五倍子、黄芩和黄连联合应用对MRSA的体外抗菌活性研究

目的:研究五倍子、黄芩和黄连联合应用对耐甲氧西林金黄色葡萄球菌(MRSA)的体外抗菌活性。方法:采用肉汤稀释法测定其对MRSA的最小抑菌浓度(MIC)值,推算出半数抑菌浓度(MIC50)和抑菌90%浓度(MIC90)值,并作比较。结果:五倍子、黄芩和黄连单药及相互配伍后对MRSA的抑菌效果从高至低依次为:黄芩-五倍子、五倍子、黄连-五倍子、黄连、黄连-黄芩、黄芩。结论:黄芩与五倍子配伍对MRSA有协同作用,与黄芩呈拮抗作用。     

三黄泻心汤三味药联合抗生素对幽门螺杆菌的体外抑菌实验研究

目的探讨组成三黄泻心汤的大黄、黄连、黄芩对幽门螺杆菌(Hp)的抑制作用,研究三味中药两两联合、每味中药分别与克拉霉素(CLR)、左氧氟沙星(LEV)、甲硝唑(MTZ)联合对Hp的增敏效果。方法菌株ATCC43504做质控及实验菌株,以药敏纸片法探讨三味中药对Hp的抑制作用;琼脂二倍稀释法检测实验药物(大黄、黄连、黄芩、CLR、LEV、MTZ)单独及联合使用对Hp菌株ATCC43504的最小抑菌浓度(MIC),计算抑菌浓度指数(FICI),确定联合抑菌效果,判断联合用药时实验药物敏感性的变化。结果黄连、大黄、黄芩的抑菌环直径:22 mm、18 mm、10 mm;MIC值:0.625 mg/ml、1.25 mg/ml、5 mg/ml;黄连与黄芩、黄连与CLR、黄连与MTZ、黄芩与MTZ联合的FICI≤0.5,呈协同作用,其余组合为相加作用,未见拮抗作用。菌株ATCC43504为抗生素MTZ的耐药菌株,联合用药时MTZ的MIC大于耐药折点,菌株依然对MTZ耐药。结论中药联合较单药有更强的抑制Hp能力。中药大黄、黄连、黄芩与抗生素联合用药能一定程度上提高抗生素敏感性。三黄泻心汤组方及三味中药可以与抗生素联合应用于根除Hp。     

抗耐甲氧西林金黄色葡萄球菌的中药筛选

目的以50种常用中药筛选抗耐甲氧西林金葡菌(MRSA)的中药。方法采用K-B纸片扩散法从50种中药初步筛选;通过琼脂平板抑菌法观察所筛选的5种抗MRSA作用最强的中药的MIC;采用微量液体平板棋盘法研究5种中药两两联合应用的抗菌作用。结果抗菌筛选实验中50种中药有35种产生抑菌圈,其中以黄连、黄柏、大黄、银柴胡和石榴皮的抑菌圈直径最大,黄连和黄柏联合应用时抗菌指数(FIC)<0.5。结论所选中药多数具有抗MRSA作用,其中以黄连、黄柏、大黄、银柴胡和石榴皮的作用最强,黄连和黄柏联合应用因协同作用抗菌作用最强,为中药抗MRSA的较好选择。     

利奈唑胺、万古霉素对甲氧西林耐药的金黄色葡萄球菌的防耐药突变体选择浓度的研究

目的：比较利奈唑胺、万古霉素对耐甲氧西林金黄色葡萄球菌的防耐药突变选择能力;研究防耐药突变体选择浓度（MPC）和最低抑菌浓度（MIC）的相关性。方法：采用琼脂微量稀释法测定利奈唑胺、万古霉素对35株耐甲氧西林金黄色葡萄球菌（MRSA）临床分离菌株的MPC和MIC;采用线性回归法比较利奈唑胺、万古霉素对MRSA的MPC和MIC的相关性;结合人体药代动力学数据,预测利夺唑胺、万古霉素对MRSA的防耐药突变体选择能力。结果：利奈唑胺、万古霉素对35株MRSA的MPC90值（抑制90％的细菌发生细菌耐药的最低防耐药突变体选择浓度）分别为16.8μg／mL,选择指数（MPC90／MIC90）均为8。两药对MRSA的MPC和MIC的线性相关系数R^2分别为0．32和0．008。结合两药药代动力学参数,利奈唑胺药物浓度在整个给药间隔落在耐药突变选择窗理论（MSW）中,万古霉素药物浓度在大部分给药间隔落在MPC之上。结论：万古霉素对MRSA的防耐药选择能力强于利奈唑胺;MPC和MIC的相关性差。     

