β-内酰胺类药物及与复方黄连注射液联合使用对金黄色葡萄球菌MSW的影响

目的测定β-内酰胺类药物单用及与复方黄连注射液联合使用对金黄色葡萄球菌ATCC29213的MIC和MPC,探讨β-内酰胺类与复方黄连注射液联合使用对耐药突变选择窗(MSW)的影响,为临床优化抗菌药物给药方案,限制耐药突变体选择性扩增提供一条新思路。方法采用MH琼脂二倍稀释法测定阿莫西林和头孢噻呋、复方黄连注射液单独用药和联合用药的最低抑菌浓度(MIC)、抑制99%接种细菌生长的最低抑菌浓度(MIC99)、防突变浓度(MPC)。结果阿莫西林单独使用时的SI(MPC/MIC99)值为15.2,与16MIC的复方黄连注射液联合使用后,SI降低至5.1,为其单独用药的1/3;头孢噻呋单独使用时其SI值为16.1,与16MIC的复方黄连注射液联合使用后,SI降低至4.2,为单独用药的1/4。结论β-内酰胺类药物和复方黄连注射液联合用药可以明显缩小MSW。     

耐药突变选择窗与抗感染药物防突变浓度

防变异浓度 (MPC)是指抗菌药物防止细菌选择第一步耐药突变的最低浓度 ,MPC与MIC(最小抑菌浓度 )的浓度范围为突变选择窗 (MSW )。当血清或组织液药物浓度低于MIC时 ,治疗无效但也不会导致细菌耐药突变体的富集 ;超过MPC时细菌要生长须同时具备两种或以上突变 ,因而不仅治疗成功并且也很难出现耐药突变体的选择性扩增 ;处于窗内时将选择出耐药突变菌 ,即使临床治疗成功率很高。该理论为有效抑制细菌耐药及制定抗菌药物应用策略提供了新的思路和参考依据。     

庆大霉素诱导粪肠球菌耐药及其对氯霉素协同敏感相关特性研究

目的 通过研究庆大霉素诱导粪肠球菌耐药突变株对氯霉素协同敏感(collateral sensitivity, CS)的相关特性,为基于协同敏感治疗策略的临床应用提供依据。方法 采用庆大霉素通过梯度浓度平板对3株庆大霉素敏感的粪肠球菌临床分离株和1株粪肠球菌标准菌株ATCC29212进行体外实验诱导耐药(experimental evolution);通过微量肉汤稀释法测定庆大霉素诱导后耐药突变株对常见抗菌药物的最低抑菌浓度(minimum inhibitory concentrations, MICs),分析抗菌药物间交叉敏感性;PCR检测诱导耐药菌株氨基糖苷类修饰酶编码基因携带情况;通过琼脂平板稀释法测定庆大霉素诱导耐药(evolved gentamicin-resistant)菌株和亲本菌株对其协同敏感药物(氯霉素)的防耐药突变浓度(mutant prevention concentration, MPC),最后,测定氯霉素对庆大霉素诱导耐药菌株和亲本菌株的时间杀菌曲线。结果 结果显示4株粪肠球菌亲本菌株经过庆大霉素诱导后,对庆大霉素MICs升高了16～64倍,并对阿米卡星表现出交...     

黄芩等6味中药对多重耐药鲍曼不动杆菌的体外抑菌活性的实验研究

目的:探究黄芩、黄连等6味中药材对多重耐药鲍曼不动杆菌(MDR-AB)的体外抑菌和杀菌活性.方法:选用黄芩、黄连、连翘、乌梅、穿心莲、金银花药材的提取物,采用药敏纸片琼脂扩散法及肉汤稀释法,测定提取物对MDR-AB的体外抑菌圈的最低抑菌浓度(MIC).结果:黄芩、黄连提取物有较强的抑菌活性,抑菌圈直径大,MIC值较低;...     

4种中药对30株广泛耐药铜绿假单胞菌的抑菌作用

目的:探讨黄芩等4种中药对广泛耐药铜绿假单胞菌的抑菌作用。方法:采用中药抗菌试验试管法测定药物的最低抑菌浓度(MIC)。结果:黄芩、连翘、黄连、金银花对30株广泛耐药铜绿假单胞菌有不同程度的体外抑菌作用,MIC均值分别为475.00,345.83,60.94,379.17 mg/m L,与标准菌株ATCC27853的MIC相近。其中黄连的抑菌作用最强。结论:4种中草药对30株广泛耐药铜绿假单胞菌均有不同程度的抑菌作用,本地与外地收集的菌株,抑菌作用无显著性差异(P>0.05)。     

