国产和进口替加环素体外抗菌活性比较

目的比较替加环素国产和进口制剂对常见临床分离菌的体外抗菌效果。方法标准肉汤稀释法测定国产与进口替加环素制剂对临床分离菌株最低抑菌浓度(MIC)。结果国产和进口替加环素制剂均具有广谱和强大体外抗菌活性。对于肠杆菌科细菌具有良好的体外抗菌作用,MIC90≤2 mg/L,其中对大肠埃希菌MIC90为0.25 mg/L;对碳青霉烯类敏感和耐药鲍曼不动杆菌的MIC90均分别为0.5 mg/L和2 mg/L;对金黄色葡萄球菌、表皮葡萄球菌、肠球菌属MIC90均为0.25 mg/L;对肺炎链球菌MIC90分别为0.25 mg/L和0.125 mg/L;对流感嗜血杆菌和卡他莫拉菌MIC90≤0.125 mg/L;对嗜麦芽窄食单胞菌抗菌活性稍差,MIC90为4 mg/L;2种制剂对各种细菌敏感率几乎相同,对各种细菌的累积抑菌曲线也几乎重叠。结论替加环素具有强大广谱体外抗菌活性,对各种耐药菌抗菌作用突出;进口与国产替加环素制剂体外抗菌效果相同。     

SEANIR监测中国15所教学医院不发酵糖革兰阴性杆菌对13种抗菌药物的药敏试验

目的分析SEANIR监测2008年中国15所教学医院医院获得性不发酵糖革兰阴性杆菌对抗菌药物的敏感性,并评价帕尼培南体外药敏试验方法。方法收集2008年分离自中国15所教学医院医院获得性感染患者的非重复鲍曼不动杆菌349株、铜绿假单胞菌359株、嗜麦芽窄食单胞菌145株和洋葱伯克霍尔德菌100株,用琼脂稀释法测定13种抗菌药物的MIC,对比MH培养基和1:40 MH培养基对帕尼培南药敏试验结果的影响。结果鲍曼不动杆菌对碳青霉烯类抗生素的敏感率仅为51.6%～63.7%;多黏菌素B和米诺环素对鲍曼不动杆菌的体外抑菌活性最强,且对亚胺培南耐药鲍曼不动杆菌仍具有较高的抑菌率(分别98.1%和72.8%)。多黏菌素B和阿米卡星对铜绿假单胞菌的抑菌率最高(分别为96.1%和83.3%),其次为用1:40 MH培养基测定帕尼培南、哌拉西林-他唑巴坦和美罗培南的抑菌率(72.4%～77.2%)。嗜麦芽窄食单胞菌和洋葱伯克霍尔德菌对米诺环素和甲氧苄啶-磺胺甲噁唑均较敏感(敏感率为78.6%～98.0%)。结论多黏菌素B对鲍曼不动杆菌和铜绿假单胞菌,米诺环素对鲍曼不动杆菌、嗜麦芽窄食单胞菌和洋葱伯克霍尔德菌,具有较强的体外抗菌活性。帕尼培南的体外药敏试验,鲍曼不动杆菌应采用MH培养基测定,铜绿假单胞菌应采用1:40 MH培养基测定,其抗菌作用与亚胺培南较为接近。     

多黏菌素B和米诺环素对泛耐药鲍曼不动杆菌体外抗菌活性的比较

目的 测定多黏菌素B和米诺环素对泛耐药鲍曼不动杆菌的体外抗菌活性,为临床治疗药物选择提供实验室依据。方法 对39株临床分离的泛耐药鲍曼不动杆菌,采用K-B法测定多黏菌素B、米诺环素的药物敏感情况。结果 38株泛耐药鲍曼不动杆菌对多黏菌素B敏感,敏感率为97.4%;20株对米诺环素敏感,敏感率为51.3%;多黏菌素B的敏感性明显高于米诺环素(P<0.05)。结论 多黏菌素B对泛耐药鲍曼不动杆菌的体外抗菌活性较高,可作为治疗这类感染的首选。     

