耐头孢曲松淋球菌菌株的体外人工诱导及多重耐药现象

Multidrug Resistance in Two Ceftriaxone-Resistant Neisseria gonorrhoeae Induced in Vitro

目的探讨体外人工诱导耐头孢曲松淋球菌的可行性,为研究淋球菌耐头孢曲松的机制提供实验菌株。方法将对头孢曲松敏感的标准株ATCC49226(MIC 0.004ug/mL)和临床株ZSSY00205(MIC 0.25ug/mL)以头孢曲松次抑菌浓度法连续传代培养,定期监测生物学和分子生物学特性,诱导耐药成功后检测耐药菌株的稳定性,并分析诱导耐药前、后菌株RAPD图谱的改变及对其它抗菌药物耐药性的改变。结果诱导后菌株ATCC49226和ZSSY00205对头孢曲松的MIC值是诱导前的125倍,诱导前、后菌株RAPD图谱未见明显改变,但头孢曲松诱导耐药后的淋球菌对青霉素、四环素、红霉素和环丙沙星的敏感性下降。结论体外头孢曲松次抑菌浓度法可诱导产生头孢曲松耐药株,淋球菌对头孢曲松产生耐药的同时,可对包括青霉素、四环素、红霉素、喹诺酮在内的多种抗菌药物产生耐药或耐药性增加,即多重耐药现象。

Objective To investigate the feasibility of induction of ceftriaxone-resistant Neisseria Gonorrhoeae in vitro. Methods Subinhibitory concentrations was used to induce the reference strain ATCCA9226 and the clinical isolated strain ZSSY00205 producing resistance to ceftriaxone. After successful induction, the stability of the induced ceftriaxone resistance was tested by series subcultures and RAPD finger print was applied to analysis the difference of genomic DNA between the parent and the mutant. Disk diffusion method was further adopted to detect the change of susceptibility to some other antimierobials. Result The MICs to eeftriaxone of ATCC49226 and ZSSY00205 were approximately 125 -fold higher than that of their parent strains. The RAPD profiles presented no significant difference on genomie DNA between the parent and the mutant. While the resistance to ceftriaxone being induced among these strains, concomitantly the decreased susceptibility to penicillin, tetracycline, azithromycin and cipro- floxacin had been observed. Conclusion Ceftriaxone-resistant N. gonorrhoeae could be induced by using the method of subinhibitory concentrations in vitro. Along with the emergence of ceftriaxone resistance, N. gonorrhoeae showed multidrug resistance to some other antimierobials, such as penicillin, tetracycline, azithromyein and ciprofloxaein, which is deserved to be further researched.