Multidrug Resistant Mycobacterium leprae from Patients with Leprosy

Sequences of the folP1, rpoB, and gyrA genes were analyzed for 88 isolates of Mycobacterium leprae from leprosy patients in Japan, Haiti, Indonesia, Pakistan, and the Philippines. Thirteen isolates (14.8%) showed representative mutations in more than two genes, suggesting the emergence of multidrug-resistant M. leprae.     

纤维支气管镜注药治疗耐多药肺结核临床研究

耐多药肺结核主要由于患者间断治疗、疗程不足或有的医务人员用药不当造成。本研究用纤支镜局部用药 +全身化疗与单纯全身化疗进行比较 ,现报告如下 :1　临床资料1.1　一般资料从我科 1998年 1月～ 2 0 0 2年 4月收治耐多药肺结核病例中选取病灶相对局限的浸润型肺结核、干酪性肺炎、支气管结核致肺不张 ,痰菌阳性共 6 4例。其中在纤支镜下注药 34例为治疗组 ,剩下 30例为对照组。治疗组有空洞形成 30例 ,合并支气管结核 2 3例 (2 3/ 34) ,对照组有空洞形成 2 8例 ,合并支气管结核 19例 (19/ 30 )。1.2　方法两组均用 2DLZAO/ 7- 10DLO…     

H7N9患者感染碳青霉烯耐药鲍曼不动杆菌的同源性分析

目的 探讨H7N9患者感染碳青霉烯类耐药鲍曼不动杆菌菌株的同源性及传播机制.方法 收集自H7N9感染患者、同期ICU病房其他患者及环境中分离的多重耐药鲍曼不动杆菌;采用K-B纸片法测定菌株对常规药物的敏感性;脂稀释法测定其对多粘菌素B的MIC;EDTA协同试验测定金属酶表型;采用PCR法测定耐药基因;PFGE法分析菌株的流行病学特征.结果 临床分离株与环境分离株具有相似的药敏谱,均对阿米卡星和多粘菌素B敏感,对其他抗菌药物耐药,包括碳青霉烯类药物;金属酶表型试验为阴性;所有菌株均扩增出OXA-23和OXA-51基因;PFGE电泳分析显示H7N9患者分离株与其他患者分离株及环境分离株为同一克隆.结论 H7N9患者所感染的多重耐药鲍曼不动杆菌为院内感染菌株,对碳青霉烯类药物耐药主要由OXA-23基因介导.     

Treatment for Multidrug Resistant Gram-Negative Infections With Cefiderocol (Fetroja)

Global concern regarding antimicrobial resistance has allowed for innovative antimicrobials to emerge specifically in the presence of infections caused by resistant gram-negative microorganisms. The outer membrane of gram-negative microorganisms can hinder antimicrobial penetration. A novel approach to infiltrate gram-negative microorganisms would be to use their own transport systems. Cefiderocol is the first approved intravenous siderophore cephalosporin to treat resistant gram-negative infections. Cefiderocol achieves direct entry into the bacteria’s periplasmic space, avoiding mechanisms of resistance encountered with antimicrobials in clinical practice. Cefiderocol can revolutionize clinical practice with its original mechanism of action and sustainable activity against resistant gram-negative microorganisms.     

持续质量改进在多重耐药菌感染控制中的应用

目的探讨持续质量改进在多重耐药菌感染控制中的应用效果。方法通过调查,针对存在的问题,实施质量改进措施,比较持续质量改进前后,多重耐药菌感染患者医院感染防控措施落实情况、多重耐药菌分离率及多重耐药菌医院感染发生比。结果持续质量改进后,临床科室各项感染控制措施落实情况较持续质量改进前明显好转(P0.05),差异有统计学意义。结论实施持续质量改进有效提高了临床科室对院感防控措施的执行力,降低了多重耐药菌的医院感染发生率。     