耐碳青霉烯类药物肺炎克雷伯菌和鲍曼不动杆菌对替加环素的敏感性分析

目的 分析耐碳青霉烯类药物肺炎克雷伯菌和鲍曼不动杆菌对替加环素的敏感性,为临床控制耐碳青霉烯类药物病菌繁殖提供理论依据。方法 收集2016年12月～2017年12月本院住院患者送检标本中分离出来的耐碳青霉烯类药物肺炎克雷伯菌112株和耐碳青霉烯类药物鲍曼不动杆菌98株,比较耐碳青霉烯类药物肺炎克雷伯菌和鲍曼不动杆菌对各类抗菌药物的耐药性差异。结果 耐碳青霉烯类药物的肺炎克雷伯菌和鲍曼不动杆菌几乎对所有抗菌类药物都有较强的耐药性;耐碳青霉烯类药物肺炎克雷伯菌对替加霉素的敏感菌数为97株,占86.61%,而耐碳青霉烯类药物鲍曼不动杆菌对替加霉素的敏感菌数为68株,占69.39%,替加环素对肺炎克雷伯菌的敏感性明显优于鲍曼不动杆菌,差异有统计学意义(χ~2=14.034,P=0.001);当MIC为4 mg/L时耐碳青霉烯类肺炎克雷伯菌的敏感率为100.00%,而碳青霉烯类鲍曼不动杆菌敏感率为71.21%,替加环素对两类菌体外敏感率分布差异有统计学意义(χ~2=18.488,P=0.002)。结论 耐碳青霉烯类药物肺炎克雷伯菌对替加环素的敏感性明显高于耐碳青霉烯类药物鲍曼不动杆菌,所以临床上采用替加环素可以有效控制耐碳青霉烯类肺炎克雷伯菌。     

5种抗菌药物与舒巴坦对临床分离鲍曼不动杆菌体外联合药敏试验

目的观察头孢哌酮、头孢他啶、亚胺培南、替加环素、黏菌素单药及其与舒巴坦联合用药对鲍曼不动杆菌的体外抗菌作用。方法选取2011-2012年抗菌药物耐药趋势监测研究(SMART)监测美罗培南耐药鲍曼不动杆菌23株、美罗培南敏感鲍曼不动杆菌21株,采取棋盘稀释法进行联合药敏试验,计算部分抑菌浓度指数(FIC)判定联合效应。结果所有组合体外均未出现拮抗作用,头孢哌酮、替加环素与舒巴坦联合应用对鲍曼不动杆菌的抗菌效应以协同作用为主,FIC指数≤0.5的菌株分别达56.8%及50.0%;亚胺培南、黏菌素与舒巴坦联合应用对鲍曼不动杆菌的抗菌效应主要表现为协同和部分协同作用,FIC指数1的菌株分别占61.4%和52.3%;头孢他啶和舒巴坦联合应用则主要表现为无关作用,FIC≥4的菌株占63.6%。结论 5种联合用药组合中,头孢哌酮与舒巴坦联合用药的体外协同作用效果最好,尤其对碳青霉烯敏感的鲍曼不动杆菌,可增强其体外抗菌活性;亚胺培南、替加环素与舒巴坦联合用药可增加对碳青霉烯耐药鲍曼不动杆菌的体外抗菌活性。临床对碳青霉烯耐药鲍曼不动杆菌引起的院内感染,可考虑联合应用亚胺培南/舒巴坦、替加环素/舒巴坦进行治疗。     

米诺环素、替加环素对多重耐药菌的体外抗菌活性比较

目的评价米诺环素、替加环素对多重耐药的耐甲氧西林金葡菌(MRSA)、肠球菌和鲍曼不动杆菌的体外抗菌活性。方法采用微量肉汤稀释法测定临床分离的多重耐药细菌对米诺环素、替加环素的敏感性。结果多重耐药的1 55株鲍曼不动杆菌,99株(63.9%)对米诺环素敏感,39株(25.2%)对米诺环素耐药,17株(11.0%)对米诺环素中介。75株多重耐药MRSA,50株(66.7%)对米诺环素敏感,20株(26.7%)对米诺环素中介,5株(6.7%)为耐药株。93株多重耐药屎肠球菌中36株(38.7%)对米诺环素敏感,57株(61.3%)对米诺环素耐药。39株粪肠球菌中25株(64.1%)对米诺环素敏感。75株MRSA对替加环素100%敏感,132株肠球菌100%敏感。5株耐万古霉素屎肠球菌和4株产新德里金属β内酰胺酶不动杆菌全部对替加环素敏感,MRSA和肠球菌对替加环素敏感性为100%。结论替加环素对米诺环素耐药的肠球菌和MRSA有很好的体外抗菌活性,替加环素对米诺环素耐药的鲍曼不动杆菌的抗菌活性也不理想。     

