含异烟肼凝胶药物介入治疗肺结核病安全性分析

目的对异烟肼凝胶联合体介入治疗的安全性进行分析和临床效果进行评价。方法利用最小抑菌浓度（MIC）和最小杀菌浓度（MBC）法测定异烟肼单体及异烟肼药物凝胶的抗结核效果，并用家兔进行经支气管的介入注药试验，进行了582例临床治疗。结果异烟肼凝胶对H37Rv标准株、牛型结核分枝杆菌、草分枝杆菌MIC值分别为10、5．0、5．0mg／L，MBC值分别为100．10和100ms／L；异烟肼凝胶与异烟肼单体MIC、MBC值无显著差异；家兔动物实验表明该药无任何毒副作用，临床治疗的显效率为73．88％。结论异烟肼凝胶具有与异烟肼单体相同的抗结核菌药效，介入用药以10～100mg／L为宜。     

抗结核药物凝胶介质肺内应用安全性评价

目的 对卡波姆凝胶和阿胶经支气管镜介入兔肺部后的安全性进行评价,为含抗结核药物凝胶肺内应用提供依据.方法 45只日本长耳兔随机分成对照组、卡波姆组和阿胶组,每组15只,实验周期4周.检测体温、体质量、血常规、T细胞亚群及病理.结果 各组间体温、体质量、血常规及外周血T细胞亚群比较差异均无统计学意义.卡波姆组和阿胶组凝胶介入前与介入后CD3+、CD4+、CD8+百分比比较差异亦无统计学意义.卡波姆组实验动物左肺底细支气管无凝胶成分残留.肺大体及光镜病理观察与对照组相比均未产生明显变化.阿胶组实验动物左肺底细支气管有少量阿胶存留,其中1只实验动物出现花斑肺,光镜病理观察可见肺泡间隔内淋巴细胞浸润.其余14只实验动物肺大体及光镜病理观察与对照组比较均未发现明显变化.结论 卡波姆凝胶和阿胶肺内应用均具有较好的安全性,可作为含抗结核药物凝胶的良好基质.     

含母牛分枝杆菌菌苗凝胶肺内应用的免疫效应研究

目的 观察含母牛分枝杆菌菌苗(微卡)凝胶在肺部介入应用后产生的局部及全身免疫应答效应.方法 60只日本长耳兔随机分成5组,每组12只.第1组为对照组,气管插管至末梢支气管注入生理盐水3 ml;第2组为单纯凝胶组,肺部注入卡波姆凝胶3 ml;第3、4、5组为微卡凝胶组,分别注入含3.75、7.50、9.37 mg/L母牛...     

含母牛分枝杆菌菌苗凝胶肺内应用的免疫效应研究

目的 观察含母牛分枝杆菌菌苗(微卡)凝胶在肺部介入应用后产生的局部及全身免疫应答效应.方法 60只日本长耳兔随机分成5组,每组12只.第1组为对照组,气管插管至末梢支气管注入生理盐水3 ml;第2组为单纯凝胶组,肺部注入卡波姆凝胶3 ml;第3、4、5组为微卡凝胶组,分别注入含3.75、7.50、9.37 mg/L母牛...     

一个新的喹诺酮,左旋氧氟沙星(DR-3355)在体外的抗分支杆菌活性

目的:检查左旋氧氟沙星在体外的抗分支杆菌活性。设计:用7H11培养基,以琼脂稀释方法测左旋氧氟沙星对不同种的分支杆菌的最小抑制浓度(MIC),并与氧氟沙星比较。左旋氧氟沙星对于被小鼠腹腔巨噬细胞吞食的结核分支杆菌和胞内分支杆菌的抗微生物活性是以菌落形成单位(CFU)的减少来衡量的。结果:左旋氧氟沙星抗结核分支杆菌、堪萨斯分支杆菌、海鱼分支杆菌、瘰疬分支杆菌、鸟分支杆菌、胞内分支杆菌、偶然分支杆菌和龟分支杆菌的MIC比氧氟沙星的MIC低2到4倍。左旋氧氟沙星减少巨噬细胞内CFU的效果高于氧氟沙星。结论:左旋氧氟沙星比氧氟沙星具有更强的体外抗分支杆菌活性。     

