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

Robinson Truong; Vincent Tang; Troy Grennan; Darrell H S Tan

doi:10.1093/jacamr/dlac009

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

JAC Antimicrob Resist. 2022 Feb 15;4(1):dlac009. doi: 10.1093/jacamr/dlac009. eCollection 2022 Mar.

Authors

Robinson Truong^{1

2}, Vincent Tang¹, Troy Grennan^{3

4}, Darrell H S Tan^{1

2

5

6}

Affiliations

¹ Faculty of Medicine, University of Toronto, 1 King's College Cir, Toronto, ON M5S 1A8, Canada.
² Centre for Urban Health Solutions, St. Michael's Hospital, 209 Victoria St, Toronto, ON M5B 1T8, Canada.
³ BC Centre for Disease Control, 655 West 12th Avenue, Vancouver, BC V5Z 4R4, Canada.
⁴ Division of Infectious Diseases and Department of Medicine, University of British Columbia, 317-2194 Health Sciences Mall, Vancouver, BC V6 T 1Z3, Canada.
⁵ Division of Infectious Diseases, St. Michael's Hospital, 36 Queen St E, Toronto, ON M5B 1W8, Canada.
⁶ Department of Medicine, St. Michael's Hospital, 36 Queen St E, Toronto, ON M5B 1W8, Canada.

Abstract

Objectives: 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.

Methods: 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.

Results: 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 (n = 3 studies), gastrointestinal (n = 2) and upper respiratory tract (n = 1) flora; one study of skin flora found no change in tetracycline-resistant Propionibacterium 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 Escherichia coli; the other two showed no difference from control.

Conclusions: 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.

Publication types

Review