替加环素等14种抗菌药物对多重耐药菌的体外抗菌活性研究

目的 评价替加环素等14种抗菌药物对多重耐药细菌的体外抗菌活性.方法 采用微量肉汤稀释法测定替加环素对临床分离的214株多重耐药细菌(MRSA、肠球菌属细菌、鲍曼不动杆菌、产ESBLs大肠埃希菌、产ESBLs肺炎克雷伯菌和肠杆菌属细菌)的MIC,并与其他13种抗菌药物进行比较.数据分析采用WHONET 5.4软件.结果 多重耐药的MRSA对替加环素、万古霉素和利奈唑胺的敏感性均为100%.多重耐药的肠球菌属(粪肠球菌和屎肠球菌)对替加环素和利奈唑胺的敏感率均为100%,万古霉素敏感率为93.1%,2株万古霉素耐药的多重耐药屎肠球菌对替加环素和利奈唑胺均呈敏感,MIC90值分别为0.064 mg/L和1 mg/L.37株多重耐药鲍曼不动杆菌对替加环素的敏感率为97.3%,MIC90值为2 mg/L,其中16株耐美罗培南的鲍曼不动杆菌对替加环素的敏感率仍为100%,MIC90值为2 mg/L.产ESBLs大肠埃希菌和肺炎克雷伯菌对替加环素和美罗培南的敏感率均为100%,但替加环素的MIC90值均高于美罗培南.多重耐药的肠杆菌属细菌(阴沟肠杆菌和产气肠杆菌)对替加环素的敏感率为86.5%,MIC90值为4 mg/L.结论 替加环素对多重耐药的常见需氧革兰阳性球菌和革兰阴性杆菌均有良好的体外抗菌活性.     

替加环素治疗鲍曼不动杆菌感染的有效性和安全性研究

鲍曼不动杆菌已经成为重症感染的主要病原菌之一,其死亡率高,临床治疗困难。当临床上常用的抗菌药物对多重耐药鲍曼不动杆菌（指对常用的五类抗菌药物中至少三类抗菌药物耐药）和广泛耐药鲍曼不动杆菌（仅对1~2种潜在有抗不动杆菌活性的药物敏感,主要指替加环素和/或多黏菌素）[1]感染无效时,替加环素便成为了抗感染的唯一选择。     

替加环素对碳青霉烯类耐药鲍曼醋酸钙复合不动杆菌的体外抗菌活性

目的 测定替加环素对碳青霉烯类耐药鲍曼醋酸钙复合不动杆菌的体外抗菌活性。方法 收集2013年12月至2014年2月本院分离的碳青霉烯类耐药鲍曼醋酸钙复合不动杆菌,采用MTS法检测替加环素MIC值,折点采用美国食品药物管理局(FDA)公布的判定标准。结果 61株碳青霉烯类耐药鲍曼醋酸钙复合不动杆菌对临床常用抗菌药物具有极高的耐药率,替加环素的灵敏度为80.3%,中介率为19.7%,无耐药菌株。MIC90为3μg/mL,而MIC50为2μg/mL。结论 替加环素对于本院分离的碳青霉烯类耐药鲍曼醋酸钙复合不动杆菌有较好的体外抗菌活性。     

头孢哌酮-舒巴坦联合多黏菌素E等6种抗菌药物对碳青霉烯类耐药鲍曼不动杆菌体外抗菌作用研究

目的 研究头孢哌酮-舒巴坦与多黏菌素E、阿米卡星、美罗培南、替加环素、左氧氟沙星和利福平联合用药对碳青霉烯类耐药鲍曼不动杆菌的体外抗菌活性,为治疗碳青霉烯类耐药鲍曼不动杆菌感染提供理论依据.方法 取临床分离的碳青霉烯类耐药鲍曼不动杆菌100株,将头孢哌酮-舒巴坦分别与上述6种抗菌药物联合,采用棋盘法对6种联合用药进行药...     

In vitro activities of various antimicrobials alone and in combination with tigecycline against carbapenem-intermediate or -resistant Acinetobacter baumannii

