康替唑胺体外抗菌作用研究

In vitro activities of contezolid against clinical isolates from China

目的评价噁唑烷酮类新药康替唑胺对临床分离菌的体外抗菌作用。方法收集全国19所医院1321株的临床分离菌,以琼脂对倍稀释法测定康替唑胺对分离菌的最低抑菌浓度(MIC)并与有关抗菌药物进行比较,测定康替唑胺的杀菌活性、抗菌药物后效应(PAE)以及不同培养条件对康替唑胺抗菌作用的影响。结果康替唑胺对革兰阳性菌中葡萄球菌属、链球菌属和肠球菌属等临床常见分离菌均显示良好的抗菌活性,包括甲氧西林耐药金黄色葡萄球菌(金葡萄)(MRSA)、青霉素耐药肺炎链球菌(PRSP)和万古霉素耐药肠球菌(VRE)等多重耐药菌株。康替唑胺对甲氧西林敏感金葡菌(MSSA)和MRSA的MIC90均为0.5 mg/L,对肺炎链球菌中青霉素敏感株(PSSP)和不敏感菌株(PNSP)的MIC90亦均为0.5 mg/L,对其他链球菌属包括化脓链球菌等β溶血链球菌和草绿色链球菌的MIC90均为1 mg/L,对肠球菌属细菌包括耐万古霉素屎肠球菌的MIC90亦均为1 mg/L。康替唑胺对包括金葡菌在内的葡萄球菌属细菌的抗菌活性较利奈唑胺略高或相仿、亦略高于替考拉宁和万古霉素;对链球菌属细菌的抗菌活性与利奈唑胺相仿,略低于万古霉素和替考拉宁;对肠球菌属细菌的活性亦与利奈唑胺相仿,对万古霉素敏感株的抗菌活性与万古霉素相仿,略低于替考拉宁,但对万古霉素耐药屎肠球菌的活性则明显优于万古霉素和替考拉宁,与利奈唑胺相仿。康替唑胺对受试的葡萄球菌和链球菌属有良好的杀菌活性,尤其对肺炎链球菌具有良好的杀菌活性,但对肠球菌属细菌与利奈唑胺一样仅具抑菌活性。康替唑胺对金葡菌和肺炎链球菌的PAE均值分别为(1.56±0.42)h和(1.77±0.99)h。培养基中pH的改变对康替唑胺体外抗菌作用无明显影响,但细菌接种菌量的改变和血清蛋白含量的增高对康替唑胺的抗菌活性有一定影响。结论康替唑胺作为一种新型的噁唑烷酮类新药,药效学研究显示其对受试的革兰阳性菌,包括MRSA和甲氧西林耐药凝固酶阴性葡萄球菌(MRCNS)、PRSP、VRE等均有强大的体外抗菌活性;并对MRSA、PRSP等具有杀菌活性以及较长的PAE。提示康替唑胺对革兰阳性菌,尤其是其中的多重耐药菌株所致感染的治疗将具有重要作用;有望用于临床对其敏感的革兰阳性菌感染。

Objective To evaluate the in vitro antimicrobial activities of contezolid.Methods This study examined the full range in vitro antimicrobial activity of contezolid and comparators against 1321 clinical bacterial strains using two-fold agar dilution method.Contezolid was also characterized in terms of bactericidal activity,post-antibiotic effect(PAE)and the effect of culture conditions on susceptibility testing.Results The results of antimicrobial susceptibility testing supported the high antimicrobial activity of contezolid against gram-positive bacteria,including multidrug resistant strains such as methicillin-resistant S.aureus(MRSA),penicillin-resistant S.pneumoniae(PRSP),and vancomycin-resistant Enterococcus(VRE).Contezolid was slightly more potent than linezolid,teicoplanin,and vancomycin in the activity against Staphylococcus.For Streptococcus,the activity of contezolid was comparable to linezolid,but slightly lower than vancomycin and teicoplanin.Contezolid and linezolid showed similar high activity against Enterococcus regardless of their susceptibility profile to vancomycin.Contezolid displayed good bactericidal activity against S.pneumoniae but bacteriostatic effect on Enterococcus strains.The average PAE of contezolid was about(1.56±0.42)h for S.aureus and(1.77±0.99)h for S.pneumoniae.Inoculum size and serum protein concentration in the testing media,but not changing pH of media,affected the in vitro activity of contezolid.Conclusions This pharmacodynamic study demonstrates that contezolid as a novel oxazolidinone antibiotic,has potent in vitro antimicrobial activities against the gram-positive bacteria tested,including MRSA,methicillin-resistant coagulase-negative Staphylococcus,PRSP,and VRE;bactericidal activity against MRSA and PRSP strains,and longer PAE.These findings suggest that contezolid will play an important role in treating the infections caused by gram-positive bacteria,especially the multidrug-resistant strains.It is expected to see its use in clinical practice to fight the infections caused by susceptible gram-positive pathogens.