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101.
目的通过对抗生素不合理应用的分析,为临床更合理使用抗生素提供参考.方法以国内外文献、论著和药理学教科书作参考总结阐述.结果不合理用药现象普遍,既影响药效又增加不良反应.结论使广大医务工作者充分认识抗生素合理应用的必要性和重要性,保证抗生素疗效、减少不良反应和耐药菌产生,有参考价值. 相似文献
102.
《Expert review of anti-infective therapy》2013,11(1):59-70
Antibiotic resistance in Helicobacter pylori is the major cause of eradication failure. Primary H. pylori susceptibility patterns, however, are becoming less predictable. Currently, high (≥20%) clarithromycin resistance rates have been observed in the USA and in developed countries in Europe and Asia, while the highest (≥80%) metronidazole-resistance rates have been reported in Africa, Asia and South America. Primary quinolone-resistance rates of 10% or more have already been reported in developed countries in Europe and Asia. Primary amoxicillin resistance has been low (0 to <2%) in Europe but higher (6–59%) in Africa, Asia and South America. Similarly, tetracycline resistance has been absent or low (<5%) in most countries and higher (9–27%) in Asia and South America. The increasing clarithromycin and quinolone resistance, and multidrug resistance detected in 0 to less than 5% in Europe and more often (14.2%) in Brazil are worrying. Growing resistance often parallels national antibiotic consumption and may vary within patient groups according to the geographic region, patient’s age and sex, type of disease, birthplace, other infections and other factors. The geographic map and evolution of primary H. pylori resistance are clinically important, should be considered when choosing eradication regimens, and should be monitored constantly at national and global levels in an attempt to reach the recently recommended goal of eradication of more than 95%. 相似文献
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We rapidly identified extended-spectrum β-lactamase (ESBL) producers prospectively among 245 gram-negative bacilli–positive cultured blood specimens using the Rapid ESBL Nordmann/Dortet/Poirel test and direct bacterial identification using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. This combination identified ESBL-producing Enterobacteriaceae within 30 min and had high predictive values. 相似文献
105.
M. Papapetropoulou G. Rodopoulou E. Giannoulaki P. Stergiopoulos 《Journal of chemotherapy (Florence, Italy)》2013,25(6):404-407
SummaryThe susceptibility of 20 strains of Pseudomonas species isolated from drinking waters (4 P. aeruginosa, 7 P. fluorescens, 5 P. stutzeri, 1 P. maltophilia, 1 P. cepacia, 1 P. putida and 1 P. pickettii) to a variety of antibiotics (gentamicin, amikacin, azlocillin, cefotaxime, chloramphenicol and polymyxin B) were determined by Stoke’s method at 20°C, 30°C, 37°C and 42°C.Minimum inhibitory concentrations (MIC) were determined for aminoglycosides on Mueller-Hinton agar at the above temperatures. There was a significant difference in susceptibility between 20°C or 30°C (most resistant), 37°C (more susceptible) and 42°C (most susceptible) to gentamicin and to a lesser degree to amikacin for P. maltophilia, P. cepacia and most strains of P. fluorescens. The P. aeruginosa, P. stutzeri, P. putida and P. pickettii strains showed no difference in susceptibility at 20°C, 30°C, 37°C and 42°C. The need for standardized conditions with special regard to temperature when antibiotic susceptibility tests are performed for P. maitophilia, P. cepacia and P. fluorescens strains is stressed. 相似文献
106.
《Surgery (Oxford)》2017,35(1):62-67
Bone and joint infections in children are uncommon, but potentially devastating. The use of effective antibiotic chemotherapy has minimized associated mortality, but prompt recognition and treatment is necessary to preserve normal growth and function of the affected bone or joint. Diagnostic challenges include inability of patients to report symptoms, non-specificity of clinical signs and low sensitivity of diagnostic tests while treatment challenges include choosing appropriate empiric antibiotics, accounting for patient and epidemiological risk factors, and ensuring adequate compliance with long antibiotic courses in children. Successful management requires regular review of clinical progress and assessment for development of complications requiring surgical intervention. This article will cover the commonest infections seen clinically. Septic arthritis and osteomyelitis are discussed separately though concurrent infection can occur, particularly in children under 2 years of age, and recognition of this can alter the duration of treatment required. 相似文献
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108.