The activities of tigecycline alone and in combination with other antimicrobials are not well defined for carbapenem-intermediate or -resistant Acinetobacter baumannii (CIRA). Pharmacodynamic activity is even less well defined when clinically achievable serum concentrations are considered. Antimicrobial susceptibility testing of clinical CIRA isolates from 2001 to 2005 was performed by broth or agar dilution, as appropriate. Tigecycline concentrations were serially increased in time-kill studies with a representative of the most prevalent carbapenem-resistant clone (strain AA557; imipenem MIC, 64 mg/liter). The in vitro susceptibility of the strain was tested by time-kill studies in duplicate against the average free serum steady-state concentrations of tigecycline alone and in combination with various antimicrobials. Ninety-three CIRA isolates were tested and were found to have the following antimicrobial susceptibility profiles: tigecycline, MIC(50) of 1 mg/liter and MIC(90) of 2 mg/liter; minocycline, MIC(50) of 0.5 mg/liter and MIC(90) of 8 mg/liter; doxycycline, MIC(50) of 2 mg/liter and MIC(90) of > or =32 mg/liter; ampicillin-sulbactam, MIC(50) of 48 mg/liter and MIC(90) of 96 mg/liter; ciprofloxacin, MIC(50) of > or =16 mg/liter and MIC(90) of > or =16 mg/liter; rifampin, MIC(50) of 4 mg/liter and MIC(90) of 8 mg/liter; polymyxin B, MIC(50) of 1 mg/liter and MIC(90) of 1 mg/liter; amikacin, MIC(50) of 32 mg/liter and MIC(90) of > or =32 mg/liter; meropenem, MIC(50) of 16 mg/liter and MIC(90) of > or =128 mg/liter; and imipenem, MIC(50) of 4 mg/liter and MIC(90) of 64 mg/liter. Among the tetracyclines, the isolates were more susceptible to tigecycline than minocycline and doxycycline, according to FDA breakpoints (95%, 88%, and 71% of the isolates were susceptible to tigecycline, minocycline, and doxycycline, respectively). Concentration escalation studies with tigecycline revealed a maximal killing effect near the MIC, with no additional extent or rate of killing at concentrations 2x to 4x the MIC for tigecycline. Time-kill studies demonstrated indifference for tigecycline in combination with the antimicrobials tested. Polymyxin B, minocycline, and tigecycline are the most active antimicrobials in vitro against CIRA. Concentration escalation studies demonstrate that tigecycline may need to approach concentrations higher than those currently achieved in the bloodstream to adequately treat CIRA bloodstream infections. Future studies should evaluate these findings in vivo.     

中国14家教学医院院内菌血症与肺炎和腹腔感染病原菌的抗生素耐药监测

目的 监测2006年10月-2007年10月我国不同地区14家教学医院分离的院内获得病原菌的分布和体外药物敏感性.方法 收集来自于院内菌血症、肺炎和腹腔感染患者标本的病原菌.菌株经中心实验室复核后,采用琼脂稀释法测定29种抗菌药物对菌株的MICs,数据输入WHONET5.4软件进行耐药性分析.结果 本研究共收集到2 660株病原菌.引起菌血症(BSI)的病原菌中分离率位于前3位的分别为大肠埃希菌(30.0%)、肺炎克雷伯菌(12.O%)和金黄色葡萄球菌(11.2%);引起院内获得性肺炎(HAP)的病原菌中分离率位于前3位的分别为铜绿假单胞菌(23.4%)、鲍曼不动杆菌(17.4%)和肺炎克雷伯菌(13.8%);引起腹腔感染(IAI)的病原菌中分离率位于前3位的分别为大肠埃希菌(38.8%)、肺炎克雷伯菌(10.2%)和铜绿假单胞菌(9.2%).对于大肠埃希菌和克雷伯菌,敏感性大于80%的药物包括替加环素(100%)、美罗培南(99.3%～100%)、亚胺培南(98.5%～100%)和哌拉西林/三唑巴坦(83.8%～95.1%),氟喹诺酮类药物的敏感性为12.4%～44.9%.对于肠杆菌属、柠檬酸杆菌属、沙雷菌属,替加环素的敏感性为99.2%-100%,亚胺培南和美罗培南的敏感性为96.6%-100%.另外,敏感性较高的抗菌药物还有阿米卡星(82.8%～96.6%)、哌拉西林/三唑巴坦(73.4%～93.1%)、头孢吡肟(69.O%～82.8%)和头孢哌酮/舒巴坦(72.6%～75.9%),氟喹诺酮类药物的敏感性为55.2%-82.8%.多苇耐药的铜绿假单胞菌和鲍曼不动杆菌的发生率分别为18.7%和54.O%.多黏菌素B对铜绿假单胞菌的敏感性最高(93.5%),其次为阿米卡星和哌拉西林/三唑巴坦(均为75.1%).多黏菌素B对鲍曼不动杆菌的敏感性最高(96.2%),其次为替加环素(92.1%)、亚胺培南(59.4%)、米诺环素(59.4%)和美罗培南(56.5%).金黄色葡萄球菌中MRSA的发生率为64.5%,凝同酶阴性葡萄球菌巾MRSCoN的发生率为82.8%.所有葡萄球菌对替加环素、万古霉素和替考拉宁的均敏感.本次监测中发现9株万古霉素耐药的肠球菌(VRE),VRE发生率为4.3%.结论 替加环素、碳青霉烯类、哌拉西林/三唑巴坦、阿米卡星和头孢吡肟对医院分离的肠杆菌科菌保持较高的抗菌活性;多黏菌素B对铜绿假单胞菌和鲍曼不动杆菌均体现出高抗菌活性,鲍曼不动杆菌对替加环素的敏感率达92.1%;替加环素、万古霉素和替考拉宁对院内革兰阳性球菌保持高的抗菌活性.     

