BACKGROUND & AIMS: :Bovine tuberculosis (bTB) is a chronic disease of cattle that is difficult to control and eradicate in part due to the costly nature of surveillance and poor sensitivity of diagnostic tests. Like many countries, bTB prevalence in Uruguay has gradually declined to low levels due to intensive surveillance and control efforts over the past decades. In low prevalence settings, broad-based surveillance strategies based on routine testing may not be the most cost-effective way for controlling between-farm bTB transmission, while targeted surveillance aimed at high-risk farms may be more efficient for this purpose. To investigate the efficacy of targeted surveillance, we developed an integrated within- and between-farm bTB transmission model utilizing data from Uruguay's comprehensive animal movement database. A genetic algorithm was used to fit uncertain parameter values, such as the animal-level sensitivity of skin testing and slaughter inspection, to observed bTB epidemiological data. Of ten alternative surveillance strategies evaluated, a strategy based on eliminating testing in low-risk farms resulted in a 40% reduction in sampling effort without increasing bTB incidence. These results can inform the design of more cost-effective surveillance programs to detect and control bTB in Uruguay and other countries with low bTB prevalence.

背景与目标： : 牛结核病 (bTB) 是一种牛的慢性疾病，由于监测的成本高昂和诊断测试的敏感性差，很难控制和根除。与许多国家一样，由于过去几十年来的密集监测和控制工作，乌拉圭的bTB患病率逐渐下降到较低水平。在低流行率的环境中，基于常规测试的基础广泛的监测策略可能不是控制农场间bTB传播的最具成本效益的方法，而针对高风险农场的针对性监测可能为此目的更有效。为了研究目标监测的有效性，我们利用乌拉圭综合动物运动数据库中的数据开发了一个集成的农场内和农场间bTB传播模型。使用遗传算法将不确定的参数值 (例如皮肤测试和屠宰检查的动物级敏感性) 拟合到观察到的bTB流行病学数据。在评估的十种替代监测策略中，基于消除低风险农场测试的策略导致采样工作量40% 减少，而不会增加bTB发生率。这些结果可以为设计更具成本效益的监测计划提供信息，以检测和控制乌拉圭和其他bTB患病率较低的国家的bTB。

BACKGROUND & AIMS: :We report the synthesis of 5'-modified thymidines (16, 18, 21, 23) and 5,5'-bis-substituted 2'-deoxyuridine analogues (30, 47) as inhibitors of thymidine monophosphate kinase of Mycobacterium tuberculosis (TMPKmt). These analogues were evaluated for their capacity to inhibit TMPKmt and solely two 5'-modified thymidines were found to possess moderate inhibitory activity. In addition, a feasibility study of protecting groups for the 5-CH(2)OH moiety of 2'-deoxyuridines is described that enables to introduce the desired 5'-modification.

背景与目标： : 我们报告了5 '-修饰的胸苷 (16,18，21,23) 和5,5'-双取代的2 '-脱氧尿苷类似物 (30,47) 作为结核分枝杆菌 (TMPKmt) 的胸苷单磷酸激酶抑制剂的合成。评估了这些类似物抑制TMPKmt的能力，仅发现两种5 '修饰的胸苷具有中等抑制活性。此外，描述了保护2 '-脱氧尿苷的5-CH(2)OH部分的基团的可行性研究，该研究能够引入所需的5'-修饰。

