Background: Extrapulmonary tuberculosis (EPTB) is a significant health problem which can lead to severe morbidity and mortality. In clinical practice, EPTB can have a variety of nonspecific clinical manifestations and can be concurrent with other types of EPTB. As information pertaining to concurrent EPTB is scarce, research efforts are needed to find concurrent EPTB types and to explore the association networks and rules of concurrent EPTB. Materials and Methods: An observational multicenter study was carried out at 21 hospitals from 15 provinces in China from Jan 1, 2011, to Dec 31, 2017. All the adult EPTB inpatients (≥ 15 years) were included. Multivariable logistic regression analysis was used to examine the associations of gender and age group for concurrent EPTB. The association network and rules for concurrent EPTB were analyzed by the Apriori algorithm. Results: A total of 75,993 adult EPTB inpatients (not including EPTB concurrent with PTB) were included. The ratio of male:female was 1.32. The most common types of EPTB lesions were tuberculous pleurisy (46.47%). In the fully adjusted multivariable logistic regression models, it was found that female EPTB patients (aOR = 1.129, 95% CI: 1.081-1.178) were more likely to have concurrent EPTB. As age increased, the risk of concurrent EPTB decreased (aOR < 1, p value for trend < 0.001). The association network graph showed that almost all the EPTB diseases may be concurrent with other types of EPTB. Ureteric tuberculosis and sacral tuberculosis diseases existed mainly in concurrence with other types of EPTB (about 80%). Tuberculous pleurisy and tuberculous lymphadenitis of the neck could be concurrent with more than 60 other types of EPTB disease. The most common concurrent EPTB types were tuberculous peritonitis concurrent with tuberculous pleurisy (1.64%). Sacral tuberculosis concurrentwith lumbar vertebra tuberculosis had the highest confidence value (68.56%). The strongest association rule was found for vesical tuberculosis concurrent with ureteric tuberculosis (lift = 166.18) and ureteric tuberculosis concurrent with vesical tuberculosis (lift = 166.18). Conclusion: The present study revealed the occurrence of concurrent EPTB types and analyzed the association network and rules among adult EPTB for the first time in a large sample population. Clinicians should be alert to the incidence of concurrent EPTB and that these patients require administration of customized treatment regimens in order to achieve the best outcomes.

Background. Tuberculosis (TB), a multisystemic disease with protean presentation, remains a major global health problem. Although concurrent pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) cases are commonly observed clinically, knowledge regarding concurrent PTB-EPTB is limited. Here, a large-scale multicenter observational study conducted in China aimed to study the epidemiology of concurrent PTB-EPTB cases by diagnostically defining TB types and then implementing association rules analysis. Methods. The retrospective study was conducted at 21 hospitals in 15 provinces in China and included all inpatients with confirmed TB diagnoses admitted from Jan 2011 to Dec 2017. Association rules analysis was conducted for cases with concurrent PTB and various types of EPTB using the Apriori algorithm. Results. Evaluation of 438,979TB inpatients indicated PTB was the most commonly diagnosed (82.05%) followed by tuberculous pleurisy (23.62%). Concurrent PTB-EPTB was found in 129,422 cases (29.48%) of which tuberculous pleurisy was the most common concurrent EPTB type observed. The multivariable logistic regression models demonstrated that odds ratios of concurrent PTB-EPTB cases varied by gender and age group. For PTB cases with concurrent EPTB, the strongest association was found between PTB and concurrent bronchial tuberculosis (lift = 1.09). For EPTB cases with concurrent PTB, the strongest association was found between pharyngeal/laryngeal tuberculosis and concurrent PTB (lift = 1.11). Confidence and lift values of concurrent PTB-EPTB cases varied with gender and age. Conclusions. Numerous concurrent PTB-EPTB case types were observed, with confidence and lift values varying with gender and age. Clinicians should screen for concurrent PTB-EPTB in order to improve treatment outcomes.