中药黄连对临床常见耐药菌株的体外抑菌活性分析

摘 要 目的：观察中药黄连浸提液对耐甲氧西林金黄色葡萄球菌（MRSA）、产广谱β 内酰胺酶（ESBL）肺炎链球菌（S. pneumoniae）、耐亚胺培南铜绿假单胞菌（P. aeruginosa）、产ESBL大肠埃希菌（E. coli）等4种常见临床耐药菌株的体外抑菌活性分析。方法: 选取中药黄连制备水浸提液,依据CLSI标准,初步采用纸片琼脂扩散法（K B法）测算黄连浸提液对MRSA、产ESBL的E. coli和S. peneumoniae、耐亚胺培南P. aeruginosa等菌株的抑菌直径并参考相应的标准菌株实验结果,再采用肉汤稀释法观察黄连浸提液对其相应抑菌活性,测定其相应的最小抑菌浓度（MIC）。结果: 黄连浸提液对S. peneumoniae、MRSA、E. coli和P. aeruginosa等耐药菌株的抑菌直径分别为21,17,15,10 mm;MIC分别为15.63,62.50,125,250 mg·ml-1。结论: 黄连水浸提液对4种临床常见的耐药菌都有较好的抑菌效果,其中产ESBL的S. peneumoniae的抑菌效果最为明显,MRSA效果次之,其次为产ESBL的E. coli和耐亚胺培南P. Aeruginosa。本研究结果对肺炎链球菌及MRSA感染治疗具有重要的参考价值。     

雷公藤与苦参配伍的体外抑菌试验

雷公藤、苦参都具有较强的抗菌、消炎、杀虫作用犤１犦。临床常与其他中药配伍或单独使用配制成外用制剂，治疗多种皮肤病。将雷公藤与苦参配伍使用，临床上还未见报道。为了证实上述二味药配伍使用时的抑菌效果，我们分别将雷公藤、苦参和二味药等量混合后的乙醇提取物进行最小抑菌浓度试验，结果显示，雷公藤与苦参配伍使用时抗菌作用具有协同效果。１试验方法１．１样品的来源雷公藤（StriterygiuWlfordiHook．f）产地湖南，为带皮干根；苦参（SophoraflarescensAit）产地河南，为干燥根。二药均经河南中医学院鉴定。１．２样品的提取…     

基于中药超分子与肠道菌相互作用探讨大黄-黄连配伍和合的物质基础

基于中药超分子与肠道菌相互作用过程探讨大黄-黄连配伍和合的物质基础。采用扫描电子显微镜和动态光散射法表征大黄单煎液、黄连单煎液与配伍共煎液的形态学差异,通过建立体外抑菌模型(大肠杆菌E. coli,屎肠球菌E. faecium与枯草杆菌B. subtilis)初步评价大黄黄连配伍对肠道菌的损伤作用;通过超高效液相色谱-串联质谱技术分析单煎与共煎的化学组分变化规律。大黄黄连共煎煮后呈浑浊状,电镜下可见300～400 nm的类球形颗粒,且较单煎液相比其汤剂相态更均一稳定;并直接观察到二者配伍后形成的超分子和肠道菌的相互作用与单煎液相比明显不同,超分子与肠道菌相互作用过程中维持类球形状态,封闭着黄连或大黄中的药效成分,可有效缓和对肠道菌的损伤,为后续大黄-黄连配伍“和合”调控肠道菌群稳态研究提供参考。     

