Outcomes of adjunctive therapy with intrathecal or intraventricular administration of colistin for post-neurosurgical meningitis and ventriculitis due to carbapenem-resistant acinetobacter baumannii

The efficacy and safety of intrathecal (ITH) or intraventricular (IVT) colistin in addition to intravenous (IV) colistin for meningitis and ventriculitis due to carbapenem-resistant Acinetobacter baumannii (CRAB) is unclear. In this retrospective observational study of 40 patients with post-neurosurgical meningitis and ventriculitis due to CRAB, 33 patients without concomitant infection received appropriate dosage regimens of IV colistin. Of the 33 patients, 17 received additional ITH/IVT colistin and 16 received only IV colistin. The 14-day, 30-day and in-hospital mortality rates were nominally lower for patients who received ITH/IVT colistin adjunctive therapy versus patients who received only IV colistin (24% vs. 38%, 29% vs. 56% and 29% vs. 56%, respectively). The costs of treatment were significantly lower, the lengths of hospital and intensive care unit (ICU) stay were significantly shorter, and the number of ventilator days was significantly less among patients who received ITH/IVT colistin compared with patients who did not receive ITH/IVT colistin. The initial Acute Physiology and Chronic Health Evaluation (APACHE) II and Glasgow Coma Scale (GCS) scores were associated with 30-day mortality with odds ratios (95% confidence intervals) of 1.21 (1.08–1.46) and 0.77 (0.44–0.85), respectively. Chemical meningitis from ITH/IVT colistin was mild and resolved spontaneously. Treatment of post-neurosurgical CRAB meningitis and ventriculitis with ITH/IVT colistin as an adjunct to IV colistin was associated with shorter lengths of hospital and ICU stay and a trend to lower mortality, especially among severely ill patients.     

Carbapenem-Resistant Enterobacteriaceae in Children,United States, 1999–2012

The prevalence of carbapenem-resistant Enterobacteriaceae (CRE) infections is increasing in the United States. However, few studies have addressed their epidemiology in children. To phenotypically identify CRE isolates cultured from patients 1–17 years of age, we used antimicrobial susceptibilities of Enterobacteriaceae reported to 300 laboratories participating in The Surveillance Network–USA database during January 1999–July 2012. Of 316,253 isolates analyzed, 266 (0.08%) were identified as CRE. CRE infection rate increases were highest for Enterobacter species, blood culture isolates, and isolates from intensive care units, increasing from 0.0% in 1999–2000 to 5.2%, 4.5%, and 3.2%, respectively, in 2011–2012. CRE occurrence in children is increasing but remains low and is less common than that for extended-spectrum β-lactamase–producing Enterobacteriaceae. The molecular characterization of CRE isolates from children and clinical epidemiology of infection are essential for development of effective prevention strategies.     

Use of adjuvants in the treatment of Acinetobacter baumannii

The current antibiotic crisis to treat infections by Acinetobacter baumannii is linked with the increase of antimicrobial resistance and the lack of development of new antimicrobial drugs. For this reason, new alternatives for the treatment and control of infections by A. baumannii are necessary. Several studies have reported the effect of adjuvants to restore the efficacy of existing antimicrobial agents. Herein, we analyzed the main results on the development of adjuvant drugs, as monotherapy or in combination therapy with existing antimicrobial agents, which have shown promising results in vitro and in vivo. However, caution is needed and further extensive in vivo studies have to be performed to confirm the potential use of these adjuvants as true therapeutic alternatives.     

Multidrug resistance mediated by co-carriage of extended-spectrum beta-lactamases,AmpC and New Delhi metallo-beta-lactamase-1 genes among carbapenem-resistant Enterobacteriaceae at five Indian medical centres

In this study, we evaluated the coexistence of extended-spectrum beta-lactamases (ESBL), AmpC and New Delhi metallo-beta-lactamase-1 (NDM-1) genes among carbapenem-resistant Enterobacteriaceae (CRE) recovered prospectively from patients at multiple sites. The study included 285 CRE strains from 2782 Gram-negative Bacilli collected from multiple centres during 2007–2010, of which 87 were characterised. Standard and reference laboratory methods were used for resistance determination. Detection of bla_NDM-1, bla_AmpC, bla_TEM, bla_SHV and bla_CTX-M was done by polymerase chain reaction. High levels of antimicrobial resistance observed among study isolates. Co-carriage of ESBLs, AmpC and NDM-1 was 26.3%. Nosocomial origin among the co-carriage isolates was 64.3%, with 9.2% associated mortality.     