Aims: A high proportion of all patients with tuberculosis (TB) present with extrapulmonary TB (EPTB), including concurrent EPTB involving more than one extrapulmonary lesion site. However, previous reports only characterized lesions of single-site EPTB cases. This study aimed to investigate epidemiological characteristics and association rules of concurrent EPTB cases in China. Methods: An observational multi-centre study of 208,214 patients with EPTB lesions was undertaken in China from January 2011 to December 2017. Multi-variable logistic regression analysis was used to identify associations between gender and concurrent EPTB, and age and concurrent EPTB. Association rules were analysed for significance using the Apriori algorithm. Results: The most common EPTB lesion was tuberculous pleurisy (49.8%), followed by bronchial TB (14.8%) and tuberculous meningitis (7.6%). The most common type of concurrent EPTB was tuberculous pleurisy concurrent with tuberculous peritonitis (1.80%). In total, 22 association rules, including 20 strong association rules, were identified; among these, the highest confidence rates were found for tuberculous myelitis concurrent with tuberculous meningitis, and sacral TB concurrent with lumbar vertebral TB. The association rules of EPTB concurrent with other EPTB types were found to vary with gender and age. The confidence rate of tuberculous myelitis concurrent with tuberculous meningitis was higher in females (83.67%) than males, and was highest in patients aged 25-34 years (87.50%). Conclusions: Many types of concurrent EPTB were found. Greater awareness of concurrent EPTB disease characteristics is needed to ensure timely clinical diagnosis and treatment of this disease. (C) 2021 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.

目的 探讨耐多药肺结核病患者服药依从性情况及影响因素.方法 选取在我科室治疗的123例耐多药肺结核病患者,对其进行问卷调查,结果显示,治疗依从性差者43例(34.96％).采用单因素分析和多因素logistic回归分析不同患者年性别、年龄、居住地、文化程度、婚姻状况、医疗方式、家庭月收入、心理困扰程度等数据,确定影响治疗依从性的因素.结果 123名MDR-TB患者的Morisky服药依从性量表得分情况:其中第3条(治疗期间,当您觉得症状加重或出现其他症状时,您是否未告知医生而自行减少药量或停止服药服药)的依从性最高为0.84±0.364;其次为第2条信息在过去的两周内,您是否有一天或几天忘记服药为0.83±0.378;最低的是第7条您是否觉得要坚持抗结核病治疗计划有困难是0.59±0.493.凯斯勒心理困扰量量表得分情况:其中第1条过去30天内,你有多久无缘无故得觉得疲倦的心理困扰最高为2.72±1.163;其次为第8条信息在过去30天内,你有多久觉得做什么事很费劲为2.38±1.238;最低的是第4条过去30天内,你有多久觉得绝望是1.82±1.025;单因素分析显示,文化程度、家庭月收入、心理困扰程度为影响耐多药肺结核病患者治疗依从性的相关因素(P<0.05);多因素logistic回归分析显示,家庭月收入、心理困扰程度为影响耐多药肺结核病患者治疗依从性的独立危险因素(P<0.05).结论 耐多药肺结核病患者可由于文化程度、家庭月收入、心理困扰程度导致治疗依从性差,针对主要影响因素加强心理疏导及减轻治疗的经济负担等措施,提高患者治疗依从性.

目的 调查某结核专科医院头孢西丁超说明书用药情况,为临床合理用药和进一步规范的超说明书用药研究提供依据.方法 收集某院2016年～2018年使用头孢西丁的住院患者的用药情况,按照药品说明书判断其超说明书用药情况.结果 共分析使用头孢西丁的患者312例,其中超说明书使用174例(55.77％),头孢西丁超说明书使用主要表现为超适应症用药(98.86％)和超剂量用药(1.14％),超说明书用药人数前3的科室是内一科、外一科、内四科.结论 头孢西丁超适应症用药现象比较普遍,也有充分用药指征和证据支持,但超剂量使用在理论和现实上仍有差异,需进一步研究,以探索统一、有效、可行的剂量,保障患者安全有效的用药.

