Estimating the fitness cost and benefit of cefixime resistance in Neisseria gonorrhoeae to inform prescription policy: A modelling study.
估计头孢克肟耐药性在淋病奈瑟菌中的适应度成本和收益,以告知处方政策: 一项建模研究。


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.


背景: 淋病是英国最常见的细菌性性传播感染之一。2015年记录了 41,000 多例病例,其中一半以上发生在男男性行为者 (MSM)。由于细菌依次对每一种一线抗生素产生了耐药性,我们需要更好地了解抗生素耐药性的健康效益和成本,以告知控制政策和规划。从 2005年到 2010年,头孢克肟被推荐作为淋病的单剂量治疗,在此期间耐药性增加,随后下降。方法和结果: 我们开发了一个随机隔室模型,该模型代表了英国 MSM 中淋病奈瑟菌的头孢克肟敏感和头孢克肟抗性菌株的自然历史和传播, 该数据应用于 2008年至 2015 间的诊断和处方数据。我们估计无症状携带者在整体传播动态中起着至关重要的作用,37% (95% 可信区间 CrI 24%-52%) 的感染仍然无症状且未治疗, 占向前传输的 89% (95% CrI 82%-93%)。在没有使用头孢克肟的情况下,头孢克肟耐药性的适应成本估计是由耐药菌株引起的二次感染数量只有敏感菌株的一半左右, 这不足以保持持久性。然而,我们估计,在 83% (95% CrI 53%-99%) 的病例中,用头孢克肟治疗头孢克肟抗性菌株是不成功的,这代表了抗性的健康益处。当 31% (95% CrI 26%-36%) 的病例用头孢克肟治疗,当超过 55% (95% CrI 44%-66%) 时,这种益处足以抵消健康成本在用头孢克肟治疗的病例中,耐药菌株比敏感菌株具有净适应性优势。局限性包括数据稀疏导致关键模型参数的大间隔以及复杂流行病学过程建模中的必要假设。结论: 据我们所知,我们的研究提供了与淋球菌对临床相关抗生素的耐药性相关的适应度成本和收益的首次估计。我们的发现对抗生素管理和公共卫生政策具有重要意义,特别是表明以前放弃的抗生素可以再次用于治疗少数淋病病例,而不会提高耐药性水平。


呼吸 头孢菌素类药物 药物
概述  :  

药物概述头孢克肟为口服第三代头孢菌素,抗菌谱广,抗菌活性强,尤其对多数肠杆菌科细菌有较强活性,优于头孢克洛、头孢氨苄和头孢羟氨苄。金黄色葡萄球菌、表皮葡萄球菌、肠球菌属及青霉素耐药肺炎球菌一般对本品耐药,铜绿假单胞菌、不动杆菌属、无色杆菌属、黄杆菌属、梭杆菌属等也均耐药,类杆菌属和消化链球菌也多对本品耐药。适用于敏感菌引起的呼吸道、泌尿系统、胆道感染,猩红热及耳鼻喉感染。口服:成人 400mg,qd,或200mg,bid;治疗单纯性尿路感染用400mg单剂即可。儿童 8mg/(kg·d

Cefixime   /sefə'leksɪn/

释    义   头孢克肟

例    句   The methods is reliable and accurate, it can be used for quality control the cefixime buccal tablets. 该方法可靠精准,可用于头孢克肟口含片的质量控制。