五种中草药提取物对致龋菌的体外抑菌作用研究

目的 探讨黄连、金银花、厚朴、桔梗与大黄五种中药对常见致龋菌的体外抑菌作用。方法 按照标准方法分别提取5种中药的主要成分,观察提取物对变形链球菌、粘性放线菌生长的影响,并测量抑菌圈直径,检测最小抑菌浓度（MIC）。结果 厚朴、黄连、大黄对变形链球菌与粘性放线菌的抑制作用较强,厚朴提取物对常见致龋菌的抑菌作用较强,其中,对变形链球菌的最小抑菌浓度为1.25 mg/mL,对粘性放线菌的最小抑菌浓度为0.63 mg/mL,抑菌作用强于黄连与大黄。结论 厚朴、黄连、大黄对常见致龋菌有较大的抑制作用,具有一定的研究与开发价值。     

大黄配伍药对的泻下作用变化及其共性关系研究

目的：研究大黄配伍药后对其泻下作用的变化及其共性关系。方法：将140只实验动物随机分为生理盐水组、果导组及大黄药对组（15 g·kg^-1、7.5 g·kg^-1,以大黄生药计）,按10 mL·kg^-1的剂量给药后,分别用代谢笼积分法、酚红糊排空法、炭末推进作用及Na⁺-K⁺-ATPase活性实验,比较大黄配伍药对对大鼠的正常泻下作用、酚红糊肠推进功能、炭末推进率及Na⁺-K⁺-ATPase活性。结果：大黄与药对配伍后泻下作用均有不同程度的改变,与生理盐水组比较,大黄、大黄牡丹及大黄桃仁15 g·kg^-1剂量组显著增加正常小鼠泻下作用、促进肠推进功能、提高炭末推进率及抑制Na⁺-K⁺-ATPase活性,表明其泻下作用有显著差异;且与大黄组比较,大黄桃仁及大黄牡丹配伍后的泻下作用有差异,其中泻下作用最显著的是大黄牡丹组。结论：大黄与牡丹、桃仁、甘遂配伍可促进其泻下作用,与枳实、黄连配伍则可抑制其泻下作用,这可能与配伍中药的主要化学成分引起大黄中蒽醌类化合物的溶出量变化及药对间的相使相须作用有关。     

桂皮醛联合伏立康唑对临床分离烟曲霉菌的体外作用研究

摘要： 目的 评价桂皮醛与伏立康唑（VRC）联合应用对临床分离烟曲霉菌的体外抗菌活性。 方法 参照美国临床和实验室标准协会（CLSI）推荐的微量液基稀释法及棋盘法, 分别测定桂皮醛、VRC 单独使用及联合使用对 42 株临床分离烟曲霉菌的最小抑菌浓度（MIC）, 比较 2 药单用与联用的 MIC50、MIC90MIC 几何均数（MICG）及 MIC 分布; 绘制浓度-累积抑菌百分率曲线并计算分级抑菌指数（FICI）, 判断药物联合作用的类型。 结果 桂皮醛与 VRC联用后, 2 药的 MIC50、MIC90及 MICG 均较各自单用时明显降低（P＜ 0.01）, MIC 峰值分布及浓度-累积抑菌百分率曲线较单用时左移; 2 药联用的 FICI 值为 0.187 5~1.5, 其中 16 株（38.10%）体现为协同作用, 19 株（45.23%）为相加作用, 7 株（16.67%）为无关作用, 未出现拮抗作用。 受试菌株对 VRC 的敏感性越低, 2 药联用的 FICI 均数越小。 结论 桂皮醛与 VRC 联用对临床分离烟曲霉菌的体外联合抗菌效应主要表现为协同和相加作用,且该药物组合对VRC 敏感性较低的烟曲霉菌表现出较强的协同抗菌作用。     

