替加环素鞘内注射治疗多重耐药鲍曼不动杆菌颅内感染

目的探讨替加环素治疗多重耐药鲍曼不动杆菌(MDRAB)颅内感染的临床经验。方法分析中国人民解放军总医院第四医学中心神经外科2014年10月1日—2016年8月1日收治的6例MDRAB颅内感染患者的临床资料。记录患者脑脊液(CSF)的性状,细菌学及药敏试验结果。所有患者均根据CSF检验结果在常规治疗的基础上,给予替加环素50 mg(首次100 mg)静脉注射,1次/12 h;并以浓度为0.5 mg/mL的替加环素10 mL缓慢鞘内注射,1次/d,疗程9~21 d,平均14 d;观察临床疗效。结果6例MDRAB感染患者颅内感染均有效控制,未出现感染相关的神经功能障碍。随访1年,患者无感染复发。结论临床上替加环素的耐药率低,对MDRAB敏感性较高,但其血-脑屏障通过率低。颅内感染MDRAB后采用替加环素静脉滴注,并且同期行鞘内注射治疗,效果明显,临床未出现药物相关的神经功能障碍。     

In vitro evaluation of a new drug combination against clinical isolates belonging to the Mycobacterium abscessus complex

The in vitro susceptibility profile to amikacin, linezolid, clarithromycin, imipenem, cefoxitin, clofazimine and tigecycline was established for 67 strains belonging to the Mycobacterium abscessus complex. Clofazimine and tigecycline were among the most effective drugs, prompting us to assess the effect of a clofazimine and tigecycline combination. Synergistic activity was found in 42% of the 19 isolates tested. The clinical impact of this new drug combination against the M. abscessus complex, as an alternative or sequential medication for the treatment of drug-resistant strains, remains to be addressed.     

Structural basis for TetM-mediated tetracycline resistance

Ribosome protection proteins (RPPs) confer tetracycline resistance by binding to the ribosome and chasing the drug from its binding site. The current model for the mechanism of action of RPPs proposes that drug release is indirect and achieved via conformational changes within the drug-binding site induced upon binding of the RPP to the ribosome. Here we report a cryo-EM structure of the RPP TetM in complex with the 70S ribosome at 7.2-Å resolution. The structure reveals the contacts of TetM with the ribosome, including interaction between the conserved and functionally critical C-terminal extension of TetM and the decoding center of the small subunit. Moreover, we observe direct interaction between domain IV of TetM and the tetracycline binding site and identify residues critical for conferring tetracycline resistance. A model is presented whereby TetM directly dislodges tetracycline to confer resistance.     

替加环素用于鲍曼不动杆菌肺部感染患者的AUC值与疗效相关性研究

目的：进行鲍曼不动杆菌肺部感染患者替加环素的AUC值与疗效间相关性研究。方法：回顾性分析某院46名鲍曼不动杆菌肺部感染并行替加环素治疗的患者,采用高效液相色谱法测定替加环素谷浓度（C₀）、峰浓度（C₁）以及中浓度（C₂）,计算曲线下面积（AUC）,并结合其临床资料,进行替加环素AUC值与患者临床疗效相关性研究。结果：患者AUC值个体差异较大,多元线性回归后,无因素与AUC值间存在显著相关性（P>0.05）。AUC值高于目标值12.8 μg·h·mL^-1时,患者炎症指标、临床疗效均表现更好,且随着细菌耐药性增加,有效患者需要达到的AUC均值也在升高。结论：对替加环素治疗的鲍曼不动杆菌肺部感染患者行治疗药物监测能更好的施行个体化给药,提高治疗有效率。     

Molecular epidemiology and mechanisms of tigecycline resistance in carbapenem-resistant Klebsiella pneumoniae isolates

BackgroundThe emergence and transmission of tigecycline‐ and carbapenem‐resistant Klebsiella pneumoniae (TCRKP) have become a major concern to public health globally. Here, we investigated the molecular epidemiology and mechanisms of tigecycline resistance in carbapenem‐resistant K pneumoniae (CRKP) isolates.MethodsForty‐five non‐duplicate CRKP isolates were collected from January 2017 to June 2019. We performed antimicrobial susceptibility tests, multilocus sequence typing (MLST), and pulsed‐field gel electrophoresis (PFGE). PCR and DNA sequencing were performed for the detection and mutation analysis of acrR, oqxR, ramR, rpsJ, tet(A), and tet(X) genes, which are related to tigecycline resistance. The expression levels of efflux pump genes acrB and oqxB and their regulator genes rarA, ramA, soxS, and marA were assessed by quantitative real‐time PCR.ResultsThe resistance rate to tigecycline in CRKP isolates was 37.8% (17/45). K pneumoniae ST307 was a predominant clone type (70.6%, 12/17) among the TCRKP isolates. The expression levels of acrB (P < .001) and marA (P = .009) were significantly higher in the tigecycline‐resistant group than in the tigecycline‐intermediate and tigecycline‐susceptible groups. Increased expression of acrB was associated with marA expression (r = 0.59, P = .013).ConclusionsWe found that the activated MarA‐induced overexpression of AcrAB efflux pump plays an important role in the emergence of tigecycline resistance in CRKP isolates.     

