Background

Gonorrhoea is one of the most common bacterial sexually transmitted infections in England. Over 41,000 cases were recorded in 2015, more than half of which occurred in men who have sex with men (MSM). As the bacterium has developed resistance to each first-line antibiotic in turn, we need an improved understanding of fitness benefits and costs of antibiotic resistance to inform control policy and planning. Cefixime was recommended as a single-dose treatment for gonorrhoea from 2005 to 2010, during which time resistance increased, and subsequently declined.

Methods and findings

We developed a stochastic compartmental model representing the natural history and transmission of cefixime-sensitive and cefixime-resistant strains of Neisseria gonorrhoeae in MSM in England, which was applied to data on diagnoses and prescriptions between 2008 and 2015. We estimated that asymptomatic carriers play a crucial role in overall transmission dynamics, with 37% (95% credible interval CrI 24%–52%) of infections remaining asymptomatic and untreated, accounting for 89% (95% CrI 82%–93%) of onward transmission. The fitness cost of cefixime resistance in the absence of cefixime usage was estimated to be such that the number of secondary infections caused by resistant strains is only about half as much as for the susceptible strains, which is insufficient to maintain persistence. However, we estimated that treatment of cefixime-resistant strains with cefixime was unsuccessful in 83% (95% CrI 53%–99%) of cases, representing a fitness benefit of resistance. This benefit was large enough to counterbalance the fitness cost when 31% (95% CrI 26%–36%) of cases were treated with cefixime, and when more than 55% (95% CrI 44%–66%) of cases were treated with cefixime, the resistant strain had a net fitness advantage over the susceptible strain. Limitations include sparse data leading to large intervals on key model parameters and necessary assumptions in the modelling of a complex epidemiological process.

Conclusions

Our study provides, to our knowledge, the first estimates of the fitness cost and benefit associated with resistance of the gonococcus to a clinically relevant antibiotic. Our findings have important implications for antibiotic stewardship and public health policies and, in particular, suggest that a previously abandoned antibiotic could be used again to treat a minority of gonorrhoea cases without raising resistance levels.

中文翻译：

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估算淋病奈瑟氏菌对头孢克肟耐药的健身成本和益处，以为处方政策提供依据：一项模型研究

背景

淋病是英格兰最常见的细菌性传播感染之一。2015年记录了超过41,000例病例，其中一半以上发生在与男性发生性关系（MSM）的男性中。由于细菌反过来又对每种一线抗生素产生了抗药性，因此我们需要对适应性益处和抗生素抗药性的成本有更好的了解，以告知控制政策和规划。从2005年到2010年，推荐使用头孢克肟作为淋病的单剂量治疗，在此期间耐药性增加，随后下降。

方法和发现

我们开发了随机隔室模型，代表了淋病奈瑟氏菌对头孢克肟敏感和头孢克肟耐药菌株的自然历史和传播在英格兰的MSM中，该数据已应用于2008年至2015年的诊断和处方数据。我们估计无症状携带者在总体传播动态中起着至关重要的作用，感染率为37％（95％可信区间CrI为24％–52％）其余无症状且未经治疗，占继续传播的89％（95％CrI 82％–93％）。据估计，在不使用头孢克肟的情况下，头孢克肟耐药性的适应性成本应使由耐药菌株引起的继发感染数量仅为易感菌株的约一半，这不足以维持持久性。但是，我们估计在83％（95％的CrI 53％–99％）的病例中用头孢克肟治疗对头孢克肟耐药的菌株是不成功的，这代表了耐药性的健康益处。当31％（95％CrI 26％–36％）的患者接受头孢克肟治疗时，以及超过55％（95％CrI 44％–66％）的患者接受治疗时，这种好处足以抵消健身成本与头孢克肟相比，抗药性菌株比易感菌株具有净适应性优势。局限性包括稀疏数据，导致关键模型参数的间隔较大，而复杂的流行病学过程的建模则需要必要的假设。

结论

就我们所知，我们的研究提供了对淋球菌对临床相关抗生素的耐药性相关的适应性成本和收益的初步估计。我们的发现对抗生素管理和公共卫生政策具有重要意义，尤其是表明，先前放弃的抗生素可以再次用于治疗少数淋病患者，而不会提高耐药水平。