大肠埃希菌高产AmpC酶的检测及耐药性分析

目的了解深圳市人民医院高产AmpC酶大肠埃希菌的存在现状及其耐药性。方法采用Tris-ED-TA纸片裂菌法检测148株大肠埃希菌的AmpC酶。用琼脂稀释法测定产酶株对11种抗生素的最低抑菌浓度（MIC）。结果 148株大肠埃希菌中6株检出AmpC酶,检出率为4.1%。所有产AmpC酶大肠埃希菌对亚胺培南敏感,MIC为0.12～0.25μg/ml;对头孢吡肟的MIC值也较低,为0.5～32.0μg/ml,仅1株耐头孢吡肟。所有产AmpC酶大肠埃希菌对头孢西丁耐药,MIC为32～128μg/ml;对氨苄西林/舒巴坦、阿莫西林/克拉维酸和哌拉西林/他唑巴坦等加酶抑制剂复合物耐药性较强。结论深圳市人民医院大肠埃希菌高产AmpC酶检出率为4.1%。产酶株对多种抗生素耐药性较高。     

新生儿医院感染产超广谱β-内酰胺酶细菌流行状况及耐药性分析

目的了解新生儿医院感染中产超广谱β-内酰胺酶（ESBLs）细菌流行状况及耐药性,为预防和控制感染提供依据。方法对2011年1月至2013年12月间新生儿医院感染病原菌分布及耐药性进行回顾性分析;用VITEK-2 Compact微生物鉴定系统鉴定菌种和药敏试验。结果共检出病原菌192株,105株为肺炎克雷伯菌和大肠埃希菌,占54.7%;检出产ESBLs菌58株,全部来自肺炎克雷伯菌和大肠埃希菌;产ESBLs菌对青霉素类、头孢菌素类、单内酰环类抗菌药物高度耐药,耐药率〉80.0%,对头孢哌酮/舒巴坦、哌拉西林/他唑巴坦耐药率较低,耐药率〈20.0%,未检测到亚胺培南和美罗培南耐药株。结论产ESBLs肺炎克雷伯菌和大肠埃希菌是新生儿医院感染中主要的病原菌,且对常用抗菌药物耐药率较高,临床应加强病原菌的耐药性监测,合理使用抗菌药物。     

Antibiotic susceptibility and molecular mechanisms of cephalosporins resistance in Klebsiella isolates from patients with hospital-acquired infections]

Antibiotic susceptibility of nosocomial Klebsiella isolates from inpatients of 30 medical centres in 15 various regions of Russia was studied. In total 212 strains were tested. The Klebsiella genus was represented by the following species: Klebsiella pmeumoniae ss. pneumoniae (182 isolates, 85.8%), Klebsiella pneumonia ss. ozaenae (1 isolate, 0.5%), Klebsiella oxytoca (29 isolates, 13.7%). The susceptibility was determined by the broth microdilution method. Carbapenems (imipenem and meropenem) remained to be the most active antibacterial agents. However, 1 imipenem resistant strain and 2 meropenem resistant strains were isolated. As for the 3rd generation cephalosporins, the lowest MICs were observed with the use of the inhibitor-protected agents, such as ceftazidime/clavulanic acid (MIC50 0.25 mcg/ml, MIC90 64 mcg/ml). 48.8%, 16.9%, 29.7% and only 10.5% of the isolates was susceptible to cefepime, cefotaxime, ceftazidime and cefoperazone respectively. Detecting of the beta-lactamase genes (TEM, SHV and CTX) was performed by PCR in 42 strains of Klebsiella pneumoniae ss. pneumoniae. Alone or in various combination the TEM type beta-lactamases were detected in 16 (38.1%) isolates. SHV and CTX were detected in 29 (69%) and 27 (64.3%) isolates respectively. Combinations of 2 and 3 different determinants of resistance to beta-lactams were revealed in 23.8% and 26.2% of the isolates respectively. No isolates producing class B MBL among the carbapenem resistant nosocomial Klebsiella strains were detected.     