BACKGROUND & AIMS: :Organized bacterial communities, or biofilms, provide an important reservoir for persistent cells that are inaccessible or tolerant to antibiotics. Curli pili are cell-surface structures produced by certain bacteria and have been implicated in biofilm formation in these species. In order to determine whether these structures, which were suggested to be encoded by the Rv3312A (mtp) gene, have a similar role in Mycobacterium tuberculosis, we generated a Δmtp mutant and a mtp-complemented strain of a clinical isolate of M. tuberculosis and analyzed these strains for their ability to produce pili in comparison to the wild-type strain. Phenotypic analysis by transmission electron microscopy proved the essentiality of mtp for piliation in M. tuberculosis. We then compared biofilm formation of the derived strains in detergent-free Sauton's media. Biofilm mass was quantified spectrophotometrically using crystal violet. Furthermore, we examined mtp gene expression by quantitative real-time PCR in wild-type cells grown under biofilm versus planktonic growth conditions. We found a 68.4 % reduction in biofilm mass in the mutant compared to the wild-type strain (P = 0.002). Complementation of the mutant resulted in a restoration of the wild-type biofilm phenotype (P = 0.022). We, however, found no significant difference between mtp expression in cells of the biofilm to those growing planktonically. Our findings highlight a crucial, but non-specific, role of pili in the biofilm lifestyle of M. tuberculosis and indicate that they may represent an important target for the development of therapeutics to attenuate biofilm formation, thereby potentially reducing persistence.

背景与目标： : 有组织的细菌群落或生物膜为无法接触或耐受抗生素的持久性细胞提供了重要的储库。Curli菌毛是由某些细菌产生的细胞表面结构，并与这些物种的生物膜形成有关。为了确定这些被建议由Rv3312A (mtp) 基因编码的结构在结核分枝杆菌中是否具有类似的作用，我们产生了结核分枝杆菌临床分离株的 Δ mtp突变体和mtp补充株，并分析了这些菌株与野生型菌株相比产生菌毛的能力。透射电子显微镜的表型分析证明了mtp对结核分枝杆菌的重要性。然后，我们比较了不含洗涤剂的Sauton培养基中衍生菌株的生物膜形成。使用结晶紫分光光度法定量生物膜质量。此外，我们通过定量实时PCR检查了在生物膜与浮游生长条件下生长的野生型细胞中mtp基因的表达。我们发现与野生型菌株相比，突变体的生物膜质量68.4% 减少 (P = 0.002)。突变体的互补导致野生型生物膜表型的恢复 (P = 0.022)。然而，我们发现生物膜细胞中的mtp表达与浮游生长的细胞之间没有显着差异。我们的发现强调了菌毛在结核分枝杆菌的生物膜生活方式中至关重要但非特异性的作用，并表明它们可能是发展减少生物膜形成的疗法的重要目标，从而可能减少持久性。

BACKGROUND & AIMS: :A series of 14 patients suffering from tuberculosis of the sternum with a mean follow-up of 2.8 years (2 to 3.6) is presented. All were treated with antitubercular therapy: ten with primary therapy, two needed second-line therapy, and two required surgery (debridement). All showed complete healing and no evidence of recurrence at the last follow-up. MRI was useful in making the diagnosis at an early stage because atypical presentations resulting from HIV have become more common. Early adequate treatment with multidrug antitubercular therapy avoided the need for surgery in 12 of our 14 patients.

背景与目标： : 介绍了14例胸骨结核患者，平均随访2.8年 (2至3.6年)。所有患者均接受抗结核治疗: 10例接受主要治疗，2例需要二线治疗，2例需要手术 (清创术)。所有患者均显示完全愈合，并且在最后一次随访中没有复发的迹象。MRI可用于早期诊断，因为HIV引起的非典型表现已变得越来越普遍。在我们的14例患者中，有12例通过多药抗结核治疗进行早期的适当治疗避免了手术的需要。