Background World Health Organization recommends countries introducing new drug and short treatment regimen for drug resistant tuberculosis (DR-TB) should develop and implement a system for active pharmacovigilance that allows for detection, reporting and management of adverse events. The aim of the study is to evaluate the frequency and severity of adverse events (AEs) of bedaquiline-containing regimen in a cohort of Chinese patients with multidrug-resistant (MDR)/extensively drug-resistant (XDR)-TB based on active drug safety monitoring (aDSM) system of New Drug Introduction and Protection Program (NDIP). Methods AEs were prospectively collected with demographic, bacteriological, radiological and clinical data from 54 sites throughout China at patient enrollment and during treatment between February, 2018 and December, 2019. This is an interim analysis including patients who are still on treatment and those that have completed treatment. A descriptive analysis was performed on the patients evaluated in the cohort. Results By December 31, 2019, a total of 1162 patients received bedaquiline-containing anti-TB treatment. Overall, 1563 AEs were reported, 66.9% were classified as minor (Grade 1–2) and 33.1% as serious (Grade 3–5). The median duration of bedaquiline treatment was 167.0 [interquartile range (IQR): 75–169] days. 86 (7.4%) patients received 36-week prolonged treatment with bedaquiline. The incidence of AEs and serious AEs was 47.1% and 7.8%, respectively. The most frequently reported AEs were QT prolongation (24.7%) and hepatotoxicity (16.4%). There were 14 (1.2%) AEs leading to death. Out of patients with available corrected QT interval by Fridericia's formula (QTcF) data, 3.1% (32/1044) experienced a post-baseline QTcF ≥ 500 ms, and 15.7% (132/839) had at least one change of QTcF ≥ 60 ms from baseline. 49 (4.2%) patients had QT prolonged AEs leading to bedaquiline withdrawal. One hundred and ninety patients reported 361 AEs with hepatotoxicity ranking the second with high occurrence. Thirty-four patients reported 43 AEs of hepatic injury referred to bedaquiline, much lower than that referred to protionamide, pyrazinamide and para-aminosalicylic acid individually. Conclusions Bedaquiline was generally well-tolerated with few safety concerns in this clinical patient population without any new safety signal identified. The mortality rate was generally low. These data inform significant positive effect to support the WHO recent recommendations for the wide use of bedaquiline.

目的 探讨CYP2C19基因多态性检测对预测侵袭性肺曲霉患者伏立康唑相关不良反应的指导作用,为临床此类患者个体化用药提供依据.方法 采用回顾性非随机对照方法,选择我院2018年1月至2019年10月诊断为侵袭性肺曲霉病并使用伏立康唑的患者,查阅所有患者在院期间的验单和病程记录,观察是否发生不良反应及类型.结果 共筛选出168例符合要求的患者,其中基因组84例,对照组84例,两组患者在年龄、性别、体质量差异无统计学意义(P>0.05).基因组患者快、中、慢代谢型占39.29％、45.24％和15.47％.168例患者发生ADR的类型上差异有统计学意义,以肝功能异常发生率最高(46.23％),其次是肾功能异常(17.86％)和胃肠道不适(14.28％).基因组和对照组的ADR发生率比较差异有统计学意义(P<0.05),基因组发生ADR较多;基因组中快、中、慢代谢型患者间ADR发生率两两比较差异均有统计学意义(P<0.05),以快代谢型(24.2％)最小,其次是中间代谢型(52.6％),慢代谢型最高(53.8％).结论 获知使用伏立康唑的肺曲霉患者CYP2C19的基因型,有助于针对性处置药物相关ADR,提高用药的安全性.