高龄患者血液感染常见革兰阴性杆菌及其耐药性分析

目的分析本院80~100岁高龄患者血液感染常见革兰阴性杆菌的种类及其耐药状况,为本院合理使用抗生素提供依据。方法采用BacT/Alert 3D血培养仪对血液标本进行阳性鉴定;VITEK-2Compact全自动微生物鉴定仪进行鉴定;K-B纸片扩散法对抗菌药物进行敏感性测定;使用WHONET 5.4分析软件分析数据。结果本院高龄患者血液培养阳性标本中共分离出革兰阴性杆菌108株,以肠杆菌科细菌为主,其次为非发酵菌,前者主要为大肠埃希菌52株(48.15%)和肺炎克雷伯菌37株(34.26%),后者主要包括铜绿假单胞菌10株(9.26%)和鲍曼不动杆菌8株(7.41%)。其中大肠埃希菌和肺炎克雷伯菌对亚胺培南的耐药率分别为1.92%和13.51%,两者对氨苄西林、氨苄西林/舒巴坦、头孢唑林、头孢呋辛的耐药率均高于50.00%;铜绿假单胞菌和鲍曼不动杆菌对亚胺培南的耐药率分别为20.00%和25.00%,后者对其他抗菌药物的耐药率均高于前者。结论碳青酶烯类抗生素可作为本院高龄患者常见革兰阴性杆菌所致血液感染的首选药物;但在治疗中应考虑细菌的耐药特点及患者的代谢特点合理选择抗生素。     

Infectivity and resistance to antibiotics of bacterial strains isolated from patients hospitalised in intensive care units

The aim of this study was to evaluate the frequency of isolation and antimicrobial resistance testing of bacterial strains isolated from clinical specimens from patients hospitalized in three Intensive Care Units in Wroc?aw. The susceptibility of bacteria (107 strains) to selected antibiotics was determined. The results clearly show that non-fermentative rods were identified as the main agents causing pneumonia (58% of isolates). The second commonest pathogens were Gram-positive cocci (29%). The P. aeruginosa and E. cloacae strains were resistant to ampicillin, amoxicillin/clavulanate, cefuroxime and cefotaxime. All isolates of A. baumanii were susceptible only to imipenem. The rods of K. pneumoniae and E. coli were resistant to ampicillin, about 55% strains of both bacteria were sensitive to other antibiotics, except piperacillin/tazobactam, imipenem and ciprofloxacin. About 90% of methicillin resistant S. epidermidis strains were resistant to all antibiotics, except vancomycin (100% isolates were sensitive). ESBL were detected among E. cloace, K. pneumoniae and E. coli. We found P. aeruginosa rods producing MBL.     

社区与医院感染中肺炎克雷伯杆菌和大肠埃希菌耐药性分析

目的探讨社区和医院感染中肺炎克雷伯杆菌和大肠埃希菌产ESBLs的情况及耐药特性。方法采用体外扩散确证试验检测ESBLs,同时用Micro scan wat RA way-40系统全自动细菌鉴定/药敏分析仪及K-B琼脂扩散法进行细菌鉴定和体外药敏试验。结果社区感染标本中分离出肺炎克雷伯杆菌79株,产ESBLs20株,阳性率为25.3%,大肠埃希菌177株,产ESBLs27株,阳性率为15.3%;医院感染标本中分离出肺炎克雷伯杆菌82株,产ES-BLs33株,阳性率为40.2%,大肠埃希菌135株,产ESBLs42株,阳性率为31.1%,社区与医院感染菌株产ESBLs比较差异均有统计学意义(P均<0.05);ESBLs阳性菌株对多种抗生素耐药,其耐药性明显高于ESBLs阴性菌株。结论肺炎克雷伯杆菌和大肠埃希菌产ESBLs菌株在临床分离率较高,医院感染标本要显著高于社区感染标本,并且对多种抗生素具有高度耐药性,产ESBLs菌株耐药性显著高于不产ESBLs菌株,临床上应加强对ESBLs的控制,以防感染流行。     

Cadmium resistance in some members of Enterobacteriaceae

Strains of members of Enterobacteriaceae, namely Escherichia coli (18), Klebsiella aerogenes (16), and Serratia marcescens (16) were screened for Cd resistance or sensitivity. Only one strain each of these was resistant to high levels (25 n moles/0.05 ml) CdCl2. The Minimal inhibitory concentration (MIC) of sensitive strains ranged from 0.8-5 micrograms/ml. All the resistant strains were simultaneously resistant to a number of antibiotics. Treatment with sodium dodecyl sulfate eliminated resistance to Cd and to some antibiotics.     