BACKGROUND & AIMS: :The malonyl coenzyme A (CoA)-acyl carrier protein (ACP) transacylase (MCAT) plays a key role in cell wall biosynthesis in Mycobacterium tuberculosis and other bacteria. The M. tuberculosis MCAT (MtMCAT) is encoded by the FabD gene and catalyzes the transacylation of malonate from malonyl-CoA to holo-ACP. Malonyl-ACP is the substrate in fatty acid biosynthesis and is a by-product of the transacylation reaction. This ability for fatty acid biosynthesis enables M. tuberculosis to survive in hostile environments, and thus understanding the mechanism of biosynthesis is important for the design of new anti-tuberculosis drugs. The 2.3 A crystal structure of MtMCAT reported here shows that its catalytic mechanism differs from those of ScMCAT and EcMCAT, whose structures have previously been determined. In MtMCAT, the C(beta)-O(gamma) bond of Ser91 turns upwards, resulting in a different orientation and thus an overall change of the active pocket compared to other known MCAT enzymes. We identify three new nucleophilic attack chains from the MtMCAT structure: His90-Ser91, Asn155-Wat6-Ser91 and Asn155-His90-Ser91. Enzyme activity assays show that His90A, Asn155A and His90A-Asn155A mutants all have substantially reduced MCAT activity, indicating that M. tuberculosis MCAT supports a unique means of proton transfer. Furthermore, His194 cannot form part of a His-Ser catalytic dyad and only stabilizes the substrate. This new discovery should provide a deeper insight into the catalytic mechanisms of MCATs.

背景与目标： : 丙二酰辅酶a (CoA)-酰基载体蛋白 (ACP) 转酰基酶 (MCAT) 在结核分枝杆菌和其他细菌的细胞壁生物合成中起关键作用。结核分枝杆菌MCAT (MtMCAT) 由FabD基因编码，可催化丙二酸从丙二酰辅酶a转酰化为holo-ACP。丙二酰-ACP是脂肪酸生物合成中的底物，是转酰化反应的副产物。这种脂肪酸生物合成的能力使结核分枝杆菌能够在恶劣的环境中生存，因此了解生物合成的机理对于设计新的抗结核药物很重要。本文报道的MtMCAT的2.3 A晶体结构表明其催化机理不同于ScMCAT和EcMCAT的催化机理，ScMCAT和EcMCAT的结构先前已经确定。在MtMCAT中，与其他已知的MCAT酶相比，Ser91的C (β)-O (γ) 键向上旋转，导致不同的方向，从而导致活性口袋的整体变化。我们从MtMCAT结构中识别出三个新的亲核攻击链: His90-Ser91，Asn155-Wat6-Ser91和Asn155-His90-Ser91。酶活性测定表明His90A，Asn155A和His90A-Asn155A突变体均具有显着降低的MCAT活性，表明结核分枝杆菌MCAT支持质子转移的独特手段。此外，His194不能形成His-Ser催化二联体的一部分，只能稳定底物。这一新发现将为MCATs的催化机制提供更深入的了解。

BACKGROUND & AIMS: :Tuberculosis (TB) is an enormous global public health problem. Cases of extensively drug-resistant TB (XDR-TB) are being reported in increasing numbers across the globe. A large outbreak of XDR-TB associated with rapid and nearly universal mortality has been reported among patients with human immunodeficiency virus infection or acquired immunodeficiency disease in South Africa who have been receiving standard TB therapy and antiretrovirals. Epidemiologic features of this outbreak make it highly suspicious for health care-associated transmission. We urge the Infectious Diseases Society of America and its members to increase involvement in ongoing international TB prevention and treatment efforts and to develop a registry of experts in infection control and laboratory and disease management. We urge advocacy for increased funding for domestic and global TB control programs, including expanded access to sputum culture and drug susceptibility testing, as well as funding for TB clinical trials and research capacity. We believe that substandard TB diagnostic tests are not acceptable for TB control in resource-poor countries. We urge the development of shorter, less toxic TB treatment and prevention regimens. Funding of TB control and research should be reassessed to prevent budget cuts at a time when the disease is killing as many as 2 million people a year.