利奈唑胺、去甲万古霉素等抗菌药物对耐甲氧西林金黄色葡萄球菌的抗菌活性

目的:研究北京市三家医院耐甲氧西林金黄色葡萄球菌(MRSA)耐药现状,评价利奈唑胺、去甲万古霉素等药物的抗菌活性。方法:收集解放军总医院、北京医院、北京协和医院三家医院分离的非重复MRSA111株,头孢西丁纸片法确认MRSA,采用琼脂稀释法测定抗菌药物的最低抑菌浓度(MIC)。结果:111株MRSA,对β-内酰胺类的耐药率为100%,对红霉素的耐药率为92.8%,对氨基糖苷类(奈替米星、庆大霉素)的耐药率为99.1%,对氟喹酮类(加替沙星、莫西沙星、左氧氟沙星)的耐药率为91.9%~99.1%,对氯霉素的耐药率为3.6%,对去甲万古霉素、利奈唑胺全部敏感,对去甲万古霉素MIC50和MIC90分别为0.5和1μg/mL,对利奈唑胺的MIC50和MIC90均为2μg/mL。结论:北京三家医院分离的MRSA对本研究的大多数抗菌药物均耐药,去甲万古霉素和利奈唑胺对于MRSA有很高的抗菌活性。     

环丙沙星的临床应用及不合理联合用药问题

环丙沙星(CPLX)具有优良的抗菌效能,广谱、安全及独特的抗菌后效应,在临床上受到广泛的关注,本文就其临床应用及不合理联合用药问题做一简要概述.一、抗泌尿道感染疗效显著体外实验表明:CPLX在同类药物中抗泌尿道感染病原体活性最高,包括对喹诺酮类敏感性差的绿脓杆菌,其MIC90≤ug/lm.文献报道治疗急慢性泌尿道感染1111例,经统计平均治愈率为84.4%,对复杂性泌尿道感染的平均有效率亦达75%,对单纯性泌尿道感染过100%.平均治疗时间为7d,剂量为0.25～0.5g/次,bid.CPLX尚具有良好的脏器移行率,其前列腺组织浓度大大超过血清浓度,而头孢菌素则相对分布较差.据报道对50例接受前列腺术的患者于手术前后口服CPLX预防术后感染,菌尿症发生率为6%,而未服CPLX的对照组则高达38%.     

左氧氟沙星联合万古霉素缩小金黄色葡萄球菌耐药突变选择窗的初步研究

目的:在体外初步探讨联合用药可缩小单药对细菌的耐药突变选择窗(MSW),为临床合理使用现有抗菌药物,防止细菌耐药产生提供理论依据。方法:应用肉汤法富集1010CFU/mL细菌,琼脂平板二倍稀释法测定左氧氟沙星、万古霉素单药和两药联用对金黄色葡萄球菌ATCC29213的最低药物浓度(MPC)和MSW。结果:左氧氟沙星、万古霉素单药对金黄色葡萄球菌ATCC29213的MSW分别为16和64。万古霉素和左氧氟沙星联合用药(1MIC 8MIC,2MIC 4MIC)使左氧氟沙星单药对ATCC29213的MSW缩小2～4倍。左氧氟沙星联合万古霉素用药(1MIC 16MIC,2MIC 8MIC)使万古霉素对ATCC29213的MSW缩小4～8倍。结论:万古霉素和左氧氟沙星联合用药可缩小各自单药对金黄色葡萄球菌ATCC29213的MSW。     

左氧氟沙星和美洛培南体外诱导铜绿假单胞菌耐药的外排机制研究

目的:研究左氧氟沙星和美洛培南对铜绿假单胞菌耐药的诱导作用及诱导耐药的外排机制。方法:多步诱导法对3株铜绿假单胞菌进行诱导耐药试验,对诱导出的菌株用微量肉汤稀释法测定加与不加外排泵抑制剂(苯丙氨酸-精氨酸-!萘酰胺)的最小抑菌浓度(MIC)的变化,PCR法检测外排泵基因oprM和mexB,并扩增mexR基因进行DNA测序。结果:3株菌均诱导出稳定的耐左氧氟沙星和美洛培南的耐药株,MIC值与原菌比较分别增加了16倍～64倍和2倍～16倍,加外排泵抑制剂后左氧氟沙星的MIC值降低了4倍～8倍;3株菌诱导前后均扩增出外排泵基因oprM和mexB,mexR测序结果与GenBankU23763比较,核苷酸序列第222位(C→T),氨基酸序列(CTG→TTG)均为LEU,为无义突变,核苷酸序列第436位插入1bp(A)移码框。结论:左氧氟沙星和美洛培南可诱导铜绿假单胞菌产生获得性耐药,其耐药机制与主动外排相关。     

