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Efficacy and Safety of Combined Bedaquiline and Delamanid Use among Patients with Multidrug-Resistant Tuberculosis in Beijing,China
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作者 Can Guo Lihui Nie +6 位作者 Yanhua Song Rongmei Liu Xiaoguang Wu Yuanyuan Shang Xuxia Zhang Yu Pang Mengqiu Gao 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2024年第10期1195-1203,共9页
Objectives The combined use of bedaquiline and delamanid(BDQ-DLM)is limited by an increased risk of prolonging the QTc interval.We retrospectively evaluated patients who received DLM/BDQcontaining regimens at a TB-spe... Objectives The combined use of bedaquiline and delamanid(BDQ-DLM)is limited by an increased risk of prolonging the QTc interval.We retrospectively evaluated patients who received DLM/BDQcontaining regimens at a TB-specialized hospital.We aimed to present clinical efficacy and safety data for Chinese patients.Methods This case-control study included patients with multidrug-resistant tuberculosis(MDR-TB)treated with BDQ alone or BDQ plus DLM.Results A total of 96 patients were included in this analysis:64 in the BDQ group and 32 in the BDQ+DLM group.Among the 96 patients with positive sputum culture at the initiation of BDQ alone or BDQ combined with DLM,46 patients(71.9%)in the BDQ group and 29(90.6%)in the BDQ-DLM group achieved sputum culture conversion during treatment.The rate of sputum culture conversion did not differ between the two groups.The time to sputum culture conversion was significantly shorter in the BDQ-DLM group than in the BDQ group.The most frequent adverse event was QTc interval prolongation;however,the frequency of adverse events did not differ between the groups.Conclusion In conclusion,our results demonstrate that the combined use of BDQ and DLM is efficacious and tolerable in Chinese patients infected with MDR-TB.Patients in the BDQ-DLM group achieved sputum culture conversion sooner than those in the BDQ group. 展开更多
关键词 multidrug resistant TUBERCULOSIS Bedaquiline Delamanid EFFICACY Safety
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Diarrheal Diseases: A Review on Gastroenteritis Bacteria Global Burden and Alternative Control of Multidrug-Resistant Strains
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作者 Ahéhéhinnou Ulrich Hilarion Adjovi Yann Christie Sissinto Fossou Joli Prince Mintognissè 《Advances in Microbiology》 CAS 2024年第10期493-512,共20页
Diarrheal diseases represent a significant and pervasive health challenge for humanity. The aetiology of diarrheal diseases is typically associated with the presence of enteropathogens, including viruses, bacteria and... Diarrheal diseases represent a significant and pervasive health challenge for humanity. The aetiology of diarrheal diseases is typically associated with the presence of enteropathogens, including viruses, bacteria and parasites. The implementation of preventive measures, including the maintenance of good food hygiene, effective water sanitation, and the development of rotavirus vaccines, has resulted in a notable reduction in the prevalence of the disease. However, the emergence of bacterial multidrug resistance due to the past or present inappropriate use of antibiotics has rendered bacterial infections a significant challenge. The objective of this review is threefold: firstly, to provide an overview of diarrheal diseases associated with bacteria;secondly, to offer a concise analysis of bacterial multidrug resistance on a global scale;and thirdly, to present the potential of filamentous fungi as an alternative solution to the challenge posed by multidrug-resistant strains. Campylobacter spp. is the most dangerous bacteria, followed by Shigella spp. and Vibrio cholerae in all age groups combined. However, Shigella spp. was the deadliest in children under five years of age and, together with E. coli, are the most antibiotic-resistant bacteria. With their highly developed secondary metabolism, fungi are a reservoir of natural bioactive compounds. 展开更多
关键词 Diarrheal Disease BACTERIA multidrug Resistance Fungal Metabolites
