Tigecycline displays bactericidal activity against multidrug-resistant Neisseria gonorrhoeae and enhances clearance from a mouse infection model.

چکیده اصلی

OBJECTIVES: The global emergence of ceftriaxone-resistant Neisseria gonorrhoeae threatens current first-line treatment and necessitates alternative therapeutic options. Tigecycline, a last-line glycylcycline antibiotic approved for complicated infections, was evaluated for repurposing against N. gonorrhoeae through in vitro and in vivo activity studies. METHODS: Antimicrobial susceptibility testing was performed for 616 clinical isolates (2011-2024) from Hangzhou, China, and bactericidal activity was determined in time-kill assays. A mouse vaginal tract infection model was used to evaluate in vivo tigecycline activity. Chequerboard assays were performed to assess interactions between tigecycline and ceftriaxone. RESULTS: Tigecycline demonstrated potent activity (MIC50: 0.125 mg/L; MIC90: 0.25 mg/L), including against tetracycline-resistant (tetracycline MIC50: 2 mg/L; MIC90: 64 mg/L) and high-level ceftriaxone-resistant (ceftriaxone MIC50: 0.03 mg/L; MIC90: 0.125 mg/L) strains. Time-kill assays (2 strains) revealed concentration-dependent bactericidal activity, with 4×MIC achieving ≥105-fold killing. In the mouse vaginal tract infection model, high-dose tigecycline (25 mg/kg) significantly enhanced bacterial clearance, eliminating infection within 3-6 days compared to 8-12 days in vehicle controls, and substantially reduced bacterial burden. Chequerboard assays against 21 isolates (10 ceftriaxone-susceptible, 11 ceftriaxone-resistant) demonstrated indifferent interactions between tigecycline and ceftriaxone (fractional inhibitory concentration indices 1.03-2.56), indicating no antagonism. CONCLUSIONS: These findings establish that tigecycline exhibits potent, rapid bactericidal activity against N. gonorrhoeae, including against high-level ceftriaxone-resistant strains, with robust in vivo efficacy. They support further investigation of tigecycline as a potential repurposing candidate for multidrug-resistant gonorrhoea, although its clinical role remains to be defined.

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