社区获得性泌尿系感染病原菌分布及耐药性分析

目的分析社区获得性泌尿系感染病原菌的种类及对常用抗生素的耐药性。方法收集2008年5月至2013年3月分离自社区获得性泌尿系感染患者中段尿的菌株,分析病原菌种类并测试主要病原菌对常用抗生素的体外敏感性。结果在215株细菌中,以革兰阴性杆菌155株（72. 1% ）为主。分离前5位的细菌为大肠埃希菌（48.4% ）、肠球菌属（10. 7% ）、肺炎克雷伯菌（7.4% ）、链球菌属（6. 0% ）、假丝酵母属（6. 0% ）。大肠埃希菌和肺炎克雷伯菌中,共63株产ESBL,占52. 5%。产ESBL菌株对头孢替坦、哌拉西林/他唑巴坦、阿米卡星、呋喃妥因、亚胺培南等5种抗生素的耐药率低于10%,对其他抗生素耐药率则超过70%。不产ESBL的菌株除对氨苄西林、氨苄西林/舒巴坦、环丙沙星、左氧氟沙星和复方新诺明的耐药率超过30%外,对其他常用抗生素的耐药率均在10%以下。肠球菌属和链球菌属分别对呋喃妥因和青霉素的耐药率较低（3/23和0/23）,未发现对万古霉素耐药株。结论引起社区获得性泌尿系感染的病原菌以大肠埃希菌为代表的革兰阴性杆菌为主,但由于不同菌株对抗生素的敏感性差异较大,用药之前进行尿培养是避免因抗生素使用不合理造成感染慢性化的一项重要措施。     

2009年度宁波市妇儿医院主要病原菌的临床分布及耐药性分析

目的了解宁波市妇儿医院主要病原菌的临床分布及耐药性分析。方法血液培养采用法国生物梅里埃公司的BacT/Alert3D,菌株鉴定采用法国生物梅里埃公司的VITEK 60分析仪,药敏试验采用K-B法,纸片扩散确证试验检测ESBLs。结果前10位细菌构成比依次是大肠埃希菌(13.4%)、白色念珠菌(8.7%)、阴道加德纳菌(7.8%)、表皮葡萄球菌(6.9%)、金黄色葡萄球菌(5.6%)、肺炎克雷伯菌(4.9%)、鲍曼复合醋酸钙不动杆菌(3.9%)、粪肠球菌(D群)(3.1%)、铜绿假单胞菌(2.7%)和溶血葡萄球菌(2.0%)。大肠埃希菌539株中产ESBLs阳性率为52.5%,肺炎克雷伯菌195株中产ESBLs阳性率为45.2%。大肠埃希菌主要分离于尿液,其次是脓液/切口。肺炎克雷伯菌在痰及咽拭子中所占比例最高。46株铜绿假单胞菌和11株鲍曼复合醋酸钙不动杆菌对亚胺培南耐药。结论对产ESBLs的肺炎克雷伯菌和大肠埃希菌、耐甲氧西林金黄色葡萄球菌(MRSA)和耐甲氧西林凝固酶阴性葡萄球菌(MRCNS)、耐亚胺培南的鲍曼复合醋酸钙不动杆菌和铜绿假单胞菌,应加强隔离预防,控制在医院内的扩散,减少耐药菌株产生。     