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Apatinib reduces liver cancer cell multidrug resistance by modulating NF-κB signaling pathway
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作者 XIAOXIAO HE XUEQING ZHOU +4 位作者 JINPENG ZHANG MINGFEI ZHANG DANHONG ZENG HENG ZHANG SHUCAI YANG 《BIOCELL》 SCIE 2024年第9期1331-1341,共11页
Objectives:This investigation aimed to elucidate the inhibitory impact of apatinib on the multidrug resistance of liver cancer both in vivo and in vitro.Methods:To establish a Hep3B/5-Fu resistant cell line,5-Fu conce... Objectives:This investigation aimed to elucidate the inhibitory impact of apatinib on the multidrug resistance of liver cancer both in vivo and in vitro.Methods:To establish a Hep3B/5-Fu resistant cell line,5-Fu concentrations were gradually increased in the culture media.Hep3B/5-Fu cells drug resistance and its alleviation by apatinib were confirmed via flow cytometry and Cell Counting Kit 8(CCK8)test.Further,Nuclear factor kappa B(NF-κB)siRNA was transfected into Hep3B/5-Fu cells to assess alterations in the expression of multidrug resistance(MDR)-related genes and proteins.Nude mice were injected with Hep3B/5-Fu cells to establish subcutaneous xenograft tumors and then categorized into 8 treatment groups.The treatments included oxaliplatin,5-Fu,and apatinib.In the tumor tissues,the expression of MDRrelated genes was elucidated via qRT-PCR,immunohistochemistry,and Western blot analyses.Results:The apatinibtreated mice indicated slower tumor growth with smaller size compared to the control group.Both the in vivo and in vitro investigations revealed that the apatinib-treated groups had reduced expression of MDR genes GST-pi,LRP,MDR1,and p-p65.Conclusions:Apatinib effectively suppresses MDR in human hepatic cancer cells by modulating the expression of genes related to MDR,potentially by suppressing the NF-κB signaling pathway. 展开更多
关键词 Apatinib Liver cancer multidrug resistance NF-κB signaling pathway
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Identification of FDA-Approved Drugs as Modulators of Multidrug Resistance Protein 2 (MRP2/ABCC2) Expression Levels in MRP2-Overexpressing Cells: Preliminary Data
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作者 Vivian Osei Poku Surtaj Hussain Iram 《Journal of Biosciences and Medicines》 2024年第10期32-44,共13页
Multidrug Resistance Protein 2 (MRP2) is an ATP-dependent transmembrane protein that plays a pivotal role in the efflux of a wide variety of physiological substrates across the plasma membrane. Several studies have sh... Multidrug Resistance Protein 2 (MRP2) is an ATP-dependent transmembrane protein that plays a pivotal role in the efflux of a wide variety of physiological substrates across the plasma membrane. Several studies have shown that MRP2 can significantly affect the absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles of many therapeutic drugs and chemicals found in the environment and diet. This transporter can also efflux newly developed anticancer agents that target specific signaling pathways and are major clinical markers associated with multidrug resistance (MDR) of several types of cancers. MDR remains a major limitation to the advancement of the combinatorial chemotherapy regimen in cancer treatment. In addition to anticancer agents, MRP2 reduces the efficacy of various drug classes such as antivirals, antimalarials, and antibiotics. The unique role of MRP2 and its contribution to MDR makes it essential to profile drug-transporter interactions for all new and promising drugs. Thus, this current research seeks to identify modulators of MRP2 protein expression levels using cell-based assays. A unique recently approved FDA library (372 drugs) was screened using a high-throughput In-Cell ELISA assay to determine the effect of these therapeutic agents on protein expression levels of MRP2. A total of 49 FDA drugs altered MRP2 protein expression levels by more than 50% representing 13.17% of the compounds screened. Among the identified hits, thirty-nine (39) drugs increased protein expression levels whereas 10 drugs lowered protein expression levels of MRP2 after drug treatment. Our findings from this initial drug screening showed that modulators of MRP2 peregrinate multiple drug families and signify the importance of profiling drug interactions with this transporter. Data from this study provides essential information to improve combinatorial drug therapy and precision medicine as well as reduce the drug toxicity of various cancer chemotherapies. 展开更多