儿童下呼吸道感染患者痰液耐甲氧西林金黄色葡萄球菌分离株耐药性及基因分型

目的:研究儿童下呼吸道感染耐甲氧西林金黄色葡萄球菌(MRSA)分离株的耐药性及基因分型,为临床诊疗提供参考。方法:对2009年1月-2010年12月收治的50例肺炎患儿进行临床调查,采集下呼吸道的痰液标本作细菌培养,用头孢西丁纸片法鉴定MRSA,并用琼脂稀释法测定MRSA对12种抗菌药物的最低抑菌浓度(MIC);用多重PCR方法检测MRSA的葡萄球菌染色体盒mec(SCCmec)基因分型。结果:MRSA所致的下呼吸道感染多见于低龄儿童(15 d～6岁),SCCmec基因分型中以Ⅲ型、Ⅳ型和Ⅴ型为主。所有MRSA的分离株都对青霉素和苯唑西林耐药,对万古霉素敏感,对其他抗菌药物的耐药率较高并且存在多重耐药。结论:儿童下呼吸道感染MRSA分离株多见于学龄前的儿童,SCCmec基因分型以Ⅲ型、Ⅳ型和Ⅴ型常见,MRSA对多种抗菌药物具有较高的耐药性并且存在多重耐药。     

碳青霉烯类药物对铜绿假单胞菌体外抗菌行为比较

目的:比较不同碳青霉烯类药物对临床分离铜绿假单胞菌体外抗菌行为差异,包括体外抗菌活性以及细菌形态学改变.方法:采用纸片法和标准琼脂稀释法测定临床分离的铜绿假单胞菌对亚胺培南、美洛培南、帕尼培南和头孢他啶的敏感性;电镜观察铜绿假单胞菌在不同浓度的亚胺培南、美洛培南、帕尼培南和头孢他啶中不同时间细菌形态变化.结果:14%的铜绿假单胞菌在美洛培南纸片周围呈"双环"抑菌形态;在MH培基中,帕尼培南的MIC值明显高于亚胺培南和美洛培南,但在MM培养基中,帕尼培南的MIC值是原来的1/8～1/2;亚胺培南和帕尼培南使铜绿假单胞菌细胞呈圆球形改变,头孢他啶使细菌伸长如丝状,低浓度美洛培南的细菌呈纺锤形改变.结论:帕尼培南体外抗菌作用受培养基种类影响大,MH培养基测定结果可能无法准确反映其抗菌活性;美洛培南杀菌作用不完全且诱导细菌呈纺垂体样改变,可能导致内毒素释放增加,影响临床严重感染的预后.     

环丙沙星与氧氟沙星注射液治疗细菌性感染的疗效观察

以乳酸环丙沙星（ＣＰＬＸ）注射液和氧氟沙星（ＯＦＬＸ）注射液随机分组治疗各种细菌性感染４０例及４２例，并以注射用头孢噻肟钠（ＣＴＸ）治疗４９例作对照。三组平均年龄、体重、疗程及病情程度相比无显著性差异，具可比性。病种分布以消化道感染最多，共８１例，占总数的６１．８％。三组１３１例病人细菌阳性率为９４．７％。一疗程ＣＰＬＸ组、ＯＦＬＸ组、ＣＴＸ组治愈率分别为８７．２％、８３．３％、７１．４％，有效率     

氟喹诺酮类药物浓度对预防肺炎链球菌耐药的影响研究

目的检测氟喹诺酮类药物对肺炎链球菌临床耐药的预防作用,并比较防突变浓度（MPC）与最低抑菌浓度（MIC）间的关系,为临床合理用药提供依据。方法采用琼脂二倍稀释法检测5种抗菌药物的MIC值,计算MIC50和MIC90值;采用新鲜制备的1010 CFU/mL菌液测定MPC值,测定MPC值,接种细菌浓度〉1010,计算MPC50和MPC90值,并比较MPC/MIC。结果在5种药物中,莫西沙星的MPC50和MPC90值最低,分别为1mg/L和2mg/L,环丙沙星最高,为16mg/L和32mg/L;测定菌株对莫西沙星、左氧沙星的MPC/MIC范围主要在8～16,对加替沙星、司巴沙星的MPC/MIC范围主要在16～32,对环丙沙星的MPC/MIC范围主要在32～64。结论莫西沙星、左氧沙星抗菌谱广,而且MPC值较低,并可以防止肺炎链球菌突变的发生。     

