Tigecycline as a therapeutic option in Stenotrophomonas maltophilia infections

Abstract

Trimethoprim-sulfamethoxazole (TMP-SMZ) is recommended as the treatment of choice for Stenotrophomonas maltophilia infections. However, when the administration of TMP-SMZ is not possible, alternative treatment options for S. maltophilia infections has not been clearly established. We compare the efficacy of tigecycline treatment with TMP-SMZ in nosocomial S. maltophilia infections during a 3-year period. For the treatment of S. maltophilia infection, 26 (57·8%) patients received TMP-SMZ and 19 (42·2%) patients received tigecycline. Culture positivity rate was 95·7% in TMP-SMZ group and 70·6% in tigecycline group at the seventh day (P?=?0·028), whereas 26·3% versus 18·8% at the fourteenth day (P?=?0·700). Clinical improvement was observed 69·2% in TMP-SMZ group and 68·4% in tigecycline group at the fourteenth day (P?=?0·954). Mortality rates at the thirtieth day were respectively, 30·8 and 21·1% in TMP-SMZ and tigecycline groups (P?=?0·517). There were no significant differences in mortality and clinical response rates between TMP-SMZ and tigecycline treatment. Tigecycline can be considered as an alternative option beyond TMP-SMZ in treatment of S. maltophilia infections.     

Antimicrobial susceptibility among E. faecalis and E. faecium from France,Germany, Italy,Spain and the UK (T.E.S.T. Surveillance Study, 2004-2009)

Abstract

We report on antimicrobial activity against E. faecalis and E. faecium collected in France, Germany, Italy, Spain, and the UK between 2004 and 2009 as part of the Tigecycline Evaluation and Surveillance Trial (UK in vitro data not included due to low isolate numbers). Overall, 1·1% (n?=?23/2068) of E. faecalis and 11·5% (n?=?103/893) of E. faecium were vancomycin-resistant. High levels of minocycline-resistant E. faecalis were reported in Germany, Spain, France, and Italy (40·2–44·2%); levofloxacin resistance was high in Germany, Italy, and Spain (31·1–41·6%). Minocycline non-susceptibility increased significantly among E. faecalis in Spain and Italy (P<0·001). No tigecycline-resistant E. faecalis were reported. Among E. faecium, resistance ranged from 72·9% (France) to 93·3% (Germany) for ampicillin, from 56·1% (France) to 90·2% (Germany) for levofloxacin, and from 75·3% (Italy) to 94·7% (Germany) for penicillin. Levofloxacin non-susceptibility increased significantly among E. faecium in France and Spain (P<0·001). The lowest rates of antimicrobial resistance among E. faecium were reported for tigecycline (2/893; 0·2%) and linezolid (3/893; 0·3%).     

替加环素单药及与5种抗菌药物联用对耐碳青霉烯类鲍曼不动杆菌的体外抑菌及生物膜清除作用研究#br#

目的 评价替加环素单用及与其他5种临床常用抗菌药物分别联合使用，对耐碳青霉烯类鲍曼不动杆菌(carbapenems-resistant Acinetobacter baumannii, CRAB)的体外抑菌及生物膜清除作用。方法 微量肉汤稀释法测定替加环素、阿米卡星、美罗培南、环丙沙星、黏菌素和舒巴坦对42株CRAB的最低抑菌浓度(minimal inhibititory concentration, MIC)和最低生物被膜清除浓度(minimal biofilm eradication concentration, MBEC)。棋盘稀释法测定替加环素分别联用阿米卡星、美罗培南、环丙沙星、黏菌素和舒巴坦对42株CRAB的MIC值和MBEC值，并计算分级抑菌浓度指数(fractional inhibitory concentration index, FICI)和分级生物膜清除浓度指数(fractional eradication concentration index, FECI)。结果 替加环素与5种抗菌药物分别联用后，对CRAB的抑菌作用和生物被膜清除作用表现为协同或无关，均未发现拮抗现象。其中替加环素与阿米卡星联用后具有较高的协同抑菌率(47.6%, 20/42)，而替加环素与环丙沙星联用后则具有较高的生物膜协同清除率(30.9%, 13/42)。结论 与单药相比，替加环素与5种药物分别联用，对CRAB的体外抑菌及生物膜清除作用具有一定的增强效果。     