2009年中国13家教学医院院内感染病原菌的抗生素耐药性监测

目的 监测2009年我国不同地区13家教学医院院内获得病原菌的分布和体外药物敏感性.方法 收集来自13家医院院内BSI、HAP和IAI患者标本的病原菌.菌株经中心实验室复核后,采用琼脂稀释法测定替加环素等抗菌药物的MIC值,数据输入WHONET5.6软件进行耐药性分析.结果 共收集到2 502株病原菌.引起BSI的前3位病原菌分别为大肠埃希菌[27.1%(285/1 052)]、凝固酶阴性葡萄球菌[12.6%(133/1 052)]和肺炎克雷伯菌[10.8%(114/1 052)];引起HAP的前3位病原菌分别为鲍曼不动杆菌[28.8%(226/785)]、铜绿假单胞菌[16.1%(126/785)]和肺炎克雷伯菌[14.6%(115/785)];而IAI的主要病原菌为大肠埃希菌[31.0%(206/665)]、肺炎克雷伯菌[11.3%(75/665)]和屎肠球菌[10.8%(72/665)].对于大肠埃希菌和克雷伯菌,敏感率大于80%的药物包括亚胺培南和美罗培南(98.1%～100%)、替加环素(95.3%～100%)、哌拉西林-三唑巴坦(88.6%～97.1%)和阿米卡星(88.3%～92.5%).对于肠杆菌属、柠檬酸杆菌属和沙雷菌属,替加环素的敏感率为93.5%～100%,亚胺培南和美罗培南的敏感率为92.9%～100%,敏感率较高的抗萧药物还包括阿米卡星(85.2%～96.7%)、哌拉西林-三唑巴坦(82.4%～96.4%)、头孢吡肟(79.6%～96.7%)和头孢哌酮-舒巴坦(78.7%～90.0%).铜绿假单胞菌对多黏菌素B的敏感率最高(100%),其次为阿米卡星和哌拉西林-三唑巴坦(81.9%和80.1%).鲍曼不动杆菌对多黏菌素B的敏感率最高(98.8%),其次为替加环素(90.1%)和米诺环素(72.O%).CRAB的发生率为60.1%.金黄色葡萄球菌中MRSA的发生率为60.2%,凝固酶阴性葡萄球菌中MRSCoN的发生率为84.2%.所有葡萄球菌对替加环素、万占霉素和利奈唑胺敏感,仅有1株溶血葡萄球菌对替考拉宁中介.本次监测发现2株利奈唑胺中介的粪肠球菌和1株万古霉素和替考拉宁耐药的屎肠球菌,替加环素对这3株肠球菌的MIC值范围为0.032～0.064μg/ml.结论 替加环素、碳青霉烯类、哌拉西林-三唑巴坦、阿米卡星和头孢吡肟对医院分离的肠杆菌科菌保持了较高的抗菌活性;多黏菌素B对铜绿假单胞菌和鲍曼不动杆菌体现出高抗菌活性,替加环素对鲍曼不动杆菌抗菌活性较高;替加环素、万古霉素和替考拉宁、利奈唑胺对院内获得革兰阳性球菌保持了较高的抗菌活性.