The PK/PD index (CMAX/MIC) for ciprofloxacin in patients with cystic fibrosis

In order to evaluate the efficacy of an antibacterial therapy, three basic PK/PD indexes were defined: the ratio between the maximum drug concentration obtained after a single dose and minimum inhibitory concentration MIC (CMAX/MIC), the ratio between the area under the curve of dependence between the drug concentration in blood and time within 24 hours to MIC (AUC24/MIC), and the time when the concentration of the drug in blood is higher than MIC (T > MIC). The aim of the study was an analysis of the pharmacokinetics of ciprofloxacin and the PK/PD: CMAX/MIC index in patients with cystic fibrosis. Six patients with cystic fibrosis, with the identified microbiological factor were subjected to the examination. The patients received ciprofloxacin in the dose of 400 mg/12 h (i.v.). Plasma drug concentration was measured by HPLC-UV method after the first dose (Cmax1) and at steady state (Cssmax, Cssmin). The following mean values of ciprofloxacin blood concentrations were obtained from the analyzed patients: Cmax1 = 2.34 (+/- 1.15) microg/mL, Cssmax = 2.49 (+/- 1.44) pg/mL, Cssmin = 0.42 (+/- 0.22) pg/mL. The mean values of the Cmax1/MIC and Cssmax/MIC indexes were 3.66 +/- 2.34) and 3.38 (+/-1.73), respectively. Low values of the Cmax/MIC index for ciprofloxacin in the analyzed patients may indicate too low concentrations of the drug in the blood in relation to the MIC value of pathogens and the need to verify the assumed administration scheme.     

论临床结核病耐药性变化趋势的动态监测分析与研究

目的对临床结核病耐药性的变化趋势的动态监测的方法进行探讨。方法选择2008年至2011年经确诊的2000例肺结核患者作为研究对象,对其耐药菌株进行治疗前与治疗后的动态监测,并对药敏结果进行统计与分析,最终确定治疗前后耐药菌谱的变化情况。结果本组2000例肺结核患者的耐药均值在治疗前与治疗后对抗结核药物的耐单药例数是有一定差异的,以乙胺丁醇（Ethambutol,EMB）药物的耐药例数发生了较为明显的变化,耐药性显著增加,前后对比呈显著的统计学差异（P〈0．01）;对丁胺卡那霉素（Amikacin,AMK）、卷曲霉素（Capreomycin,CPM）以及对氨基水杨酸（Sodium Aminosalicylate,PAS）三种药物的初始耐药率及复敏率较高。结论对耐多药肺结核患者的耐药菌株进行动态监测,可以准确获取耐药菌株耐药性信息,具有重要的临床意义与价值;同时对目前使用EMB等药物治疗的方案提出警示与质疑,尽快地开发新一代的毒性低、效率高的抗结核药物是目前解决抗结核治疗困境的一个当务之急。     

丰都县人民医院儿科病房大肠埃希菌耐药性分析

目的:分析本院儿科病房大肠埃希菌对临床常用抗菌药物的耐药特征,为临床用药提供参考.方法:大肠埃希菌的鉴定/药敏采用合肥恒星科技HX-21细菌鉴定药敏分析仪和配套鉴定药敏卡C板,MIC参照CLSI 2009和2010版标准.用大肠埃希菌ATCC25922作为质控菌株进行药敏质控.结果:筛选出的66株大肠埃希菌对各种抗菌药物的敏感率分别为:β-内酰胺类抗菌药物10.61％～27.27％(其中氨苄西林最低,10.61％);哌拉西林/他唑巴坦、阿米卡星、呋喃妥因均为98.48％;氯霉素、左氧氟沙星、氧氟沙星、环丙沙星为59.09％～74.24％;头孢哌酮/舒巴坦钠为95.45％;亚胺培南为100％.结论:儿科病房中大肠埃希菌对常用抗菌药物耐药率较高,临床应根据药敏结果合理使用抗菌药物,预防耐药菌株的产生与扩散.     

我院临床药师参与抗菌药物分级管理效果分析

目的:分析临床药师参与我院抗菌药物分级管理的效果.方法:临床药师广泛参与我院抗菌药物分级管理的各个环节,抗菌药物处方及病历点评,"特殊使用"抗菌药物会诊,细菌耐药率及血药浓度监测等,对临床抗菌药物使用进行干预.结果:临床药师干预后,特殊使用的抗菌药物较干预前用量明显减少,细菌耐药率有所下降,手术预防使用抗菌药物趋于合理.结论:临床药师参与抗菌药物分级管理,能够明显提高抗菌药物使用的合理性和有效性,延缓耐药菌的产生.     

