Roster Kirstin I Oliveira, Mittelstaedt Rachel, Reyes Jordan, Aatresh Aishani V, Grad Yonatan H
Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA.
Center for Communicable Disease Dynamics, Harvard T.H. Chan School of Public Health, Boston, MA.
medRxiv. 2024 May 7:2024.05.07.24306823. doi: 10.1101/2024.05.07.24306823.
Doxycycline post-exposure prophylaxis (Doxy-PEP) reduces bacterial sexually transmitted infections (STIs) but may select for tetracycline resistance in Neisseria gonorrhoeae and co-resistance to other antibiotics, including ceftriaxone.. The implementation of doxy-PEP should be accompanied by monitoring doxycycline resistance, but the optimal strategy to detect changes in the prevalence of resistance has not been established. We used a deterministic compartmental model of gonorrhea transmission to evaluate the performance of two strategies in providing early warning signals for rising resistance: (1) phenotypic testing of cultured isolates and (2) PCR for tetM in remnants from positive Nucleic Acid Amplification Tests (NAATs) used for gonorrhea diagnosis. For each strategy, we calculated the resistance proportion with 90% simulation intervals as well as the time under each sampling strategy to achieve 95% confidence that the resistance proportion exceeded a resistance threshold ranging from 11-30%. Given the substantially larger available sample size, PCR for tetM in remnant NAATs detected increased high-level tetracycline resistance with high confidence faster than phenotypic testing of cultured specimens. Our results suggest that population surveillance using molecular testing for tetM can complement culturebased surveillance of tetracycline resistance in N. gonorrhoeae and inform policy considerations for doxy-PEP.
多西环素暴露后预防(Doxy-PEP)可降低细菌性性传播感染(STIs),但可能会导致淋病奈瑟菌对四环素产生耐药性,并对包括头孢曲松在内的其他抗生素产生共同耐药性。实施Doxy-PEP应同时监测多西环素耐药性,但尚未确定检测耐药性流行率变化的最佳策略。我们使用淋病传播的确定性分区模型来评估两种策略在为耐药性上升提供早期预警信号方面的表现:(1)对培养分离株进行表型检测,以及(2)对用于淋病诊断的阳性核酸扩增试验(NAATs)剩余样本进行tetM基因的聚合酶链反应(PCR)检测。对于每种策略,我们计算了耐药比例及其90%的模拟区间,以及在每种采样策略下达到95%置信度(即耐药比例超过11%-30%的耐药阈值)所需的时间。鉴于可获得的样本量大幅增加,对NAATs剩余样本进行tetM基因的PCR检测比培养标本的表型检测能更快、更有把握地检测到高水平四环素耐药性的增加。我们的结果表明,使用tetM分子检测进行人群监测可以补充基于培养的淋病奈瑟菌四环素耐药性监测,并为Doxy-PEP的政策考量提供参考。