儿童活体肝移植术后感染常见致病菌及其耐药性分析

目的分析儿童活体肝移植术后常见致病菌的分布特点及其对常用抗菌药物的耐药性情况,为合理使用抗生素提供参考。方法回顾性分析重庆医科大学附属儿童医院自2006年6月至2009年12月术后监护的42例儿童活体肝移植患儿送检共152份标本进行菌株鉴定及药敏试验。结果经培养共分离出66株致病菌,阳性率为43.4%,以呼吸道来源为主,占71.2%。66株致病菌中革兰阴性菌（G^-）63.6%,革兰阳性菌（G^＋）27.3%,真菌9.1%。常见G^-菌为铜绿假单胞菌、阴沟肠杆菌、大肠埃希菌和肺炎克雷伯菌肺炎亚种。常见G^＋菌为金黄葡萄球菌和肺炎链球菌。真菌主要为白色假丝酵母菌。药敏结果显示细菌耐药性明显增强,G^-菌中阴沟肠杆菌、大肠埃希菌和肺炎克雷伯菌肺炎亚种对美洛培南、亚胺培南100%敏感,对环丙沙星、左旋氧氟沙星、阿米卡星和氯霉素敏感在85.7%以上;超广谱β-内酰胺酶（ESBLs）菌株检出率为66.7%100%。铜绿假单胞菌仅对环丙沙星、左旋氧氟沙星、庆大霉素、阿米卡星和多粘菌素敏高度感度,敏感度在91.6%以上。G^＋菌中金黄色葡萄菌对万古霉素、替考拉宁、利奈唑胺、呋喃妥因、阿米卡星和环丙沙星100%敏感,β-内酰胺酶检出率为100%。肺炎链球菌对万古霉素、利奈唑胺、头孢西丁、美洛培南、左旋氧氟沙星和头孢吡肟均有83.3%以上的敏感性,对于阿莫西林仍有66.7%的敏感性,但对于大环内酯类100%耐药。白色假丝酵母菌对两性霉素B 100%敏感。结论儿童活体肝移植术后常见致病菌以G^-菌为主,多为多重耐药菌株,含有β-内酰胺酶抑制剂及碳青霉烯类抗生素是治疗该类细菌的有效抗生素。万古霉素是G^＋菌感染的有效抗生素。两性霉素B是真菌感染的有效药物。为避免耐药率上升,临床应合理使用抗生素。     

Antimicrobial activity studies on some piperidine and pyrrolidine substituted halogenobenzene derivatives

The in vitro antibacterial and antifungal activities of the compounds synthesised from some 1,2,3,5-tetrahalogeno benzenes in presence of sodium piperidide and sodium pyrrolidide (2,6-dipiperidino-1,4-dihalogenobenzenes; 2,6-dipyrrolidino-1,4-dibromobenzene; 2,4,6-tripyrrolidino chlorobenzene; and 1,3-dipyrrolidino benzene) were investigated. The in vitro antimicrobial activities were screened against the standard strains: Staphylococcus aureus ATCC 25923 and Bacillus subtilis ATCC 6633 as Gram positive, Yersinia enterocolitica ATCC 1501, Escherichia coli ATCC 11230 and Klebsiella pneumoniae as Gram negative, and Candida albicans as yeast-like fungus. Compounds (3, 5, 6, 7) inhibited the growth of all the test strains at MIC values of 32-512 microg/ml. None of the four compounds (1, 2,4,8) studied showed antimicrobial activity against any of the test strains within the MIC range 0.25-512 micro/ml.     

407例老年肺癌下呼吸道感染患者病原菌分布及耐药分析

目的 分析老年肺癌下呼吸道感染患者痰培养物的病原菌分布及耐药状况.方法 回顾性分析407例老年肺癌下呼吸道感染患者痰标本细菌培养、鉴定及药敏结果.结果 共分离出病原菌238株,革兰阴性菌163株,占68.49％;革兰阳性菌33株,占13.87％;真菌42株,占17.65％.主要病原菌为肺炎克雷伯菌、大肠埃希菌、铜绿假单胞菌、鲍曼不动杆菌、表皮葡萄球菌和金黄色葡萄球菌.其中,肺炎克雷伯菌和大肠埃希菌ESBLs阳性菌株的比例分别为36.73％、28.85％.结论 老年肺癌患者因长期使用抗生素,呼吸道菌群失调,不同病原菌对抗菌药耐药率均较高,以革兰阴性菌感染为主,肺炎克雷伯菌和大肠埃希菌产ESBLs的菌株有较高比例,二重感染比例较高;革兰阳性菌均对万古霉素敏感,未发现耐药菌株.因此临床医生根据药敏结果合理选用抗生素,对于改善患者肺部微生态失衡,延长生存时间具有重要指导意义.     

