莫西沙星治疗耐多药肺结核患者的药效学研究

目的探讨莫西沙星片口服给药和局部介入治疗用药量的依据。方法莫西沙星血清中浓度采用高效液相色谱法测定,时间-杀菌、MIC、MBC及耐药梯度等试验在体外检测。结果 10例肺结核患者血峰浓度于1.81h到达（3.11±0.53）mg/L,1次单剂量给药24h后最低血药浓度为（0.26±0.06）mg/L,表观分布容积V/FC为（150.02±32.63）L,该药MIC.MBC值为0.20mg/L,1mg/L,耐药梯度范围在0.20～8mg/L。结论服用莫西沙星片治疗耐药肺结核患者,体内血药浓度24h应维持在最低杀菌浓度之上,介入治疗用药浓度应在8μg/ml以上。     

左旋氧氟沙星的体外抗结核作用

目的观察左旋氧氟沙星(利复星)在体外的抗结核活性.方法通过最低抑菌浓度(MIC),最低杀菌浓度(MBC)的测定及左旋氧氟沙星对结核菌的瞬间-杀菌试验,时间-杀菌试验,综合评价左旋氧氟沙星的抗结核作用.结果左旋氧氟沙星在所试3种培养基中对人型结核菌(H37RV),本院住院病人耐药株的MIC分别为1mg*L-1及2mg*L-1,MBC为2mg*L-1.左旋氧氟沙星对结核菌的瞬间杀菌作用效果不佳,左旋氧氟沙星浓度为2mg*L-1,菌浓度为105CFV*ml-1时,10～24h,60d未能培养出菌,耐药株12～24h60d未能培养出菌.结论左旋氧氟沙星具有较强的抗结核活性,对结核菌无瞬间杀菌作用,体外杀菌时间一般不得低于8h,临床使用时注意使左旋氧氟沙星的体内药物浓度24h维持在最低杀菌浓度之上.     

吡嗪酰胺介入凝胶体外抗结核活性及安全性评价

目的 :观察吡嗪酰胺凝胶体外抗结核作用和支气管介入的安全性。方法 :手工法、仪器法分别测定吡嗪酰胺单体、吡嗪酰胺凝胶的最小抑菌浓度 (MIC)和最小杀菌浓度 (MBC)及家兔经支气管介入的安全性试验。结果 :吡嗪酰胺凝胶对人型结核分枝杆菌标准株、牛型结核分枝杆菌、草分枝杆菌MIC值分别为1mg/L、1mg/L、10mg/L ,MBC值分别为10mg/L、10mg/L、40mg/L ;吡嗪酰胺凝胶与吡嗪酰胺单体MIC、MBC值无显著性差异 ;动物安全性试验阴性。结论 :吡嗪酰胺凝胶具有与吡嗪酰胺单体相同的抗结核菌药效 ,卡波姆基质不影响吡嗪酰胺的抗菌活性 ;卡波姆基质吡嗪酰胺凝胶应用安全     

异烟肼介入凝胶体外抗结核作用及安全性评价

目的：观察异烟肼凝胶体外抗结核活性和支气管介入的安全性。方法：手工法，仪器法分别测定异烟肼、异烟肼凝胶的最小抑菌浓度和最小杀菌浓度及家兔经支气管介入的安全性。结果：异烟肼凝胶对H37RV标准株，牛型结核分枝杆菌MIC值均为1mg.L^-1，对草分枝杆菌MIC值为8mg.L^-1，对H37RV标准株，牛型结核分枝杆菌MBC值均为4mg.L^-1，对草分枝杆菌MBC值为16mg.L^-1，异烟肼凝胶与异烟肼单体MIC、MBC值差异无显著性；动物安全性试验阴性，结论：异烟肼凝胶具有与异烟肼单体相同的抗结核菌药效，卡波姆基质不影响异烟肼的抗菌活性；卡波姆基质异烟肼凝胶应用安全。     

