Antimicrobial Resistance (AMR) Consequences of the use of Doxycycline for Prevention of Bacterial Sexually Transmitted Infections (STIs): A Systematic Review.

BACKGROUND: Canada has experienced rising rates of bacterial sexually transmitted infections (STIs)-notably syphilis, chlamydia, and gonorrhoea-over the past two decades, especially among gay, bisexual, and other men who have sex with men. Doxycycline pre- and post-exposure prophylaxis (Doxy-PrEP/PEP) has emerged as a potential prevention strategy. However, concerns about antimicrobial resistance (AMR) have prompted further investigation. METHODS: We conducted a systematic review of English-language studies (2013-2023) using PubMed, Embase, Cochrane, and MedRxiv. We included randomized controlled trials (RCTs), cohort, case-control, ecological studies, and systematic reviews that reported on prolonged or recurrent doxycycline use for any indication across all populations. Data were summarized descriptively due to heterogeneity, and risk of bias and GRADE assessments were conducted to rate level of evidence. RESULTS: Sixteen studies across 17 publications met inclusion criteria. Included studies comprised two systematic reviews, eight RCTs, three cohort studies, two cross-sectional studies, and one modeling study. Seven studies assessed tetracycline/doxycycline resistance in STI pathogens and 12 focused on non-STI organisms. Findings were mixed with some studies reporting increased resistance, others minimal or no change. N. gonorrhoeae showed high baseline doxycycline resistance. Evidence on resistance in skin and gut flora was limited and inconsistent, and no clear pattern of co-resistance to other antimicrobials was found. Overall, the quality of evidence was low to very low. CONCLUSION: Evidence on AMR risks from Doxy-PrEP/PEP published up to 2023 was limited and uncertain. Findings are inconsistent and underpowered and emerging evidence could change these conclusions.