背景与目标： : 结核病 (TB) 是一个巨大的全球公共卫生问题。全球范围内广泛耐药结核病 (xdr-tb) 的病例越来越多。据报道，在南非接受标准结核病治疗和抗逆转录病毒药物治疗的人类免疫缺陷病病毒感染或获得性免疫缺陷性疾病患者中，广泛耐药结核病的大规模爆发与快速和几乎普遍的死亡率相关。这次疫情的流行病学特征使其高度怀疑与医疗保健相关的传播。我们敦促美国传染病学会及其成员更多地参与正在进行的国际结核病预防和治疗工作，并建立感染控制、实验室和疾病管理专家登记册。我们敦促倡导增加对国内和全球结核病控制计划的资助，包括扩大对痰培养和药物敏感性测试的获取，以及对结核病临床试验和研究能力的资助。我们认为，在资源匮乏的国家，不合格的结核病诊断测试对于结核病控制是不可接受的。我们敦促开发更短、毒性更小的结核病治疗和预防方案。应该重新评估结核病控制和研究的资金，以防止在该疾病每年造成多达200万人死亡的时候削减预算。

BACKGROUND & AIMS: :Laboratory diagnosis of tuberculosis (TB) traditionally relies on smear microscopy and culture of Mycobacterium tuberculosis from clinical samples. With recent advances in technology, there have been numerous efforts to develop new diagnostic tests for TB that overcome the low sensitivity and specificity and long turnover time associated with current diagnostic tests. Molecular biological tests based on nucleic acid amplification have brought an unprecedented opportunity for the rapid and specific detection of M. tuberculosis from clinical specimens. With automated sequencing analysis, species identification of mycobacteria is now easier and more accurate than with conventional methods, and rapid detection of mutations in the genes associated with resistance to TB drugs provides early information on the potential drug resistance for each clinical isolate or for clinical samples. In addition, immunological tests for the detection of M. tuberculosis antigens and antibodies to the antigens have been explored to identify individuals at risk of developing TB or with latent TB infection (LTBI). The recent introduction of commercial IFN-gamma assay kits for the detection of LTBI provides a new approach for TB control even in areas with a high incidence of TB. However, these molecular and immunological tools still require further evaluation using large scale cohort studies before implementation in TB control programs.

背景与目标： : 结核病 (TB) 的实验室诊断传统上依赖于涂片显微镜检查和临床样本中结核分枝杆菌的培养。随着技术的最新发展，已经做出了许多努力来开发新的结核病诊断测试，以克服与当前诊断测试相关的低敏感性和特异性以及长周转时间。基于核酸扩增的分子生物学检测为从临床标本中快速、特异性地检测结核分枝杆菌带来了前所未有的机遇。通过自动测序分析，与传统方法相比，分枝杆菌的物种鉴定现在更容易，更准确，并且快速检测与结核病药物耐药性相关的基因突变，可以为每种临床分离株或临床样本提供有关潜在耐药性的早期信息。此外，已经探索了用于检测结核分枝杆菌抗原和抗原抗体的免疫学测试，以识别有发展结核病或潜伏性结核感染 (LTBI) 风险的个体。最近推出的用于检测LTBI的商用IFN-γ 测定试剂盒为结核病控制提供了一种新方法，即使在结核病高发地区也是如此。然而，在实施结核病控制计划之前，这些分子和免疫学工具仍需要使用大规模队列研究进行进一步评估。

BACKGROUND & AIMS: :The sternum wound infection, caused by Mycobacterium tuberculosis after a cardiac surgery, is an extremely rare postoperative complication. It requires a high degree of suspicion for a correct diagnosis. Often a successful treatment is impeded by the insidious nature of tuberculosis infection and the time-consuming diagnosis process. We report two cases in which we successfully treated this infection with sternum resection, wound debridement, and antituberculosis medication.

背景与目标： 胸骨伤口感染是由结核分枝杆菌在心脏手术后引起的，是一种极为罕见的术后并发症。正确诊断需要高度怀疑。结核感染的阴险性质和耗时的诊断过程通常会阻碍成功的治疗。我们报告了两例病例，其中我们通过胸骨切除，伤口清创术和抗结核药物成功治疗了这种感染。