蒙特卡洛模拟评价中国成人持续静脉输注万古霉素治疗开颅术后MRSA脑膜炎感染的给药方案

目的 应用蒙特卡洛模拟(MCs)评价中国成人开颅术后脑膜炎患者持续静脉输注万古霉素(VAN)治疗耐甲氧西林金黄色葡萄球菌(MRSA)感染的给药方案。方法 搜集我国开颅术后脑膜炎感染患者的群体药动学参数，以及成都区域VAN对MRSA的最低抑菌浓度(minimal inhibitory concentration, MIC)值和其分布频率，MCs 10000例次后得到对应的目标获得概率(PTA)与累计反应分数(CFR)。结果 当MIC为0.03mg/L时予1g/d VAN即可达到满意的抗菌活性；当MIC为0.06mg/L时予1.5g/d VAN即可达到满意的抗菌活性；当MIC为0.12mg/L时予3g/d VAN可达到相对满意的抗菌活性(PTA＞90%)；但当MIC为0.25~2mg/L时即使予3g/d也不能达到满意的抗菌活性；各给药方案的CFR均小于90%。结论 开颅术后治疗MRSA脑膜炎感染采用持续静脉输注常规给药剂量(2g/d)的VAN可能偏低，经验性持续静脉输注VAN可考虑联合用药或改用其他给药途径方式。     

Antibacterial activities of various aminoglycosides against clinically isolated methicillin-resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) were isolated from samples collected from various patients during 1986, and antibacterial activities of 6 aminoglycosides (AGs) (netilmicin (NTL), gentamicin (GM), sisomicin (SISO), dibekacin (DKB), tobramycin (TOB) and amikacin (AMK] and 4 beta-lactam antibiotics (cefazolin (CEZ), cefmetazole (CMZ), cloxacillin (MCIPC) and methicillin (DMPPC) against these MRSA were evaluated. Among these 6 AGs, NTL was the most potent, and its MIC50 and MIC80 were 1.56 and 3.13 micrograms/ml, respectively. Antibacterial activities of GM, SISO, DKB and TOB were weak, and MIC50's of GM and DKB were both 100 micrograms/ml, while those of SISO and TOB were 50 and greater than 100 micrograms/ml, respectively. Frequency of highly resistant specimens to AMK was rather low and its MIC50 and MIC80 were 12.5 and 25 micrograms/ml, respectively. As for antibacterial activities of the above 4 beta-lactam antibiotics, the MIC50 and MIC80 of CMZ were 6.25 and 12.5 micrograms/ml, respectively, and therefore, its antibacterial activity to MRSA is relatively good. However, MIC50's of CEZ, MCIPC and DMPPC were all greater than 100 micrograms/ml, showing poor antibacterial activities. Recently, MRSA became a problem in various fields of clinical practice, and a number of literatures reporting refractory infections caused by MRSA have been published. Since MRSA is featured as multiply resistant bacteria, it is known that MRSA is resistant to the majority of existing antibiotics (penicillins, cephems, macrolides, AGs, etc.). In 1985, we reported results of our study concerning the antibacterial activities of a number of CEPs and some of AGs against multiply resistant S. aureus including MRSA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Combined effects of arbekacin with other antibiotics against methicillin-resistant Staphylococcus aureus. I. The combined effect of arbekacin with fosfomycin or clavulanic acid/ticarcillin]

As arbekacin (ABK) has a highly potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), its combined effects with fosfomycin (FOM) and clavulanic acid/ticarcillin (CVA/TIPC) against MRSA were examined. The obtained results are summarized as follows. 1. Against MRSA either combination, FOM+ABK or CVA/TIPC+ABK showed a strong antibacterial effect at the MIC or the sub MIC of ABK in the blood expected from clinical observations. The MIC of ABK by the combination use seemed to be equivalent to the MBC value. 2. Effective concentrations of antibiotics in these combinations appeared to be strongly dependent on the effective concentration of ABK and less dependent on that of FOM or CVA/TIPC. Therefore, the antibacterial activity of a combination seems to mostly depend on the antibacterial activity and the concentration of ABK. 3. As FOM and CVA/TIPC have antibacterial activities against Pseudomonas aeruginosa, combinations of ABK with these antibiotics are likely to be effective against double infection with P. aeruginosa in MRSA infected patients.     