Tim R. Blower Benjamin H. Williamson Robert J. Kerns James M. Berger 《Proceedings of the National Academy of Sciences of the United States of America》2016,113(7):1706-1713
Mycobacterium tuberculosis (Mtb) infects one-third of the world’s population and in 2013 accounted for 1.5 million deaths. Fluoroquinolone antibacterials, which target DNA gyrase, are critical agents used to halt the progression from multidrug-resistant tuberculosis to extensively resistant disease; however, fluoroquinolone resistance is emerging and new ways to bypass resistance are required. To better explain known differences in fluoroquinolone action, the crystal structures of the WT Mtb DNA gyrase cleavage core and a fluoroquinolone-sensitized mutant were determined in complex with DNA and five fluoroquinolones. The structures, ranging from 2.4- to 2.6-Å resolution, show that the intrinsically low susceptibility of Mtb to fluoroquinolones correlates with a reduction in contacts to the water shell of an associated magnesium ion, which bridges fluoroquinolone–gyrase interactions. Surprisingly, the structural data revealed few differences in fluoroquinolone–enzyme contacts from drugs that have very different activities against Mtb. By contrast, a stability assay using purified components showed a clear relationship between ternary complex reversibility and inhibitory activities reported with cultured cells. Collectively, our data indicate that the stability of fluoroquinolone/DNA interactions is a major determinant of fluoroquinolone activity and that moieties that have been appended to the C7 position of different quinolone scaffolds do not take advantage of specific contacts that might be made with the enzyme. These concepts point to new approaches for developing quinolone-class compounds that have increased potency against Mtb and the ability to overcome resistance.The causative agent of tuberculosis (TB), Mycobacterium tuberculosis (Mtb), is one of the most important pathogens of humans, second only to the HIV in the number of deaths caused annually (1). Mtb is estimated to latently infect one-third of the world’s population (2), thereby also creating a huge reservoir for future disease. Particularly problematic are cases of multidrug-resistant (MDR)-TB, which is defined as resistance to two primary anti-TB drugs, rifampicin and isoniazid. MDR-TB now represents 3.5% of new TB cases; of these, 9% are classified as extensively drug-resistant (XDR)-TB (1), which is defined as MDR-TB with additional resistance to any fluoroquinolone and one injectable second-line drug (3). TB isolates are also being recovered that are totally drug-resistant (3–5). Thus, controlling TB, in particular drug-resistant TB, is a major health problem.Fluoroquinolones are one of the most successful classes of drugs against bacterial pathogens, accounting for 24% of the $10 billion antibiotic market (6). Fluoroquinolones are also currently receiving considerable attention in the treatment of TB, with two new C8-methoxy derivatives, moxifloxacin and gatifloxacin, currently under evaluation as promising first-line therapeutics (7–10). These compounds have been used to restrict the development of XDR-TB from MDR-TB; however, emerging resistance threatens both first-line and second-line use (11). The widespread testing of fluoroquinolones against TB has revealed considerable variation in efficacy of different drug variants against Mtb. For example, ciprofloxacin is only marginally active, and its early use with Mtb was halted in favor of ofloxacin and levofloxacin (7). These two agents are now proving to be less effective than moxifloxacin and gatifloxacin (7, 10); however, the newest two compounds also exhibit some nonideality. For example, gatifloxacin can elicit side effects such as hypo/hyperglycemia (12), whereas moxifloxacin has potential cardiovascular risks (13). Although recent clinical trials that have included fluoroquinolones as part of an alternative drug regimen have faltered (14), there are prospects for other nonfluoroquinolone molecules to make an impact on the treatment of MDR- and XDR-TB (15, 16). Moreover, a promising recent trial that uses moxifloxacin as part of a three-drug regimen together with pretomanid and pyrazinamide reports superior bactericidal activity against TB and MDR-TB versus current regimens (17). These new data make it clear that new quinolone-class agents, which are also capable of circumventing known resistance mutations, might be useful therapeutic agents in the treatment of TB.Progress is presently being made toward developing new fluoroquinolone derivatives. For example, a methoxy group at fluoroquinolone position C8 (Fig. 1A) increases activity against mycobacteria, particularly resistant mutants (18–20). Indeed, moxifloxacin, along with a more active C8-methyl derivative, retains high inhibitory activity against purified Mtb gyrase even when the enzyme contains commonly acquired fluoroquinolone-resistance substitutions [as described in the accompanying paper by Aldred et al. (21)]. In another example, quinazolinediones (diones) have been shown to have an ability to bypass existing resistance within mycobacteria and other bacterial species (20, 22–24). Thus, there still exist opportunities to design more effective quinolone-class molecules for treatment of TB.Open in a separate windowFig. 