2012-2014年广州地区沙眼衣原体常用抗菌药的敏感性测定北大核心

目的 2012年1月至2014年11月保存的泌尿生殖道沙眼衣原体临床株对几种临床常用代表药物的体外敏感性进行检测和对比,分析药物敏感性的变化情况。方法用McCoy细胞培养法,以能够抑制沙眼衣原体包涵体生长的最低药物浓度为该药对沙眼衣原体的最低抑菌浓度(MIC)。对扩增后感染率达90%以上的70株菌株进行MIC值测定。结果喹诺酮类药物MIC值2012年组明显高于其他两组,已达耐药水平。2013年组及2014年组MIC值明显下降,抗菌活性恢复到敏感水平。各组的MIC90分别为:2012年组:左氧氟沙星MIC90=8.0mg/L,司帕沙星MIC90=5.12mg/L,莫西沙星MIC90=2.0mg/L。2013年组:左氧氟沙星MIC90=0.5mg/L,司帕沙星MIC90<0.04mg/L,莫西沙星MIC90=0.0032mg/L。2014年组:左氧氟沙星MIC90=0.5mg/L,司帕沙星MIC90<0.04mg/L,莫西沙星MIC90<0.0016mg/L。另外,2013年及2014年组阿奇霉素的MIC90较2012年组升高4倍,但仍属于敏感水平,分别为:2012年:0.0064mg/L;2013年:0.025mg/L;2014年:0.025mg/L。其余药物三组间MIC值大致相同。结论 2013年及2014年组较2012年组喹诺酮类药物的MIC值有明显下降,提示敏感性有提高。四环素类及大环内酯类药物的敏感性无明显变化。     

刃天青显色法测定氟喹诺酮对结核杆菌的最小抑菌浓度

目的：用刃天青显色法快速测定4种氟喹诺酮对结核分枝杆菌的最小抑菌浓度（MIC）,探讨不同氟喹诺酮对结核分枝杆菌的作用和可能的交叉耐药性。方法：用65株对氧氟沙星敏感的菌株（包括42株MDR-TB）和60株氧氟沙星耐药的菌株为试验菌株,在96孔酶标板中,用Middle brook 7H9液体培养基将药物进行连续对倍稀释后,加入一定浓度菌液,用显色法测定MIC。结果：氧氟沙星通过ROC曲线分析所确定的折点浓度为2μg/ml,敏感度为98.3%,特异度为96.9%,准确度为97.6%。加替沙星和莫西沙星对结核分枝杆菌的MIC50和MIC90比氧氟沙星、环丙沙星要低4～8倍,具有比氧氟沙星和环丙沙星更好的抗结核分枝杆菌活性。结论：新一代氟喹诺酮加替沙星和莫西沙星具有比第3代氟喹诺酮氧氟沙星和环丙沙星更低的MIC,更好的抗菌活性,有可能用于低度氧氟沙星耐药MDR-TB的治疗。     

鸟分枝杆菌复合群对16种抗感染药物药敏试验的分析

目的 通过比较3种新型喹诺酮类药物(西他沙星、加替沙星和莫西沙星)与其他13种抗感染药物对鸟分枝杆菌复合群(MAC)分离株的体外活性,初步探讨喹诺酮类药物用于治疗MAC疾病的可能性.方法 琼脂梯度稀释法测定上述16种抗感染药物对MAC分离株的最低抑菌浓度(MIC),比较其能抑制90%菌株生长的MIC(MIC90).结果 与胞内分枝杆菌相比,鸟分枝杆菌菌株的MIC范围分布更广,且MIC90多高于胞内分枝杆菌.4种大环内酯类药物中,克拉霉素对鸟分枝杆菌和胞内分枝杆菌的MIC90最低,分别为32和16 mg/L;4种利福霉素类化合物中利福拉齐对鸟分枝杆菌和胞内分枝杆菌的MIC90最低,分别为0.5和0.25 mg/L;5种喹诺酮类药物中西他沙星对鸟分枝杆菌和胞内分枝杆菌的MIC90最低,均为4 mg/L,加替沙星和莫西沙星均为8 mg/L.2株克拉霉素敏感株(MIC=0.5 mg/L)对其他抗感染药物均接近或达到MIC范围的下限,3株克拉霉素不敏感株(MIC=64 mg/L)对除喹诺酮类以外的抗感染药物均接近MIC范围的上限.结论 利福拉齐、西他沙星、加替沙星和莫西沙星对MAC分离株具有较强的体外活性.     