吡嗪酰胺介入凝胶体外抗结核活性及临床应用

目的观察吡嗪酰胺凝胶体外抗结核作用和支气管介入的安全性。方法手工法、仪器法分别测定吡嗪酰胺单体、吡嗪酰胺凝胶的最小抑菌浓度(MIC)和最小杀菌浓度(MBC)及家兔经支气管介入的安全性试验。结果吡嗪酰胺凝胶对人型结核分枝杆菌标准株、牛型结核分枝杆菌、草分枝杆菌MIC值分别为1.0、1.0、10mg/L,MBC值分别为10、10、40mg/L;吡嗪酰胺凝胶与吡嗪酰胺单体MIC、MBC值无显著性差异;动物安全性试验阴性。结论吡嗪酰胺凝胶具有与吡嗪酰胺单体相同的抗结核菌药效,卡波姆基质不影响吡嗪酰胺的抗菌活性;卡波姆基质吡嗪酰胺凝胶应用安全。     

帕司烟肼介入凝胶体外抗结核活性及安全性研究

目的 观察帕司烟肼凝胶体外抗结核作用和支气管介入的安全性。方法 手工法、仪器法分别测定帕司烟肼及其凝胶的最小抑菌浓度和最小杀菌浓度及家兔经支气管介入的安全性试验。结果 帕司烟肼凝胶对H37Rv标准株、牛型结核分枝杆菌、草分枝杆菌MIC值分别为0．1、0，1、0．4mg／L，MBC值分别为0，2、0．2和1．6mg／L；帕司烟肼凝胶与帕司烟肼单体MIC、MBC值无显著差异；动物实验表明该药应用安全。结论 帕司烟肼凝胶具有与帕司烟肼单体相同的抗结核菌药效，卡波姆基质不影响帕司烟肼的抗菌活性；以卡波姆为基质的帕司烟肼凝胶应用安全。     

阿莫西林与红霉素对肺炎链球菌的体外抗菌效果

目的研究阿莫西林(β内酰胺类抗生素)和红霉素(大环内酯类抗生素)联合应用体外对肺炎链球菌的相互作用,并验证红霉素对肺炎链球菌的杀菌作用。方法用琼脂平板二倍稀释法测定阿莫西林和红霉素对肺炎链球菌的最低抑菌浓度(MIC),用影印培养法测定最低杀菌浓度(MBC)。用棋盘微量稀释法和时间-杀菌曲线分析测定两药对肺炎链球菌的联合作用效果。结果阿莫西林对44株菌株的MIC为≤0.004～2mg·L-1,MBC≤0.004～4mg·L-1;红霉素对其的MIC值为0.008～≥256mg·L-1,MBC为0.016～≥256mg·L-1。阿莫西林的MBC/MIC为1～2;红霉素的MBC/MIC的为1～4。对阿莫西林和红霉素均敏感的肺炎链球菌株联合用药时,大部分菌株较单用时相同或略下降,其FICI在1～2。结论红霉素在体外对肺炎链球菌有杀菌作用;与阿莫西林体外联合应用时,阿莫西林杀菌效果不会被减弱。     

葎草水提液的体外抑菌作用研究

目的:研究葎草水提液的体外抑菌效果。方法:采用倍比稀释法和96孔板微量肉汤稀释法对金黄色葡萄球菌、大肠埃希菌、铜绿假单胞菌进行体外抑菌试验,测定其抑菌圈直径、最小抑菌浓度(MIC)和最低杀菌浓度(MBC)。结果:该药对试验菌株呈现不同程度的敏感,大肠埃希菌的MIC和MBC值浓度同为31.25 mg·ml-1;对金黄色葡萄球菌的MIC和MBC值浓度同为3.91 mg·ml-1;对铜绿假单胞菌的MIC和MBC值分别为125 mg·ml-1和250 mg·ml-1。结论:以水煎液为研究对象,考察葎草的体外抑菌效果更贴近临床应用形式,为葎草相关制剂的深入研究提供参考。     

