Fingerhuth Stephanie M, Bonhoeffer Sebastian, Low Nicola, Althaus Christian L
Institute of Integrative Biology, ETH Zurich, Zurich, Switzerland.
Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland.
PLoS Pathog. 2016 May 19;12(5):e1005611. doi: 10.1371/journal.ppat.1005611. eCollection 2016 May.
The sexually transmitted bacterium Neisseria gonorrhoeae has developed resistance to all antibiotic classes that have been used for treatment and strains resistant to multiple antibiotic classes have evolved. In many countries, there is only one antibiotic remaining for empirical N. gonorrhoeae treatment, and antibiotic management to counteract resistance spread is urgently needed. Understanding dynamics and drivers of resistance spread can provide an improved rationale for antibiotic management. In our study, we first used antibiotic resistance surveillance data to estimate the rates at which antibiotic-resistant N. gonorrhoeae spread in two host populations, heterosexual men (HetM) and men who have sex with men (MSM). We found higher rates of spread for MSM (0.86 to 2.38 y-1, mean doubling time: 6 months) compared to HetM (0.24 to 0.86 y-1, mean doubling time: 16 months). We then developed a dynamic transmission model to reproduce the observed dynamics of N. gonorrhoeae transmission in populations of heterosexual men and women (HMW) and MSM. We parameterized the model using sexual behavior data and calibrated it to N. gonorrhoeae prevalence and incidence data. In the model, antibiotic-resistant N. gonorrhoeae spread with a median rate of 0.88 y-1 in HMW and 3.12 y-1 in MSM. These rates correspond to median doubling times of 9 (HMW) and 3 (MSM) months. Assuming no fitness costs, the model shows the difference in the host population's treatment rate rather than the difference in the number of sexual partners explains the differential spread of resistance. As higher treatment rates result in faster spread of antibiotic resistance, treatment recommendations for N. gonorrhoeae should carefully balance prevention of infection and avoidance of resistance spread.
性传播细菌淋病奈瑟菌已对所有曾用于治疗的抗生素类别产生耐药性,并且对多种抗生素类别耐药的菌株也已出现。在许多国家,用于淋病奈瑟菌经验性治疗的抗生素仅剩一种,因此迫切需要进行抗生素管理以应对耐药性传播。了解耐药性传播的动态和驱动因素可为抗生素管理提供更合理的依据。在我们的研究中,我们首先利用抗生素耐药性监测数据来估计耐抗生素淋病奈瑟菌在两个宿主群体(异性恋男性和男男性行为者)中的传播速率。我们发现,与异性恋男性(传播速率为0.24至0.86年 -1,平均倍增时间:16个月)相比,男男性行为者的传播速率更高(0.86至2.38年 -1,平均倍增时间:6个月)。然后,我们建立了一个动态传播模型,以再现淋病奈瑟菌在异性恋男性和女性群体以及男男性行为者群体中的传播动态。我们使用性行为数据对模型进行参数化,并根据淋病奈瑟菌的流行率和发病率数据进行校准。在模型中,耐抗生素淋病奈瑟菌在异性恋男性和女性群体中的传播中位数速率为0.88年 -1,在男男性行为者中的传播中位数速率为3.12年 -1。这些速率对应的中位数倍增时间分别为9个月(异性恋男性和女性群体)和3个月(男男性行为者)。假设不存在适应性代价,该模型表明宿主群体的治疗率差异而非性伴侣数量差异解释了耐药性的差异传播。由于较高的治疗率会导致抗生素耐药性传播更快,淋病奈瑟菌的治疗建议应仔细权衡感染预防和耐药性传播避免之间的关系。