三种方法评估替加环素对多重耐药鲍曼不动杆菌体外药敏结果分析

目的　比较3 种药敏检测方法检测替加环素对多重耐药鲍曼不动杆菌敏感性的差异。方法　收集2018 年临床 分离耐碳青霉烯类鲍曼不动杆菌60 株,采用MIC Test Strip（MTS）法、VITEK-2 法、纸片扩散法分别检测替加环素对 耐碳青霉烯类鲍曼不动杆菌的敏感性。结果　按照FDA 标准,以MTS 法为参考,VITEK-2 法的一致率较高,纸片扩 散法的一致率较低。Vitek-2 法的MIC 值比MTS 法的MIC 值低1 ~ 2 个稀释度,利用MTS 法检测替加环素对耐碳青霉 烯鲍曼不动杆菌的耐药率达到23.3%,出现耐药株。结论　对于耐碳青霉烯类鲍曼不动杆菌,Vitek-2 法和纸片扩散法 均不适合检测替加环素的敏感性,不能作为常规方法,需用MTS 法确认。     

结核分枝杆菌耐药分析及基因检测研究

目的了解长春市结核分支杆菌菌株的耐药状况,建立适合我国国情的结核分支杆菌耐药株的快速检测手段。方法采用普通改良罗氏培养,对2004年7月-2007年12月间分离培养的结核分支杆菌进行菌株鉴定及药物敏感实验,并利用PCR反向斑点杂交技术(RDB)和测序方法对rpoBr、psL、KatG和embB基因进行检测。结果 625株结核分支杆菌中,其耐药比例为32.96%。耐药顺位次序为INH 18.17%、RIF 17.26%S、M 10.74%、EMB 7.31%。复治患者的耐药率高于初治患者。在随机抽取的菌株中,RDB检出的rpoBr、psL、KatG和embB基因突变率分别为88.9%、83.3%、91.6%和86.1%,和测序结果的符合率分别为87.9%,87.9%、91.4%和89.1%。结论长春市结核病患者总耐药比例高于我国结核病总耐药率,耐药状况具有本市的耐药特点,耐药的产生与菌株基因突变有较为密切的关系。结核病人耐药情况比较严重,需要更严格的执行结核病控制策略,防止耐药病人及耐药菌株的产生和传播。     

大黄素对HL-60／ADR耐药细胞多药耐药逆转作用的研究

本研究旨在探讨大黄素（emodin）对人急性白血病HL-60／ADR耐药细胞多药耐药（mulfidrugresistance,MDR）逆转作用及其相应的作用机制。采用MTT法检测HL-60／ADR细胞对大黄素以及8种临床常用化疗药物的耐药性,比较大黄素联合化疗药物后对HL-60／ADR细胞耐药逆转效果,应用DNA倍体和DNALadder分析检测大黄素与阿霉素联合用药后细胞凋亡改变,RT-PCR和Westernblot分别检测耐药相关基因和蛋白表达变化,流式细胞术检测大黄素处理后HL-60／ADR细胞内阿霉素荧光阳性率和柔红霉素平均荧光强度（MFI）,激光共聚焦显微镜检测细胞内柔红霉素分布变化。结果表明：大黄素对HL-60／ADR耐药株和相应HL-60细胞敏感株的IC5值接近,分别为24．09±1.72μmol/L和23．18±0．87μmol／L,对阿霉素（ADR）、柔红霉素（DNR）、依托泊苷（VP16）、长春新碱（VCR）、阿糖胞苷（Ara-C）、高三尖杉酯碱（HHT）、米托蒽醌（MTZ）和吡柔比星（THP）呈现不同程度耐药。小剂量大黄素对8种药物耐药逆转倍数介于1．58-4．12之间,其中对ADR的耐药细胞逆转效果最好。大黄素与ADR联合用药组可见明显的亚二倍体凋亡峰和典型的DNA降解梯状带形成。与单药组比较,联合用药组MRP1、TOPOⅡB、GSTπ、BcL-2耐药相关基因mRNA和蛋白表达水平下调明显,细胞内ADR和DNR蓄积水平增加,胞浆和胞核DNR分布增加,该作用与大黄素呈浓度依赖性。结论：大黄素具有逆转HL-60／ADR细胞多药耐药作用,其作用机制可能与下调耐药相关基因表达水平、增加细胞内化疗药物蓄积和促进细胞凋亡作用有关。     

