β-lactams against emerging ‘superbugs’: progress and pitfalls

Bacterial resistance to antimicrobial agents is an ever-growing problem. So-called ‘superbugs’, such as multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa harboring multiple resistance determinants, including extended-spectrum β-lactamases, carbapenemases, efflux pumps and downregulated outer-membrane proteins or porins, are becoming more prevalent in hospital, intensive and long-term care settings. Enterobacteriaceae are also acquiring a myriad of β-lactamases, such as class A and D carbapenemases, and plasmid-borne class C cephalosporinases. Gram-positive superbugs, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate or heteroglycopeptide-intermediate S. aureus, vancomycin-resistant S. aureus and penicillin-resistant Streptococcus pneumoniae (PRSP), are problematic pathogens, both in the hospital and in the community (e.g., community-acquired MRSA and PRSP). β-lactam antibiotics remain among the most effective and safest anti-infectives in use, although their utility is being severely challenged by these superbugs. This review will discuss aspects of resistance seen in these pathogens and will review some of the newer β-lactam agents, both investigational and in clinical use, that target these superbugs.     

β-lactamase genotyping of multi-drug resistant Acinetobacter baumannii in a neonatal intensive care unit

Objective To investigate the correlation between drug resistance and β-actamase genes of multi-drug resistance Acinetobacter baumannii (MDR-AB) in neonatal intensive care unit to provide evidence for rational antibiotics administration and nosocomial infection control.Methods Twenty-six MDR-AB strains were separated and collected from clinical specimens.The minimum inhibitory concentrations of 13 antimicrobial agents were determined by agar dilution method.Genotypes of β-lactamase were detected by polymerase chain reaction.Results The resistant rates of the 26 strains to Ceftazidime,Cefoxitin,Piperacillin-tazobactam and Ciprofloxacin were 100.0%.About 80.8% to 96.2% of these strains were resistant to the other antimicrobial drugs.Among the 26 MDR-AB strains,100% (26/26) strains possessed oxa-51,77% (20/26) possessed oxa-23 gene,54% (14/26) carried arnpC gene,both oxa-23 and ampC were identified in 42% (11/26) strains,while oxa-24,oxa-58,imp-1,imp-4 and vim-2 gene were not identified.Conclusions The drug resistance of Acinetobacter baumannii is serious,oxa-23 and ampC are the major plactamase genes carried by MDR-AB in neonatal intensive care unit.     

OXA-51-like β-lactamases and their association with particular epidemic lineages of Acinetobacter baumannii

Sixty diverse clinical Acinetobacter baumannii isolates of worldwide origin were assigned to sequence groups, based on a multiplex PCR for the ompA , csuE and bla _OXA-51-like genes. The majority (77%) of isolates belonged to sequence groups 1 and 2 (SG1 and SG2), with sequence group 3 (SG3) and non-grouped isolates accounting for the remainder. The isolates were not closely related according to pulsed-field gel electrophoresis (PFGE), and the majority were sensitive to imipenem and meropenem. The construction of a linkage map of OXA-51-like β-lactamase sequence relationships revealed two closely related clusters of enzymes, one focused around OXA-66 and the other around OXA-69. Isolates belonging to SG1 encoded an enzyme from the OXA-66 cluster, while those belonging to SG2 encoded an enzyme from the OXA-69 cluster. All SG3 isolates encoded OXA-71, which does not form part of a close enzyme grouping. Major multinational lineages accounted for a significant proportion of A. baumannii clinical isolates, and the evolution of the OXA-51-like enzymes appears to be an ongoing process.     

全耐药鲍氏不动杆菌的随机扩增DNA多态性分析

目的 通过全耐药鲍氏不动杆菌随机扩增DNA多态性(RAPD)基因分型同源性分析,以用于医院感染的追踪控制和流行病学的调查研究.方法 收集8个月内从医院分离的15株全耐药鲍氏不动杆菌,提取DNA后进行RAPD分型,同时进行抗菌药物敏感试验和流行病学分析.结果 15株全耐药菌株被分为6个RAPD型,其中ICU1、ICU2分别存在两株克隆株,从ICU1转入外科病区的患者,同源件与其完全相同,全敏感菌株与全耐药菌株的同源性差异性很明显.结论 ICU存在全耐药鲍氏不动杆菌的局部流行.     