异质性万古霉素耐药金黄色葡萄球菌的抗生素后效应

目的 了解异质性万古霉素耐药金黄色葡萄球菌（h-VRSA）对万古霉素的抗生素后效应（PAE）等药代动力学特点,探讨h-VRSA的存在,对万古霉素的杀菌活性及其临床应用方面的影响。方法 分别检测ATCC29213和h-VRSA（原代培养）的最低抑菌浓度（MIC）、最低杀菌浓度（MBC）以段PAE。结果 ATCC29213的MIC和MBC分别为1μg/ml和16μg/ml,h-VRSA（原代）的MIC和MBC分别为2μg/ml和64μg／ml;两者PAE分别为0.9h和2．2h、结论 与ATCC 29213不同,hVRSA的PAE明显延长;MIC为2μg／ml的h-VRSA其MBC可以达到6μg/ml．已经高于万古霉素的有效血药浓度峰值（20～40）μg／ml;提示单独使用万古霉素已经不能完清清除h-VRSA．     

蒜氨酸、蒜酶及蒜氨酸+蒜酶对白假丝酵母菌生长的影响

目的 检测蒜氨酸、蒜酶及蒜氨酸+蒜酶对白假丝酵母菌的体外抑菌作用.方法 采用液体稀释法、平板计数法测定三者对白假丝酵母菌的最低抑菌浓度(MIC)、最低杀菌浓度(MBC),并采用菌落法绘制时间-杀菌曲线.结果 蒜氨酸和蒜氨酸+蒜酶均可抑制、杀伤白假丝酵母菌,MIC分别为50、1.56 mg·mL-1,MBC分别为100、3.12 mg·mL-1;而蒜酶单体无此作用.结论 蒜氨酸和蒜氨酸+蒜酶均对白假丝酵母菌有抑菌作用.     

Thymol nanospheres as an effective anti-bacterial agent

Among thymol, carvacrol, citronellal, eugenol and terpinen-4-ol, thymol showed the highest antibacterial activity against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Thymol was then encapsulated into water dispersible submicron sized ethylcellulose/methylcellulose spheres, attaining the relatively high thymol loading level of 43.53% (weight of encapsulated thymol to weight of the thymol-loaded spheres). When tested against the same three bacterial strains, the encapsulated thymol gave comparable minimal inhibition concentration (MIC) and minimal bactericidal concentration (MBC) values to the unencapsulated compound while mostly showing lower MIC and MBC values than the conventionally used preservative, methyl-p-hydroxybenzoate (methylparaben). The use of encapsulated thymol at 0.078, 0.156 and 0.625 mg ml(-1) (0.52, 1.04 and 4.16 mmol(-1), respectively) in cosmetic lotion formulations provided total suppression of viable E. coli, S. aureus and P. aeruginosa growth (all initially seeded at 10(5) cfu ml(-1)), respectively, over the three month test period, whereas unencapsulated thymol showed effective suppression for only 2-4 weeks. Effective bacterial suppression by encapsulated thymol was also observed when used in cream and aqueous gel cosmetic formulations.     

诺氟沙星的体外抗菌作用评价

目的：评价诺氟沙星对烧烫伤创面常见致病菌的抑菌、杀菌作用。方法：用浊度法测定诺氟沙星对金黄色葡萄球菌（ATCC6538）、大肠杆菌（ATCC8099）和铜绿假单胞菌[CMCC（B）10110]的最小抑菌浓度（MIC）和最小杀菌浓度（MBC）,实验平行3次,观察诺氟沙星培养液的浊度。结果：诺氟沙星对金黄色葡萄球菌的MIC为0．15μg·ml^-1,MBC为0．25μg·ml^-1;对大肠杆菌的MIC为0．25μg·ml^-1,MBC为5．0μg·ml^-1;对铜绿假单胞菌的MIC为4．57μg·ml^-1,MBC为14．0μg·ml^-1。结论：诺氟沙星在体外对烧烫伤创面常见致病菌均具有较强的抗菌作用,可为临床创面用药剂量的筛选提供一些依据。     

Colorimetric in vitro susceptibility testing of penicillins, cephalosporins, macrolides, streptogramins, tetracyclines, and aminoglycosides against Borrelia burgdorferi isolates