替加环素对比左氧氟沙星治疗社区获得性肺炎疗效与安全性的Meta分析

摘 要 目的:系统评价替加环素与左氧氟沙星治疗社区获得性肺炎的疗效与安全性。方法：计算机检索 The Cochrane library, PubMed, Web of science,中国知网、万方数据库、维普期刊数据库,搜索替加环素对比左氧氟沙星治疗社区获得性肺炎的随机对照试验, 并对获得的研究进行质量评价,综合纳入符合条件的文献用Rev Man 5.0统计学软件进行Meta 分析。结果：共纳入3项RCT,合计1 275例患者,Meta分析结果显示,基于临床有效（CE）人群,替加环素对比左氧氟沙星治疗社区获得性肺炎(CAP）临床治疗有效率的差异无统计学意义(OR_合并=1.40,95%CI[0.92,2.15],P=0.12);基于临床意向性分析（c-mITT）人群, 两组临床治疗有效率的差异无统计学意义(OR_合并=1.11, 95%CI[0.82,1.49], P=0.5）,因此替加环素与左氧氟沙星相比治疗CAP效果相当。两组总不良反应发生率的差异有统计学意义(OR_合并=1.57, 95%CI[1.25,1.97], P＜0.000 1）, 两组消化系统不良反应发生率的差异无统计学意义(OR_合并=2.29, 95%CI[1.75,3.01], P＜0.000 01）。结论：本研究证据表明替加环素可以作为社区获得性肺炎的替代治疗药物,但与左氧氟沙星相比其不良反应风险会增加,治疗费用也会大大增加,不作为社区获得性肺炎的首选。本研究纳入的随机对照试验（RCT）质量高,但是数量较少,随着更多RCT的开展,结论将被进一步论证。     

In-vitro activity of the novel fluorocycline eravacycline against carbapenem non-susceptible Acinetobacter baumannii

The activity of eravacycline was compared with that of anti-Acinetobacter reference antimicrobials against carbapenem non-susceptible Acinetobacter baumannii isolates associated with an acquired OXA or up-regulation of the intrinsic OXA-51-like enzyme. Antimicrobial susceptibility testing was performed by broth microdilution of 286 non–duplicate, carbapenem non-susceptible A. baumannii isolates to eravacycline, amikacin colistin, doxycycline, imipenem, levofloxacin, meropenem, minocycline, sulbactam, tigecycline and tobramycin.Eravacycline showed greater activity than the comparators of the tetracycline class, levofloxacin, amikacin, tobramycin and colistin. The eravacycline MIC_50/90 values were 0.5/1?mg/L and those for tigecycline, minocycline and doxycycline were 1/2, 4/8 and 32/?≥?64?mg/L, respectively. In conclusion, eravacycline was the most potent antibiotic of those tested against A. baumannii, including isolates that were resistant to sulbactam, imipenem/meropenem, levofloxacin and amikacin/tobramycin. Eravacycline has the potential to become a useful addition to the limited armamentarium of drugs that can be used to treat this problem pathogen.     

Differences in the rate of carbapenem-resistant Enterobacteriaceae colonisation or Clostridium difficile infection following frontline treatment with tigecycline vs. meropenem for intra-abdominal infections

Objectives

We hypothesised that treatment with a tigecycline-based antimicrobial regimen for intra–abdominal infection (IAI) could be associated with lower rates of subsequent carbapenem-resistant Enterobacteriaceae (CRE) colonisation or Clostridium difficile infection (CDI) compared with a meropenem-based regimen.