替加环素联合注射用头孢哌酮舒巴坦钠对ICU多重耐药菌感染患者症状改善及细菌清除率的影响

目的:探讨ICU多重耐药菌感染患者采用替加环素联合头孢哌酮舒巴坦钠(舒普深)治疗的临床疗效。方法:随机将2015年1月~2017年12月收治的88例ICU多重耐药菌感染患者分为两组。A组采用舒普深治疗,B组采用舒普深联合替加环素治疗,比较两组的治疗效果。结果:B组患者体温、肺部啰音、胸部X线平片和白细胞计数等症状体征恢复时间明显短于A组,且B组细菌清除率、治疗总有效率明显高于A组,差异有统计学意义(P<0.05)。结论:ICU多重耐药菌感染患者采用头孢哌酮舒巴坦钠联合替加环素治疗,能有效改善患者的症状体征,清除细菌,促进患者康复。     

The current state of antibacterial research

‵...some would say that the era of once-daily HAART is upon us. Others would advocate for randomized controlled trials including more established twice-daily combinations before such a statement can be made. Although these studies may be interesting, there are a number of individual patients who will not wait.′     

肠杆菌科细菌SDD菌株特征及替加环素药敏结果分析

目的 分析医院肠杆菌科细菌剂量依赖性敏感(SDD)菌株的药物敏感性情况和检出分布特征,并检测产超广谱β内酰胺酶(ESBLs)大肠埃希菌和肺炎克雷伯菌对替加环素的敏感性,以指导临床对SDD菌株的抗菌药物及对ESBLs产酶株替加环素的选择.方法 采用VITEK 2 COMPACT全自动微生物分析仪进行细菌鉴定及仪器法抗菌药物敏感性试验.对50株ES-BLs阳性大肠埃希菌和50株肺炎克雷伯茼分别采用微量肉汤稀释法、MTS测试条法、Vitek2仪器检测法、纸片扩散法检测替加环素的敏感性.结果 采用M100-S24标准头孢吡肟判断为敏感的肠杆菌科细菌有3.58％～12.50％的菌株为SDD菌株;ESBLs阳性大肠埃希菌和肺炎克雷伯菌的SDD菌株检出率分别为13.31％和8.60％,显著高于ESBLs阴性菌株(P＜0.05);所有肠杆菌科细菌SDD菌株最低抑菌浓度(MIC)4 mg/L菌株检出率显著高于SDD菌株MIC 8 mg/L茼株检出率(P＜0.05);ESBLs阳性大肠埃希菌和肺炎克雷伯采用微量肉汤稀释法和MTS测试条法的敏感率均为100％.结论 当肠杆菌科细菌头孢吡肟MIC为4 mg/L或8 mg/L时,实验室应在检验报告提示SDD菌株的检出.替加环素对ESBLs阳性大肠埃希菌和肺炎克雷伯菌的敏感率为100％.     

New antimicrobial agents for the treatment of Gram-positive bacterial infections.

Since the 1970s, resistance to antimicrobial agents has become an escalating problem. In the last 25 years, treatment of infections caused by Gram-positive bacteria has been more problematical than ever, with infections being caused by multidrug-resistant organisms, particularly methicillin-resistant staphylococci, penicillin- and erythromycin-resistant pneumococci, and vancomycin-resistant enterococci. There is a continuing effort in the pharmaceutical industry to develop new antimicrobial agents for the treatment of resistant infections. Linezolid, quinupristin-dalfopristin, daptomycin, tigecyline, new glycopeptides and ceftobiprole are the main agents recently introduced or under clinical development. This review summarises their major properties, the results of recent studies with these agents, and future treatment possibilities.     

30例危重症感染儿童使用替加环素的回顾性分析

目的：探索替加环素在临床重症感染儿童中应用的有效性和安全性,为临床医生用药提供参考。方法：采用回顾性研究方法,收集某院2年中使用替加环素的儿童30例,并对其应用状况进行分析。结果：重症感染儿童使用替加环素治疗有效率为46.67%,不良发生发生率为43.33%,全因死亡率为6.67%。结论：替加环素可能是儿童危重症感染尤其是多药耐药菌感染治疗的又一选择,但其有效性和安全性数据需要更多大规模、长周期、设计严谨的临床试验进一步证实。