头孢曲松次抑菌浓度诱导淋球菌耐药及交叉/多重耐药现象的探讨

Study on Cross-Resistance and Multi-Resistance of Neisseria Gonorrhoeae Induced with Ceftriaxone Subinhibitory Concentration

目的：利用体外次抑菌浓度法诱导耐头孢曲松淋球菌,探讨其交叉耐药与多重耐药现象,为淋球菌耐头孢曲松机制的研究提供菌株和初步的理论基础。方法：将对头孢曲松敏感的标准株WHOA、WHOC、WHOD、WHOE及临床株ZSSY016以头孢曲松次抑菌浓度法连续传代培养,定期监测生物学特性,分析诱导前后菌株RAPD图谱的改变结果,并以琼脂稀释法检测诱导前后及诱导过程中菌株对其他抗生素耐药性的变化。结果：诱导后菌株对头孢曲松的M IC值提高了4~256倍,对青霉素、头孢呋辛的M IC值也发生了不同程度的耐药,对四环素、环丙沙星及大观霉素的耐药性变化未发生显著改变。结论：体外次抑菌浓度法可诱导耐头孢曲松淋球菌,诱导易感性存在菌株间的个体差异,耐头孢曲松机制与交叉耐药/多重耐药机制存在多样性。淋病治疗应合理足量应用抗生素,以防止体内诱导产生耐药菌株。

Objective：To obtain the model of neisseria gonorrhoeae resistant to ceftriaxone by subinhibinhibitory induction producre,to investigate on the mechanism of ceftriaxone resistance and cross resistance/multi resistance. Methods：Four stains of neisseria gonorrhoeae,such as WHOA、WHOC、WHOD、WHOE and one clinical isolate ZSSY016 were exposed to subinhibitory concentration of ceftriaxone for generations,and biochemical tests and RAPD finger print test were applied to identify the strains during induction.MICs of parent and mutant strains to different antibiotics were also detected.Results：The MICs to ceftriaxone of the five strains were enhanced to 4~256 fold,and showed cross-resistance to penicillin and cefuroxime to different degrees and showed no obvious changes in tetracycline,ciprofloxacin and spectinomycin.Conclusion：Ceftriaxone-resistant neisseria gonorrhoeae can be obtained by subinhibitory induction in vitro.Diverse ceftriaxone-resistance and cross-resistance/multi-resistance mechanism might be existed.Antibiotics should be applied reasonably to avoid resistant strains induced in vivo.