Vanbaelen Thibaut, Manoharan-Basil Sheeba Santhini, Kenyon Chris
STI Unit, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, 2000, Belgium.
Division of Infectious Diseases and HIV Medicine, University of Cape Town, Cape Town, 7700, South Africa.
Curr Res Microb Sci. 2024 Apr 8;6:100234. doi: 10.1016/j.crmicr.2024.100234. eCollection 2024.
Two recently published randomized trials of doxycycline post exposure prophylaxis (PEP) have concluded that this intervention is highly effective at reducing the incidence of bacterial sexually transmitted infections (STIs) and has little or no risk of promoting the spread of antimicrobial resistance (AMR). In this perspective piece, we review four types of evidence that suggest that the risk of promoting AMR has been inadequately assessed in these studies. 1) The studies have all used proportion resistant as the outcome measure. This is a less sensitive measure of resistogenicity than MIC distribution. 2) These RCTs have not considered population-level pathways of AMR selection. 3) In populations with very high antimicrobial consumption such as PrEP cohorts, the relationship between antimicrobial consumption and resistance may be saturated. 4) Genetic linkage of AMR means that increased tetracycline use may select for AMR to not only tetracyclines but also other antimicrobials in STIs and other bacterial species. We recommend novel study designs to more adequately assess the AMR-inducing risk of doxycycline PEP.
最近发表的两项关于多西环素暴露后预防（PEP）的随机试验得出结论，这种干预措施在降低细菌性性传播感染（STIs）发病率方面非常有效，并且几乎没有促进抗菌药物耐药性（AMR）传播的风险。在这篇观点文章中，我们回顾了四类证据，这些证据表明在这些研究中对促进AMR的风险评估不足。1）这些研究都使用耐药比例作为结果指标。这是一种比最低抑菌浓度（MIC）分布对耐药性诱导性更低敏的测量方法。2）这些随机对照试验（RCTs）没有考虑AMR选择的人群水平途径。3）在像暴露前预防（PrEP）队列这样抗菌药物消耗量非常高的人群中，抗菌药物消耗与耐药性之间的关系可能已达到饱和。4）AMR的基因连锁意味着增加四环素的使用可能不仅会选择对四环素耐药，还会选择对性传播感染和其他细菌物种中的其他抗菌药物耐药。我们建议采用新的研究设计，以更充分地评估多西环素PEP诱导AMR的风险。