The spectrum of antibiotic susceptibility of Borrelia burgdorferi has been only partially defined. In the present study the effectiveness of 12 antimicrobials, belonging to six different antibiotic classes have been tested against Borrelia burgdorferi s.s. (N=3), Borrelia garinii (N=3), Borrelia afzelii (N=3), Borrelia valaisiana (N=1), and Borrelia bissettii (N=1) isolates. These isolates were analysed by a new standardised colorimetric minimal inhibitory concentration (MIC) method based upon colour changes that result from actively metabolizing spirochaetes after 72 h of incubation. Piperacillin (MIC90: 0.08 mg/l), ceftriaxone (MIC90: 0. 04 mg/l), cefotaxime (MIC90: 0.15 mg/l), azithromycin (MIC90: 0.015 mg/l), roxithromycin (MIC90: 0.05 mg/l) and quinupristin/dalfopristin (MIC90: 0.12 mg/l) gave the lowest MIC values. Minimal inhibibitory activity of amoxycillin (MIC90: 1.04 mg/l), cefixime (MIC90: 1.33 mg/l), cefoperazone (MIC90: 0.83 mg/l) tetracycline (MIC90: 0.29 mg/l) and minocycline (MIC90: 0.30 mg/l) was slightly lower, whereas borrelia were resistant to amikacin (MIC90: >128 mg/l). Mean minimal borreliacidal concentrations (MBCs) were representatively determined for piperacillin (MBC: 1.8 mg/l), ceftriaxone (MBC: 2.0 mg/l), azithromycin (MBC: 0.82 mg/ml), roxithromycin (MBC: 1.8 mg/l), quinupristin/dalfopristin (MBC: 5.0 mg/l), minocycline (MBC: 5.8 mg/l), and amikacin (MBC: >128 mg/l) by using conventional subculture for three weeks in combination with dark-field microscopy. B. garinii proved to be the most susceptible of the genospecies tested. Our study showed excellent in vitro antimicrobial activity of all classes of antibiotics tested, except the aminoglycosides and hence their suitability for therapy of Lyme disease.     

Photodynamic activity of the haematoporphyrin derivative with rutin and arginine substituents (HpD-Rut(2)-Arg(2)) against Staphylococcus aureus and Pseudomonas aeruginosa.

The impact of the new photosensitizer HpD-Rut(2)-Arg(2)on the growth of methicillin-resistant Staphylococcus aureus(MRSA), methicillin-susceptible Staphylococcus aureus (MSSA) and Pseudomonas aeruginosa clinical strains isolated from infected burn wounds was examined. The susceptibility of the isolates to the photodynamic action of the sensitizer was evaluated by the determination of minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) using the newly developed microdilution method. The results were compared with the previously investigated HpD-Arg(2). All clinical isolates examined proved to be susceptible to the photodynamic action of HpD-Rut(2)-Arg(2). The MIC of this newly synthetized photosensitizer ranged from 0.8 to 12.5 microg ml(-1) for MRSA, from 0.4 to 6.2 microg ml(-1) for MSSA and from 6.2 to 50 microg ml(-1) for P. aeruginosa. While MBC ranged from 1.6 to 12.5 microg ml(-1) for MRSA, 0.4 to 6.2 microg ml(-1) for MSSA and 6.2 to 100 microg ml(-1) for P. aeruginosa. This photosensitizer is more effective in its bactericidal photodynamic action than previously tested HpD-Arg(2).     

Electron-microscopic study of the bactericidal effect of OPB-2045, a new disinfectant produced from biguanide group compounds, against methicillin-resistant Staphylococcus aureus

