Early administration of appropriate antimicrobial agents to improve the outcome of carbapenem-resistant Acinetobacter baumannii complex bacteraemic pneumonia

Carbapenem-resistant Acinetobacter baumannii complex (CRABC) is an emerging pathogen that causes bloodstream infections and nosocomial pneumonia. This study aimed to describe severe infection associated with CRABC bacteraemic pneumonia and to investigate risk factors for 28-day mortality. All patients aged ≥18 years with CRABC bacteraemic pneumonia were enrolled retrospectively at five teaching hospitals in South Korea. Empirical antimicrobial therapy was defined as appropriate if administration of at least one antimicrobial agent, to which the causative pathogen was susceptible, for >48?h, within 5 days of the onset of bacteraemia. During the study period, 146 patients with CRABC bacteraemic pneumonia were enrolled. Among them, 128 (87.7%) patients were treated in the intensive care unit; of these, 110 (75.3%) had ventilator-associated pneumonia. A total of 42 patients (28.8%) received appropriate empirical therapy. There was no difference in baseline characteristics between the appropriate and inappropriate empirical treatment groups. However, 28-day mortality was higher in the inappropriate therapy group (54.8% vs. 76.9%; P?=?0.008). Multivariate Cox regression analysis revealed that Acute Physiology and Chronic Health Evaluation (APACHE) II score ≥20 [hazard ratio (HR)? =?1.28, 95% confidence interval (CI) 1.04–1.58; P?=?0.02], septic shock (HR?=?3.49, 95% CI 2.15–5.67; P?<0.001) and inappropriate empirical therapy (HR?=?3.24, 95% CI 1.94–5.42; P?<0.001) were independently associated with an adverse outcome. In conclusion, the mortality rate of CRABC bacteraemic pneumonia was extremely high. Appropriate empirical therapy might improve the outcome of patients with CRABC bacteraemic pneumonia.     

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。     

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).     

2018—2019年北京市海淀医院多重耐药鲍曼不动杆菌临床感染特点及耐药性分析

目的 分析北京市海淀医院多重耐药鲍曼不动杆菌（multidrug-resistant Acinetobacter baumannii,MDR-AB）临床感染的特点及耐药性,为临床用药提供一定的理论依据。方法 将北京市海淀医院2018年10月—2019年10月分离的178株鲍曼不动杆菌（Acinetobacter baumannii）作为研究对象,对其相关临床资料及体外药物敏感性试验结果进行分析。结果 鲍曼不动杆菌多重耐药率为46.6%,且97.6% MDR-AB为耐碳青霉烯鲍曼不动杆菌（CR-AB）。MDR-AB主要分离自高龄（>60岁）患者（86.7%）和重症监护室（ICU）患者（65.1%）,且86.7% MDR-AB分离自痰液标本。MDR-AB对各种常用抗菌药物的耐药率明显高于普通鲍曼不动杆菌,差异具有统计学意义（P<0.05）;MDR-AB中同时耐碳青霉烯类、氟喹诺酮类、抗铜绿假单胞菌青霉素加酶抑制剂类、广谱头孢菌素类、氨基糖苷类、四环素类等抗菌药物的菌株的占比最高（39.8%）。结论 高龄和ICU患者是MDR-AB的主要易感人群,MDR-AB对各种常用抗菌药物的耐药率明显高于普通鲍曼不动杆菌,替加环素对MDR-AB的耐药率相对低于其他抗菌药物,临床应合理使用抗菌药防止MDR-AB的产生和传播。     