不动杆菌败血症的血清学研究

作者对6例Lwoff不动杆菌败血症患者做了血清外—斐氏反应(Ox19)结果均为阳性。经动物免疫、交叉吸收试验证明,Lwoff不动杆菌与变形杆菌Ox19有部分共同抗原成份,表明不动杆菌感染可致外—斐氏反应阳性。对150名健康人行血清学检测,结果为:不动杆菌凝集试验血清效价均不高于1:40(+)。由此结合临床提出,凝集试验血清效价高于1:40(+)为不动杆菌感染的寺参考诊断效价。     

鲍曼不动杆菌β内酰胺酶基因表达和对抗生素的耐药性研究

目的：调查淮南地区临床分离的鲍曼不动杆菌耐药性及卢内酰胺酶基因型。方法：采用K-β法测定临床分离的32株鲍曼不动杆菌对14种抗菌药物的敏感性，采用聚合酶链反应(PCR)及序列分析的方法分析β内酰胺酶基因型。结果：鲍曼不动杆菌对亚胺培南(100％)、头孢吡肟(87．5％)、阿米卡星(87.5％)和舒普深(84．4％)敏感，对其他抗菌药物的耐药率均较高。卢内酰胺酶基因型分布TEM—1阳性率100％(32／32)，SHV—12阳性40％(12／32)，OXA-2阳性12．5％(4／32)，CTX-M各型均阴性，VEB和PER均阴性。结论：淮南地区临床分离的鲍曼不动杆菌耐药严重，至少存在3种不同类型的卢内酰胺酶，基因型分别为TEM—1、SHV—12、OXA-2。     

Colistin treatment in patients with ICU-acquired infections caused by multiresistant Gram-negative bacteria: the renaissance of an old antibiotic

A retrospective case series study was performed in a 30-bed general intensive care unit (ICU) of a tertiary care hospital to assess the effectiveness and safety of colistin in 43 critically ill patients with ICU-acquired infections caused by multiresistant Gram-negative bacteria. Various ICU-acquired infections, mainly pneumonia and bacteraemia caused by multiresistant strains of Pseudomonas aeruginosa and/or Acinetobacter baumannii, were treated with colistin. Good clinical response (cure or improvement) was noted in 74.4% of patients. Deterioration of renal function occurred in 18.6% of patients during colistin therapy. Nephrotoxicity was elevated significantly in those patients with a history of renal failure (62.5%). All-cause mortality amounted to 27.9%. In this group of critically ill patients, an age of >50 years (OR, 5.4; 95% CI 1.3-24.9) and acute renal failure (OR, 8.2; 95% CI 2.9-23.8) were independent predictors of mortality. Colistin should be considered as a treatment option in critically ill patients with infection caused by multiresistant Gram-negative bacilli.     

鲍曼不动杆菌的耐药性分析

目的研究鲍曼不动杆菌的耐药性。方法收集2001年1月-2004年12月我院细菌室分离的鲍曼不动杆菌，采用琼脂扩散法作敏感试验。结果4年共分离鲍曼不动杆菌1101株，主要分布在呼吸科病房，占33、2％（366／1101），其次为外科监护病房（27．3％）、外科（24．7％）、内科（8、5％）和急诊科（6．2％）等。痰标本分离的鲍曼不动杆菌最多见，占87、8％，其次为伤口分泌物等。鲍曼不动杆菌的分离率在4年内逐年增加。鲍曼不动杆菌对多种抗菌药物的耐药率较高，其耐药率在各科室之间有差异，以呼吸科ICU分离菌株耐药率最高，除对亚胺培南敏感率较高外，对其他抗菌药物的耐药率均在80％以上。结论鲍曼不动杆菌的分离率逐年增加，且对多种抗菌药物耐药，以呼吸科明显，应引起高度重视．     

鲍曼不动杆菌血流感染临床分析

目的研究鲍曼不动杆菌血流感染患者的临床特征、感染危险因素及细菌耐药性。方法回顾性分析我院2001年1月至2006年12月间由鲍曼不动杆菌所致血流感染患者的临床及微生物学资料。结果21例患者入选，病死率33．3％。所有患者均有发热，发生血流感染时血白细胞计数平均14．5×10^9／L（4．77×10^9～36．01×10^9／L）。患者有手术史10例，中心静脉导管14例，气管插管或气管切开13例，原发感染灶不明10例（47．6％），继发于下呼吸道感染9例（42．9％），中心静脉插管来源的3例，其他感染灶包括外科伤口等2例。死亡组与存活组相比APACHEⅡ评分高，死亡组菌株耐药性高于存活组。结论鲍曼不动杆菌血流感染病死率高，且多为耐药菌株感染，应引起重视。