The bactericidal effect of OPB-2045, a new disinfectant produced from biguanide group compounds, against methicillin-resistant Staphylococcus aureus (MRSA), MRSA IID 1677, was investigated by transmission electron microscopy. OPB-2045 showed strong bactericidal activity against MRSA. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of OPB-2045 against the test strain were 0.78 and 1.56 microg mL(-1), respectively. The test bacteria were incubated in the presence of OPB-2045 at 1/2 MIC (0.39 microg mL(-1)), 1 MIC (0.78 microg mL(-1)), 2 MIC (1 MBC, 1.56 microg mL(-1)), 4 MIC (2 MBC, 3.13 microg mL(-1)) or 10 MIC (5 MBC, 7.8 microg mL(-1)) at 37 degrees C for 30 s, 3 min, 30 min or 6h. The morphology of the cells was examined by transmission electron microscopy. The cell damage observed after 30-min or 6-h incubation in the presence of OPB-2045 at 1/2 or 1 MIC was the same as that at 2, 4 or 10 MIC. The numbers of damaged MRSA cells increased according to the increase in concentration of added disinfectant, and the image of bacteriolysis was observed, too. After treatment at 1/2 or 1 MIC, a few leaking cells were recognized, but no destroyed cells were found. No morphological changes were observed after treatment at 1 or 2 MIC for 30 s, 3 min or 30 min. When the incubation time was extended to 6 h, morphological changes in the MRSA cells treated at 1 or 2 MIC were observed. When examining the relationship between the numbers of surviving bacteria and the MIC (MBC) values in soybean casein digest broth, no decrease in MRSA cell numbers was recognized in the untreated control or at 1/2 MIC, but a marked decrease in MRSA cell numbers was recognized as the OPB-2045 concentration was increased. The new disinfectant OPB-2045 would make a useful contribution to the medical field for the prevention of infections caused by pathogenic bacteria such as MRSA.     

Synthesis and antimicrobial activities of some new tetrahydro-2H-1,3,5-thiadiazine-2-thione derivatives of amoxicillin

A number of 6-[2-(dihydro-5-substituted-6-thioxo-2H-1,3,5-thiadiazine-3( 4H)-yl)-2-(4-hydroxyphenyl)acetamido]penicillanic acids has been synthesized as prodrugs by incorporating the amine group of amoxicillin trihydrate into tetrahydro-2H-1,3,5-thiadiazine-2-thione ring. The compounds have been prepared by the reaction of various alkyl or aralkyl amines with potassium hydroxide, carbon disulfide, formaldehyde and amoxicillin trihydrate. The structures of the compounds have been elucidated by UV, IR, 1H-NMR spectra and elementary analysis. The in vitro activity of these compounds against gram-positive bacteria (Staphylococcus aureus, Streptococcus faecalis), gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa) and yeast-like fungi (Candida albicans, C. parapsilosis, C. stellatoidea, C. pseudotropicalis) was investigated by the tube dilution method and compared with the activity of amoxicillin trihydrate. By this way their minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC) and minimal fungicidal concentration (MFC) values were determined. Compound I and Compound VII were significantly more effective than amoxicillin trihydrate against S. aureus (MBC: 6.25 micrograms/ml). Compound VI and Compound XI were effective against S. faecalis (MBC: 6.25 micrograms/ml) and Compound I and Compound VI were effective against E. coli (MBC: 12.5 micrograms/ml). All of the compounds and amoxicillin trihydrate were ineffective against P. aeruginosa (MIC: greater than 100 micrograms/ml). Compound IX and Compound X were the most active derivatives against yeast-like fungi; the MFC values for these compounds ranged between 6.25 and 37.5 micrograms/ml.     

聚季铵盐-1的抑菌活性及其稳定性研究

目的研究聚季铵盐-1的抑菌活性及其稳定性。方法采用营养肉汤试管二倍稀释法测定聚季铵盐-1对大肠杆菌、金黄色葡萄球菌、铜绿假单胞菌、白色念珠菌和黑曲霉的最低抑菌浓度(MIC)和最低杀菌浓度(MBC),并研究紫外光照射、温度、pH和盐浓度对聚季铵盐-1稳定性的影响。结果聚季铵盐-1对5种试验菌的MIC依次为16,4,16,8,64μg/mL;对5种试验菌的MBC依次为16,8,32,8,128μg/mL。聚季铵盐-1的抑菌活性不受紫外光和pH的影响,但会随温度和盐浓度的升高而降低。结论聚季铵盐-1在较低浓度具有抑制微生物生长的活性,对紫外照射和pH较稳定,高温易使其分解,在高渗环境下,其抑菌活性也会显著降低。