Prevalence of extended-spectrum beta-lactamases produced by nosocomial isolates of Enterobacteriaceae in Trakya University Hospital,Turkey

The prevalence of extended-spectrum beta-lactamase (ESBL) production by 194 nosocomial isolates of Enterobacteriacea recovered from 1995 to 1999 was investigated. The ESBL production was determined by the double-disk synergy test and was confirmed by the E-test ESBL strip. Twenty-three isolates (21 Klebsiella pneumoniae, one Escherichia coli, one Providencia rettgeri) were found as ESBL-producers (11.8%). These isolates were also usually resistant to non-betalactam antibiotics. Most of them contained a beta-lactamase with a pI of 7.6. All the strains conjugally transferred their ESBLs to recipient E. coli. Contrary to others, ESBL-producing K. pneumoniae strains isolated in 1999 were resistant to ciprofloxacin, and had the identical plasmid profiles suggestive of an outbreak. Ciprofloxacin resistance in these strains could not be transferred. In conclusion, K. pneumoniae was the main ESBL-producing species among nosocomial isolates of Enterobacteriacae in our hospital.     

深圳市儿童社区获得性肺炎细菌病原学及其耐药性

目的研究儿童社区获得性肺炎细菌病原学及其耐药性特征,指导临床合理应用抗菌药物。方法对2006年2月至2007年3月1年期间住院的5岁及5岁以下社区获得性肺炎病人,进行深部呼吸道吸引物细菌培养,并且检测分离菌株对常用抗菌药物的耐药性。结果1441例病人中,722例检出细菌共761株,分离阳性率为50．1％,分离菌依次为肺炎克雷伯菌170株（22．3％）、大肠埃希菌130株（17．1％）、肺炎链球菌89株（11．7％）、金黄色葡萄球菌63株（8．3％）及流感和副流感嗜血杆菌60株（7．9％）。耐甲氧西林金黄色葡萄球菌（MRSA）检出率为15．9％;对青霉素不敏感的肺炎链球菌（包括PISP和PRSP）检出率为84．3％;肺炎克雷伯菌、大肠埃希菌、粘质沙雷菌和阴沟肠杆菌产ESBLs的检出率分别为31．2％、46．2％、94．8％和16．8％;流感嗜血杆菌和副流感嗜血杆菌对氨苄西林的耐药率为36％和40％;铜绿假单胞菌和鲍曼复合不动杆菌对亚胺培南的耐药率分别为10．7％和13．2％。结论在深圳儿童社区获得性肺炎的分离菌中,革兰阴性菌明显多于革兰阳性菌,分离菌依次为肺炎克雷伯菌、大肠埃希菌、肺炎链球菌、金黄色葡萄球菌及流感和副流感嗜血杆菌。分离细菌对常用抗菌药物的耐药性较为严重。     

小儿呼吸道感染肺炎克雷伯杆菌耐药性和基因型研究

目的探讨临海地区小儿呼吸道感染肺炎克雷伯杆菌产超β-内酰胺酶（ESBLs和AmpC酶）的耐药性及耐药基因型分布情况。方法采用VITEK-60型全自动细菌鉴定仪鉴定细菌,按CLSI推荐的确证试验检测ESBLs和K-B纸片法测定药敏结果;采用头孢西丁纸片扩散法筛选产AmpC酶阳性菌株,采用PCR检测AmpC酶基因,并对产物进行测序分析基因型。结果113株肺炎克雷伯杆菌ESBLs和AmpC酶总检测率分别为29．20％和18．58％,其中单产ESBLs、单产AmpC酶和同产AmpC酶＋ESBLs检出率分别为23．01％、12．39％和6．19％;AmpC酶阳性菌株的耐药基因型：16株为DHA-1型,5株为ACT-1型。药敏试验：所分离的肺炎克雷伯杆菌对亚胺培南全部敏感,对喹诺酮类耐药率很低,对大多β-内酰胺类抗生素耐药率较高,并且产酶株的耐药性明显高于非产酶株,耐药现象在同产ES-BLS和AmpC酶菌株中更为严重。结论临海地区小儿呼吸道分离的肺炎克雷伯杆菌产ESBLs和AmpC酶检出率较高;AmpC酶以DHA-1基因型流行为主,产酶株呈现出高度多重耐药性。     

