45 years of tetracycline post exposure prophylaxis for STIs and the risk of tetracycline resistance a systematic review and meta-analysis

There is considerable interest in the use of doxycycline post exposure prophylaxis (PEP) to reduce the incidence
of bacterial sexually transmitted infections (STIs). An important concern is that this could select for tetracycline
resistance in these STIs and other species. We searched PubMed and Google Scholar, (1948–2023) for randomized
controlled trials comparing tetracycline PEP with non-tetracycline controls. The primary outcome was antimicrobial
resistance (AMR) to tetracyclines in all bacterial species with available data. Our search yielded 140 studies, of which
three met the inclusion criteria. Tetracycline PEP was associated with an increased prevalence of tetracycline resist‑
ance in Neisseria gonorrhoeae, but this efect was not statistically signifcant (Pooled OR 2.3, 95% CI 0.9-3.4). PEP had
a marked efect on the N. gonorrhoeae tetracycline MIC distribution in the one study where this was assessed. Pro‑
phylactic efcacy was 100% at low MICs and 0% at high MICs. In the one study where this was assessed, PEP resulted
in a signifcant increase in tetracycline resistance in commensal Neisseria species compared to the control group (OR
2.9, 95% CI 1.5-5.5) but no signifcant efect on the prevalence of tetracycline resistance in Staphylococcus aureus. The
available evidence suggests that PEP with tetracyclines could be associated with selecting tetracycline resistance in N.
gonorrhoeae and commensal Neisseria species