Background:
Doxycycline post-exposure prophylaxis (doxy-PEP) is highly effective in reducing N. gonorrhoeae (GC), C. trachomatis (CT), and syphilis among men who have sex with men (MSM) and transgender women (TGW). Understanding the effect of doxy-PEP use on antimicrobial resistance (AMR) in N.gonorrhoeae and bacteria which can cause disease (S.aureus) or transmit resistance (Neisseria spp) is unknown.
Methods:
DoxyPEP is a randomized open-label trial among MSM/TGW living with HIV or on PrEP with GC, CT, or early syphilis in the past year; participants were randomized 2:1 to 200 mg doxycycline within 72 hours of condomless sex or no doxycycline (SOC). At months 0 (M0) and 12 (M12), nasal/oropharyngeal swabs were cultured for S. aureus (SA) with doxycycline resistance (doxy-R) defined as MIC ≥16 µg/ml by E-test and oropharyngeal swabs cultured for commensal Neisseria (doxy-R: MIC ≥2 µg/ml by E-test). Participants with a positive GC test were instructed to return for swabs for GC culture through the CDC SURRG program (TCN-R: MIC≥2.0 µg/ml by agar dilution). Overall proportion with growth or AMR at M12 were compared by Fisher’s exact test.
Results:
Of 501 participants as of May 2022, S.aureus was cultured at M0 in 44.2% and doxy-R SA in 6.3% (Table). At M12, S.aureus was cultured from 29.2% in the doxy-PEP arm and 45.2% in the SOC arm (p=0.036), with doxy-R SA present in 11.7% and 4.8% (p= 0.19), respectively. At M0, methicillin-resistant-SA (MRSA) was cultured from 5.9%, and at M12, 1.5% in the doxy-PEP arm and 6.5% in SOC arm (p=0.077). At M0, Neisseria spp were cultured from 86.8% with doxy-R Neisseria in 61.8%. At M12, Neisseria spp were cultured from 85.2% in the doxy-PEP arm and 89.3% in the SOC arm (p = 0.64), and doxy-R was 69.7% and 44.6%, respectively (p=0.017). Among GC diagnoses, 17% (44/256) had phenotypic susceptibility results; M0 TCN-R was 28.4% (4/15), and after enrollment, 38.5% (5/13) in the doxy-PEP arm and 12.5% (2/16) in the SOC arm.
Conclusions:
Doxy-PEP reduced S.aureus colonization by 16% without a significant increase in doxy-R SA. A majority had doxy-R commensal Neisseria at baseline, with an unexpected decrease in doxy-R Neisseria spp in the SOC arm. These modest changes in doxy-R S.aureus and Neisseria spp are unlikely to have clinical significance and must be considered in context of >60% STI reduction with doxy-PEP. Doxy-PEP may be less protective against incident TCN-R GC; surveillance for the impact of TCN-R GC on doxy-PEP efficacy and doxy-PEP on GC resistance is needed.
S.aureus, Neisseria spp, and N. gonorrhoeae: Bacterial isolation and phenotypic resistance to the tetracycline antibiotic class at enrollment and during DoxyPEP study