抗结核药物对非结核分枝杆菌菌种鉴定的试验

报告２２种非结核分枝杆菌典型株对１２种抗结核药物的敏感性试验结果,２２种非结核分枝杆菌在食ＴＨ１３２１,ＴＢ１,ＰＡＳ,ＩＮＨ培养其呈现不同程度耐药性,胞内分枝杆菌等１３种非结核分枝杆菌在含ＳＭ,ＥＭＢ,ＲＦＰ培养基呈现不同程度耐药性,鸟分枝杆菌等６种非结核分支杆菌在含ＮＦＬＸ,ＯＦＬＸ,ＣＦＬＸ培养基呈现不同程度耐药性,海分枝杆菌等３种非结核分枝杆菌在含ＣＰＭ培养其呈现不同程度耐药性,龟分枝杆菌     

23株非结核分枝杆菌药物敏感性试验分析

目的 对自贡市临床分离鉴定的23株非结核分枝杆菌分别进行26种抗生素的药物敏感试验,了解非结核分枝杆菌对不同抗生素的耐药性,为非结核分枝杆菌病临床治疗提供依据。方法 采用微孔板阿尔玛蓝测定法(microplate Alamarblue assay,MABA)测试每种药物对每株非结核分枝杆菌的最低抑菌浓度(MIC值),通过MIC值判断该菌对此种抗生素是否耐药。结果 非结核分枝杆菌对大部分抗结核药物耐药,并且对部分药物的耐药存在种间差异。其中脓肿分枝杆菌耐药率达84.6%,鸟分枝杆菌与胞内分枝杆菌分别达53.8%与52.3%,堪萨斯分枝杆菌耐药率最低为38%。结论 对临床非结核分枝杆菌肺病,快速菌株鉴定及药敏试验是治疗的关键。     

抗脓肿分枝杆菌肺病严重超敏反应2例及文献复习

<正>脓肿分枝杆菌为常见的一种非结核分枝杆菌,致病性强、耐药性高,其导致的肺病是临床上治疗难度极大的一种非结核分枝杆菌肺病。目前临床上针对脓肿分枝杆菌肺病治疗的方案以大环内酯类、氨基糖苷类、头孢西丁等为核心的多药联合治疗方案。由于治疗时间较长,经常出现各种药物副反应。这里我们就临床工作中碰到的两例脓肿分枝杆菌肺病治疗过程中出现严重不良反应的病例进行报道。     

康乐霉素A体外抗结核活性的初步研究

目的发现新安莎类抗生素，康乐霉素A体外抗结核活性。方法应用色谱技术从地中海诺卡氏菌康乐变株1747-64发酵液中分离康乐霉素A，并采用试管二倍稀释法，进行康乐霉素A对耻垢分枝杆菌（ATCC14468），结核分枝杆菌H37Rv（ATCC27294），H37Ra（ATCC25177），临床分离的氧氟沙星（OFLX）敏感结核分枝杆菌以及临床分离的耐氧氟沙星结核分枝杆菌最低抑制浓度（Minimal Inhibitor Concentration，MIC）的试验。结果康乐霉素A对耻垢分枝杆菌活性弱，MIC为64μg／ml，对结核分枝杆菌H37Rv，H37Ra的MIC为8μg／ml，对临床分离的氧氟沙星敏感结核分枝杆菌菌株的MIC范围为1～8μg／ml，临床分离的耐氧氟沙星结核分枝杆菌菌株的MIC范围为1～16μg／ml。结论新安莎类抗生素，康乐霉素A体外具有明显的抗结核活性，有望成为新抗结核药物或先导化合物。     

某高级中学结核病突发疫情的实验室鉴定

自然界中分枝杆菌种类很多，由于其生物学特性、对药物的敏感性以及对人的致病性不同，因此，不同分枝杆菌在疾病治疗、预防中的意义不同。结核分枝杆菌是引起人类结核病的常见病原菌，随着研究进展，近年由非结核分枝杆菌引起的非结核分枝杆菌病的报道有逐年增多的趋势。在当前报道的一百余种非结核分枝杆菌中，只有少数为致病菌，大多数为条件致病菌，它们往往对多种抗结核药物耐药，     