关键词 ABC Transporters multidrug Resistance MRP2/ABCC2 MRP2 Modulators ELISA
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Multidrug-Resistant of Escherichia coli and Salmonella spp. Strains in Chicken Feces Intended for Consumption in Open Spaces of Ouagadougou, Burkina Faso
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作者 Stéphanie Lynseh Carine Sita Bénao Dabiré Amana Métuor +7 位作者 Abdoul Karim Ouattara Rahimatou Yasmine Wendkouni Tiemtoré Nicolas Ouédraogo Blandine Ouédraogo Rhaina Olivia Badini Lionel Eliada Benoit Bambara Serge Sougué Jacques Simporé 《Open Journal of Applied Sciences》 2024年第4期881-892,共12页
Resistant bacteria can be transmitted to humans through feces or contaminated meat from local chickens. Bacterial strains were isolated from the intestinal contents of 400 local chicken samples from various sales site... Resistant bacteria can be transmitted to humans through feces or contaminated meat from local chickens. Bacterial strains were isolated from the intestinal contents of 400 local chicken samples from various sales sites. These strains were then characterized using bacteriological and biochemical methods to identify resistant strains. In a study conducted in Ouagadougou, we systematically collected chicken fecal samples from 20 locations across the city, followed by isolation and identification of Salmonella spp. using specific enrichment and culture methods, as well as Escherichia coli. Bacterial strains were characterized using antibiotic resistance profiles were determined through agar diffusion tests, revealing sensitivity or resistance to a range of antibiotics based on established scientific criteria. The results showed that out of the 400 samples collected, 81.25% and 63.5% were contaminated by Escherichia coli and Salmonella spp., respectively. Among these, 86.15% of identified Escherichia coli and 50.78% of Salmonella spp. displayed resistance to at least one tested antibiotic. Among 280 Escherichia coli isolates identified resistant to at least one antibiotic, 31.07% were resistant to cefotaxime (CTX), 20.35% to ceftazidime (CAZ), 21.07% to ceftriaxone (CTR), 75% to amoxicillin clavulanic acid (AMC), 23.57% aztreoname (ATM) and 27.14% were resistant to imipenem (IMP). In the case of the 129 Salmonella spp. isolates resistant to at least one tested antibiotic, 34.88% were resistant to CTX;41.08% to CAZ;35.65% to CTR, 92% to AMC, 39.53% to ATM and finally 47.28% were resistant to IMP. Our study revealed high prevalence of resistance in bacterial strains isolated from local chickens sold outdoors in Ouagadougou. These findings raise significant public health concerns, due to the possible transmission of these resistant strains to humans through the consumption of contaminated meat, thus complicating the treatment of bacterial infections. 展开更多
关键词 multidrug-RESISTANT CHICKEN OUAGADOUGOU Escherichia coli Salmonella spp. Antibiotic
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Multidrug dissolvable microneedle patch for the treatment of recurrent oral ulcer 被引量:2
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作者 Yuqiong Wang An’an Sheng +7 位作者 Xinran Jiang Shanshan Yang Long Lin Mingzhu Yang Fengshuo Zhu Yongyan Hu Jian Li Lingqian Chang 《Bio-Design and Manufacturing》 SCIE EI CAS CSCD 2023年第3期255-267,共13页