Abstract：

Objective To investigate distribution and antimicrobial resistance among nosocomial pathogens from 13 teaching hospitals in China in 2009. Methods Non-repetitive pathogens from nosocomial BSI, HAP and IAI were collected and sent to the central lab for MIC determination by agar dilution method.WHONET5.6 software was used to analyze the data. Results A total of 2 502 clinical isolates were collected. The top three pathogens of BSI were Escherichia coli [27. 1% (285/1 052 )] , coagulase-negutive staphylococcus [12. 6% ( 133/1 052)] and Klebsiella pneumoniae [10. 8% ( 114/1 052)]. The top three pathogens of HAP were Acinetobacter baumannii [28. 8% (226/785)], Pseudomonas aeruginosa [16. 1% (126/785)] and Klebsiella pneumoniae [14.6% (115/785 )] . The top three pathogens of IAI were Escherichia coli[31.0% ( 206/665 )], Klebsiella pneumonia [11.3% ( 75/665 )] and Enterococcus faecium [10. 8% (72/665)]. Against Escherichia coil and Klebsiella spp. , the antimicrobial agents with higher than 80% susceptibility rate included imipenem and meropenem (98. 1%-100% ), tigecycline (95.3%-100% ), piperacillin-tazobactam ( 88.6% -97. 1% ) and amikacin ( 88. 3% -92. 5% ). Against Enterobacter spp. , Citrobacter spp. and Serratia spp. , the susceptibility rates of tigecycline were 93.5% -100% whereas the value of imipenem and meropenem were 92.9% -100%. Other antimicrobial agents with high activity included amikacin ( 85.2% -96. 7% ), pipcracillin-tazobactam ( 82.4% -96.4% ), cefepime ( 79. 6% -96. 7% ) and cefoperazonc-sulbactam (78. 7%-90. 0% ). Polymyxin B showed the highest susceptibility rateagainst Pseudomonas aeruginosa ( 100% ), followed by amikacin ( 81.9% ) and piperacillin-tazobactam (80.1% ). Polymyxin B also showed the highest susceptibility rate against Acinetobacter baumannii (98. 8% ), followed by tigecycline (90. 1% ) and minocycline (72. 0% ). The incidence of carbapenemresistant Acinetobacter baumannii was 60. 1%. The MRSA rate was 60. 2% and the MRSCoN rate was 84. 2%. All Staphylococcus strains were susceptible to tigecycline, vancomycin, teicoplanin and linezolid except for one isolate of Staphylococcus haemolysis with intermediate to teicoplanin. Two Enterococcus faecalis isolates which were intermediate to linezolid and one Enterococcus faecium isolate which was resistant to vancomycin and teicoplanin was found in this surveillance, while the MICs of tigecycline against these three isolates were 0. 032-0. 064 μg/ml. Conclusions Tigecycline, carbapenems, piperacillin-tazobactam,amikacin and cefepime remain relatively high activity against nosocomial Enterobacteriaceae. Pseudomonas aeruginosa exhibite high susceptibility to polymyxin B, while Acinetobacter baumanni shows high susceptibility to polymyxin B and tigecycline. Tigecycline, vancomycin, teicoplanin and linezolid remain high activity against nosocomial gram-positive cocci.     

Relationship between beta-lactamase production,outer membrane protein and penicillin-binding protein profiles on the activity of carbapenems against clinical isolates of Acinetobacter baumannii

Twenty blood isolates of Acinetobacter baumannii were studied, representing eight pulsed-field gel electrophoresis patterns and all different antimicrobial susceptibility patterns observed during 1995-97 at the University Hospital Virgen Macarena, Seville, Spain. The MIC(90)s (mg/L) of imipenem and meropenem decreased from 16 to 0.5 and from 8 to 4, respectively, in the presence of BRL 42715 (BRL) but not clavulanic acid. Hydrolysing activity (nmol/min/mg) of bacterial supernatants against cefaloridine ranged from 8.8 to 552.3 for A. baumannii type I (imipenem MICs < or = 2), which expressed only a beta-lactamase of pI > or = 9, and from 12.3 to 1543.5 for A. baumannii type II (imipenem MICs > or = 4), which expressed a beta-lactamase of pI > or = 9 and two others of pI 6.3 and 7. The hydrolysing activities of A. baumannii type II against imipenem, meropenem and oxacillin were higher than those observed for A. baumannii type I. Ten outer membrane protein (OMP) profiles (A. baumannii types I and II) were visualized on 10% SDS-PAGE gels with 6 M urea, whereas only five OMP profiles (A. baumannii types I and II) were differentiated in 12% SDS-PAGE gels. Five A. baumannii with OMP profile type B, characterized by the absence of a 22.5 kDa OMP, were resistant to meropenem and/or imipenem. Twelve penicillin-binding protein (PBP) patterns were observed. PBP patterns of A. baumannii type II were characterized by the absence of a 73.2 kDa band (PBP 2). We concluded that production of beta-lactamases of pI 6.3 and 7.0 and reduced expression of PBP 2 are the most frequently observed mechanisms of resistance to carbapenems. In some isolates, loss of a 22.5 kDa OMP is also related to resistance to carbapenems.     