微孔板Alamar blue显色法检测结核分枝杆菌氧氟沙星耐药性的研究

目的 评价微孔板Alamar blue显色法检测结核分枝杆菌氧氟沙星耐药性的可行性。方法 用微孔板Alamar blue显色法对78株结核分枝杆菌检测氧氟沙星的最小抑菌浓度,记录获得结果时间,利用ROC曲线确定氧氟沙星的最佳耐药阈值,并和传统的药物敏感性实验罗氏培养基比例法进行比较。结果 微孔板Alamar blue显色法获得结果平均时间为8 d,氧氟沙星的最佳耐药阈值为2 μg/mL,以罗氏培养基比例法为金标准,氧氟沙星的灵敏度和特异度分别为88.6%和94.1%。结论 微孔板Alamar blue显色法是一种简便、敏感、快速的药物敏感性检测方法,可用于结核分枝杆菌氧氟沙星耐药性的快速检测。     

氟喹诺酮类药物对动物源MRSA和MSSA的防耐药变异浓度比较

目的比较4种氟喹诺酮类药物对动物源性MRSA和MSSA的耐药突变体的选择能力。方法采用琼脂平板稀释法分别测定环丙沙星、左氧沙星、加替沙星和吉米沙星对MRSA和MSSA的MIC值和MPC值,并计算MIC90和MPC90。结果 4种氟喹诺酮药物对85株动物源性MSSA的MPC90值分别为4mg/L、2mg/L、0.5mg/L、0.5mg/L,加替沙星的MPC90/MIC90比值最小;对21株动物源性MRSA的MPC90值分别为128mg/L、64mg/L、16mg/L、8mg/L,吉米沙星的MPC90/MIC90比值最小。结论对动物源性MSSA,加替沙星防耐药突变能力优于其它,加替沙星和吉米沙星单药能有效限制耐药突变株的选择,而左氧沙星和环丙沙星则易选择耐药菌株。对动物源性MRSA,4种药物单药给药均不能有效限制耐药突变株的选择。     

左氧氟沙星的抗结核作用研究

目的 以氧氟沙星（ＯＦＬＸ）为对照,通过药效学、药代动力学、临床试验三方面评价左氧氟沙星（ＬＶＬＸ）的抗结核作用。方法 采用二倍稀释法测定最低抑菌浓度氏杀菌浓度,以半数动物存活时间为指标比较药物对实验性结核病的疗效。高效液相色谱法测定健康志愿者口服３００ｍｇＬＶＬＸ或６００ｍｇＯＦＬＸ血药浓度,求两药各药代动力学参数并进行ｔ检验。将１３８例初、复治菌阳性结核患者随机分入ＬＶＬＸ治疗组或ＯＦＬＸ对照     

氯法齐明对不同耐药类型结核分枝杆菌的体外抑菌活性研究

目的 评价氯法齐明对不同耐药类型的MTB临床分离菌株的体外抑菌活性,为临床应用提供依据.方法 应用微孔板观察法,测定氯法齐明对MTB标准株H37Rv及临床分离敏感、单耐药、多耐药、耐多药和广泛耐药菌株各15株的MIC,并将氯法齐明对不同耐药类型的MTB菌株体外活性与异烟肼、利福平、阿米卡星、卷曲霉素和氧氟沙星进行比较.结果 氯法齐明对敏感菌株的MIC(0.06～4.00mg/L)高于异烟肼(0.06～0.25 mg/L)和利福平(0.06～0.25 mg/L),与氧氟沙星(0.06～2.00mg/L)、阿米卡星(0.06～4.00mg/L)和卷曲霉素(0.50～4.00mg/L)相似;氯法齐明对单耐药菌株的MIC(0.03～4.00mg/L)与异烟肼(0.06～0.25 mg/L)和利福平(0.06～0.25 mg/L)相似,低于氧氟沙星(0.25～8.00mg/L)、阿米卡星(0.06～4.00mg/L)和卷曲霉素(0.50～8.00mg/L);氯法齐明对耐多药菌株的MIC(0.06～8.00mg/L)与阿米卡星(0.25～8.00mg/L)相似,优于氧氟沙星(0.125～8.00mg/L)和卷曲霉素(0.50～8.00mg/L);氯法齐明对广泛耐药菌株的MIC(0.03～8.00mg/L)明显优于其他药物.结论 氯法齐明对MTB菌株,尤其是耐多药和广泛耐药MTB菌株,均有较好的体外抑菌活性.