国产米诺环素对耐甲氧西林金葡球菌的体外抗菌活性观察

用琼脂稀释法进行国产米诺环素对１０４株耐甲氧西林金葡球菌（ＭＲＳＡ）和１２０株甲氧西林敏感金葡球菌（ＭＳＳＡ）的抗菌活性研究，并与日本产米诺环素等进行了抗菌作用比较。结果表明国产米诺环素对ＭＲＳＡ和ＭＳＳＡ的抑菌效果，与日本产米诺环素基本一致。对ＭＲＳＡ的ＭＩＣ５０和ＭＩＣ９０前者分别为２和８ｍｇ／Ｌ，而后者分别为２和４ｍｇ／Ｌ。两者对ＭＳＳＡ的ＭＩＣ５０和ＭＩＣ９０均为０．５和４ｍｇ／Ｌ。国产米诺环素与其它６种抗生素比较，除去甲万古霉素外，其对ＭＲＳＡ和ＭＳＳＡ的抗菌效果，均优于头孢唑林等抗生素     

临床分离耐甲氧西林金黄色葡萄球菌的耐药性及分子流行病学研究

目的研究我国临床分离的耐甲氧西林金黄色葡萄球菌(MRSA)的耐药性及分子流行病学特点。方法菌株来源于全国17家医院分离的MRSA共计160株,用标准平皿二倍稀释法测定对23种抗菌药物的最低抑菌浓度(M IC);用脉冲场凝胶电泳技术(PFGE)对其中133株MRSA菌株进行同源性分析。结果 160株MRSA对多种抗菌药物呈现不同程度的耐药。其中,133株MRSA菌株的PFGE图谱显示,共有A～E 5种类型,以A型为主,为88株(A1型27株,A2型25株,A3型22株,A4型12株,A5型2株);B型为25株(B1型19株,B2型3株,B3、B4和B5型各1株);C型为8株(C1型7株,C2型1株);另有12株为散发菌株。结论临床分离的MRSA呈多重耐药性,我国不同医院流行的MRSA菌株基因型主要为A1、A2、A3和B1型;且不同地区的医院流行的菌株基因型不同,同一医院流行的菌株基因型也不同。     

黄芩和黄柏对耐甲氧西林金葡萄球菌的疗效对比观察

目的了解黄芩和黄柏对耐甲氧西林金黄色葡萄球菌(MRSA)的体外抗菌活性。方法用琼脂扩散法和琼脂稀释法,检测黄芩和黄柏对100株MRSA的体外抗菌活性。结果黄芩对MRSA的MIC50、MIC90分别为0.84、6.7mg。黄柏对MRSA的MIC50、MIC90分别1.48、11.8mg。结论与黄柏相比较,黄芩更适合作为MRSA敏感的抗菌药物用于临床治疗。     

蒙特卡洛模拟评价鞘内注射万古霉素治疗耐甲氧西林金黄色葡萄球菌颅内感染的给药方案

目的 应用蒙特卡洛模拟评价万古霉素鞘内注射治疗成人开颅术后耐甲氧西林金黄色葡萄球菌(MRSA)颅内感染的给药方案.方法 查阅有关成都地区万古霉素对MRSA菌株的最低抑菌浓度值(MIC)及其分布频率与中国成人开颅术后脑膜炎感染患者的群体药动学资料,Crystal Ball软件模拟5 000例次后得到相应目标获得概率(PTA)和累计反应分数(CFR).结果 当MIC值分别为0.03、0.06、0.12、0.25、0.50、1、2 mg·L-1时,万古霉素对MRSA的MIC分布频率分别为12.79％、12.79％、12.79％、12.79％、12.79％、29.07％和6.98％.当MIC分别为≤0.25、0.05、1、2mg·L-1时,分别予2.5、5、10、20 mg·d-1即可达到满意的抗菌活性(PTA=100％);鞘内注射10 mg·d-1的给药方案,其CFR大于90％.结论 结合各MIC分布频率与达满意抗菌活性的最低剂量可知,大多数成人开颅术后MRSA颅内感染的患者鞘内注射万古霉素10 mg·d-1时均可达到满意的治疗效果,经验性鞘内注射万古霉素时可考虑10 mg·d-1的给药剂量方案.     

