approved, we aimed to evaluate how to deploy a new drug to maximise its clinically useful lifespan. We used a compartmental model of gonorrhoea transmission in a US population of men who have sex with men (MSM) to compare strategies for introducing a new antibiotic for gonorrhoea treatment. The MSM population was stratified into three sexual activity groups (low, intermediate, and high) characterised by annual rates of partner change. The four introduction strategies tested were: (1) random 50–50 allocation, where each treatment-seeking infected individual had a 50% probability of receiving either drug A (current drug; a ceftriaxone-like antibiotic) or drug B (a new antibiotic), effective at time 0; (2) combination therapy of both the current drug and the new antibiotic; (3) reserve strategy, by which the new antibiotic was held in reserve until the current therapy reached a 5% threshold prevalence of resistance; and (4) gradual switch, or the gradual introduction of the new drug until random 50–50 allocation was reached. The primary outcome of interest was the time until 5% prevalence of resistance to each of the drugs (the new drug and the current ceftriaxone-like antibiotic); sensitivity of the primary outcome to the properties of the new antibiotic, specifically the probability of resistance emergence after treatment and the fitness costs of resistance, was explored. Secondary outcomes included the time to a 1% resistance threshold for each drug, as well as population-level prevalence, mean and range annual incidence, and the cumulative number of incident gonococcal infections. Under baseline model conditions, a 5% prevalence of resistance to each of drugs A and B was reached within 13·9 years with the reserve strategy, 18·2 years with the gradual switch strategy, 19·2 years with the random 50–50 allocation strategy, and 19·9 years with the combination therapy strategy. The reserve strategy was consistently inferior for mitigating antibiotic resistance under the parameter space explored and was increasingly outperformed by the other strategies as the probability of de novo resistance emergence decreased and as the fitness costs associated with resistance increase