康乐霉素A体外抗结核活性的初步研究

目的发现新安莎类抗生素,康乐霉素A体外抗结核活性。方法应用色谱技术从地中海诺卡氏菌康乐变株1747-64发酵液中分离康乐霉素A,并采用试管二倍稀释法,进行康乐霉素A对耻垢分枝杆菌（ATCC14468）,结核分枝杆菌H₃₇Rv（ATCC27294）,H₃₇Ra（ATCC25177）,临床分离的氧氟沙星（OFLX）敏感结核分枝杆菌以及临床分离的耐氧氟沙星结核分枝杆菌最低抑制浓度（Minimal Inhibitor Concentration,MIC）的试验。结果康乐霉素A对耻垢分枝杆菌活性弱,MIC为64μg/ml,对结核分枝杆菌H₃₇Rv,H₃₇Ra的MIC为8μg/ml,对临床分离的氧氟沙星敏感结核分枝杆菌菌株的MIC范围为18μg/ml,临床分离的耐氧氟沙星结核分枝杆菌菌株的MIC范围为116μg/ml。结论新安莎类抗生素,康乐霉素A体外具有明显的抗结核活性,有望成为新抗结核药物或先导化合物。     

铜陵地区结核与非结核分枝杆菌菌型鉴定及耐药性分析

目的通过检测本地区分枝杆菌感染菌株类型以及耐药性,制订化疗方案提供依据。方法采取两种试剂鉴定菌株,绝对浓度法检测药敏耐药性。结果 80株分枝杆菌中人型结核分枝杆菌58例,占72.5%;牛型结核分枝杆菌15例,占18.8%;非结核分枝杆菌7例,占8.7%。结核分枝杆菌复合群耐多药率9.6%。非结核分枝杆菌耐多药率85.7%。牛型结核分枝杆菌对药物敏感性大于人型结核分枝杆菌,人型结核分枝杆菌对药物敏感性大于非结核分枝杆菌。耐药以耐R、H、TH1321、Rtf、PAS多见。结论本地区肺部感染分枝杆菌菌株以结核分枝杆菌复合群为主,耐多药率及非结核分枝杆菌感染率略高于全国水平。     

29例非结核分枝杆菌的药敏实验分析

目的 观察非结核分枝杆菌(NTM)的耐药情况.方法 我院分枝杆菌培养阳性并鉴定为非结核分枝杆菌的病例,对其药敏结果进行分析.结果 748例分枝杆菌培养阳性病例中,29株为非结核分枝杆菌,占3.9％,29株非结核分枝杆菌对异烟肼、利福平、链霉素、乙胺丁醇、对氨基水杨酸、阿米卡星、对氨基水杨酸异烟肼、卷曲霉素、左氧氟沙星、利福喷丁、丙硫异烟胺等11种常用药物有不同程度的耐药,耐药率高达100％.结论 非结核分枝杆菌对抗结核药的高耐药应引起重视.     

44例痰非结核分枝杆菌耐药情况分析

目的观察分析痰非结核分枝杆菌（NTM）的耐药情况。方法回顾近年太原市第四人民医院痰分枝杆菌培养阳性并鉴定为非结核分枝杆菌的病例,对其药敏结果进行分析。结果 437例痰分枝杆菌培养阳性病例中,44株为非结核分枝杆菌,占10.07%,44株非结核分枝杆菌对异烟肼、对氨基水杨酸钠、乙胺丁醇、利福平、链霉素等常用药物有不同程度的耐药,耐药率高达97.7%,且大都同时对多种药物耐药。结论非结核分枝杆菌对抗结核药的高耐药应引起重视,应对可疑NTM肺病及早做痰培养和尽可能多的药物敏感性测定,研究抗NTM新药与更有效的诊治手段是当前的迫切需要。     

结核分枝杆菌耐利奈唑胺相关基因研究进展

耐多药结核病(MDR-TB)及耐利福平结核病(RR-TB)均需采用二线抗结核药物治疗。利奈唑胺属恶唑烷酮类抗生素,是治疗MDR-TB及RR-TB的二线核心抗结核药物之一,其抗结核作用较强,但近年来结核分枝杆菌对利奈唑胺耐药现象增多且具体耐药机制尚未完全明确。本文综述了结核分枝杆菌耐利奈唑胺相关基因,旨在为结核分枝杆菌对利奈唑胺的耐药机制研究提供参考。     

Macrolides in cystic fibrosis

Macrolide antibiotics have been licensed since the 1950s and have an important role in the treatment of a diverse range of infectious diseases. Macrolide antibiotics have antibacterial activity against gram-positive bacteria, some gram-negative bacteria and intracellular pathogens. The spectrum of antibacterial activity combined with excellent intracellular and tissue penetration has led to the extensive use of this class of drugs in respiratory disease. Macrolide antibiotics also have demonstrated anti-inflammatory properties in various in vitro and in vivo model systems. Novel antimicrobial and anti-inflammatory properties of macrolide may result in clinical benefits, particularly in conditions where the infectious agent is inherently resistant to macrolides. Three randomized control trials have demonstrated improved lung function in patients treated with the macrolide antibiotic, azithromycin. Azithromycin was generally well tolerated and resulted in reduction in the inflammatory response which may be due to an immunomodulatory role. Short term studies (three to six months) have not demonstrated the development of increased bacterial resistance or the emergence of new pathogens following azithromycin.     