基于全基因组序列的耐碳青霉烯鲍曼不动杆菌的耐药与毒力研究

目的明确耐碳青霉烯类鲍曼不动杆菌（CRAB）临床主要流行株CC92克隆复合群（CC92）基因组中耐药基因和毒力基因的分布,并探讨CRAB耐药和毒力的分子特征。 方法本研究共纳入2019年1～7月自首都医科大学附属北京地坛医院检验科分离的33株CRAB分离株,行细菌全基因组测序研究。利用CLC Genomics Workbench v10.0软件对全基因组测序数据进行序列的质量修整后,开展序列拼接、组装与注释,并进行耐药基因与毒力基因研究,分析CC92克隆复合群CRAB基因组中携带的耐药基因和毒力基因的分布。 结果基因组测序数据分析表明,33株CRAB菌株中30株为CC92型克隆复合群（包括ST195、ST208、ST369和ST540）,2株为ST229型,1株为国际上未报道新序列型别。以上CRAB中包括大量的耐药基因,包括大环内酯类、四环素和链霉素耐药基因在内的8～18个耐药基因,以及包括编码与侵袭和黏附等毒力功能相关的12种毒力基因。同时,本研究发现CC92克隆复合群,除携带碳青霉烯类耐药基因以外,还携带了其他非CC92克隆群不具备的耐药基因（如bla_OXA-66和bla_TEM-1D）和毒力基因（如bauA和bap基因）。此外,在CC92克隆复合群中可能存在大环内脂类耐药基因[msr（E）和mph（E）]、氨基糖苷类的耐药基因（armA）、链霉素耐药基因（strA、strB）与四环素耐药基因[tet（B）]的重组。 结论CC92克隆复合群的CRAB基因组存在大量耐药基因和毒力基因,且存在耐药基因重组现象,迫切需要对CRAB进一步开展全基因组水平监测,为临床病原诊断和治疗提供必要的依据。     

含多粘菌素E多药联合方案与单药方案的有效性和安全性Meta分析

目的:系统评价多粘菌素E与其他抗菌药物的联合治疗方案(联合方案)与单药治疗方案(单药方案)的有效性和安全性。方法:计算机检索PubMed,Embase和Cochrane Library,查找其联合方案与单药方案的临床对照研究文献。检索时限截至2013年5月,按纳入与排除标准筛选文献,采用RevMan 5.0统计软件进行Meta分析。结果:共纳入14篇相关文献,其中死亡率结果共纳入5篇文献,单药方案的死亡率显著大于联合方案的死亡率(OR:2.30,95%CI:1.28,4.13,P=0.005);临床疗效共纳入11篇文献,总体结果显示,单药方案优于联合方案[OR=1.59,95%CI:1.03,2.45,P=0.04],但亚组分析结果显示,前瞻性研究中,单药方案与联合方案没有显著性差异(OR:1.02,95%CI:0.53,1.94,P=0.96);微生物结果共纳入4篇文献,结果显示,单药方案与联合方案的微生物根除结果无显著性差异(OR:1.25,95%CI:0.66,2.36,P=0.50);肾毒性结果共纳入4篇文献,联合方案的肾毒性与单药方案的无显著性差异(OR:0.90,95%CI:0.31,2.61,P=0.85)。结论:联合方案在临床结果和微生物根除结果与单药方案相当,但在提高患者生存率上,联合方案要优于单药方案。多药联合治疗不增加多粘菌素E的肾毒性。     

Antibiotic resistance and OXA-type carbapenemases-encoding genes in airborne Acinetobacter baumannii isolated from burn wards

The study was conducted to investigate drug resistance, OXA-type carbapenemases-encoding genes and genetic diversity in airborne Acinetobacter baumannii (A. baumannii) in burn wards. Airborne A. baumannii were collected in burn wards and their corridors using Andersen 6-stage air sampler from January to June 2011. The isolates susceptibility to 13 commonly used antibiotics was examined according to the CLSI guidelines; OXA-type carbapenemases-encoding genes and molecular diversity of isolates were analyzed, respectively. A total of 16 non-repetitive A. baumannii were isolated, with 10 strains having a resistance rate of greater than 50% against the 13 antibiotics. The resistance rate against ceftriaxone, cyclophosvnamide, ciprofloxacin, and imipenem was 93.75% (15/16), but no isolate observed to be resistant to cefoperazone/sulbactam. Resistance gene analyses showed that all 16 isolates carried OXA-51, and 15 isolates carried OXA-23 except No.15; but OXA-24 and OXA-58 resistance genes not detected. The isolates were classified into 13 genotypes (A-M) according to repetitive extragenic palindromic sequence PCR (REP-PCR) results and only six isolates had a homology ≥90%. In conclusion, airborne A. baumannii in the burn wards had multidrug resistance and complex molecular diversity, and OXA-23 and OXA-51 were dominant mechanisms for resisting carbapenems.     