In Vitro Activity of Polymyxin B plus Imipenem,Meropenem, or Tigecycline against KPC-2-Producing Enterobacteriaceae with High MICs for These Antimicrobials

We evaluated the in vitro activity of polymyxin B plus imipenem, meropenem, or tigecycline against six KPC-2-producing Enterobacteriaceae strains with high MICs for these antimicrobial agents. Polymyxin B with carbapenems, especially meropenem, were the most active combinations for Klebsiella pneumoniae and Enterobacter cloacae regardless of the polymyxin B concentration used in the time-kill assay. This combination was also synergistic against two Serratia marcescens strains that are intrinsically resistant to polymyxins. Polymyxin B and tigecycline also presented synergistic activity in most experiments.     

替加环素对414株需氧革兰阴性和革兰阳性临床分离菌株的体外抗菌活性

目的测定替加环素等15种抗菌药物对我院2004年和2005年临床分离的414株革兰阴性菌和革兰阳性需氧菌的体外抗菌活性。方法采用微量肉汤稀释法测定替加环素等15种抗菌药物对所测菌株的MIC,数据分析采用WHONET5.3软件。结果MRSA对替加环素、利奈唑胺及万古霉素的敏感率均为100%,替加环素对MRSA的MIC90是所测抗菌药物中最低者;万古霉素耐药肠球菌(VRE)对替加环素及利奈唑胺敏感率均为100%,替加环素对所有肠球菌的MIC90分别是利奈唑胺和万古霉素的MIC90的1/8和1/16;替加环素对青霉素中介肺炎链球菌(PISP)的MIC90为0.5mg/L,对青霉素耐药肺炎链球菌(PRSP)的MIC范围是0.25~1mg/L,其他抗菌药物对PISP和PRSP的MIC90是替加环素的1~32倍;替加环素对亚胺培南耐药的鲍曼不动杆菌的MIC范围是其他抗菌药物的1/2~1/64;对铜绿假单胞菌的MIC90是32mg/L;产ESBLs大肠埃希菌和肺炎克雷伯菌对替加环素、美罗培南和亚胺培南敏感率均为100%。结论替加环素对铜绿假单胞菌的抗菌活性较差,对其他需氧革兰阴性杆菌有较好的体外抗菌活性;对需氧革兰阳性球菌的抗菌活性最强。     

Resistance profile of Bacteroides fragilis isolated in Brazil. Do they shelter the cfiA gene?

The epidemiology of antimicrobial resistance of clinical isolates and human intestinal strains of Bacteroides fragilis has assumed great importance in the last few years since this microorganism, like other members of the B. fragilis group, can be responsible for the spread of resistance determinants. It is possible that the presence of B. fragilis in polluted aquatic environments might contribute to the spread of resistance. The antimicrobial resistance profile of 44 clinical B. fragilis strains isolated from 1981-1988 and 1991-1998 from the University hospital of Rio de Janeiro, and of 17 faecal and 17 polluted aquatic environmental B. fragilis strains isolated between 1991 and 1998 was determined. The susceptibility tests against penicillin, cefoxitin, imipenem, meropenem, clindamycin, chloramphenicol and metronidazole were performed by Etest in Wilkins-Chalgren agar enriched with 5% sheep blood. Motivated by some high MIC values for cefoxitin and meropenem, the cfiA gene, which codes for a metallo-beta-lactamase, was investigated among all strains, using PCR amplification. The resistance to penicillin was high in the samples from 1981 to 1988 (92.9%) and also in those from 1991 to 1998 (100%), although the MIC90 decreased from 256 mg/L to 24 mg/L. An increase in the resistance level to clindamycin and cefoxitin was seen from one decade to the other, the MIC90 values changing from 4 mg/L to 12 mg/L and from 8 mg/L to 32 mg/L, respectively. The susceptibility profile for metronidazole, chloramphenicol, imipenem and meropenem remained stable, although two clinical strains showed MICs of 6 mg/L and 8 mg/L against meropenem. Almost all human intestinal strains were resistant to penicillin and all of them were susceptible to imipenem, meropenem, chloramphenicol and metronidazole. The MICs of meropenem against two strains isolated from a polluted aquatic environment were 6 mg/L and 32 mg/L. The cfiA gene was detected in five strains, two of which were isolated from clinical specimens against which the MIC values of cefoxitin were high and three from an aquatic environment, whose susceptibility to both cefoxitin and meropenem ranged from sensitive to resistant.     