BACKGROUND & AIMS: OBJECTIVE:A continual increase in intrapatient HIV-1 heterogeneity is thought to contribute to evasion of host immune response and eventual progression to AIDS. Tuberculosis (TB) is diagnosed both early and late during the course of HIV-1 disease and may increase diversity of HIV-1 quasispecies by activating the HIV-1 immune response and increasing HIV-1 replication. We examined whether HIV-1 heterogeneity is altered in HIV-1-infected individuals with TB. METHODS:Blood samples were obtained from 7 HIV-1-infected patients with active TB (HIV/TB patients) and 9 HIV-1-infected patients (HIV patients) in Kampala, Uganda (CD4 counts of 0-650 cells/microl and HIV loads of 700-750,000 RNA copies/ml). The C2-C3 region of the HIV-1 envelope gene (env) was amplified by nested polymerase chain reaction (PCR) from lysed peripheral blood mononuclear cells (PBMCs) of each patient, and then subject to sequencing, clonal-quasispecies analysis and heteroduplex tracking analysis (HTA). RESULTS:HTA of env DNA fragments showed increased heterogeneity in the HIV/TB individuals compared with the HIV group. Further sequence and HTA analysis on ten individual env clones for each patient showed significantly greater HIV mutation frequencies in HIV/TB patients than in HIV patients. CONCLUSION:An increase in HIV-1 heterogeneity may be associated with a TB-mediated increase in HIV-1 replication. However, a diverse HIV-1 quasispecies population in HIV/TB patients as opposed to tight quasispecies clusters in HIV patients suggests a possible dissemination of lung-derived HIV-1 isolates from the TB-affected organ.

背景与目标：

BACKGROUND & AIMS: :Hepatotoxicity is a major side-effect of the medicines used in tuberculosis therapy. Although the guidelines for the management of antituberculosis drug induced hepatitis have been published from varieties of health institutes and organizations, they are to a great extent highly similar, there are nevertheless some important differences. We report a case of hepatitis in a renal transplant recipient admitted with pulmonary and extra pulmonary (abdominal) tuberculosis and review the literature on this topic. The introduction of antimicrobial teams, including specialist pharmacists, microbiologists and infectious disease physicians, is a major factor to improve the quality of care and faces the overcoming of antimicrobial resistance. Reintroducing one antituberculosis drug at a time with close monitoring of liver enzymes seems to be the optimal approach in the management of antituberculosis drug induced hepatitis. With multi-disciplinary clinical approach the patient has been successfully cured and has returned to normal active life.

背景与目标： : 肝毒性是结核病治疗中使用的药物的主要副作用。尽管已从各种卫生机构和组织中发布了《抗结核药物性肝炎管理指南》，但它们在很大程度上高度相似，但仍存在一些重要差异。我们报告了一例患有肺和肺外 (腹部) 结核的肾移植受者的肝炎病例，并回顾了有关该主题的文献。引入抗菌小组，包括专业药剂师，微生物学家和传染病医师，是提高护理质量并克服抗菌素耐药性的主要因素。一次重新引入一种抗结核药物并密切监测肝酶似乎是治疗抗结核药物引起的肝炎的最佳方法。通过多学科的临床方法，患者已成功治愈并恢复了正常的活动生活。

BACKGROUND & AIMS: :Rifampicin is a key component of treatment for tuberculosis and its efficacy is determined by the blood levels attained after therapeutic doses. However, there is a high variability of rifampicin blood levels that is related to both the patient and the formulation used. To date, the effect of diabetes mellitus on the plasma levels of rifampicin was low exploited, which could be relevant either by the significant increase of the comorbidity worldwide as by the probable influence of diabetes on the rifampicin exposure. The study aims to evaluate whether diabetes mellitus contribute to the variation of the maximum concentration of rifampicin in patients with tuberculosis treated with a daily dose of 10mg/kg. Rifampicin and glycated hemoglobin were measured by high-performance liquid chromatography, and blood glucose by spectrophotometry. A total of 62 male patients were included in the study, and 26 presented diabetes mellitus. Rifampicin plasma levels in 2-h plasma samples collected at day 61 ranged from 3μg/mL to 14.2μg/mL. Drugs levels were similar between diabetic and non-diabetic patients and were not correlated with blood glucose and glycated hemoglobin. Moreover, a high percentage of patients in both groups presented low levels of rifampicin.