Tuberculosis (TB) remains a serious global public health problem in the present. TB also affects other sites (extrapulmonary tuberculosis, EPTB), and accounts for a significant proportion of tuberculosis cases worldwide. In order to comprehensively understand epidemiology of EBTB in China, and improve early diagnosis and treatment, we conducted a large-scale multi-center observational study to assess the demographic data and the prevalence of common EPTB inpatients, and further evaluate the prevalence of EPTB concurrent with Pulmonary tuberculosis (PTB) and the associations between multiple EPTB types and gender-age group in China. All consecutive age≥15yr inpatients with a confirmed diagnosis of EPTB during the period from January 2011 to December 2017 were included in the study. The descriptive statistical analysis included median and quartile measurements for continuous variables, and frequencies and proportions with 95% confidence intervals (CIs) for categorical variables. Multinomial logistic regression analysis was used to compare the association of multiple EPTB types between age group and gender. The results showed that the proportion of 15-24 years and 25-34 years in EPTB inpatients were the most and the ratio of male: female was 1.51. Approximately 70% of EPTB inpatients were concurrent with PTB or other types of EPTB. The most common of EPTB was tuberculous pleurisy (50.15%), followed by bronchial tuberculosis (14.96%), tuberculous lymphadenitis of the neck (7.24%), tuberculous meningitis (7.23%), etc. It was found that many EPTB inpatients concurrent with PTB. The highest prevalence of EPTB concurrent with PTB was pharyngeal/laryngeal tuberculosis (91.31%), followed by bronchial tuberculosis (89.52%), tuberculosis of hilar lymph nodes (79.52%), tuberculosis of mediastinal lymph nodes (79.13%), intestinal tuberculosis (72.04%), tuberculous pleurisy (65.31%) and tuberculous meningitis (62.64%), etc. The results from EPTB concurrent with PTB suggested that females EPTB inpatients were less likely to be at higher risk of concurrent PTB (aOR = 0.819, 95%CI:0.803-0.835) after adjusted by age. As age increasing, the trend risk of concurrent PTB decreased (aOR = 0.994, 95%CI: 0.989-0.999) after adjusted by gender. Our study demonstrated that the common EPTB were tuberculous pleurisy, bronchial tuberculosis, tuberculous lymphadenitis of the neck, tuberculous meningitis, etc. A majority of patients with pharyngeal/laryngeal tuberculosis, bronchial tuberculosis, tuberculosis of hilar/mediastinal lymph nodes, intestinal tuberculosis, tuberculous pleurisy, tuberculous meningitis, etc. were concurrent with PTB. Female EPTB inpatients were less likely to be at higher risk of concurrent PTB, and as age increasing, the trend risk of concurrent PTB decreased. The clinicians should be alert to the presence of concurrent tuberculosis in EPTB, and all suspected cases of EPTB should be assessed for concomitant PTB to determine whether the case is infectious and to help for early diagnosis and treatment.

目的 评价利奈唑胺治疗耐多药结核时不同给药方案的疗效.方法 将利奈唑胺1200、600和300 mg/d的给药方案进行5000次蒙特卡洛模拟,对得到的不同达标概率(PTA)和对靶值的累积反应分数(CRF)进行比较,评价各方案可能达到的疗效.结果 对耐药结核菌(MDR-TB)和泛耐药结核菌(XDR-TB)利奈唑胺在1200 mg/d的累积反应分数(CFR)为95.09％和91.88％,在600 mg/d的CFR为90.98％和86.37％,在300 mg/d的CRF为67.65％和73.85％.结论 利奈唑胺在1200 mg/d的给药方案对MDR-TB和XDR-TB取得良好效果的概率高,但600、300 mg/d的给药方案对高MIC菌株感染时取得良好效果的概率降低.