替加环素不同治疗方案对ICU泛耐药鲍曼不动杆菌肺部感染的临床效果对比观察#br#

目的 对不同替加环素治疗方案对重症监护室(ICU)泛耐药鲍曼不动杆菌肺部感染的临床疗效和安全性进行对比分析,为替加环素的合理用药提供临床依据。方法 回顾性分析我院ICU 2014年1月-2017年6月使用替加环素治疗的62例泛耐药鲍曼不动杆菌肺部感染的临床资料,其中29例患者单独使用替加环素治疗,33例患者使用替加环素联合头孢哌酮/舒巴坦治疗,其疗程均超过7d,采用t检验或χ²检验对两组患者的临床特征、炎症指标、临床疗效、微生物清除率及不良反应等指标进行比较。结果 替加环素单独用药组和联合用药组在性别、年龄、疾病严重程度及加倍剂量应用替加环素病例数均无统计学差异(P＞ 0.05),联合用药组的临床有效率(21/33, 63.6%)高于单独用药组(11/29, 37.9%)(χ²=4.084, P＜0.05)。其中,患者APACHEⅡ评分≤15分的临床有效率70%(14/20)高于APACHEⅡ评分＞15分的42.9%(18/42)(χ²=3.997, P＜0.05);接受替加环素加倍剂量的临床有效率69.6%(16/23)高于常规剂量的41.0%(16/39)(χ²=4.719, P＜0.05)。替加环素单独用药组和联合用药组患者治疗后PCT、WBC和CRP水平与治疗前相比均显著降低(P＜0.05),且联合用药组的PCT水平下降更为明显(P＜0.05)。两组微生物学清除率(31.0% vs 38.7%)、不良反应发生率(13.8% vs 15.2%)均无统计学差异(P＞0.05)。临床疗效相关影响因素的logistic回归分析,也表明联合用药组疗效优于单独用药组,且用药前患者APACHE评分,CRP值,剂量加倍对临床疗效均存在影响。结论 替加环素联合头孢哌酮/舒巴坦治疗ICU泛耐药鲍曼不动杆菌肺部感染有较好的临床疗效,替加环素是否加倍剂量以及患者APACHEⅡ评分的高低可能影响其治疗效果,且不增加不良反应的发生率,值得在临床进一步推广。     

替加环素单药与联合方案治疗多重耐药菌感染疗效对比的系统评价#br#

目的 替加环素是一种广谱的新型四环素类抗生素,长期单独使用可能存在耐药菌出现增多的问题。本文将系统性评价以替加环素为基础的联合治疗方案与替加环素单药方案治疗多重耐药菌感染疗效的对比。方法 通过检索PubMed、Embase、the Cochrane Library、CNKI、维普、万方等数据库及手工检索会议论文,寻找有关替加环素单药和联合治疗方案比较的随机对照研究、队列研究、病例丛和个案报道。检索日期截止到2016年12月31日。英文数据库的检索词为“tigecycline”、“tygacil”、“monotherapy”以及“combination”。中文数据库的检索词为“替加环素”、“单药”及“联合”。相关综述研究也一并手工检索。结果 仅1篇符合筛选条件的相关RCT研究。最终纳入9项对比研究(含1510个事件)和22项非对比性研究(含26个事件)。对比研究显示基于替加环素的联合治疗方案与替加环素单药治疗方案相比疗效上无显著差异。然而26例个案报道中23例显示替加环素联合的治疗方案临床效果会更佳。此外,研究还显示,与替加环素组合的治疗方案中最常见的抗菌药物是多黏菌素、碳青霉烯类、氨基糖苷类和氟喹诺酮类。结论 替加环素为基础的联合方案似乎更优于单药方案,常见有效的联合药物为多黏菌素、碳青霉烯类、氨基糖苷类和氟喹诺酮类。未来需要进行更多的前瞻性、随机对照、双盲研究来探索联合治疗方案和单药治疗方案疗效对比以及何种药物与替加环素的联合会更适宜。     

Antimicrobial susceptibility of extended-spectrum beta-lactamase producers and multidrug-resistant Acinetobacter baumannii throughout the United States and comparative in vitro activity of tigecycline, a new glycylcycline antimicrobial

As part of the Tigecycline Evaluation and Surveillance Trial, isolates of Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii were collected in the United States between January 2004 and January 2006. Determinations of antimicrobial susceptibility and extended-spectrum beta-lactamase (ESBL) production were carried out according to the Clinical and Laboratory Standards Institute guidelines. A high percentage of ESBL-producing K. pneumoniae (>or=19.0%) was detected in New Jersey, Massachusetts, New York, and Missouri, and for E. coli, in the District of Columbia (9.5%). Against ESBL-producing isolates, the lowest MIC(90)s were for tigecycline (0.5-2 microg/mL) and imipenem (0.5-8 microg/mL). Overall, 282 (27.5%) A. baumannii isolates were resistant to >or=3 antimicrobial classes. The most common phenotype (33.0%) was resistance to cefepime, ceftazidime, ceftriaxone, levofloxacin, and piperacillin-tazobactam. Against multidrug-resistant A. baumannii, tigecycline and minocycline were the most active agents (MIC(90), 2 and 8 microg/mL, respectively).