Doxycycline postexposure prophylaxis associated with increased antimicrobial resistance markers in Neisseria gonorrhoeae infectionsDoxycycline Use Linked to Increased Antibiotic Resistance in Gonorrhea

BACKGROUND: Prevention of bacterial sexually transmitted infections prevention by doxycycline postexposure prophylaxis (DoxyPEP) in men who have sex with men has raised concerns about antimicrobial resistance (AMR). We studied the impact of DoxyPEP on Neisseria gonorrhoeae (gonococcus [GC]) AMR in the ANRS 174 DOXYVAC trial. METHODS: Men who have sex with men and were on human immunodeficiency virus preexposure prophylaxis randomized to DoxyPEP (n = 362) or no-postexposure prophylaxis (PEP) (n = 183) arms were tested for GC at baseline and every 3 months thereafter, by culture and nucleic acid amplification test (NAAT). Minimum inhibitory concentrations (MICs) were determined with Etest (bioMérieux) and interpreted according to European Committee on Antimicrobial Susceptibility Testing guidelines. We performed whole-genome sequencing and/or polymerase chain reaction sequencing on GC isolates and NAAT-positive samples, using Fisher exact tests for comparisons. RESULTS: From January 2021 to February 2023, MICs were determined for 78 GC isolates, and 233 NAAT-only GC-positive samples were analyzed to identify the molecular determinants of resistance. All GC isolates were resistant to tetracycline with a significant increase in the rate of high-level tetracycline resistance mediated by the tetM gene in the DoxyPEP arm compared with the no-PEP arm (35.5 vs 12.5%, respectively; P = .043). The MICs of ceftriaxone, fluoroquinolones, and azithromycin were similarly distributed in the DoxyPEP and no-PEP arms. All GC isolates were susceptible to ceftriaxone and cefixime, but isolates with decreased susceptibility to cefixime linked to the mosaic penA34.007 allele were more frequent in the DoxyPEP arm than the no-PEP arm (32.3% vs 10.0%, respectively; P = .033). CONCLUSIONS: DoxyPEP use was associated with a significant increase in high-level tetracycline resistance and decreased susceptibility to cefixime in GC. AMR should therefore be closely monitored when using this strategy.