1.DNA cleavage by Mtb gyrase induced by fluoroquinolones. (A) Fluoroquinolones tested in this study. The constant quinolone core of each drug is highlighted in orange, numbered as shown around C8-Me-moxifloxacin. (B) DNA cleavage assays with full-length Mtb gyrase, using WT (upper gels) and a GyrA A90S (lower gels) sensitizing mutant. Each fluoroquinolone is titrated against a constant amount of protein (125 nM) and supercoiled (SC) plasmid DNA substrate (12.5 nM). The “no protein” control shows the supercoiled substrate DNA, along with a nicked (N) and linear (L) control lanes. Each gel is representative of triplicate data. (C) Graphical analysis of data in B. The relative amount of DNA cleavage is plotted as an increase in linear product (obtained by densitometry) compared with the zero drug control as a function of drug concentration. (Left) WT. (Right) A90S. Data points and error bars represent the mean and SD of triplicate data, respectively.DNA gyrase is a heterotetrameric (GyrA2GyrB2) enzyme that transiently catalyzes dsDNA breaks as it negatively supercoils DNA. Fluoroquinolones prevent the resealing of the ds breaks that normally follows DNA strand passage (25), generating persistent, covalent enzyme–DNA adducts called cleaved complexes. Cleaved-complex formation, which is reversible, blocks bacterial growth; at elevated fluoroquinolone concentrations, release of DNA breaks from the complexes leads to chromosome fragmentation and cell death (26). Although numerous crystallographic studies have defined the primary binding site of fluoroquinolones against gyrase (and against topoisomerase IV, a gyrase paralog) (27–30), there has been debate as to whether fluoroquinolones use a magnesium ion to bridge their interaction with the enzyme (28, 29). Resolving this question is important, because the intrinsic resistance of certain species of gyrase to quinolones (e.g., Mtb) has been proposed to result from natural sequence variation that leads to the loss of a magnesium-ion “bridge” formed between the drug and enzyme (31–33). At the same time, there currently exists no clear chemical explanation as to why certain fluoroquinolone derivatives act with different efficacies against Mtb gyrase.To better understand such questions, we carried out a structural and biochemical analysis of Mtb gyrase in the presence of a panel of four different, clinically used fluoroquinolones (ciprofloxacin, levofloxacin, gatifloxacin, and moxifloxacin) and one new fluoroquinolone derivative (C8-Me-moxifloxacin). X-ray crystallography revealed that Mtb gyrase indeed makes an intrinsically low number of interactions with a magnesium ion that accompanies fluoroquinolone binding, and that the introduction of a drug-sensitizing mutation (GyrA A90S) restores interactions seen in nonresistant gyrase homologs. In vitro, we find that C8-Me-moxifloxacin and moxifloxacin are most effective at promoting cleaved complex formation and inhibiting DNA supercoiling by Mtb gyrase, followed by gatifloxacin, and then ciprofloxacin and levofloxacin; however, crystal structures of the DNA-binding-and-cleavage core of Mtb gyrase with both DNA and drug surprisingly failed to reveal any substantial differences in the contacts formed between the protein and different drugs. Further biochemical investigations using an assay that monitors the stability of preformed cleaved complexes largely corroborated the rank order of inhibition seen in DNA cleavage experiments and moreover resulted in drug efficacy trends that closely accord with clinical effectiveness. Collectively, our data explain why Mtb gyrase is naturally quinolone-resistant and show that the relative activities of existing panels of anti-TB quinolone therapeutics are heavily influenced by base-stacking interactions and have yet to take advantage of direct gyrase contacts to maximize therapeutic potential. 相似文献
109.
110.
目的:分析2010年江苏省O1群霍乱疫情分离株病原学特征,为霍乱疫情分析及临床治疗提供实验室依据?方法:对2010年江苏省O1群霍乱疫情分离株进行毒力基因检测?ctxB基因序列分析?抗生素敏感性实验?脉冲场凝胶电泳分子分型分析?结果:2010年江苏省O1群霍乱疫情分离株均携带毒力基因ctxA?ace?zot? toxR? tcpI?ompU?rtxC?tcpAEL?hlyAEL,且CTXB氨基酸序列为古典型;对庆大霉素?诺氟沙星?环丙沙星100%敏感,对复方新诺明?链霉素100%耐药,且均为多重耐药株;除VC201014外,其余14株菌脉冲场凝胶电泳图谱相似度达100%?结论:2010年9月初至10月初,发生在江苏省徐州?淮安?宿迁?南京4个地市的O1群霍乱疫情可能是有关联的暴发流行,2010年8月底发生在连云港的O1群霍乱疫情是一起散发疫情,与上述四地的霍乱疫情可能没有流行病学关联,所有疫情的病原均为非典型埃尔托型霍乱弧菌,庆大霉素?诺氟沙星?环丙沙星可作为临床治疗的首选药物? 相似文献