In clinical practice, PTB patients have concurrent many types of comorbidities such as pneumonia, liver disorder, diabetes mellitus, hematological disorder, and malnutrition. Detecting and treating specific comorbidities and preventing their development are important for PTB patients. However, the prevalence of most comorbid conditions in patients with PTB is not well described. We conducted a large-scale, multicenter, observational study to elucidate and illustrate the prevalence rates of major comorbidities in inpatients at 21 hospitals in China. The 19 specific comorbidities were selected for analysis in this patient cohort, and stratified the inpatient cohort according to age and gender. A total of 355,929 PTB inpatients were included, with a male:female ratio of 1.98 and the proportion of ≥ 65 years PTB inpatients was the most. Approximately 70% of PTB inpatients had at least one defined type of comorbidity. The prevalence of 19 specific comorbidities in inpatients with PTB was analyzed, with pneumonia being the most common comorbidity. The prevalence of most comorbidities was higher in males with PTB except thyroid disorders, mental health disorders, etc. The prevalence of defined most comorbidities in patients with PTB tended to increase with increasing age, although some specific comorbidities tended to increase initially then decrease with increasing age. Our study describes multiple clinically important comorbidities among PTB inpatients, and their prevalence between different gender and age groups. The results will enhance the clinical aptitude of physicians who treat patients with PTB to recognize, diagnose, and treat PTB comorbidities early.

目的探讨住院肺结核患者并发肺外结核的发生情况及其与性别、年龄的关系。方法采用观察性研究方法,由参加过统一培训的调查员从医院信息管理系统（HIS系统）收集2011年1月1日至2017年12月31日我国15省21家医疗机构360 187例住院肺结核患者的性别、年龄,以及结核病灶累及部位等信息,比较分析肺结核患者并发肺外结核的发生情况及其与性别、年龄的关系。结果 360 187例肺结核患者中,男238 910例（66.33%）,女121 277（33.67%）,年龄中位数（四分位数）[M（Q 1 ,Q 3 ）]为47（28,62）岁;42 987例（11.93%）并发肺外结核,并发率依次为结核性脑膜炎[2.72%（9809例）]、颈部淋巴结结核[1.93%（6966例）]、结核性腹膜炎[1.59%（5733例）]、结核性心包炎[0.94%（3399例）]、肠结核[0.94%（3380例）]等。男性肺结核患者并发结核性脑膜炎、颈部淋巴结结核、结核性腹膜炎、结核性心包炎、结核性多浆膜炎、腰椎结核、胸椎结核、胸壁结核的并发率分别为2.44%（5829例）、1.44%（3429例）、1.41%（3376例）、0.90%（2138例）、0.75%（1791例）、0.67%（1604例）、0.64%（1522例）、0.60%（1438例）,均明显低于女性[分别为3.28%（3980例）、2.92%（3537例）、1.94%（2357例）、1.04%（1261例）、0.90%（1093例）、0.79%（960例）、0.76%（924例）、0.66%（805例）]（χ~2=215.235,930.541,144.480,18.061,23.272,16.442,18.585,4.976;P值均＜0.05）。不同年龄组（1～岁组至≥65岁组）肺结核患者并发结核性脑膜炎、颈部淋巴结结核、结核性腹膜炎、肠结核、结核性心包炎、结核性多浆膜炎、腰椎结核、胸椎结核、胸壁结核、咽喉结核的并发率差异均有统计学意义（χ~2=3870.549,2939.502,1830.620,673.372,115.428,319.078,52.512,19.308,439.177,136.619;P值均＜0.05）。除胸椎结核的并发率未呈现出随年龄变化的趋势(χ 趋势 ~2=0.814,P=0.367),结核性心包炎呈现出随年龄增长而增高的趋势(χ 趋势 ~2=62.087,P＜0.001)外,其他肺外结核的发生率均呈现出随年龄增长而降低的趋势（P值均＜0.001）。多因素logistic回归分析结果显示,肺结核并发肺外结核患者的风险女性高于男性[(OR（95%CI）=1.325（1.297～1.353）];其他各年龄组风险均高于≥65岁年龄组[1～岁组、15～岁组、25～岁组、35～岁组、45～岁组、55～岁组的OR（95%CI）值分别为:4.995（4.655～5.360）、2. 481 （2.397～2.568）、2.053 （1. 982～2.126）、1.683 （1.619～1.749）、1.276 （1.228～1.326）、1.109（1.067～1.153）];在控制了性别的影响后,肺结核并发肺外结核患者的风险随年龄的增长而降低[OR（95%CI）=0.817（0.812～0.821）]。结论肺结核患者可并发结核性脑膜炎、颈部淋巴结结核、结核性腹膜炎、结核性心包炎和肠结核等多种肺外结核;且并发肺外结核的风险女性高于男性,并呈现出随年龄的增长而降低的趋势。

