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Purpose: The study aimed to evaluate meropenem, fosfomycin, berberine hydrochloride, and doxycycline minimum inhibitory concentrations (MICs) of Neisseria gonorrhoeae collected from eight provinces in China in 2018. Methods: The MICs of 540 Neisseria gonorrhoeae isolates (451 isolates selected randomly and 89 isolates selected with preference) were determined to meropenem, fosfomycin, berberine hydrochloride, and doxycycline using the agar dilution method, and the MICs of ceftriaxone and azithromycin were detected for comparison. Results: Among 451 randomly selected isolates, the MIC90 was 0.06 mg/L for meropenem, 64 mg/L for fosfomycin, 64 mg/L for berberine hydrochloride, and 16 mg/L for doxycycline. All isolates showed the MIC ≤ 0.125 mg/L to meropenem, 13 isolates (2.9%) showed MIC > 64 mg/L to fosfomycin, 8 isolates (1.8%) demonstrated MIC > 64 mg/L to berberine hydrochloride, and 271 isolates (60.1%) demonstrated MIC > 1 mg/L to doxycycline. Comparing all 540 tested isolates, a correlation of r = 0.50 (P < 0.001) between meropenem and ceftriaxone MIC was observed. In 24 ceftriaxone-decreased susceptibility isolates, all isolates showed an MIC ≤ 0.125 mg/L for meropenem, 1 isolate (4.2%) showed an MIC > 64 mg/L for fosfomycin, 1 isolate (4.2%) showed an MIC > 64 mg/L for berberine hydrochloride, and 13 isolates (54.2%) showed an MIC > 1 mg/L for doxycycline. In 87 azithromycin resistant isolates, all isolates showed an MIC ≤ 0.125 mg/L for meropenem, 2 isolates (2.3%) showed an MIC > 64 mg/L for fosfomycin, 4 isolates (4.6%) showed an MIC > 64 mg/L for berberine hydrochloride, and 64 isolates (73.6%) showed an MIC > 1 mg/L for doxycycline. Conclusion: The in vitro results suggest that meropenem might be a promising treatment option for resistant gonococcal infections, while the effects of fosfomycin and berberine hydrochloride should be further evaluated as potential therapeutic agents. The effectiveness of these drugs in animal experiments and clinical use may need further study. [ABSTRACT FROM AUTHOR]