Tetracycline-resistant global estimates-impacts on doxycycline post-exposure prophylaxis implementation and monitoring: a systematic review.

Objectives: Doxycycline post-exposure prophylaxis (doxyPEP) can reduce incident sexually transmitted infections including gonorrhoea for MSM and transgender women. Its effectiveness depends on the level of tetracycline resistance in , which varies by country. Countries implementing doxyPEP should have robust antimicrobial resistance (AMR) surveillance using standardized, quality-assured methods. This systematic review estimates the proportion of tetracycline-resistant isolates by country/region and describes the contribution of sex and infection site to these estimates.

Methods: We searched bibliographic databases (1 January 2000 to 26 August 2024) for English-language studies reporting tetracycline MIC with a sample size of >10 isolates. Data on country, year, sex, sexual orientation and infection site were collected. Countries were grouped into seven World Bank regions. Tetracycline resistance (MIC > 1 mg/L) was reported by country, region and time period (2010-23 versus 1996-2009).

Results: Sixty-seven included studies from 51 countries studying 80 645 isolates (91% from 2010-23) were analysed. Overall median tetracycline resistance was 54.2% (range 4.0%-100.0%). Highest resistance occurred in East Asia and Pacific (82.1%, 18%-100%) and sub-Saharan Africa (81.6%, 44%-100%), and lowest in North America (26.5%, 4%-78%). Only 16% (11/67) of studies reported MSM, 18% (12/67) included oropharyngeal isolates and 9% (6/67) included women. Resistance increased by 3-4-fold in South Asia [relative risk (RR) 3.8] and North America (RR 4.1) over time.

Conclusions: High and rising tetracycline resistance limits doxyPEP's potential to prevent gonorrhoea. More data are needed from MSM, women and oropharyngeal sites to understand AMR trends and transmission dynamics between MSM and women.