产ESBLs大肠埃希菌和肺炎克雷伯菌呼吸道分离株的基因分型及耐药性分析

目的了解深圳市人民医院大肠埃希菌和肺炎克雷伯菌呼吸道分离株超广谱β-内酰胺酶(ESBLs)的基因型特点及耐药性。方法采用临床实验室标准化协会(CLSI)推荐的表型确证试验筛选出该院呼吸道分离株产ESBLs大肠埃希菌和肺炎克雷伯菌共78株。应用PCR及DNA测序法分析产酶株的TEM、SHV及CTX-M3种β-内酰胺酶基因,用琼脂稀释法测定细菌最低抑菌浓度(MIC)。结果 37株产ESBLs大肠埃希菌中,28株(75.7%)检出CTX-M-14基因,4株(10.8%)检出CTX-M-9基因,其他型较少见。41株肺炎克雷伯菌中,25株(61.0%)检出SHV-12基因,4株(9.8%)检出SHV-11基因,其他SHV型较少。20株(48.8%)检出CTX-M-14基因,5株(12.2%)检出CTX-M-3基因,其他型较少。产ESBL菌株均对亚胺培南敏感,对氨苄西林/舒巴坦的耐药率最高(90%),对其他抗生素有不同程度耐药。结论深圳市人民医院呼吸道分离的产ESBLs大肠埃希菌以CTX-M-14型为主,产酶肺炎克雷伯菌以SHV-12和CTX-M-14型为最常见。     

674例新生儿败血症病原学及耐药性分析

目的:了解新生儿败血症病原学特点和致病菌耐药酶的产生与抗生素应用的相关性,为临床及时明确病原、正确选用抗生素提供依据。方法:对12年间新生儿科5 350例发热新生儿患儿无菌采集血液进行细菌培养,同时进行药敏分析和耐药酶检测,并了解采集标本前抗生素的应用情况。结果:5 350份血液标本中检出需氧菌674株,阳性率12.6%,其中革兰阴性杆菌155株,占23.0%,革兰阳性球菌504株,占74.8%。排在前八位的菌种是表皮葡萄球菌、溶血葡萄球菌、嗜麦芽假单胞菌、人葡萄球菌、肺炎克雷伯菌、大肠埃希菌、不动杆菌、粪肠球菌。革兰阳性球菌对青霉素,哌拉西林,苯唑西林耐药性高,对万古霉素100%敏感;革兰阴性杆菌对氨苄西林、哌拉西林,头孢呋辛耐药性高,对亚胺培南、头孢三代较敏感;感染产耐药酶菌患儿在检测前使用抗生素比率高于感染但未产耐药酶菌的患儿比率(X2=6.55,P<0.05),尤其第三代头孢菌素的应用,差异更显著(X2=12.17,P<0.005)。结论:新生儿败血症病原菌以表皮葡萄球菌和非发酵菌为主,但溶血葡萄球菌有上升趋势。加强各类标本的细菌学检测,预防败血症,减少耐药菌株的产生。     

Isolation rate of gram negative microflora and its sensitivity to antibiotics in hemoblastosis patients