Streptomycin (STR) is the first antibiotic used in the treatment of tuberculosis (TB) and the earliest antituberculosis drug with acquired resistance developed by Mycobacterium tuberculosis. The high prevalence of such resistance in many parts of the world limits its use for treating multidrug-resistant (MDR) TB. The aims of this study are to characterize of mutations in rpsL, rrs, and gidB genes in MDR M. tuberculosis isolates originating from southern China and to investigate possible relationship between mutations and strain genotypes for precise diagnosis and treatment. Sequences of rpsL, rrs, and gidB genes and the resistance profiles were analyzed for 218 MDR M. tuberculosis isolates. Our study showed that 68.35% of MDR M. tuberculosis isolates were resistant to STR and 89.91% of STR-resistant (STR (R)) isolates were Beijing lineage strains. Mutations were observed in STR (R) MDR M. tuberculosis isolates at the following rates: 72.48% in rpsL, 36.91% in rrs, and 15.44% in gidB. Compared with the phenotypic data, the combination of mutations in rpsL, rrs, and gidB has sensitivity and specificity of 96.64% and 100.00%, respectively. The most common mutations in STR (R) isolates were rpsL128,263 and rrs514,1401, of which rpsL128 showed association with Beijing lineage (p < 0.001). It is noteworthy that a1401g mutation was present in rrs, while MDR M. tuberculosis isolates were resistant to both STR and amikacin. Twenty two novel mutations were found in STR (R) isolates. These findings could be helpful to develop rapid molecular diagnostic methods and understand STR resistance in China for developing TB precision medicine and disturbance of drug-resistant TB transmission.

OBJECTIVES:Amikacin is the only second-line injectable antituberculosis (anti-TB) drug still recommended for multidrug-resistant tuberculosis (MDR-TB) treatment when a short MDR-TB regimen is designed. Mutations in rrs and eis are reported to be associated with resistance to amikacin. In this study, we investigated the incidence of rrs, eis, tap and whiB7 mutations in amikacin-resistant Mycobacterium tuberculosis clinical isolates to find the proportion of different mutations related to amikacin resistance. METHODS:A total of 395 clinical isolates of M. tuberculosis were used for phenotypic drug susceptibility testing (DST) to 10 drugs with the Löwenstein-Jensen (L-J) method. We sequenced rrs, eis, tap and whiB7 genes in 178 M. tuberculosis clinical isolates (89 amikacin-resistant isolates and 89 of 306 amikacin-susceptible isolates). RESULTS:Our data showed that 22.53% (89/395) M. tuberculosis clinical isolates were resistant to amikacin. Of the 89 amikacin-resistant isolates, 89.89% (80/89) were MDR-TB, of which 12.36% (11/89) were pre-extensively drug-resistant TB (pre-XDR-TB) and 77.53% (69/89) were XDR-TB. The rrs mutations were found in 82% (73/89) in amikacin-resistant M. tuberculosis clinical isolates. The A1401G alteration in the rrs gene was the most dominant mutation (80.90%; 72/89). Five mutations were detected as new in rrs, tap and whiB7. Notably, 13.48% (12/89) amikacin-resistant isolates had no known mutation in these genes. CONCLUSIONS:Our data reveal that the rrs mutation is a predominant molecular marker of amikacin resistance in southern China. Analysis of the rrs gene mutations will significantly reduce the time and cost to diagnose amikacin resistance in TB patients. Other unknown amikacin resistance mechanism(s) exist.