耐多药铜绿假单孢菌感染对极重度慢性阻塞性肺疾病急性加重期患者预后的影响

目的：分析耐多药铜绿假单孢菌感染对极重度慢性阻塞性肺疾病（COPD）急性加重期患者预后的影响。方法：回顾性分析50例铜绿假单孢菌感染极重度COPD急性加重期患者的临床资料,按其痰或支气管—肺泡灌洗液细菌培养结果分为耐多药菌组及非耐多药菌组,对比分析两组间的住院14d内出院例数、机械通气使用例数、病死例数。结果：两组间住院14d内出院率、机械通气使用率和病死率差异均有统计学意义,P〈0.05。结论：极重度COPD急性加重期患者发生耐多药铜绿假单孢菌感染后住院时间延长,需要应用机械通气的机率升高,且病死率升高,预后差。     

不同入院途径新生儿多重耐药菌分布特点及感染防控要点

目的 对不同入院途径新生儿的多重耐药菌分布情况进行统计,分析医院感染高危因素,避免新生儿多重耐药菌交叉感染的发生。方法 2012年1月-2013年7月期间,共监测新生儿2 124例,按入院类型其中门诊组1119例,院内组782例,外院组223例。分析不同入院途径、住院时间及体质量与医院感染之间的关系。结果 新生儿科标本共检出105株多重耐药菌,其中门诊组57株,院内组27株,外院组21株,外院组患儿耐药菌阳性率（9.42%）最高;住院时间〉14d,体质量≤1500g的患儿为耐药菌株引起医院内感染高发人群;不同入院途径患儿其监测出的耐药菌种基本一致。结论 在加强对门诊收入患儿入室筛查、隔离防控的同时,不能忽视对院内转入患儿的感染防控,特别应加强对住院时间〉14d、体质量≤1500g的患儿防控工作,减少新生儿科多重耐药菌交叉感染的发生。     

Real-time PCRs assay for serogrouping Listeria monocytogenes and differentiation from other Listeria spp.

A 5′-exonuclease real-time triplex-PCR assay was developed for serogrouping Listeria monocytogenes, and differentiation from other Listeria spp. The assay was evaluated on 109 Listeria cultures, and results were compared with a previously validated gel-based multiplex-PCR procedure. All L. monocytogenes were correctly classified into four serogroups, including atypical serotype 4b strains, and differentiated from other Listeria species. The assay is a rapid method for categorisation of suspect L. monocytogenes.     

含莫西沙星和左氧氟沙星方案治疗耐多药肺结核的前瞻性临床研究

[目的]评价含新一代氟喹诺酮类药物莫西沙星治疗方案对耐多药肺结核病的临床疗效及安全性.[方法]110例耐多药肺结核病患者随机分为含莫西沙星方案的治疗组（A组）及含左氧氟沙星方案的对照组（B组）,每组55例,A组采用6ADL2EM/18DL2EM方案,B组采用6ADL2EV/18DL2EV方案,疗程均为24个月,记录观察项目的结果并询问症状改善情况及有无不良反应出现.[结果]治疗结束时可评价疗效的患者A组为52例、B组51例.A组的痰菌阴转率、病灶吸收率、空洞闭合率分别为90.4%（6个月时）、88.5%、54.2%,B组痰菌阴转率、病灶吸收率、空洞闭合率分别为70.6%（6个月时）、80.4%、50.0%,两组比较A组痰菌阴转率高于B组（P＜0.05）,A组病灶吸收率、空洞闭合率也高于B组,但结果无统计学显著性差异（P＞0.05）;A组的药物不良反应发生率为32.6%,B组为39.2%,两者差异无统计学显著性（P＞0.05）.[结论]含莫西沙星方案和左氧氟沙星方案对耐多药肺结核均有可靠疗效,前者在治疗6个月时痰菌转阴率明显优于后者.     