Recurrent oral ulcer is a painful oral mucosal disorder that affects 20%of the world’s population.The lack of a radical cure due to its unknown underlying cause calls for innovative symptomatic treatments.This work r... Recurrent oral ulcer is a painful oral mucosal disorder that affects 20%of the world’s population.The lack of a radical cure due to its unknown underlying cause calls for innovative symptomatic treatments.This work reports a hyaluronic acid-based dissolvablemicroneedle patch(ROUMNpatch,short for recurrent oral ulcer microneedle)loaded with dexamethasone acetate,vitamin C and tetracaine hydrochloride for the treatment of recurrent oral ulcers.The ROUMN patch shows enhancement in both the anti-inflammatory effect elicited by dexamethasone and the pro-proliferation effect of vitamin C.In vitro experiments show that ROUMN has a higher efficiency in suppressing lipopolysaccharide(LPS)-induced interleukin-6(IL-6)expression than dexamethasone alone.Cell proliferation and migrationwere also significantly promoted byROUMNcompared to vitamin C alone.The healing-promoting effect of ROUMN was also verified in vivo using an acetic acid-cauterized oral ulcer model in rats.ROUMN as a treatment accelerated the healing process of oral ulcers,shortening the total healing time to 5 days compared with the 7 days required by treatment using watermelon frost,a commonly used over-the-counter(OTC)drug for oral ulcers.The rapid dissolution of the hyaluronic acid-based microneedles and the superior healing-promoting effect of the drug combination could lead to a broad application prospect of the ROUMN patch in the treatment of recurrent oral ulcers. 展开更多
关键词 Recurrent oral ulcer Dissolvable microneedle Hyaluronic acid microneedle multidrug ANTI-INFLAMMATION Healing promoting effect
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Genotyping Characteristics of Human Fecal Escherichia coli and Their Association with Multidrug Resistance in Miyun District, Beijing
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作者 ZHANG Wei Wei ZHU Xiao Lin +11 位作者 DENG Le Le HAN Ya Jun LI Zhuo Wei WANG Jin Long CHEN Yong Liang WANG Ao Lin TIAN Er Li CHENG Bin XU Lin Hua CHEN Yi Cong TIAN Li Li HE Guang Xue 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2023年第5期406-417,共12页
Objective To explore the genotyping characteristics of human fecal Escherichia coli(E. coli) and the relationships between antibiotic resistance genes(ARGs) and multidrug resistance(MDR) of E. coli in Miyun District, ... Objective To explore the genotyping characteristics of human fecal Escherichia coli(E. coli) and the relationships between antibiotic resistance genes(ARGs) and multidrug resistance(MDR) of E. coli in Miyun District, Beijing, an area with high incidence of infectious diarrheal cases but no related data.Methods Over a period of 3 years, 94 E. coli strains were isolated from fecal samples collected from Miyun District Hospital, a surveillance hospital of the National Pathogen Identification Network. The antibiotic susceptibility of the isolates was determined by the broth microdilution method. ARGs,multilocus sequence typing(MLST), and polymorphism trees were analyzed using whole-genome sequencing data(WGS).Results This study revealed that 68.09% of the isolates had MDR, prevalent and distributed in different clades, with a relatively high rate and low pathogenicity. There was no difference in MDR between the diarrheal(49/70) and healthy groups(15/24).Conclusion We developed a random forest(RF) prediction model of TEM.1 + baeR + mphA + mphB +QnrS1 + AAC.3-IId to identify MDR status, highlighting its potential for early resistance identification. The causes of MDR are likely mobile units transmitting the ARGs. In the future, we will continue to strengthen the monitoring of ARGs and MDR, and increase the number of strains to further verify the accuracy of the MDR markers. 展开更多
关键词 E.COLI multidrug resistance Whole-genome sequencing Antibiotic resistance genes Randomforest
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Meta‑analysis of influencing factors associating with treatment outcome of multidrug resistant tuberculosis
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作者 LUO Qie-ning OUYANG Fan-xian +2 位作者 LIANG Cui-dan WANG Wei-tong YU Huang 《Journal of Hainan Medical University》 CAS 2023年第13期42-49,共8页