Background Tuberculosis (TB) is a multi-systemic disease with a protean presentation and remains a major global health problem. Concurrent pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) are common in clinical practice. However, the information about concurrent PTB-EPTB is scarce. This study aimed to study the epidemiology of concurrent PTB-EPTB by summarizing the diagnostic types of TB and determine the association rules by a large-scale multi-center observational study in China. Methods The study was performed at 21 hospitals from 15 provinces in China. All the consecutive inpatient with confirmed TB diagnosis during the years from Jan 2011 to Dec 2017 was included in the study. The association rules of concurrent PTB-EPTB were analyzed by Apriori algorithm. Results Of 438,979 TB inpatients evaluated, the most common were PTB (82.05%), followed by tuberculous pleurisy (23.62%), etc. Concurrent PTB-EPTB occurred in 129,422 cases (29.48%). Concurrent PTB and tuberculous pleurisy was the most common concurrent PTB-EPTB types. In the fully adjusted multivariable logistic models, the odds ratio of concurrent PTB-EPTB was different by gender and age group. In PTB with concurrent EPTB, the strongest association rule was PTB with concurrent bronchial tuberculosis (lift=1.09). In EPTB with concurrent PTB, the strongest association rule was pharyngeal /laryngeal tuberculosis with concurrent PTB (lift=1.11). The confidence and lift of concurrent PTB-EPTB varied with gender and age. Conclusions There were many types of concurrent PTB-EPTB. The confidence and lift of concurrent PTB-EPTB varied with gender and age. The clinicians should be alert to the presence of concurrent PTB-EPTB and take effective treatment regimen.

目的 分析抗菌药超说明使用情况,为结核病医院抗菌药指标的科学管理提供依据.方法 对该院2017和2018年纳入和排除左氧氟沙星、莫西沙星、阿米卡星、克拉霉素、利奈唑胺、头孢西丁6种抗菌药后的住院患者抗菌药使用率、使用强度(AUD)进行统计、比较和分析.结果 该院两年抗菌药物的各项指标呈下降趋势,但差异不大(P＞0.05);排除6种药物后指标下降明显(P＜0.01),排除后抗菌药使用率平均下降28.8％,使用强度平均下降45％;具体科室中使用率和使用强度下降最明显的是NTM病病区、耐药结核和重症结核病区.结论 该院抗菌药物使用指标总体呈下降趋势,但超说明书使用对抗菌药指标影响明显,对结核专科医院的抗菌药指标管理需区别对待.

Background: Tuberculosis remains a serious and substantial global public health problem today. Pulmonary tuberculosis (PTB) is the most common clinical presentation of TB. In clinical practice, PTB patients have concurrent many types of co-morbidities such as pneumonia, liver disorder, diabetes mellitus, hematological disorder, malnutrition, hemoptysis, etc. This causes the condition of PTB patients complicated. Detecting and treating specific co-morbidities and preventing their development are important for PTB patients. However, the prevalence of most co-morbid conditions in patients with PTB is not well described.Methods: We conducted a large-scale, multi-center, observational study using admission data at 21 hospitals in China from Jan 1, 2011 to Dec 31, 2017, to elucidate and illustrate the prevalence rates of major co-morbidities in inpatients admitted to hospital for pulmonary TB. The 20 specific co-morbidities were selected for analysis in this patient cohort, and stratified the patient cohort according to age and gender.Findings: A total of 355,929 PTB inpatients were included, with a male:female ratio of 1.97 and the median age 47 (IQR:28~62) years old. The prevalence of 20 specific co-morbidities in patients with PTB was analyzed, with pneumonia being the most common co-morbidity. The prevalence of most co-morbidities were higher in males with PTB except thyroid disorders, mental health disorders, etc. The prevalence of defined most co-morbidities in patients with PTB tended to increase with increasing age, although some specific co-morbidities tended to increase initially then decrease with increasing age.Interpretation: Early identification and management of co-morbidities in patients with PTB may positively influence treatment outcomes for PTB patients. Our study, together with future research into co-morbidity trends in non-hospitalized PTB patients, may be useful in determining community based prevalence rates for PTB co-morbidities, thus enhancing diagnostic and therapeutic decision-making, and clinical outcomes in all PTB patients.Funding Statement: Key Project of Chinese National Programs (Grant No. 2015ZX10003001), ‘Beijing Municipal Administration of Hospitals’ Ascent Plan (No. DFL20181601) and Tongzhou District Science and Technology Committee [No.KJ2017CX054].Declaration of Interests: All the authors declare no conflicts of interest.Ethics Approval Statement: The Ethics Committee of Beijing Chest Hospital, Capital Medical University approved this study with a waiver of informed consent from the patients involved.

