Doxycycline post exposure prophylaxis could select for cross-resistance to other antimicrobials in various pathogens: an in silico analysis

BACKGROUND: A number of randomized controlled trials have found that doxycycline post exposure prophylaxis (PEP) can reduce the incidence of gonorrhoea, chlamydia and syphilis in men who have sex with men (MSM). If tetracycline resistance is associated with resistance to other antimicrobials in a range of bacterial species, then doxycycline PEP could have the unintended effect of selecting for resistance to other antimicrobials in these bacterial species.

METHODS: Antimicrobial susceptibility data were retrieved from two sources: pubMLST (https://pubmlst.org/) and Pathogenwatch (https://pathogen.watch/) for the following bacterial pathogens: Klebsiella pneumoniae, Salmonella enterica subsp. Enterica serovar Typhi, Campylobacter jejuni, Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus pyogenes. We assessed if tetracycline resistance was associated with resistance to six relevant antimicrobials.

RESULTS: We found evidence of cross resistance to various antimicrobials in all six bacterial species assessed. Cross resistance was found in 4 of 5 antimicrobials for K. pneumoniae, 1 of 2 for C. jejuni, 3 of 5 for S. enterica subsp. Enterica serovar Typhi, 5 of 5 for S. aureus, 5 of 6 for S. pneumoniae and 2 of 3 for S. pyogenes. These associations include a higher prevalence of methicillin resistance in tetracycline resistant S. aureus, penicillin resistance in S. pneumoniae, macrolide and clindamycin resistance in S. pyogenes, fluoroquinolone resistance in S. enterica subsp. Enterica serovar Typhi and third-generation cephalosporin resistance in K. pneumoniae.

CONCLUSION: These results suggest that studies evaluating the effects of doxycycline PEP should include the effects of doxycycline on resistance not only to doxycycline but also to other antimicrobials and in a broader array of bacterial species than has been included in doxycycline PEP studies thus far.