Objective:To systematically review the influencing factors of the treatment outcome of multidrug-resistant pulmonary tuberculosis and provide reference for the prevention and treatment of multidrug-resistant pulmonary... Objective:To systematically review the influencing factors of the treatment outcome of multidrug-resistant pulmonary tuberculosis and provide reference for the prevention and treatment of multidrug-resistant pulmonary tuberculosis.Method:Case control studies on the factors influencing the treatment outcome of multidrug-resistant pulmonary tuberculosis in Chinese databases(CNKI,VIP,Wanfang,Sinomed)and English databases(Pubmed,Web of science,Medline,Embase,Scopus)were searched and collected by computer.The search period was from the establishment of the database to January 2023.After screening and quality evaluation,RevMan5.4 was used for meta-analysis.Result:Totally 18 articles were ultimately included,with a sample size of 7328 people.The results showed that retreatment,complications,adverse reactions,and gender were related to the treatment outcome of multidrug-resistant pulmonary tuberculosis.The OR values and 95%CI of each factor were 0.22(0.17-0.29),0.38(0.32-0.46),0.27(0.17-0.44),and 0.43(0.33-0.56),respectively.Conclusion:Complications,retreatment,adverse reactions,and male gender are effective risk factors for the treatment outcome of multidrug-resistant pulmonary tuberculosis.In clinical practice,more targeted measures are needed for different types of patients.Due to the limitations of the number of studies,the above conclusions require more research to support them. 展开更多
关键词 multidrug resistant tuberculosis Treatment outcome Meta‑analysis
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百里香酚对犊牛源生物被膜阳性金黄色葡萄球菌耐药性的消除作用 被引量:1
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作者 赵红霞 顾珂瑞 +5 位作者 宋晨 李培锋 孙月 樊宏亮 郭宇 徐文琦 《中国兽医杂志》 CAS 北大核心 2024年第1期66-71,共6页
为了了解内蒙古地区犊牛病料中生物被膜阳性金黄色葡萄球菌的流行情况、耐药情况及百里香酚对生物被膜阳性金黄色葡萄球菌耐药性的消除作用。本试验采用生化鉴定和PCR方法,对采集到的104份犊牛病料进行金黄色葡萄球菌的分离鉴定;采用K-... 为了了解内蒙古地区犊牛病料中生物被膜阳性金黄色葡萄球菌的流行情况、耐药情况及百里香酚对生物被膜阳性金黄色葡萄球菌耐药性的消除作用。本试验采用生化鉴定和PCR方法,对采集到的104份犊牛病料进行金黄色葡萄球菌的分离鉴定;采用K-B法检测了金黄色葡萄球菌分离株对18种抗菌药物的敏感性;采用改良结晶紫染色法测定分离株的生物被膜形成能力;选取2株生物被膜强阳性菌株,采用微量肉汤稀释法测定百里香酚对分离株的最小抑菌浓度,并进行百里香酚耐药性消除试验。结果显示,在104份犊牛病料中共分离鉴定获得43株金黄色葡萄球菌。药敏试验结果显示,金黄色葡萄球菌分离株对氨苄西林、头孢西丁、卡那霉素、复方新诺明和红霉素5种抗菌药物的耐药率达到50.0%以上;74.4%(32/43)的分离株为多重耐药株。生物被膜形成能力强、中、弱和无生物被膜形成能力的分离株分别占比23.3%(10/43)、16.3%(7/43)、32.6%(14/43)和27.9%(12/43);生物被膜阳性株中83.9%(26/31)为多重耐药株。百里香酚对2株生物被膜强阳性株的最小抑菌浓度均为256 mg/mL,经百里香酚处理后均恢复了对头孢噻肟的敏感性。结果表明,百里香酚对生物被膜阳性金黄色葡萄球菌具有一定的耐药消除作用。 展开更多
关键词 犊牛源金黄色葡萄球菌 生物被膜 多重耐药性 百里香酚 耐药消除
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Sensorineural Hearing Loss in Multidrug-Resistant Tuberculosis Patients in Kinshasa (Democratic Republic of Congo): Prospective Cohort Study of Therapeutic Regimen with Aminoglycoside versus Bedaquiline
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作者 Mireille A. Mpwate Eddy M. Mbambu +11 位作者 Christian N. Matanda Gabriel M. Lema Michel K. Kaswa Murielle L. Aloni Nicole M. Anshambi Fabrice M. Matuta Luc L. Lukasu Dominique M. Mupepe Serge K. Mpwate Pierre Z. Akilimali Zacharie M. Kashongwe Richard N. Matanda 《Journal of Tuberculosis Research》 2023年第3期109-119,共11页
Context: Multidrug-resistant tuberculosis (MDR-TB) remains a major public health problem in developing countries such as the Democratic Republic of Congo (DRC), which continues to face the emergence of MDR-TB cases. B... Context: Multidrug-resistant tuberculosis (MDR-TB) remains a major public health problem in developing countries such as the Democratic Republic of Congo (DRC), which continues to face the emergence of MDR-TB cases. Because of the ototoxic effects of AGs, the World Health Organization (WHO) has recommended the introduction of the bedaquiline regimen. However, very few data are available regarding the susceptibility of bedaquiline to induce hearing loss, hence the present study set out to compare the AG-based regimen and the bedaquiline-based regimen in the occurrence of hearing loss in MDR-TB patients. Methods: This is a prospective multicenter cohort study that included 335 MDR-TB patients, performed in Kinshasa (DRC) during the period from January 2020 to January 2021. Sociodemographic, clinical, biological and audiometric data were analyzed using Stata 17. Repeated-measures analysis of variance was used to compare changes in the degree of hearing loss over time between the two groups of patients on AG and bedaquiline regimens. The double-difference method was