Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases · 2026
Impact of doxycycline post-exposure prophylaxis on Neisseria gonorrhoeae antimicrobial resistance to doxycycline and ceftriaxone in Milan, Italy.
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Raccagni Angelo Roberto, Sagramoso Chiara, Capra Nicolò, Lolatto Riccardo, Cirillo Daniela Maria, Carletti Silvia, Loi Gabriele, Bruzzesi Elena, Castagna Antonella, Nozza Silvia
Аннотация
OBJECTIVES: Doxycycline post-exposure prophylaxis (DoxyPEP) reduces bacterial sexually transmitted infections, but it selects for tetracycline-resistant gonorrhoea and might co-select for ceftriaxone resistance. The aim of this study was to assess DoxyPEP association with gonorrhoea phenotypic antimicrobial resistance and MICs in a real-world setting.
METHODS: This was a retrospective cohort study of people with culture-confirmed gonorrhoea at San Raffaele Hospital (1 January 2022-30 June 2025). DoxyPEP was offered from August 2022; episodes after self-reported DoxyPEP use were classified as exposed. MICs for ceftriaxone, ciprofloxacin, tetracycline, azithromycin, and benzylpenicillin were measured by gradient strips and interpreted with European Committee on Antimicrobial Susceptibility Testing criteria version 15.0. High-level tetracycline resistance was MIC > 8 mg/L; decreased ceftriaxone susceptibility was MIC > 0.032 mg/L (epidemiological cut-off). Associations with resistance outcomes were estimated using generalized estimating equation logistic regression, with Firth correction applied for sparse outcomes; log-MIC generalized estimating equation models compared adjusted geometric mean MICs (adjusted for age, HIV status, pre-exposure prophylaxis use, and prior bacterial sexually transmitted infections).
RESULTS: A total of 318 individuals with 376 gonorrhoea episodes (373 of 376 (99.2%) in men) were included (median age 34.8 years, interquartile range 30.0-39.8); 217 of 376 (57.7%) occurred during pre-exposure prophylaxis, and 76 of 376 (20.2%) were among people with HIV. Seventy-seven of 376 episodes (20.5%) were DoxyPEP-exposed. Overall, resistance was frequent: tetracycline 360 of 375 (96.0%), high-level tetracycline resistance 64 of 375 (17.1%), ciprofloxacin 250 of 342 (73.1%), azithromycin 36 of 360 (10.0%), and benzylpenicillin 40 of 340 (11.8%); β-lactamase positivity was 17.3% (58 of 335). Decreased ceftriaxone susceptibility occurred in 2.1% (8 of 375), with no ceftriaxone-resistant isolates. In adjusted models, DoxyPEP exposure was associated with high-level tetracycline resistance (19 of 77 (25.0%) vs. 45 of 298 (15.1%); adjusted OR 1.87; 95% CI, 1.01-3.47; p 0.045) and decreased ceftriaxone susceptibility (5 of 77 (6.5%) vs. 3 of 298 (1.0%); adjusted OR = 7.34; 95% CI, 1.69-31.90; p 0.008). After correction for multiple comparisons, only the association with decreased ceftriaxone susceptibility remained significant. Adjusted geometric mean MICs overlapped between exposed and unexposed episodes.
CONCLUSIONS: In this setting of near-universal gonococcal tetracycline resistance, the contribution of DoxyPEP in selecting high-level tetracycline resistance was limited. Possible association with rare cases of decreased ceftriaxone susceptibility was observed, without evidence of broader MIC shifts or ceftriaxone resistance.
METHODS: This was a retrospective cohort study of people with culture-confirmed gonorrhoea at San Raffaele Hospital (1 January 2022-30 June 2025). DoxyPEP was offered from August 2022; episodes after self-reported DoxyPEP use were classified as exposed. MICs for ceftriaxone, ciprofloxacin, tetracycline, azithromycin, and benzylpenicillin were measured by gradient strips and interpreted with European Committee on Antimicrobial Susceptibility Testing criteria version 15.0. High-level tetracycline resistance was MIC > 8 mg/L; decreased ceftriaxone susceptibility was MIC > 0.032 mg/L (epidemiological cut-off). Associations with resistance outcomes were estimated using generalized estimating equation logistic regression, with Firth correction applied for sparse outcomes; log-MIC generalized estimating equation models compared adjusted geometric mean MICs (adjusted for age, HIV status, pre-exposure prophylaxis use, and prior bacterial sexually transmitted infections).
RESULTS: A total of 318 individuals with 376 gonorrhoea episodes (373 of 376 (99.2%) in men) were included (median age 34.8 years, interquartile range 30.0-39.8); 217 of 376 (57.7%) occurred during pre-exposure prophylaxis, and 76 of 376 (20.2%) were among people with HIV. Seventy-seven of 376 episodes (20.5%) were DoxyPEP-exposed. Overall, resistance was frequent: tetracycline 360 of 375 (96.0%), high-level tetracycline resistance 64 of 375 (17.1%), ciprofloxacin 250 of 342 (73.1%), azithromycin 36 of 360 (10.0%), and benzylpenicillin 40 of 340 (11.8%); β-lactamase positivity was 17.3% (58 of 335). Decreased ceftriaxone susceptibility occurred in 2.1% (8 of 375), with no ceftriaxone-resistant isolates. In adjusted models, DoxyPEP exposure was associated with high-level tetracycline resistance (19 of 77 (25.0%) vs. 45 of 298 (15.1%); adjusted OR 1.87; 95% CI, 1.01-3.47; p 0.045) and decreased ceftriaxone susceptibility (5 of 77 (6.5%) vs. 3 of 298 (1.0%); adjusted OR = 7.34; 95% CI, 1.69-31.90; p 0.008). After correction for multiple comparisons, only the association with decreased ceftriaxone susceptibility remained significant. Adjusted geometric mean MICs overlapped between exposed and unexposed episodes.
CONCLUSIONS: In this setting of near-universal gonococcal tetracycline resistance, the contribution of DoxyPEP in selecting high-level tetracycline resistance was limited. Possible association with rare cases of decreased ceftriaxone susceptibility was observed, without evidence of broader MIC shifts or ceftriaxone resistance.