乳山市两所医院鲍曼不动杆菌耐药性及流行性分析

目的分析乳山市两所医院鲍曼不动杆菌的耐药性及流行特点。方法收集乳山市人民医院、乳山市中医院2015年1-12月临床分离鲍曼不动杆菌,进行药敏试验,选取50株鲍曼不动杆菌采用脉冲场凝胶电泳分析菌株同源性。结果共收集鲍曼不动杆菌158株,其中乳山市人民医院108株,乳山市中医院50株。标本来源以痰液(59.9%)为主,分布科室以呼吸科(39.8%)和ICU(25.3%)为主。药敏结果显示,所检测菌株对氨曲南、氨苄西林、头孢西丁100.0%耐药,对多黏菌素B、替加环素均敏感。50株鲍曼不动杆菌可分为A~E共5种型别,其中A型又分为A1、A2、A3等3个亚型,为主要流行型别。结论乳山市两所医院鲍曼不动杆菌耐药问题较严峻,主要存在于呼吸科、ICU等科室,以引起呼吸道感染为主,在两所医院不同科室间存在播散流行。     

鲍曼不动杆菌对多黏菌素类抗菌药物耐药现状及机制研究进展

多黏菌素类抗菌药物是多重耐药鲍曼不动杆菌的最后防线，但随着临床对多黏菌素类药物使用增多，鲍曼不动杆菌对其耐药的报道也陆续出现，相关耐药机制的研究成为热点。本文对近年来国内外鲍曼不动杆菌对多黏菌素类耐药报道以及耐药机制研究进行综述，以期对临床合理应用多黏菌素类抗菌药物、保持其抗菌活性提供参考。     

鲍曼不动杆菌耐药性快速检测方法的建立与评估

目的评估对实时荧光定量聚合酶链反应(PCR)快速检测鲍曼不动杆菌耐药性方法的效果。方法设计鲍曼不动杆菌(ATCC 19606)外膜蛋白A特异性探针,采用实时荧光定量PCR准确测定63株鲍曼不动杆菌经一定浓度庆大霉素、米诺环素、美罗培南、左氧氟沙星和头孢哌酮/舒巴坦孵育后的生长情况,比较抗菌药物孵育0和6h后鲍曼不动杆菌基因组DNA量,判断鲍曼不动杆菌耐药性,并与微量肉汤稀释法结果进行对比。结果建立的实时荧光定量PCR检测鲍曼不动杆菌耐药性方法与微量肉汤稀释法一致性高,Kappa值为0.879,P0.05。以微量肉汤稀释法为参考方法,实时荧光定量PCR的符合率达93.97%,灵敏度为92.53%,特异性为95.74%,阳性预测值为96.41%,阴性预测值为91.22%,Youden指数为0.88。结论实时荧光定量PCR与微量肉汤稀释法结果有高度一致性,且前者灵敏度高、特异性强、检测速度快,可用于快速检测鲍曼不动杆菌的耐药性。     

基于全基因组测序的耐碳青霉烯类抗生素鲍曼不动杆菌耐药基因、毒力因子及同源性分析

摘要：目的 通过应用全基因组测序(whole genome sequencing, WGS)技术分析某三级医疗机构耐碳青霉烯类抗生素鲍曼不 动杆菌(carbapenem-resistant Acinetobacter baumannii, CRAB)的耐药基因、毒力因子及同源性。方法 收集该院2020年1月至3月 重症监护病房(Intensive care unit, ICU)、神经外科分离的11株医院感染CRAB菌株，通过二代测序平台进行全基因组测序, 应用 基因组流行病学中心(Center for genomic epidemiology, CGE)ResFinder 4. 0软件分析其耐药基因型，并应用MORPHEUS在线制作 热图，应用毒力因子数据库(virulence factors of pathogenic bacteria, VFDB)VFanalyzer软件筛选毒力因子，应用MLST软件检测菌 株的ST型，应用Kaptive软件检测荚膜型，应用CSI Phylogeny 1. 4软件及FigTree v1. 4. 4软件构建最大似然树(maximum likelihood tree, MLT)以分析其同源性。结果 11株CRAB对亚胺培南、美罗培南、头孢菌素、环丙沙星均呈现耐药，而对阿米卡星、左氧 氟沙星耐药的菌株株数较少。11株CRAB共检测出18种耐药基因，11株同时携带碳青霉烯酶耐药基因blaOXA-23和blaOXA-66，β-内酰 胺酶耐药基因以blaTEM-1D和blaADC-25为主，大部分菌株携带多种外排泵相关耐药基因及抗菌药物修饰酶耐药基因。11株CRAB均携 带多种毒力因子，包括外膜孔蛋白、脂多糖、生物膜、外排泵、磷脂酶和效应蛋白等，如OmpA、Lps、Csu、Pga、Ade、Plc、 Bas、Bau、Ent、Hem、Aba、Bfm、Pbp和Kat等。11株CRAB均为ST2-K22型，同源性分析结果显示C组内同源性关系相近，存 在院内传播的可能。结论 该院CRAB的耐药性、毒力特征复杂多样，同源性分析显示该院存在1种优势克隆株，该克隆株有医 院内传播的风险。     

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。