estimated using regression with fixed-effects. A p value < 0.05 was considered the threshold for statistical significance. Results: The degree of hearing loss was similar between the two groups at the first month [AGs (28 dB) vs BDQ (30 dB);p = 0.298]. At six months, the mean degree of hearing loss was significantly greater in the aminoglycoside regimen group [AGs (60.5 dB) vs BDQ (44 dB);p < 0.001]. The double difference was significant, with a greater increase in hearing loss in the AGs group (diff-in-diff 18.3;p < 0.001). After adjustment for age and serum albumin, the group receiving the AG-based regimen had a 2-point greater worsening than those with bedaquiline at the sixth month (diff-in-diff 19.8;p Conclusion: Hearing loss is frequent with both treatment regimens, but more marked with the Aminoglycoside-based regimen. Thus, bedaquiline should also benefit for audiometric monitoring in future MDR-TB patients. 展开更多
关键词 multidrug-Resistant Tuberculosis AMINOGLYCOSIDES Bedaquiline Hearing Loss
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多药耐药相关蛋白转运体在药物性肝损伤中的作用研究进展 被引量:1
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作者 王欣 史磊磊 +2 位作者 张雨涵 谢允东 刘继平 《中国药物警戒》 2024年第2期229-234,共6页
肝脏是人体新陈代谢最旺盛的器官,也是体内多种药物的解毒器官。当长期或过量使用药物时会增加药物性肝损伤(DILI)的风险。多药耐药相关蛋白(MRPs)是位于细胞膜上的功能蛋白,可转运多种药物,在DILI中发挥重要作用。MRPs功能的抑制、缺... 肝脏是人体新陈代谢最旺盛的器官,也是体内多种药物的解毒器官。当长期或过量使用药物时会增加药物性肝损伤(DILI)的风险。多药耐药相关蛋白(MRPs)是位于细胞膜上的功能蛋白,可转运多种药物,在DILI中发挥重要作用。MRPs功能的抑制、缺失是药物肝毒性产生的重要原因。本文对MRPs的结构、表达部位及功能进行归纳,并对MRPs与DILI的关系及其改善DILI的机制进行总结,期望更好地了解MRPs转运体与DILI的关系,为后续防治DILI提供参考。 展开更多
关键词 多药耐药相关蛋白 药物性肝损伤 核因子相关受体 转运
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综合护理干预对耐多药结核病患者心理状态及服药依从性的影响 被引量:2
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作者 王淑梅 热依娜·麦德力汗 《包头医学院学报》 CAS 2024年第3期79-83,共5页
目的:探讨心理干预和团体活动对耐多药结核病患者心理状态及治疗依从性的影响。方法:将200例患者随机分为常规组和干预组各100例,常规组采用常规健康教育及一般常规护理,干预组采用心理干预、团体活动等多形式干预,采用症状自评量表(sym... 目的:探讨心理干预和团体活动对耐多药结核病患者心理状态及治疗依从性的影响。方法:将200例患者随机分为常规组和干预组各100例,常规组采用常规健康教育及一般常规护理,干预组采用心理干预、团体活动等多形式干预,采用症状自评量表(symptom checklist-90,SCL-90)进行心理状况调查测评,采用服药依从性量表进行服药依从性测评。结果:SCL-90中躯体化、强迫症状、人际关系敏感、抑郁、偏执、精神病性、睡眠及饮食几个维度,干预组得分均低于常规组(P<0.05),干预组SCL-90情况总均分低于常规组(P<0.05);干预组患者治疗依从性总均分高于常规组(t=-2.740,P=0.007);其中“结核病治疗周期长,您是否觉得长期服药有困难?”“您多久会有一次忘记服药?”“在过去的2周内,是否曾经忘记服用结核药?”这3个条目的分值干预组均高于常规组(P<0.05)。结论:心理干预及团体活动可改善耐多药结核病患者的不良心理状态,提高治疗依从性,促进患者康复。 展开更多
关键词 耐多药结核病 心理健康 心理干预 团体活动 治疗依从性
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世界卫生组织对BPaLM方案治疗耐多药结核病指南的解读 被引量:1
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作者 段鸿飞 《中国医学前沿杂志(电子版)》 CSCD 北大核心 2024年第3期1-4,I0003,共5页
耐多药结核病仍是人类健康的重大危险因素,近期世界卫生组织推荐贝达喹啉(bedaquiline,Bdq)、普托马尼(pretomanid,Pa)、利奈唑胺(linezolid,Lzd)和莫西沙星(moxifloxacin,Mfx)的6个月方案(BPaLM)治疗耐多药结核病。新指南中短程方案适... 耐多药结核病仍是人类健康的重大危险因素,近期世界卫生组织推荐贝达喹啉(bedaquiline,Bdq)、普托马尼(pretomanid,Pa)、利奈唑胺(linezolid,Lzd)和莫西沙星(moxifloxacin,Mfx)的6个月方案(BPaLM)治疗耐多药结核病。新指南中短程方案适用人群扩大到耐多药结核病患者,而且适用于病变广泛的肺结核和大多数肺外结核,无疑是耐多药结核病治疗的重要事件。本文就BPaLM方案的研究历程、适用人群和注意事项作一简要介绍。 展开更多
关键词 耐多药/利福平耐药结核病 短程治疗 世界卫生组织
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治疗多重耐药结核病新药的发展史及临床特点
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作者 王心静 安慧茹 《中国抗生素杂志》 CAS CSCD 北大核心 2024年第10期1131-1137,共7页
近20年,在世界卫生组织(WHO)的推动下,先后有20余种新药或再利用药物进入临床试验,针对多重耐药结核病,WHO推荐了包含新药贝达喹啉和普托马尼/德拉马尼组成的方案。国内应用正起步,本文就这2类新药的历史背景、作用机制、药物代谢特点... 近20年,在世界卫生组织(WHO)的推动下,先后有20余种新药或再利用药物进入临床试验,针对多重耐药结核病,WHO推荐了包含新药贝达喹啉和普托马尼/德拉马尼组成的方案。国内应用正起步,本文就这2类新药的历史背景、作用机制、药物代谢特点和临床应用等内容进行综述讨论,以促进临床医生对新药的正确应用。 展开更多
关键词 多重耐药结核病 贝达喹啉 普托马尼 德拉马尼
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肠杆菌科细菌mcr-1流行病学研究
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作者 钱娇 王怡岚 +8 位作者 洪加稳 秦佳佳 王丽莎 厉世笑 许春燕 毛稳 郑淑芳 张嵘 余素飞 《浙江医学》 CAS 2024年第3期251-256,I0005,共7页
目的探讨临床常见肠杆菌科细菌携带质粒介导多黏菌素耐药基因(mcr-1)的情况,为医院感染防控提供依据。方法收集2018年1月至2022年3月浙江省台州医院临床分离得到的菌株共1980株,包括大肠埃希菌1400株,肺炎克雷伯菌580株。采用PCR检测mc... 目的探讨临床常见肠杆菌科细菌携带质粒介导多黏菌素耐药基因(mcr-1)的情况,为医院感染防控提供依据。方法收集2018年1月至2022年3月浙江省台州医院临床分离得到的菌株共1980株,包括大肠埃希菌1400株,肺炎克雷伯菌580株。采用PCR检测mcr-1基因;利用微量肉汤稀释法和E-test法检测抗生素对mcr-1阳性菌株的最低抑菌浓度;采用接合试验检测mcr-1基因在可转移质粒上的位置;通过提取细菌DNA基因组进行全基因组测序,并对测序结果进行多位点序列分型、质粒Inc分型和耐药基因识别等分析。结果在1400株大肠埃希菌中,共检测出6株携带mcr-1,阳性率为0.43%;580株肺炎克雷伯菌,仅1株检出mcr-1,阳性率为0.17%。其中5株菌株接合试验成功。6株大肠埃希菌的ST型分别是ST648、ST95、ST359、ST602、ST453、ST156,肺炎克雷伯菌是ST25。质粒Inc分型结果显示不同菌株携带相同类型质粒,提示该类质粒可以在菌株间水平传播。耐药基因分析发现7株细菌均携带大量的耐药基因,其中1株大肠埃希菌和肺炎克雷伯菌同时携带mcr-1和碳青霉烯耐药基因。结论mcr-1在大肠埃希菌和肺炎克雷伯菌中的分离率相对较低,然而考虑到含有mcr-1的质粒在不同细菌之间水平传播的潜力,以及mcr-1与同一质粒内的多个耐药基因整合的能力,在临床环境中要加强对多重耐药菌的管理。 展开更多