雾化吸入阿米卡星治疗鲍曼不动杆菌呼吸机相关肺炎的效果和安全性分析

目的：评估雾化吸入阿米卡星治疗鲍曼不动杆菌呼吸机相关肺炎的效果和安全性。方法将56例鲍曼不动杆菌呼吸机相关肺炎患者随机分为对照组和研究组各28例。对照组在头孢哌酮舒巴坦钠（3.0 g,1次/12 h）阿米卡星注射液（7.5 mg/kg,1次/d）静脉治疗的同时予生理盐水（5 ml,1次/d）呼吸机雾化吸入,研究组在头孢哌酮舒巴坦钠（3.0 g,1次/12 h）静脉治疗的同时予阿米卡星注射液（7.5 mg/kg,1次/d）呼吸机雾化吸入,分析治疗8 d后两组的支气管肺泡灌洗液培养结果转阴率、急性生理与慢性健康评分Ⅱ（APACHEⅡ）、临床肺部感染评分（CPIS）、氧合指数（PaO2/FiO2）、尿量及血肌酐（Cr）水平的变化,随访28 d,记录死亡率。结果治疗后,研究组与对照组支气管肺泡灌洗液培养转阴率分别为82.1%（23/28）、53.6%（15/28）,差异有统计学意义（P＜0.05）。治疗后,两组APACHEⅡ、CPIS较治疗前均下降,PaO2/FiO2均明显提高（P﹤0.05）。与治疗前相比,对照组尿量减少,Cr水平升高（P＜0.05）;而研究组尿量增多,血肌酐无明显变化（P＞0.05）。治疗后对照组的尿量明显少于研究组,Cr水平明显高于研究组,差异有统计学意义（P＜0.05）。研究组和对照组28 d死亡率分别为21.4%（6/28）、25.0%（7/28）,差异无统计学意义（P＞0.05）。结论雾化吸入阿米卡星治疗鲍曼不动杆菌呼吸机相关肺炎效果好,肾脏毒性小,能减少全身静脉应用抗生素的剂量。     

一株牛源约翰逊不动杆菌的分离鉴定

目的分离并鉴定1株致2018年7月四川省某肉牛场肉牛患呼吸道疾病并死亡的约翰逊不动杆菌。方法采集发病牛鼻腔拭子并从中分离得到一株优势菌株,对其进行形态学鉴定、生化鉴定、测定16s rRNA基因序列,用MEGA-X软件进行同源性分析、构建进化树,并进行药敏检测。结果分离菌为革兰染色阴性短杆菌,生化特性与约翰逊不动杆菌相符合,16S rRNA序列与GenBank中约翰逊不动杆菌株的同源性均达99%,因此将分离菌确定为约翰逊不动杆菌,并命名为ZZCNC-7B。8只SPF级昆明小鼠用1.4×10⁸ CFU/ml的ZZCNC-7B菌液腹腔注射(0.2 ml/只)后出现精神沉郁、腹式呼吸、眼部出现黏性分泌物、眼睑粘连、畏寒抱团等症状,有6只小鼠在16~36 h内死亡,另2只小鼠出现相同的症状但仍存活。剖检死亡小鼠,大体观察肺、肾充血肿大;肝、脾淤血肿大,肠道积气积液;组织学观察肺充血、出血,肝淤血,脾淤血、出血,肾小管坏死等病变。药敏试验显示,分离菌对四环素类药物四环素和磺胺类药物磺胺异恶唑耐药,对氨苄西林、亚胺培南、左氧氟沙星以及庆大霉素等药物均敏感。结论病牛分离菌为约翰逊不动杆菌,对小鼠具有较强的致病性和致死性,可引起肉牛呼吸道感染,甚至导致肉牛死亡,应引起高度重视。