Exploring alternative therapeutic options for multidrug-resistant N. Gonorrhoeae: the potential of 7,8-dihydroxyflavone.

OBJECTIVES

Neisseria gonorrhoeae (NG), a bacterium characterised by multidrug resistance, is traditionally treated with ceftriaxone, either as a monotherapy or in conjunction with azithromycin. However, the emergence of strains resistant to these antibiotics presents a considerable challenge to current therapeutic approaches, which necessitates the exploration of alternative treatment strategies.

METHODS

Agar dilution and broth microdilution to determine the minimum inhibitory concentrations (MICs) of antibiotics and 7,8-dihydroxyflavone. The development of 7,8-dihydroxyflavone drug resistance was detected under the treatment of sublethal concentration for 30 passages. Genotypic analysis was conducted to examine penA, 23S rRNA alleles and multilocus sequence typing.

RESULTS

55 clinical NG isolates emphasised the high-level rates of the current antimicrobial resistance, with a notable prevalence of the penA-60.001 FC428 clone and high-level azithromycin-resistant clones characterised by the 23S rRNA-1 (A2059G) and 23S rRNA-2 (C2611T) alleles. Among the strains that are representative of clinical circulation, 7,8-dihydroxyflavone demonstrated inhibitory activity, with MIC50 and MIC90 values of 10 mg/L and 20 mg/L, respectively, which are unlikely to induce drug resistance in NG.

CONCLUSIONS

7,8-dihydroxyflavone may represent a promising antimicrobial agent in the context of escalating antibiotic resistance.