关键词 大肠埃希菌 多黏菌素 多黏菌素耐药基因 多重耐药
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宣肺解毒方对多重耐药铜绿假单胞菌肺炎的作用机制探讨
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作者 沈婷婷 李亚 +2 位作者 李素云 李高峰 韩冰洋 《中国实验动物学报》 CAS CSCD 北大核心 2024年第6期721-732,共12页
目的探究宣肺解毒方对多重耐药铜绿假单胞菌肺炎的机理研究。方法除空白组外,其余组采用气管插管的方法建立MDR-PA(9×10^(8) CFU/mL,0.5 mL)肺炎大鼠模型,造模成功后随机分为模型组、宣肺解毒方低剂量组、宣肺解毒方中剂量组、宣... 目的探究宣肺解毒方对多重耐药铜绿假单胞菌肺炎的机理研究。方法除空白组外,其余组采用气管插管的方法建立MDR-PA(9×10^(8) CFU/mL,0.5 mL)肺炎大鼠模型,造模成功后随机分为模型组、宣肺解毒方低剂量组、宣肺解毒方中剂量组、宣肺解毒方高剂量组以及亚胺培南西司他丁组,每组12只;以上除空白组与模型组外,剩余给药组统称为干预治疗组。造模1 d后,宣肺解毒方低、中、高剂量组分别给予相应剂量的宣肺解毒方(Xuanfei Jiedu Formula,XFJDF)灌胃,亚胺培南西司他丁组给予亚胺培南西司他丁(imipenem,IPM)腹腔注射,空白组和模型组给予生理盐水灌胃,每天2次,持续7 d。观察大鼠的一般状态、体重变化、肺湿重/肺干重(W/D),采用苏木素-伊红(HE)染色法于光镜下观察大鼠肺组织病理学改变,采用酶免疫吸附测定法检测大鼠血清中IL-1β、TNF-α、TGF-β、IL-6炎症因子水平,采用比色法检测大鼠血清中GSH含量与MPO活性,采用TBA法检测大鼠血清中MDA含量,试剂盒法检测总抗氧化能力T-AOC;采用免疫组化法对肺组织中TLR4、Myd88、NF-κBp65蛋白进行定位与半定量观察,采用qPCR和Western Blot技术检测大鼠肺组织中TLR4、Myd88、NF-κBp65 mRNA和蛋白表达水平。结果与空白组比,模型组大鼠反应迟缓,呼吸频率加快、呼吸杂音增多且出现不同程度寒颤,饮食饮水减少,体重下降;肺W/D(P<0.01)显著升高,肺组织的肺泡腔以及肺支气管周围存有大量炎性细胞浸润,部分肺泡壁出现断裂融合形成气腔并伴有炎性渗出,肺间质增厚,局部可见肺纤维形成等;血清中IL-1β、TNF-α、TGF-β、IL-6水平明显升高(P<0.01),MDA含量增加、MPO活性增强、GSH含量与T-AOC能力降低(P<0.01),肺组织中TLR4、Myd88、NF-κBp65 mRNA和蛋白表达显著升高(P<0.01)。与模型组相比,干预治疗组均不同程度改善上述指标变化(P<0.05,P<0.01),以宣肺解毒方高剂量组以及亚胺培南西司他丁组最为显著(P<0.05,P<0.01)。结论宣肺解毒方能够显著改善MDR-PA大鼠的一般状态、体重、肺W/D以及肺病理,降低炎症与氧化应激反应,其作用机制可能与宣肺解毒方抑制肺组织中TLR4/Myd88/NF-κB通路表达有关。 展开更多
关键词 多重耐药菌 铜绿假单胞菌 肺炎 宣肺解毒方
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Determinants of the Sensorineural Hearing Loss in Patients with Multidrug-Resistant Tuberculosis in Kinshasa (Democratic Republic of the Congo): A Prospective Cohort Study
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作者 Mireille Avilaw Mpwate Eddy Mampuya Mbambu +13 位作者 Gabriel Mabuaka Lema Christian Nzanza Matanda Dominique Mayuku Mupepe Michel Kayomo Kaswa Murielle Luengiladio Aloni Nicole Muzutie Anshambi Fabrice Mankangu Matuta Luc Losenga Lukasu Serge Katya Mpwate Pierre Zalagile Akilimali Innocent Murhula Kashongwe Zacharie Munogolo Kashongwe Jean Marie Ntumba Kayembe Richard Nzanza Matanda 《International Journal of Otolaryngology and Head & Neck Surgery》 2023年第6期411-425,共15页
Background: The onset of the hearing loss is a major challenge during the treatment of multidrug-resistant tuberculosis (MDR-TB). Aminoglycoside-based regimens, to a lesser extent based on bedaquiline, induce ototoxic... Background: The onset of the hearing loss is a major challenge during the treatment of multidrug-resistant tuberculosis (MDR-TB). Aminoglycoside-based regimens, to a lesser extent based on bedaquiline, induce ototoxic sensorineural hearing loss. Research on risk factors is essential to enable high-risk individuals to benefit from preventive measures in settings with limited resources. Objective: This study aimed to assess the determinants of the hearing loss in patients with MDR-TB. Methods: This prospective multicenter cohort study included 337 patients with MDR-TB. It was performed in Kinshasa (Democratic Republic of the Congo) between January 2020 and January 2021. Sociodemographic, clinical, biological, therapeutic, and audiometric data were exported and analyzed using Stata 17 and MedCalc. The fixed-effect linear regression panel model was used to assess the degree of the hearing loss over time according to the following covariates: therapeutic regimen (aminoglycosides, bedaquiline, or alternate), stage of chronic kidney disease (CKD), age at inclusion, body mass index, serum albumin level, HIV status, alcohol intake, hypertension, and hemoglobin level. The Hausman test was used to select between fixed- and random-effect estimators. The threshold for statistical significance was set at p Result: A total of 236 patients (70%) received an aminoglycoside-based regimen, 61 (18%) received a bedaquiline-based regimen, and 40 (12%) received aminoglycosides relayed by bedaquiline. The frequency of the hearing loss increased from 62% to 