多药耐药K562/A02和敏感K562细胞来源的树突状细胞介导抗白血病效应对比研究

本研究探讨多药耐药(MDR)白血病K562/A02细胞和敏感K562细胞诱导树突状细胞(DC)分化及介导的抗白血病效应。采用慢性粒细胞白血病(CML)P170糖蛋白(Pgp)高表达的MDRK562/A02细胞、敏感K562细胞在含细胞因子GMCSF(1000U/ml)、IL4(500U/ml)和TNFα(100ng/ml)的RPMI1640完全培养液中诱导分化成DC,以光镜观察细胞形态、流式细胞术检测细胞表型,异基因混合淋巴细胞反应(alloMLR)检测T细胞增殖活性,MTT法测定细胞毒作用。结果表明:培养14天的K562/A02细胞和K562细胞均出现典型的DC形态特征,表达DC的相关分化抗原及共刺激分子CD1a、CD83、HLADR、CD80、CD86。alloMLR检测中,K562/A02DC较K562DC具有更强的刺激异基因T细胞增殖能力(P<0.05)。两种DC激活的CTL分别对K562/A02和K562细胞较HL60细胞具有显著的杀伤活性(P<0.01);更重要的是,K562/A02DC较K562DC激活的CTL对Pgp高表达的MDRK562/A02细胞、HL60/VCR细胞具有更强的细胞毒作用,杀伤活性分别为(40.7±1.3)%、(28.4±0.9)%(P<0.01)和(24.9±1.1)%、(8.2±0.7)%(P<0.01)。结论:Pgp高表达的MDR白血病细胞K562/A02和敏感K562细胞都可在GMCSF、IL4和TNFα作用下诱导分化为成熟DC,均可活化CTL产生特异的抗白血病效应;尤其K562/A02细胞来源的DC可介导针对Pgp高表达的多药耐药白血病的特异细胞毒作用。     

汉防己甲素、雷洛昔芬及其联合应用逆转人肝癌耐药细胞株多药耐药性的研究

目的：探讨汉防己甲素（TTD）、雷洛昔芬及其联合应用对人肝癌多药耐药细胞株Hep-3B/ADM耐药性的逆转作用。方法：通过阿霉素（ADM）浓度梯度递增诱导法,建立人肝癌多药耐药细胞株Hep-3B/ADM。MTT法检测细胞对化学疗法药物的敏感性;流式细胞仪检测P-gp的表达及细胞内ADM强度。结果：ADM对Hep-3B和Hep-3B/ADM细胞的IC50分别为0.059μg/ml和2.131μg/ml,雷洛昔芬（4.90μmol/L）及TTD（1.00μmol/L）单用和两药联合处理Hep-3B/ADM细胞时,ADM的IC50值分别为0.234μg/ml、0.168μg/ml、0.096μg/ml。TTD及雷洛昔芬可降低耐药细胞株P-gp蛋白的表达,且联用有增强效果,同时还观察到逆转剂雷洛昔芬和TTD作用后细胞内阿霉素浓度增加,两药联合作用时效果增强。结论：TTD及雷洛昔芬均可逆转耐药,且联合作用效果增强。     

Multidrug resistant Acinetobacter baumannii isolates from a teaching hospital

 Acinetobacter baumannii is the most common nosocomial pathogen among all Acinetobacter spp. A. baumannii tend to be resistant to multiple antibiotics, and represent a severe threat in the treatment of hospitalized patients. The purpose of this study was to evaluate the prevalence, biotyping, and antibiotic resistance status of A. baumannii isolates recovered from submitted hospital clinical specimens. The in-vitro activity of 29 currently used antimicrobial agents was studied in 180 isolates of A. baumannii. The prevalence was higher in wound exudates (32%) and urine samples (22%) than in other specimens. Forty-six percent of the isolates were of biotype 9. The evolution of resistance from November 1996 through October 1998 was studied. More than 75% of the isolates were multidrug resistant (MDR) and more than 70% were β-lactamase producers. Amikacin, ampicillin + sulbactam, and imipenem are still effective antimicrobial agents, but a steady rise in the values of the minimum inhibitory concentration at which 50% of the isolates were inhibited (MIC₅₀) and MIC₉₀ was observed. Resistance to aztreonam (60%), enrofloxacin (60%), imipenem (29%), moxalactam (73%), and sparfloxacin (25%) was noted; enrofloxacin and sparfloxacin are not generally used in this hospital. From the findings of the present study, no single drug appears to be suitable for empirical therapy for this nosocomial pathogen. Received: September 24, 2002 / Accepted: December 3, 2002     

