Recently, Cryptococcus and non-albicans Candida (NAC) have emerged as health-threatening pathogens for clinical fungal infections. Due to their increased resistance to existing antifungal drugs, novel antifungals are urgently needed. In this study, we evaluated the antifungal effect of VT-1161 and its comparators itraconazole and fluconazole against common fluconazole-sensitive or -resistant Cryptococcus and NAC strains. The tested strains were obtained from Chinese patients by the Invasive Fungal Infection Group within the past 2 years. The minimum inhibitory concentrations (MICs) of VT-1161 and other triazoles were measured according to the Clinical and Laboratory Standards Institute (CLSI) M27-Ed4 guidelines. We found that VT-1161 exhibited strong in vitro activity against Cryptococcus spp.. VT-1161 (geometric mean MIC = 0.024 μg/mL) was 21.7-fold and 104.5-fold more potent than itraconazole and fluconazole, respectively. Against the seven Cryptococcus neoformans isolates with higher fluconazole MICs (≥8 μg/mL based on the MIC90 value of this azole), VT-1161 maintained potent activities, with MICs ranging between 0.031 and 0.5 μg/mL. For NAC spp., VT-1161 (geometric mean MIC = 0.099 μg/mL) was 6.0-fold and 11.4-fold more effective than itraconazole and fluconazole, respectively. There is a positive correlation of the MICs between VT-1161 and itraconazole/fluconazole. The MIC values of VT-1161 against Candida glabrata and Candida tropicalis were significantly lower than those of fluconazole, whereas for Candida parapsilosis the differences in the MIC values between VT-1161 and fluconazole were not statistically significant. The results showed that tetrazole VT-1161 might be a promising candidate for treating Cryptococcus and NAC infections.

目的 了解2019年上海市东方医院(南院)菌株分布和抗菌药物敏感性.方法 用纸片扩散法(K-B法)测量抗菌药物抑菌圈直径,梅里埃自动化仪器检测最低抑菌浓度(MIC),按照美国临床实验室标准化协会(CLSI)指南M1002020版和美国食品和药物管理局(FDA)标准判断结果,用WHONET 5.6软件对本院分离细菌耐药性进行统计分析.结果 分离非重复菌株共1510株,革兰阳性菌(G+菌)487株,占32.25％;革兰阴性菌(G-菌)1023株,占67.75％.耐甲氧西林凝固酶阴性葡萄球菌(MRCNS)和耐甲氧西林金黄色葡萄球菌(MRSA)检出率分别为80.0％和54.1％.发现1株利奈唑胺耐药的粪肠球菌.β溶血链球菌以无乳链球菌为主,占77.1％,而无乳链球菌对青霉素96.3％敏感.肺炎链球菌均来自成年人的痰液,50％对青霉素敏感.大肠埃希菌和肺炎克雷伯菌超广谱β内酰胺酶(ESBLs)阳性率分别为52.6％和61.0％.耐碳青霉烯类肺炎克雷伯菌、大肠埃希菌、鲍曼不动杆菌和铜绿假单胞菌检出率分别为53.1％,2.2％,91.1％和38.1％.结论 本院细菌耐药率高,应加强及重视细菌耐药监测.

目的 监测上海地区2019年三级甲等医院临床分离菌对抗菌药物的耐药性.方法 对上述医院临床分离菌采用纸片扩散法或自动化仪器法,按上海市细菌真菌耐药监测网技术方案进行抗菌药物敏感性试验.按2019年CLSI文件标准判断结果 .结果 收集2019年1-12月监测网内三级医院临床分离菌共119318株,其中革兰阳性菌占29.1％(34756/119318),革兰阴性菌占70.9％(84562/119318).金黄色葡萄球菌、表皮葡萄球菌和其他凝固酶阴性葡萄球菌中甲氧西林耐药株(MRSA、MRSE和其他MRCNS)的检出率分别为43.4％、83.2％和76.6％.甲氧西林耐药株(MRSA、MRSE和其他MRCNS)对绝大多数抗菌药物的耐药率均显著高于甲氧西林敏感株(MSSA、MSSE和其他MSCNS).MRSA对甲氧苄啶-磺胺甲(噁)唑和利福平的耐药率低,分别为5.2％和3.0％,MRSE对利福平耐药率低(7.6％),未发现万古霉素和利奈唑胺耐药株.肠球菌属中粪肠球菌对多数测试抗菌药物的耐药率均显著低于屎肠球菌;粪肠球菌中未发现万古霉素耐药株,但对利奈唑胺耐药率达1.7％;屎肠球菌对万古霉素和利奈唑胺耐药率分别为0.4％和0.2％.2019年儿童和成人中分离的肺炎链球菌中青霉素敏感株(PSSP)分别占96.8％和96.9％,检出率较2018年有所上升,中介和耐药株(PISP和PRSP)的检出率则有所下降.肠杆菌目细菌对碳青霉烯类抗生素仍较敏感,多数菌属的耐药率低于20.0％(除克雷伯菌属外).此外,不动杆菌属对亚胺培南和美罗培南的耐药率分别为63.4％和63.1％,铜绿假单胞菌对上述两药的耐药率分别为30.0％和26.1％.结论 临床分离菌对常见抗菌药物的耐药性仍呈增长趋势,尤其是碳青霉烯类耐药革兰阴性杆菌.上海市三级医院的耐药形势仍然严峻,需各相关部门协作以遏制耐药细菌流行播散.