Abstract：

Objective To study the in vitro antituberculous activities of clofazimine (CLF) to different drug-resistant types of Mycobacterium tuberculosis.Methods The minimal inhibitory concentration (MIC) of CLF and isoniazid (INH), rifampicin (RFP), ofloxacin (OFLX), amikacin (AK), and capreomycin (CPM) against sensitive, single-drug resistant (SDR), poly-drug resistant (PDR), multi-drug resistant (MDR), and extensive-drug resistant (XDR) Mycobacterium tuberculosis strains isolated clinically were determined by microplate assays.Results The MICs of CLF for sensitive, SDR, PDR, MDR and XDR strains of clinically isolated Mycobacterium tuberculosis were 0.06 -4.00 mg/L, 0.03 -4.00 mg/L, 0.06 -8.00 mg/L, 0.06 - 8.00 mg/L, 0.03 - 8.00 mg/L.For the sensitive group, the MIC of CLF ( 0.06 -4.00 mg/L) was higher than that of INH (0.06 -0.25 mg/L) and RFP (0.06 -0.25 mg/L), while there was no significant difference among OFLX (0.06 -2.00 mg/L), AK (0.06 -4.00 mg/L), and CPM (0.50 -4.00 mg/L).For the single-drug resistant group, there was no significant difference among CLF (0.03-4.00 mg/L), INH (0.06-0.25 mg/L), and RFP (0.06-0.25 mg/L), but the MIC of CLF was lower than that of OFLX ( 0.25 - 8.00 mg/L), AK ( 0.06 - 4.00 mg/L ), and CPM ( 0.50 - 8.00 mg/L).For the MDR group, there was no significant difference between CLF (0.06 -8.00 mg/L) and AK (0.25 - 8.00 mg/L), but the MIC of CLF was lower than that of OFLX (0.125 - 8.00 mg/L) and CPM (0.50 -8.O0 mg/L).For the XDR group, the MIC of CLF (0.03 -8.00 mg/L) was lower than that of others.Conclusion CLF showed good in vitro activity against Mycobacterium tuberculosis, especially MDR and XDR strains.     

Comparison of bacteriostatic and bactericidal activity of isoniazid and ethionamide against Mycobacterium avium and Mycobacterium tuberculosis

Minimal inhibitory and bactericidal concentrations (MIC and MBC) of isoniazid and ethionamide were determined in 7H12 broth in experiments with 68 Mycobacterium avium strains and 14 wild drug-susceptible M. tuberculosis strains. MICs of isoniazid for M. tuberculosis were from 0.025 to 0.05 microgram/ml, and for M. avium from 0.6 to greater than 10.0 micrograms/ml. MICs of ethionamide for M. tuberculosis were from 0.3 to 1.25 micrograms/ml, and 42.7% of M. avium strains were within the same range. Isoniazid and ethionamide were highly bactericidal against M. tuberculosis, but they had very low bactericidal activity against M. avium.     

左氧氟沙星联合阿米卡星对肺炎克雷伯菌耐药突变选择窗的研究

目的探讨左氧氟沙星联合阿米卡星对肺炎克雷伯菌突变选择窗(MSW)的影响。方法琼脂倍比稀释法测定左氧氟沙星及其与阿米卡星联合对30株肺炎克雷伯菌的防突变浓度(MPC)和最低抑菌浓度(MIC),计算并比较左氧氟沙星单独及其与阿米卡星联合对肺炎克雷伯菌的选择指数(SI)。结果与阿米卡星联合,使左氧氟沙星对肺炎克雷伯菌的MPC范围由2～16 mg/l降至1～8 mg/L,MPC50由2 mg/L降至1 mg/L,MPC90由8 mg/L降至2 mg/L,P<0.01;左氧氟沙星单药及与联合阿米卡星对肺炎克雷伯菌的选择指数(SI)范围均在2～64,两组SI50均为16;SI90均为32,P>0.05;左氧氟沙星联合阿米卡星组较左氧氟沙星组SI降低的菌株有15株,无变化的有11株,增高的为4株。结论联合阿米卡星可降低左氧氟沙星对肺炎克雷伯菌的MPC,主要使左氧氟沙星对肺炎克雷伯菌的MSW变窄。     

In vitro activity of linezolid against clinical isolates of Mycobacterium tuberculosis, including multidrug-resistant and extensively drug-resistant strains from Beijing, China

The in vitro activity of linezolid was evaluated against 84 clinical isolates of Mycobacterium tuberculosis, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains, isolated from the center for tuberculosis research and treatment of the Chinese army. Linezolid showed excellent activity, with minimum inhibitory concentrations (MICs) of 0.125-0.5 μg/mL against all tested isolates. There were no differences in the MIC(50) and MIC(90) of linezolid between susceptible, isoniazid-resistant, MDR, and XDR. Indeed, all of the groups displayed identical MIC(90) values of 0.25 μg/mL, which is lower than previously reported in similar studies. We conclude that linezolid may be a more effective drug against M. tuberculosis and may play an important role in treating drug-resistant tuberculosis in China.     