In vitro anti-mycobacterial activity of some new amino-glycoside antibiotics.

Four new aminoglycoside antibiotics, namely gentamycin, amikacin, tobramycin and sisiomycin were tested against several pathogenic strains of so-called 'typical' and 'atypical' mycobacteria. Only amikacin exhibited considerable in vitro anti-mycobacterial activity against Mycobacterium tuberculosis and not against other mycobacterial pathogens. None of the other three antibiotics exhibited activity against any of the mycobacteria at low concentrations.     

Effects of macrolide antibiotics against mucoid Pseudomonas aeruginosa

Macrolide antibiotics at concentrations by far lower than their MICs proved to inhibit the production of alginate, elastase, and protease by mucoid Pseudomonas aeruginosa. The morphological study of mucoid P. aeruginosa under the electron microscope revealed the slime-like structures common to the cell morphology of the organism in cultured colonies and foci in a model for respiratory tract infection in mice, and the strains of mucoid P. aeruginosa which had been allowed to get in contact with the drugs proved to produced obviously fewer slime-like structures than control strains. The effect of a 14-membered macrolide, erythromycin, against mucoid P. aeruginosa was also observed with a 16-membered macrolide, rokitamycin this effect appeared to be common to the macrolide.     

23S rRNA base pair 2057-2611 determines ketolide susceptibility and fitness cost of the macrolide resistance mutation 2058A-->G

The 23S rRNA A2058G alteration mediates macrolide, lincosamide, and streptogramin B resistance in the bacterial domain and determines the selectivity of macrolide antibiotics for eubacterial ribosomes, as opposed to eukaryotic ribosomes. However, this mutation is associated with a disparate resistance phenotype: It confers high-level resistance to ketolides in mycobacteria but only marginally affects ketolide susceptibility in streptococci. We used site-directed mutagenesis of nucleotides within domain V of 23S rRNA to study the molecular basis for this disparity. We show that mutational alteration of the polymorphic 2057-2611 base pair from A-U to G-C in isogenic mutants of Mycobacterium smegmatis significantly affects susceptibility to ketolides but does not influence susceptibility to other macrolide antibiotics. In addition, we provide evidence that the 2057-2611 polymorphism determines the fitness cost of the 23S rRNA A2058G resistance mutation. Supported by structural analysis, our results indicate that polymorphic nucleotides mediate the disparate phenotype of genotypically identical resistance mutations and provide an explanation for the large species differences in the epidemiology of defined drug resistance mutations.     

Activity of azithromycin (CP-62,993) and erythromycin against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum in vitro.

Several antibiotics, including the macrolide erythromycin and the azalides azithromycin (CP-62,993) and CP-63,956, that inhibit protein synthesis on 70S ribosomes demonstrated antimalarial effects in vitro against two strains of Plasmodium falciparum, one sensitive to chloroquine and the other resistant. In 48-hr incubations, erythromycin was 10-fold less potent than the azalides against the chloroquine-resistant strain. Erythromycin and the azalides were essentially equipotent against the chloroquine-sensitive strain. An additive effect occurred with the azalides in combination with chloroquine against both strains, but this was not seen with erythromycin.     

Effect of pH on the in vitro activity of and propensity for emergence of resistance to fluoroquinolones, macrolides, and a ketolide

Antibiotic activity against common respiratory pathogens can be affected by the pH of the medium (in vitro) or the bodily fluid (in vivo) in which bacteria are present. The ionized fraction of an antibiotic is not able to efficiently penetrate bacterial or mammalian membranes, reducing the quantity of molecules able to exert their antibacterial effect resulting in elevated MIC values This study shows that the activity of macrolide antibiotics is particularly sensitive to acidic conditions, whereas a ketolide and fluoroquinolones are much less affected. Furthermore, induction of spontaneous and multistep macrolide resistance is greatly increased in acidic medium. In contrast, telithromycin and moxifloxacin did not induce resistance at any pH. Antibiotics which are less likely to induce resistance in vitro may also be less likely to induce the development of resistance in patients with respiratory tract infections.     