Candida and Cryptococcus are the main pathogens of clinical fungal infection associated with high morbidity and mortality. SHR8008 (in fact, this is the only official name in China and it is called VT-1161 by FDA) is a novel tetrazole agent that selectively inhibits fungal CYP51A compared to mammalian cytochrome P450 enzymes to achieve a better antifungal effect. The in vitro activities of SHR8008 and its comparators itraconazole and fluconazole were determined in 127 Candida and 50 Cryptococcus strains isolated from Chinese patients in the last 2 years by Invasive Fungal Infection Group. The MICs of SHR8008 and other triazoles were measured by the Clinical and Laboratory Standards Institute guidelines M27-E4. For Candida spp., SHR8008 (geometric mean MIC=0.078 μg/mL) was 6.5-fold and 11.2-fold more potent than itraconazole and fluconazole, respectively. There is a good correlation of MICs between SHR8008 and itraconazole/fluconazole. The MIC values of SHR8008 against Candida glabrata and Candida tropicalis were significantly lower than those of fluconazole, while for Candida albicans and Candida parapsilosis , the differences between SHR8008 and fluconazole were not statistically significant, either. For Cryptococcus spp., SHR8008 (geometric mean MIC=0.024 μg/mL) was 21.7-fold and 104.5-fold more potent than itraconazole and fluconazole, respectively. Against the seven Cryptococcus neoformans isolates with elevated fluconazole MICs (≥8μg/mL based on the MIC90 value for this azole), SHR8008 maintained potent activity, with MICs ranging between 0.031 and 0.5 μg/mL. The results showed that tetrazole SHR8008 was more promising in the treatment of Candida and Cryptococcus infection than itraconazole and fluconazole.

BACKGROUND Oxacillin-susceptible mecA-positive Staphylococcus aureus (OS-MRSA) represents an important issue, as its oxacillin susceptibility has contributed to misidentification by conventional susceptibility tests and consequently potential therapeutic failure, but limited data on the current status of OS-MRSA infection in Chinese hospitals are available. METHODS This multicenter study performed a battery of susceptibility tests and diagnostic tests for 956 S. aureus isolates from 10 hospitals, including automated susceptibility testing on VITEK 2, broth microdilution, disk diffusion, and detection of PBB2a, mecA gene and mecC gene. For all identified OS-MRSA, multi-locus sequence typing (MLST), together with spa typing, SCCmec typing and PVL detecting, was carried out. RESULTS OS-MRSA, most of which were from pediatric inpatients, represented 1.8% (17/956) of total isolates. Of these 17 OS-MRSA, 10 were ST59, followed by ST965 (3/17), and 11 carried SCCmec type IV, while 5 carried SCCmec type V, but only one was Panton-Valentine leucocidin (PVL)-positive, also, 16 had one or two point mutations within mecA promoter. OS-MRSA had inducible oxacillin resistance and significantly lower MDR (Multi-Drug Resistant) rate. We observed that the VITEK 2 system exhibited some deficiency in OS-MRSA detection, whereas cefoxitin disk diffusion was shown to be a reliable and cost-saving alternative and should be supplemented in detecting S. aureus with borderline oxacillin susceptible MICs. CONCLUSION This study has characterized phenotypically and molecularly OS-MRSA in China, and provided insights into more effective management of OS-MRSA.