A randomized, crossover design study of the pharmacology of extended-spectrum fluoroquinolones for pneumococcal infections.

STUDY OBJECTIVES: The objectives of this study were to characterize the single-dose and steady-state plasma pharmacokinetics of IV levofloxacin and IV alatrofloxacin, and to compare the results to pneumococcal isolate sensitivities in order to estimate the clinical efficacy of current community-acquired pneumonia treatment regimens against pneumococcal infections. DESIGN: Two-way, open-label, randomized, crossover study. PARTICIPANTS: Each of 12 healthy volunteer subjects received IV levofloxacin, 500 mg qd for 7 days, and IV alatrofloxacin, 200 mg qd for 7 days. The two regimens were separated by a 2-week washout period. MEASUREMENTS AND RESULTS: Plasma concentration profiles were collected around the first and final doses of both regimens and were assayed for their respective quinolone concentrations. When the peak concentrations for both agents were compared to standard twofold dilution minimum inhibitory concentration (MIC) values for pneumococcal isolates, it was discovered that the breakpoint MIC value at which each compound would no longer achieve a peak plasma concentration/MIC ratio of at least 12:1 was 0.5 mg/L for levofloxacin and 0.25 mg/L for alatrofloxacin. CONCLUSIONS: Based on the MIC that inhibits 90% of isolates of Streptococcus pneumoniae for both of these agents (1.0 to 2.0 mg/L for levofloxacin and 0.125 to 0.25 mg/L for trovafloxacin), our results indicate that although the once-daily regimen of alatrofloxacin appears to be appropriate for this pathogen, a more aggressive regimen may need to be investigated to optimize the clinical and microbiological effects of levofloxacin.     

In vitro antimycobacterial activity of a new quinolone,levofloxacin (DR3355)

Obiective: To examine in vitro antimycobacterial activity of levofloxacin.Design: Minimum inhibitary concentrations (MICs) of levofloxacin for various mycobacterial species were determined by the agar dilution method using 7H11 medium and compared with those of ofloxacin. Antimicrobial activity of levofloxacin against Mycobacterium tuberculosis and M. intracellulare phagocytosed in murine peritoneal macrophages was measured in terms of reducing cell-associated bacterial colony forming units (CFUs).Results: MICs of levofloxacin against M. tuberculosis, M. kansasii, M. marinum, M. scrofulaceum, M. avium, M. intracellulare, M. fortuitum, and M. chelonae were 2 to 4 times lower than those of ofloxacin. Levofloxacin exhibited higher efficacy in reducing bacterial CFUs in macrophages than ofloxacin.Conclusion: Levofloxacin possessed more potent in vitro antimycobacterial activities as compared to that of ofloxacin.     

噬菌体生物扩增法快速测定结核分枝杆菌左氧氟沙星耐药性

目的建立快速测定结核分枝杆菌左氧氟沙星耐药性的噬菌体生物扩增法,并探讨其在耐药性测定中的应用价值。方法应用噬菌体生物扩增法测定456株结核分枝杆菌左氧氟沙星耐药性。并与绝对浓度法结果进行比较,对不符合的菌株采用BactecMGIT960测定其最低抑菌浓度(MIC)。结果噬菌体测定456株结核分枝杆菌临床分离株左氧氟沙星敏感267株,耐药189株,绝对浓度法敏感279株,耐药177株。两法测定均为敏感257株,均为耐药167株。在32株噬菌体法与绝对浓度法测定结果不符合的菌株中30株噬菌体法与MIC测定结果相符。如以绝对浓度法药敏结果判断标准,则噬菌体法测左氧氟沙星耐药性的敏感性为94.35%,特异性为92.11%,阳性预测值为88.36%。阴性预测值为96.26%,准确性为92.98%。结论噬菌体生物扩增法测定左氧氟沙星耐药性需2d,操作简便.不需要特殊仪器设备,可作为结核分枝杆菌左氧氟沙星耐药性的快速筛选方法。