Multidrug resistance-encoding plasmid from Aeromonas sp. strain P2G1

Clin Microbiol Infect 2012; 18: E366-E368 ABSTRACT: A plasmid (pP2G1), which confers multidrug resistance in an environmental Aeromonas species, was completely sequenced using a shotgun approach. Plasmid pP2G1 encoded resistance to aminoglycosides and quinolones [aac(6')-Ib-cr], β-lactams (bla(OXA-1) ), chloramphenicol (catB3), macrolides [mphA-mrx-mphR], quaternary ammonium compounds (qacEΔ1), quinolones (qnrS2), rifampicin (arr-3) and sulphonamides (sul1). These findings suggest that Aeromonas species may potentially act as reservoirs of antibiotic resistance genes.     

Milk and rice

The following short article is an account of Israeli nurses caring for Syrian wounded. These wounded are shuffled across the Syrian border into Israeli hospitals. Until today and including today, we are considered ‘enemy countries’ with no diplomatic relations and fire arms pointing at each other. Six months ago when the Syrian wounded started trickling into our hospitals, the nurses did not know how to react and stood on shaky ground. The casualties were admitted directly into the intensive care units and emergency rooms without knowledge of mechanism of injury, date or circumstances of injury, and alone with no family support. We were told not to communicate with them. However, that request was quickly overlooked and relationships developed. The following report is that of one of the bedside nurses in an Israeli border hospital and her experience of caring for a Syrian casualty.     

Multidrug resistance gene family and chemical carcinogens.

The data discussed in this review indicate that the coordinated induction of both the mdr gene family and a subfamily of the cytochrome P-450 supergene family provide a unified response of the organism to prevent lethal accumulation of xenobiotics. Consequently, a distinct physiological role for the mdr multigene family now exists. Furthermore, recent evidence suggests the existence of multiple receptors with overlapping substrate specificity that are involved in the induction of both mdr and P-4501A gene families. The increased expression of mdr gene(s) in the early stages of liver carcinogenesis and presumably in other tissues is associated with the development of xenobiotic resistance that is observed in the preneoplastic cell populations. These observations may have important clinical implications and may provide an explanation for resistance to chemotherapy of tumors in organs such as liver and colon that are frequently exposed to both environmental and dietary xenobiotics.     

Crystal Structures of Bifunctional Penicillin-Binding Protein 4 from Listeria monocytogenes

Penicillin-binding proteins (PBPs), which catalyze the biosynthesis of the peptidoglycan chain of the bacterial cell wall, are the major molecular target of bacterial antibiotics. Here, we present the crystal structures of the bifunctional peptidoglycan glycosyltransferase (GT)/transpeptidase (TP) PBP4 from Listeria monocytogenes in the apo-form and covalently linked to two β-lactam antibiotics, ampicillin and carbenicillin. The orientation of the TP domain with respect to the GT domain is distinct from that observed in the previously reported structures of bifunctional PBPs, suggesting interdomain flexibility. In this structure, the active site of the GT domain is occluded by the close apposition of the linker domain, which supports the hypothesis that interdomain flexibility is related to the regulation of GT activity. The acylated structures reveal the mode of action of β-lactam antibiotics toward the class A PBP4 from the human pathogen L. monocytogenes. Ampicillin and carbenicillin can access the active site and be acylated without requiring a structural rearrangement. In addition, the active site of the TP domain in the apo-form is occupied by the tartrate molecule via extensive hydrogen bond interactions with the catalytically important residues; thus, derivatives of the tartrate molecule may be useful in the search for new antibiotics to inhibit PBPs.