Kline Madeleine C, Roster Kirstin Oliveira, Helekal David, Rumpler Eva, Grad Yonatan H
Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Center for Communicable Disease Dynamics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
medRxiv. 2025 Jul 3:2025.07.01.25330638. doi: 10.1101/2025.07.01.25330638.
Drug resistance in is an urgent public health threat. The anticipated approval of two new antimicrobials for gonorrhea prompts the need for evidence-based rollout strategies that minimize drug resistance.
We used a stochastic compartmental model of men who have sex with men (MSM) in the United States (U.S.) to compare two main strategies-equal allocation and sequential drug deployment-for two new and one existing drug and measured the time for each drug to reach a resistance prevalence threshold of 5%. We conducted broad analyses assessing the sensitivity of our results to wide variation in parameters governing the baseline behavior of the model and drug resistance evolution and fitness.
Compared to the equal allocation strategy, the sequential strategy had reached the resistance prevalence threshold i) for each drug individually in at least as many simulations; ii) for all three drugs in at least as many simulations; and iii) for at least as many drugs on average. After 10 years, no equal allocation strategy simulations had met the 5% resistance prevalence threshold for any of the drugs, whereas 99.6% of sequential simulations had for the first drug, of which 3.5% had also met the threshold for the second drug. The sequential strategy was worse for nearly every reasonable combination of model parameters.
In a model of U.S. MSM, the equal allocation strategy for introducing new drugs for gonorrhea matched or outperformed the strategy of sequential introduction in terms of resistance prevalence.
淋病的耐药性是一项紧迫的公共卫生威胁。两种新型抗淋病药物预计将获批,这促使我们需要基于证据的推广策略,以尽量减少耐药性。
我们使用了一个美国男男性行为者(MSM)的随机分区模型,来比较两种主要策略——均等分配和序贯药物部署——针对两种新药和一种现有药物,并测量每种药物达到5%耐药率阈值所需的时间。我们进行了广泛分析,评估结果对控制模型基线行为以及耐药性演变和适应性的参数的广泛变化的敏感性。
与均等分配策略相比,序贯策略在以下方面达到了耐药率阈值:i)在至少同样多的模拟中,每种药物单独达到阈值;ii)在至少同样多的模拟中,所有三种药物都达到阈值;iii)平均而言,至少有同样多的药物达到阈值。10年后,没有均等分配策略的模拟达到任何一种药物5%的耐药率阈值,而99.6%的序贯模拟中第一种药物达到了该阈值,其中3.5%的模拟中第二种药物也达到了该阈值。对于几乎每一种合理的模型参数组合,序贯策略的效果都更差。
在美国男男性行为者模型中,就耐药率而言,淋病新药引入的均等分配策略与序贯引入策略相当或更优。