背景与目标： : 利福平是结核病治疗的关键成分，其疗效取决于治疗剂量后达到的血液水平。然而，利福平血液水平的高度变异性与患者和所用制剂均有关。迄今为止，糖尿病对利福平血浆水平的影响很低，这可能与世界范围内合并症的显着增加以及糖尿病对利福平暴露的可能影响有关。该研究旨在评估每日剂量为10mg/kg的结核病患者中，糖尿病是否会导致利福平最大浓度的变化。用高效液相色谱法测定利福平和糖化血红蛋白，用分光光度法测定血糖。该研究共纳入62名男性患者，其中26名患有糖尿病。在第61天收集的2小时血浆样品中的利福平血浆水平范围为3 μ g/mL至14.2 μ g/mL。糖尿病和非糖尿病患者的药物水平相似，并且与血糖和糖化血红蛋白无关。此外，两组患者的利福平水平均较低。

BACKGROUND & AIMS: :Tuberculosis (TB) is an intricate infectious disease that causes a large number of deaths in the population. Interleukin (IL)-6 and IL-13 play functional roles in host resistance to Mycobacterium tuberculosis infection. Our aim in this study was to explore the association of IL-6 and IL-13 polymorphisms with TB susceptibility in the Western Chinese Han population. The case and control groups comprised 900 TB patients and 1534 healthy controls, respectively, and four single-nucleotide polymorphisms (SNPs) were genotyped in IL-6 and five SNPs in IL-13 through the improved multiplex ligation detection reaction method. We found no genetic variants in the IL-6 or IL-13 genes that were related to TB susceptibility in the analysis of alleles, genotypes, genetic models, and TB clinical subtypes, except for a trend toward low pulmonary tuberculosis and extrapulmonary tuberculosis susceptibility for the SNPs rs1295686 and rs20541. Our study did not find a link between IL-6 and IL-13 polymorphisms and TB susceptibility in the Western Chinese Han population. Therefore, our present data revealed the challenge of applying IL-6 and IL-13 SNPs as genetic markers for TB and that increased sample sizes and additional races are needed for further studies.

背景与目标： : 结核病 (TB) 是一种复杂的传染病，导致人口大量死亡。白细胞介素 (IL)-6和IL-13在宿主对结核分枝杆菌感染的耐药性中起着重要作用。我们在这项研究中的目的是探讨IL-6和IL-13多态性与中国西部汉族人群结核病易感性的关系。病例组和对照组分别包括900例结核病患者和1534例健康对照者，通过改进的多重连接检测反应方法对4个单核苷酸多态性 (SNPs) 和5个IL-13进行IL-6基因分型。在等位基因，基因型，遗传模型和结核病临床亚型的分析中，我们没有发现与结核病易感性相关的IL-6或IL-13基因中的遗传变异，除了SNPs rs1295686和rs20541的低肺结核和肺外结核易感性趋势。我们的研究没有发现中国西部汉族人群IL-6和IL-13多态性与结核病易感性之间的联系。因此，我们目前的数据揭示了应用IL-6和IL-13 snp作为结核病遗传标记的挑战，并且需要增加样本量和其他种族来进行进一步的研究。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: AIMS:This study aimed to investigate the ability of CpG7909 adjuvant to enhance immunogenicity and protective efficacy of a subunit vaccine composed of ESAT6-Ag85A fusion protein (Pe685a) of Mycobacterium tuberculosis. METHODS AND RESULTS:ELISA was used to detect specific antibody and IFN-γ expression in sera; ELISPOT, to detect IFN-γ expression in splenocytes; MTT assay and FACS, to detect T-lymphocytes proliferation in spleens; and RT-PCR, to detect cytokines expression in lungs of mice after immunization. Bacterial load and histopathological lesions in lungs or spleens of mice challenged with Myco. tuberculosis H37Rv strain were analysed. Compared with incomplete Freund's adjuvant, CpG7909 induced more potent production of Pe685a-specific IgG2a/IgG1 antibody and higher expression of IFN-γ in sera, stimulated more generation of antigen-specific IFN-γ-secreting splenocytes, enhanced frequencies of CD3(+) CD4(+) and CD3(+) CD8(+) T-lymphocytes in spleen and increased transcription of TNF-α, IFN-γ, IL-6 and TLR9 in lung. However, lower bacterial load in lung and less severe lung pathology were not observed in CpG7909 group mice. CONCLUSIONS:CpG7909 is able to enhance immunological effects of Pe685a subunit vaccine, but does not confer significant protective efficacy against Myco. tuberculosis infection. SIGNIFICANCE AND IMPACT OF THE STUDY:CpG7909 as an adjuvant of subunit vaccine against Myco. tuberculosis is worthy of further investigation.