Revisiting the mechanism of macrolide-antibiotic resistance mediated by ribosomal protein L22

Bacterial antibiotic resistance can occur by many mechanisms. An intriguing class of mutants is resistant to macrolide antibiotics even though these drugs still bind to their targets. For example, a 3-residue deletion (ΔMKR) in ribosomal protein L22 distorts a loop that forms a constriction in the ribosome exit tunnel, apparently allowing nascent-chain egress and translation in the presence of bound macrolides. Here, however, we demonstrate that ΔMKR and wild-type ribosomes show comparable macrolide sensitivity in vitro. In Escherichia coli, we find that this mutation reduces antibiotic occupancy of the target site on ribosomes in a manner largely dependent on the AcrAB-TolC efflux system. We propose a model for antibiotic resistance in which ΔMKR ribosomes alter the translation of specific proteins, possibly via changes in programmed stalling, and modify the cell envelope in a manner that lowers steady-state macrolide levels.     

Comparison of in vitro antimicrobial activities of ofloxacin, levofloxacin, ciprofloxacin, and sparfloxacin against various mycobacteria

In vitro antimicrobial activities of ofloxacin (OFLX), levofloxacin (LVFX), ciprofloxacin (CPFX), and sparfloxacin (SPFX) were compared against various mycobacteria using the agar dilution method with 7H11 medium, and the following results were obtained. (1) These four new quinolones showed excellent antimicrobial activities against M. tuberculosis, M. kansasii, and M. fortuitum. (2) SPFX was most active against slowly growing mycobacteria. The activity against M. tuberculosis was in the order of SPFX > CPFX > LVFX > OFLX. The activity against M. kansasii was in the order of SPFX > LVFX > OFLX > or = CPFX. (3) On the other hand, CPFX was most active against rapidly growing mycobacteria. The activity against M. fortuitum was in the order of CPFX > SPFX > LVFX > OFLX. Considering the in vitro antimicrobial activities and the pharmacokinetics of these four drugs, they could achieve favorable clinical outcomes for all the patients with pulmonary infection due to M. tuberculosis or M. fortuitum and some of the patients with pulmonary infection due to M. kansasii or M. chelonae.     

肺炎链球菌耐药性检测及其对大环内酯类抗生素耐药机制的研究

目的了解浙江地区肺炎链球菌临床菌株对临床常用抗生素耐药性以及肺炎链球菌对大环内酯类抗生素耐药机制。方法从浙江省不同地区病人临床标本中分离并鉴定肺炎链球菌138株。采用K-B纸片法和E-test检测上述肺炎链球菌临床菌株对9种抗生素的敏感性。采用PCR检测上述菌株中与大环内酯类抗生素耐药性密切相关的ermB和mefE基因携带情况。分析ermB和mefE基因携带、分布状况与红霉素耐药性关系。结果138株肺炎链球菌临床菌株中,对红霉素耐药率高达93.5%(129/138),对头孢噻肟、头孢呋辛、阿莫西林和左氧氟沙星的耐药率较低(2.9%~4.3%)。上述菌株er-mB基因检测阳性率(91.3%,126/138)明显高于mefE基因(33.3%,46/138)(P0.05),其中27.5%菌株(38/138)同时携带。不携带ermB和mefE基因菌株均对红霉素敏感,仅携带mefE基因菌株对红霉素耐药率(62.5%)明显低于同时携带两种基因菌株耐药率(100%)及仅携带ermB基因菌株耐药率(97.7%)(P0.05)。结论红霉素已不适合作为治疗肺炎链球菌感染性疾病的药物。ermB基因是肺炎链球菌临床菌株携带的红霉素耐药相关优势基因。ermB基因可使肺炎链球菌产生较mefE基因更强的红霉素耐药性。     

Treatment of chronic rhinosinusitis with low-dose,long-term macrolide antibiotics: An evolving paradigm

The 14-membered and 15-membered ring macrolide antibiotics express immunomodulatory effects in chronic respiratory disorders in humans that are distinct from their antimicrobial properties. These drugs downregulate the excessive immune and inflammatory responses observed in these conditions while promoting tissue repair. To this end, chronic rhinosinusitis is characterized by mucosal inflammation of nasal and sinus mucosa for more than 3 months and accounts for significant health care resource allocation due to difficulties in treatment. Clinical efficacy of macrolide antibiotics as biologic response modifiers in patients with chronic rhinosinusitis is suggested by compelling basic research and small, uncontrolled clinical studies. Hence, long-term, prospective double-blind placebo-controlled clinical studies are indicated to establish the utility of these drugs in the treatment of patients with chronic rhinosinusitis.