A total of 67 patients with blood system diseases and infectious complications were examined. During the period of the examination 139 microorganisms were isolated. Of these gram negative microorganisms constituted 51%, gram positive microorganisms--34.8% and fungal flora--14.2%. Most frequently the following gram negative microorganisms were isolated from the patients: Pseudomonas sp. (including P. aeruginosa), Klebsiella pneumoniae, Escherichia coli, Haemophilus influenzae. All isolated microorganisms retained sensitivity to imipenem, with the exception of individual strains of Pseudomonas sp.; the latter exhibited sensitivity to amicacin and ceftazidim. Cefotaxime was active with respect to 75% of K. pneumoniae strains and all E. coli strains, ciprofloxacin was active with respect to 43% of E. coli strains, 80% of K. pneumoniae strains and 83.4% of Pseudomonas sp. strains, cefepim was active with respect to 85.7% of Pseudomonas sp. strains and all E. coli strains, ceftazidim was active with respect to all Pseudomonas sp. and E. coli strains. 75% of K. pneumoniae strains, 77.8% of Pseudomonas sp. strains and 86% of E. coli strains retained sensitivity to amicacin. 25% of K. pneumoniae strains required testing for ESBL production.     

N-Heterocyclic dicarboxylic acids: Broad-spectrum inhibitors of metallo-β-lactamases with co-antibacterial effect against antibiotic-resistant bacteria

In an effort to identify novel, broad-spectrum inhibitors against the metallo-β-lactamases (MβLs), several N-heterocyclic derivatives were tested as inhibitors of MβLs CcrA, ImiS, and L1, which are representative enzymes from the distinct MβL subclasses. Three N-heterocyclic dicarboxylic acid derivatives were competitive inhibitors of CcrA and L1, exhibiting K(i) values ?2μM, while only 2,4-thiazolidinedicarboxylic acid (1b) was a competitive inhibitor of ImiS. Two 2-mercapto-1,3,4-thiadiazole derivatives were noncompetitive inhibitors of CcrA and ImiS, exhibiting K(i) values <7μM; however, these same compounds did not inhibit L1. Two 2-mercapto-1,3,4-triazole derivatives were shown not to inhibit any of the tested MβLs. The N-heterocyclic derivatives were tested for antibacterial activity by examining the MIC values for existing antibiotics in the presence/absence of these derivatives. Consistent with the steady-state inhibition data, the inclusion of three N-heterocyclic dicarboxylic acid derivatives resulted in lower MIC values when using Escherichia coli BL21(DE3) cells containing the CcrA or L1 plasmids or Klebsiella pneumoniae (ATCC 700603), while 1b was the only dicarboxylic acid derivative to lower the MIC value of E. coli cells containing the ImiS plasmid. Inclusion of the 2-mercapto-1,3,4-thiadiazole derivatives resulted in lower MIC values for E. coli cells containing ImiS or L1 plasmids; however, these derivatives did not alter the MIC values for K. pneumoniae or E. coli cells containing the L1 plasmid. None of the N-heterocyclic derivatives affected the MIC of two methicillin resistant Staphylococcus aureus (MRSA) strains. Taken together, these studies demonstrate that N-heterocyclic dicarboxylic acids 1a-c and pyridylmercaptothiadiazoles 2a,b are good scaffolds for future broad-spectrum inhibitors of the MβLs.     

Antibiotic susceptibility, serum response and surface properties of Klebsiella species

Altogether 130 clinical isolates of five Klebsiella species (K. pneumoniae, K. planticola, K. oxytoca, K. ornithinolytica and K. terrigena) were characterized, for their susceptibility to five antibiotics, for susceptibility to serum bactericidal activity and for their hydrophobic properties. All strains exhibited ampicillin resistance. Ampicillin/sulbactam, gentamicin and ofloxacin showed effectiveness in 63.1, 67.7 and 71.5% of the Klebsiella isolates. K. planticola manifested the highest level of resistance to these antibiotics. The majority of Klebsiella strains (93.9%) were susceptible to cefuroxime. Sixty-four strains (49.2%) were serum resistant and intermediate serum sensitivity was shown by 57 strains (43.8%). A high percentage of serum resistant strains (65%) was found in K. planticola. Moderately hydrophobic properties determined by adherence of bacteria to xylene were demonstrated in 25 strains (19.2%).