A systematic review of the impacts of oral tetracycline class antibiotics on antimicrobial resistance in normal human flora

• Published in: JAC-antimicrobial resistance 2022-03, Vol.4 (1), p.dlac009-dlac009
• Main Authors: Truong, Robinson, Tang, Vincent, Grennan, Troy, Tan, Darrell H S
• Format: Article
• Language: English
• Subjects: Systematic Review
• ISSN: 2632-1823; 2632-1823
• DOI: 10.1093/jacamr/dlac009

There is interest in doxycycline as prophylaxis against sexually transmitted infections (STIs), but concern about antimicrobial resistance (AMR). We conducted a systematic review (CRD42021273301) of the impact of oral tetracycline-class antibiotics on AMR in normal flora. We searched MEDLINE, EMBASE, the Cochrane Library (1940-2021) and conference proceedings (2014-21) for randomized controlled trials in adults comparing daily oral tetracycline-class antibiotics to non-tetracycline controls. The primary outcome was AMR to tetracyclines; secondary outcomes included resistance to non-tetracyclines. Data were inappropriate for meta-analysis, so we analysed findings descriptively. Our search yielded 6265 abstracts of which 7 articles fulfilled inclusion criteria. Most were at moderate/high risk of bias, generally due to inadequate methodologic reporting. Studies used doxycycline, tetracycline, oxytetracycline or minocycline for 2-18 weeks. Most observed an increased burden of tetracycline resistance, including in subgingival ( = 3 studies), gastrointestinal ( = 2) and upper respiratory tract ( = 1) flora; one study of skin flora found no change in tetracycline-resistant species after 18 weeks of oxytetracycline/minocycline. Four studies reassessed AMR at 2-50 weeks post-intervention and reported varying degrees of resistance. Three articles reported on the prevalence of non-tetracycline AMR after doxycycline prophylaxis, of which one found a transient increase among gastrointestinal ; the other two showed no difference from control. Although the effects are modest and transient, limited data from small prospective studies may suggest that oral tetracyclines for 2-18 weeks increase resistance in subgingival, gastrointestinal and upper respiratory tract flora. STI prophylaxis trials should include AMR in commensal bacteria as study outcomes.