Buruli ulcer (BU) is an emerging infectious disease that causes disfiguring skin ulcers. The causative agent, Mycobacterium ulcerans , secretes toxin called mycolactone that triggers inflammation and immunopathology. Existing treatments are lengthy and consist of drugs developed for tuberculosis. Here, we report that a pyrazolo[1,5-a]pyridine-3-carboxamide, TB47, is highly bactericidal against M. ulcerans both in vitro and in vivo. In the validated mouse model of BU, TB47 alone reduces M. ulcerans burden in mouse footpads by more than 2.5 log 10 CFU compared to the standard BU treatment regimen recommended by the WHO. We show that mutations of ubiquinol-cytochrome C reductase cytochrome subunit B confer resistance to TB47 and the dissimilarity of CydABs from different mycobacteria may account for their differences in susceptibility to TB47. TB47 is highly potent against M. ulcerans and possesses desirable pharmacological attributes and low toxicity that warrant further assessment of this agent for treatment of BU.

Mycobacterium tuberculosis, a Gram-positive bacterium of great clinical relevance, is a lethal pathogen owing to its complex physiological characteristics and development of drug resistance. Several molecular genetic tools have been developed in the past few decades to study this microorganism. These tools have been instrumental in understanding how M. tuberculosis became a successful pathogen. Advanced molecular genetic tools have played a significant role in exploring the complex pathways involved in M. tuberculosis pathogenesis. Here, we review various molecular genetic tools used in the study of M. tuberculosis. Further, we discuss the applications of clustered regularly interspaced short palindromic repeat interference (CRISPRi), a novel technology recently applied in M. tuberculosis research to study target gene functions. Finally, prospective outcomes of the applications of molecular techniques in the field of M. tuberculosis genetic research are also discussed. Copyright (C) 2018, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Limited and Science Press. All rights reserved.

Ethionamide (ETA) and prothionamide (PRO) are interchangeably used in tuberculosis (TB) chemotherapy regimens. Subtle discrepancies between biochemical and genetic information on the modes of sensitivity and resistance of isoniazid (INH) and ETA warrants further studies. We report a new mutation - EthA(W21R) - in Mycobacterium bovis Bacillus Calmette-Guerin that corresponds with co-resistance to both PRO and ETA, which to the best of our knowledge has not been reported before. Our findings suggest that mutation EthA(W21R) could be used as a marker site for testing PRO and ETA cross-resistance.

Tuberculosis (TB) is a formidable infectious disease that remains a major cause of death worldwide today. Escalating application of genomic techniques has expedited the identification of increasing number of mutations associated with drug resistance in Mycobacterium tuberculosis. Unfortunately the prevalence of bacillary resistance becomes alarming in many parts of the world, with the daunting scenarios of multidrug-resistant tuberculosis (MDR-TB), extensively drug-resistant tuberculosis (XDR-TB) and total drug-resistant tuberculosis (TDR-TB), due to number of resistance pathways, alongside some apparently obscure ones. Recent advances in the understanding of the molecular/ genetic basis of drug targets and drug resistance mechanisms have been steadily made. Intriguing findings through whole genome sequencing and other molecular approaches facilitate the further understanding of biology and pathology of M. tuberculosis for the development of new therapeutics to meet the immense challenge of global health.