背景与目标：

BACKGROUND & AIMS: :Purpose. Sitafloxacin (SFX) is a new fluoroquinolone (FQ) that has shown a strong bactericidal effect against Mycobacterium tuberculosis (Mtb) in vitro. However, data on SFX efficacy against Mtb with gyrA/B mutations and its epidemiological cut-off (ECOFF) value remain limited. Therefore, we evaluated and compared the in vitro activity of SFX against gyrA/B-mutant Mtb to that of moxifloxacin (MFX), levofloxacin (LFX) and ciprofloxacin (CFX), and determined the ECOFF for SFX.Methodology. A total of 109 clinical Mtb isolates, including 73 multidrug-resistant (MDR) isolates, were subjected to minimum inhibitory concentration (MIC) analysis in oleic-albumin-dextrose-catalase (OADC)-supplemented Middlebrook 7H9 medium. Our results showed that SFX had lower cumulative MIC than MFX, LFX and CFX. Furthermore, we performed direct DNA sequencing of the quinolone-resistance-determining regions (QRDRs).Results. We identified the following mutations: D94G, D94A, A90V, D94H, D94N and G88A in gyrA; and A543V, A543T, E540D, R485C, D500A, I552S and D577A in gyrB. Based on our results, an ECOFF of 0.125 µg ml-1 was proposed for SFX. With this ECOFF, 15 % of LFX-resistant isolates with MIC ≥2 µg ml-1 were susceptible to SFX.Conclusion. SFX had the lowest cumulative MIC and a relatively low ECOFF value against Mtb, indicating that SFX was not only more effective against gyrA-mutant isolates, but also MDR isolates in Japan.

背景与目标： : 目的。西他沙星 (SFX) 是一种新型氟喹诺酮 (FQ)，在体外对结核分枝杆菌 (Mtb) 具有很强的杀菌作用。然而，关于SFX对具有gyrA/B突变的Mtb的疗效及其流行病学临界值 (ECOFF) 的数据仍然有限。因此，我们评估并比较了SFX对gyrA/B-突变体Mtb的体外活性与莫西沙星 (MFX)，左氧氟沙星 (LFX) 和环丙沙星 (CFX) 的体外活性，并确定了SFX的eoff方法学。在添加了油酸-白蛋白-葡萄糖-过氧化氢酶 (OADC) 的Middlebrook 7H9培养基中，对总共109个临床Mtb分离株 (包括73个多药耐药 (MDR) 分离株) 进行了最低抑菌浓度 (MIC) 分析。我们的结果表明，SFX的累积MIC低于MFX，LFX和CFX。此外，我们对喹诺酮类耐药决定区 (qrdr) 进行了直接DNA测序。我们鉴定了以下突变: gyrA中的D94G，D94A，A90V，D94H，D94N和G88A; gyrB中的A543V，A543T，E540D，R485C，D500A，I552S和D577A。根据我们的结果，提出了一种用于SFX的0.125  µ g   ml-1。在这种情况下，15  % 的抗LFX的MIC ≥ 2  µ g   ml-1菌株对SFX敏感。结论。SFX的累积MIC最低，对Mtb的eoff值相对较低，表明SFX不仅对gyrA突变分离株更有效，而且在日本对MDR分离株也更有效。