木犀草素与抗菌药体外联用抗耐甲氧西林金葡菌的作用研究

目的：考察木犀草素与抗菌药体外联用抗耐甲氧西林金葡菌的作用。方法：采用倍比稀释法测定药物最小抑菌浓度;通过双纸片法、微量棋盘稀释法和时间-杀菌曲线法等实验,评价木犀草素与抗菌药联用对耐甲氧西林金葡菌的抑菌效果。结果：木犀草素对受试MRSA菌株均有抑制作用,最小抑菌浓度为32～128 mg.L-1;其与某些喹诺酮类和氨基糖苷类抗菌药联用时的部分抑菌浓度指数小于或等于0.5,呈现协同抑菌作用,且联用时抗菌药用量较单用时明显减少;时间-杀菌曲线显示,其与抗菌药联用在12和24 h时的协同抑菌效果最好。结论：木犀草素具良好的抗耐甲氧西林金葡菌活性,并与喹诺酮类和氨基糖苷类抗菌药联用具协同抑菌作用。     

Combined effects of arbekacin with other antibiotics against methicillin-resistant Staphylococcus aureus. III. Combined effects of arbekacin with cefotiam or cefuzonam]

Antibacterial effects of combination use of arbekacin (ABK) with cefotiam (CTM) or cefuzonam (CZON) were evaluated against methicillin-resistant Staphylococcus aureus (MRSA) and the following results were obtained. 1. Antibacterial effects of combinations of ABK with CTM and with CZON were equally potent against MRSA at clinically expected 1 MIC of ABK in blood. However, at a sub MIC of ABK the different effects were observed between the 2 combinations. The antibacterial effect of the former was strong and that of the latter was a little weak. 2. In either combination the potency of the antibacterial activity was less dependent on the concentration of CTM or CZON, but was strongly dependent on ABK concentrations. These results suggest that antibacterial effects of the combinations were highly dependent on antibacterial potency and concentration of ABK as previously reported for combinations of ABK with other drugs. 3. The combination use of ABK with CTM appears to be useful in cases of infection by MRSA alone while the combination use of ABK with CZON appears to be useful in cases of double infection with MRSA and Gram-negative bacterium.     

Bacteriological evaluations of combination therapies with minocycline and beta-lactams for methicillin-resistant Staphylococcus aureus. I. Cefotiam plus minocycline]

Since methicillin-resistant Staphylococcus aureus (MRSA) is resistant to multiple antibiotics, only a limited number of antibacterial agents shows efficacy against this bacteria. Therefore, combination therapy is often attempted for MRSA infections. Most of the MRSA strains recently isolated, however, have been found to show very high resistance, and some of the antibiotics which had previously been effective have been failing to produce good responses in increasing numbers of patients. Thus, the drugs used for combination therapy in MRSA infections need to be reevaluated. We assessed the bacteriological efficacy of cefotiam (CTM) plus minocycline (MINO) therapy against MRSA in an in vitro system (CTM shows relatively strong antibacterial activities against MRSA with moderate resistance, and MINO shows strong antibacterial activities against highly resistant MRSA. 1. Against MINO-susceptible MRSA strains, CTM + MINO demonstrated potent antibacterial activities at MINO concentrations of MIC or sub-MIC levels, irrespective of the MIC of CTM against MRSA strains being tested. 2. Against MINO-resistant MRSA strains (strains for which MICs of MINO exceeded the upper limit of the clinically expected plasma MINO level), CTM + MINO showed no significant antibacterial activity. These results suggested that the effect of this combination was dependent on the antibacterial activity of MINO. Therefore, the usefulness of this combination in patients with MRSA infections can be predicted based on susceptibilities of involved strains to MINO. 3. The potent antibacterial effect of this combination against MINO-susceptible MRSA strains was considered to be the result of damage to the cellular membrane by MINO and the subsequent antibiotic effect of CTM.(ABSTRACT TRUNCATED AT 250 WORDS)