96.3% within six months for all therapeutic regimens. The Hearing loss worsened, with moderate (72.4%) and profound (16%) deafness being predominant. An Exposure to the treatment for more than one month (β coeff: 27.695, Se: 0.793, p β coeff: 6.102, Se: 1.779, p β coeff: 5.610, Se: 1.682, p = 0.001), and an eGFR β coeff: 6.730, Se: 2.70, p = 0.013) were the independent risk factors associated with the hearing loss in patients with MDR-TB. Conclusions: The Hearing loss was more prevalent and worsened during the treatment of the patients with MDR-TB. An Exposure for more than one month, AG-based regimens, advanced age, hypoalbuminemia, and CKD have emerged as the main determinants of the worsening of the hearing loss. 展开更多
关键词 multidrug-Resistant Tuberculosis Determinants Hearing Loss DRC
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含新药口服短程方案治疗耐多药/利福平耐药结核病三例并文献复习
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作者 李雪莲 荆玮 +2 位作者 王庆枫 初乃惠 聂文娟 《中国防痨杂志》 CAS CSCD 北大核心 2024年第11期1327-1334,共8页
目的:探讨含新药口服短程方案治疗耐多药/利福平耐药结核病的疗效和安全性,为临床医师应用该方案治疗提供更多的依据。方法:回顾性分析2023年12月北京胸科医院收治的3例应用含新药口服短程方案(贝达喹啉、康替唑胺、德拉马尼)治疗的耐多... 目的:探讨含新药口服短程方案治疗耐多药/利福平耐药结核病的疗效和安全性,为临床医师应用该方案治疗提供更多的依据。方法:回顾性分析2023年12月北京胸科医院收治的3例应用含新药口服短程方案(贝达喹啉、康替唑胺、德拉马尼)治疗的耐多药/利福平耐药结核病患者的相关临床资料,通过查阅中国知网、万方数据库及PubMed数据库,以“耐多药结核、康替唑胺”和“耐多药结核、贝达喹啉、德拉马尼”为中文关键词,以“contezolid、multidrug-resistant tuberculosis”及“multidrug-resistant tuberculosis、bedaquiline、delamanid”为英文关键词进行文献检索,共搜索到国内外相关文献11篇,本研究主要选取含新药康替唑胺、德拉马尼、贝达喹啉短程治疗的文献8篇,结合本组3例患者的病历资料进行有效性和安全性分析。结果:有效性分析显示,含康替唑胺方案治疗的患者中,84%的患者痰培养和(或)涂片结核分枝杆菌阴性,且持续为阴性。治疗期间胸部CT检查显示病灶缩小,停药后胸部CT检查提示病灶稳定。含贝达喹啉、德拉马尼方案治疗的患者中,91%的患者获得了良好的结果。在治疗第8周,痰结核分枝杆菌培养阴转率为95%,第24周时为95%。贝达喹啉联合德拉马尼组的痰涂片和培养阴转中位时间均快于贝达喹啉组。安全性分析显示,含康替唑胺方案治疗的患者未发生骨髓抑制、周围神经病变和视神经病变等在内的利奈唑胺常见不良反应。而在含贝达喹啉和德拉马尼治疗的患者中,QTcF间期相比基线延长了20.7ms(平均16.1~25.3ms),2例患者出现QT间期延长大于500ms,4例患者发生6次QTcF间期延长超过基线值60ms,在治疗期间没有发生3级或4级不良QTc延长事件,未发生心律失常,没有一例永久停药,也没有发生死亡。贝达喹啉联合德拉马尼组QTc间期延长少于贝达喹啉组。在治疗过程中,52%的患者出现骨髓抑制,42%的患者出现周围神经病变。在48周随访时,大多数不良事件得到解决。结论:含新药贝达喹啉、德拉马尼、康替唑胺的全口服方案在耐药结核病短程治疗中取得了较好的效果。治疗期间仅出现轻度药物不良反应,经对症治疗后均缓解,未出现严重药物不良反应。 展开更多
关键词 结核 抗多种药物性 抗结核药 药物疗法 联合 评价研究
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β-内酰胺酶抑制剂联合不同β-内酰胺类抗生素对耐多药结核分枝杆菌临床菌株体外活性研究
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作者 石洁 郑丹薇 +6 位作者 徐吉英 马晓光 苏茹月 朱岩昆 王少华 常文静 孙定勇 《中国感染控制杂志》 CAS CSCD 北大核心 2024年第9期1091-1097,共7页
目的体外评估5种β-内酰胺类抗生素和不同β-内酰胺酶抑制剂组合对耐多药结核分枝杆菌(MDR-TB)活性的影响,以期发现针对耐多药结核病最有效的β-内酰胺类抗生素和β-内酰胺酶抑制剂组合。方法选取2021年河南省耐药监测项目收集的MDR-TB... 目的体外评估5种β-内酰胺类抗生素和不同β-内酰胺酶抑制剂组合对耐多药结核分枝杆菌(MDR-TB)活性的影响,以期发现针对耐多药结核病最有效的β-内酰胺类抗生素和β-内酰胺酶抑制剂组合。方法选取2021年河南省耐药监测项目收集的MDR-TB菌株,使用最小抑菌浓度(MIC)法测定5种β-内酰胺类抗生素或联合β-内酰胺酶抑制剂对临床MDR-TB的MIC值,并采用聚合酶链式反应(PCR)和DNA测序法分析菌株的bla C突变情况。结果共纳入105株MDR-TB,MIC检测结果显示,多尼培南对MDR-TB抗菌活性最高,其MIC 50值为16μg/mL。与β-内酰胺酶抑制剂联合后,大部分β-内酰胺类抗生素的MIC值明显下降。共有13.33%(14株)的菌株存在bla C基因的突变,主要为3种核苷酸替代突变,分别为AGT333AGG、AAC638ACC、ATC786ATT。BlaC蛋白Ser111Arg和Asn213Thr与同义单核苷酸突变相比,增强了克拉维酸/舒巴坦与美罗培南对MDR-TB的协同作用。结论多尼培南和舒巴坦组合对MDR-TB具有最强的抗菌活性。而BlaC蛋白Ser111Arg和Asn213Thr的替代突变使MDR-TB对美罗培南的敏感性在克拉维酸/舒巴坦协同时增强。 展开更多
关键词 结核分枝杆菌 Β-内酰胺类 Β-内酰胺酶抑制剂 耐多药结核分枝杆菌
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COVID-19是多重耐药菌感染/定植的危险因素吗?——COVID-19大流行期间一项住院患者多重耐药菌感染调查
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作者 叶永康 周子筌 覃金爱 《中国感染控制杂志》 CAS CSCD 北大核心 2024年第10期1279-1285,共7页
目的医院大规模收治新型冠状病毒感染(COVID-19)患者的状况下,分析COVID-19是否为住院患者多重耐药菌(MDRO)感染/定植的潜在危险因素。方法回顾性分析2022年12月1日-2023年1月31日某三级甲等医院的住院患者资料。比较COVID-19患者与非CO... 目的医院大规模收治新型冠状病毒感染(COVID-19)患者的状况下,分析COVID-19是否为住院患者多重耐药菌(MDRO)感染/定植的潜在危险因素。方法回顾性分析2022年12月1日-2023年1月31日某三级甲等医院的住院患者资料。比较COVID-19患者与非COVID-19患者的临床资料、抗菌药物治疗情况、MDRO检出情况。将检出病原菌的患者分为MDRO组和非MDRO组,采用多因素logistic回归分析住院患者MDRO感染/定植的危险因素。结果收治各类住院患者共16710例,其中COVID-19组2403例,8.83%(113/1280)检出MDRO;非COVID-19组14307例,4.43%(167/3770)检出MDRO。COVID-19组患者耐碳青霉烯类肺炎克雷伯菌(CRKP)检出率高于非COVID-19组(48.15%VS 30.89%,P=0.028)。多因素分析结果显示,危重患者(OR=4.796,95%CI:3.524~6.527)、培养前接受抗菌药物治疗≥2 d(OR=2.330,95%CI:1.699~3.196)、培养出真菌(OR=1.780,95%CI:1.318~2.405)、住院日数长(OR=1.036,95%CI:1.030~1.042)是住院患者MDRO感染/定植的危险因素(均P<0.05)。结论医院大规模收治COVID-19患者期间,MDRO感染/定植与是否为危重患者、抗菌药物使用、培养出真菌、住院日数长有关,COVID-19不是MDRO感染/定植的危险因素。 展开更多
关键词 新型冠状病毒感染 合并感染 抗菌药物治疗 多重耐药菌
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