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

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.

Phenotypic and Genotypic Characteristics of Antimicrobial Resistance in Citrobacter freundii Isolated from Domestic Ducks (Anas platyrhynchos domesticus) in Bangladesh

“…Tetracyclines are commonly used as one of the first-line antibiotics against a wide variety of non-life-threatening infections, including C. freundii infections [ 36 ]. The development of antibiotic resistance in C. freundii limits the treatment options.…”

Interim position statement on doxycycline post-exposure prophylaxis (Doxy-PEP) for the prevention of bacterial sexually transmissible infections in Australia and Aotearoa New Zealand – the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM)

“…This was highlighted in a recent systematic review, which found that oral tetracyclines for 2-18 weeks may increase AMR in subgingival, gastrointestinal and upper respiratory tract flora. 25 The USA Doxy-PEP study assessed AMR in nasal/oropharyngeal Staphylococcus aureus and pharyngeal non-gonococcal Neisseria species among 501 participants, and at month 12 found that participants on Doxy-PEP had lower carriage of S.aureus, compared with participants not on Doxy-PEP (29.2% vs 45.2%, P = 0.036), but a greater proportion of S. aureus culture samples were doxycycline resistant in the Doxy-PEP arm (11.7% vs 4.8%, P = 0.19). They found no increase in methicillin-resistant S. aureus (MRSA) overall, nor in doxycycline-resistant MRSA.…”

Neuroprotective Effects of a Novel Demeclocycline Derivative Lacking Antibiotic Activity: From a Hit to a Promising Lead Compound

“…However, the antibiotic activity of DMC strongly decreases its potential for long-term treatments, such as those required for PD and other synucleinopathies. A systematic revision of oral tetracycline administration during 2–18 weeks showed an increase in antibiotic resistance in subgingival, gastrointestinal, and upper respiratory tract flora [ 14 ]. It is relevant to consider that the frequency of microbial antibiotic resistance continues to increase and has emerged as one of the most critical problems in medicine.…”