Antibiotic resistance among clinical isolates of Acinetobacter in the UK, and in vitro evaluation of tigecycline (GAR-936)

A survey was conducted of the antimicrobial susceptibilities of 595 Acinetobacter spp. isolated from routine clinical specimens in 54 sentinel laboratories throughout the UK during 2000. Isolates of the Acinetobacter baumannii complex (genomic groups 2, 3 and 13TU; n = 443) were distinguished from other genomic groups (n = 152) by PCR fingerprinting of tDNA spacer regions. MICs of amikacin, cefotaxime, ceftazidime, ciprofloxacin, colistin, gentamicin, imipenem, meropenem, minocycline, piperacillin, piperacillin/tazobactam, rifampicin, sulbactam and tetracycline were determined on IsoSensitest agar and interpreted, wherever possible, using BSAC breakpoints. Tigecycline (GAR-936), a new glycylcycline, was also tested. Resistance to cephalosporins, aminoglycosides and ciprofloxacin was widespread, but carbapenems, colistin, sulbactam, minocycline and tigecycline were each active against >80% of the isolates. Isolates of A. baumannii were more often resistant to cefotaxime, ceftazidime, piperacillin, piperacillin/tazobactam, ciprofloxacin, gentamicin and tetracyclines than those belonging to other genomic groups, but were less often resistant to colistin; no significant differences between genomic groups were noted in the susceptibilities to amikacin, carbapenems, rifampicin or sulbactam. The relative activities of the tetracyclines were minocycline > tigecycline > tetracycline. Thirteen carbapenem-resistant isolates (MICs > or =8 mg/L; 2.2%) were received from six centres; four centres sent single isolates; one sent three and one sent six. An allele of bla(IMP) was detected in one of these isolates, but the other 12 isolates either had carbapenemase-independent resistance, or undetectable carbapenemase activity combined with other resistance mechanisms. In conclusion, carbapenems, colistin and minocycline retained greatest activity against the Acinetobacter isolates collected. Tigecycline was less active than minocycline, but both agents overcame most tetracycline resistance.     

Doripenem (S-4661), a novel carbapenem: comparative activity against contemporary pathogens including bactericidal action and preliminary in vitro methods evaluations

OBJECTIVES: To investigate the potency of doripenem, a broad-spectrum carbapenem characterized by a wider spectrum of activity combining antimicrobial and bactericidal features of imipenem and meropenem. METHODS: This parenteral compound was studied against recent clinical isolates (2001-2002) from a worldwide organism collection. A total of 902 strains were susceptibility tested by reference methods against doripenem and six to 28 comparators including ertapenem, imipenem and meropenem. The organisms tested included: Enterobacteriaceae (281 strains), Acinetobacter spp. (33), Pseudomonas aeruginosa (35), Stenotrophomonas maltophilia (36), other non-fermenters (22), Haemophilus influenzae (61), Moraxella catarrhalis (33), oxacillin-susceptible staphylococci (39), enterococci (84), streptococci (163), various anaerobes (98), and other Gram-positive species such as Corynebacterium and Bacillus spp. (17). RESULTS: Against Enterobacteriaceae, the average doripenem MIC90 was 0.03 mg/L (range, < or =0.015-0.25 mg/L). Doripenem was two- to 16-fold more potent than imipenem and comparable to ertapenem and meropenem; all doripenem MIC values with enteric bacilli were < or =4 mg/L. Doripenem was active against Aeromonas (MIC50, 0.03 mg/L), Bacillus spp. (MIC50, 0.03 mg/L) and all tested anaerobic species (MIC range, < or =0.015-4 mg/L), but was less active against S. maltophilia (MIC90, >32 mg/L) and Enterococcus faecium (MIC90, >32 mg/L) among the enterococcal species. Time-dependent bactericidal action was observed for doripenem and broth MIC results were slightly greater when compared to agar MIC results. In pilot testing, the optimal doripenem disc concentration was 10 microg, identical to standardized reagents for other clinically available carbapenems. CONCLUSIONS: Doripenem appears to be a potent carbapenem with a spectrum resembling currently marketed antipseudomonal carbapenems, but with greater activity when tested against some non-fermentative bacillary strains. Continued evaluation of doripenem against isolates resistant to other beta-lactams appears to be warranted.