Lack of cross-resistance between efrotomycin and antibacterial agents used in the therapy of human and animal infections

Efrotomycin is an N-methylhydroxypyridone glycoside antibiotic with activity primarily against Gram-positive bacteria. It is intended for use as a feed additive for swine. Although efrotomycin is unrelated to any antibacterial drug used in human or veterinary medicine, the possibility of cross-resistance with other antibacterials is of concern. The minimum inhibitory concentrations (MICs) of efrotomycin were determined for a broad panel of bacterial isolates. In addition, the susceptibility of each isolate to 12-15 antibacterials was determined using a standardized disk susceptibility test. No evidence of cross-resistance between efrotomycin and any of the 12-15 antibacterial compounds was observed. When the MIC of efrotomycin for nine selected isolates was increased from 16- to greater than 100-fold by serial passage in subinhibitory concentrations of efrotomycin, no increased resistance to the 15 antibacterials was noted. Subinhibitory concentrations of efrotomycin had no effect on the conjugative transfer of antibacterial-resistance plasmids between K-12 strains of Escherichia coli. The data from this study suggest that if resistance to efrotomycin should occur, it is unlikely to result in the appearance of multiply-resistant bacterial populations.     

Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (2001)

From October 2001 to September 2002, we collected the specimen from 370 patients with lower respiratory tract infections in 16 institutions in Japan, and investigated the susceptibilities of the isolated bacteria to various antibacterial agents and antibiotics and patients' characteristics. Of 458 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 456 strains were investigated. The breakdown of the isolated bacteria were: Staphylococcus aureus 69, Streptococcus pneumoniae 72, Haemophilus influenzae 85, Pseudomonas aeruginosa (non-mucoid) 44, P. aeruginosa (mucoid) 13, Klebsiella pneumoniae 32, Moraxella subgenus Branhamella catarrhalis 32, and others. Of 69 S. aureus strains, those with 4 micrograms/mL or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) occupied 43.5%. Vancomycin and arbekacin showed the most potent activities against MRSA as observed in 2000. The frequency of S. pneumoniae exhibiting low sensitivity to penicillin (penicillin-intermediate S. pneumoniae: PISP + penicillin-resistant S. pneumoniae: PRSP) was 59.7% and both rates of PISP and PRSP were the highest after 1992. Carbapenems had strong activities against S. pneumoniae. Especially, panipenem and imipenem inhibited the growth of all 72 strains at 0.125 and 0.5 microgram/mL, respectively. Generally, all drugs had strong activities against H. influenzae with MIC90s of 16 micrograms/mL or less. The drug that had the strongest activity against H. influenzae was levofloxacin, which inhibited the growth of 80 of the 85 strains at 0.063 microgram/mL. Against P. aeruginosa mucoid strain, meropenem had a strong activity with MIC90 of 0.5 microgram/mL while, against non-mucoid strain, tobramycin had a strong activity with MIC90 of 2 micrograms/mL. K. pneumoniae showed good susceptibilities to all drugs except ampicillin and minocycline, and the MIC90s were 4 micrograms/mL or less. Particularly, cefmenoxime, cefpirome, and imipenem had the strongest activity (MIC90: 0.125 microgram/mL), and cefozopran had a strong activity, inhibiting the growth of all strains at 0.25 microgram/mL. Also, all drugs generally had strong activities against M. (B.) catarrhalis. MIC90s of all drugs were 4 micrograms/mL or less. The drug that had the strongest activity was minocycline and levofloxacin inhibiting all 32 strains at 0.063 microgram/mL. Most of the patients with respiratory infection were aged 70 years or older, accounting for approximately a half of the total (40.5%). As for the incidence by the diseases, bacterial pneumonia and chronic bronchitis were the highest, being noted in 39.2% and 37.3% of all the patients, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (19.3%) and S. pneumoniae (19.9%). In contrast, H. influenzae (22.0%) were frequently isolated from the patients with chronic bronchitis. Before the drug administration, the bacteria frequently isolated from the patients were S. pneumoniae (20.8%) and H. influenzae (21.5%). S. pneumoniae and H. influenzae decreased after the initiation of drug administration while S. aureus increased. The isolation frequency of P. aeruginosa was higher after than before the initiation of drug administration. The bacteria were frequently isolated from the patients who had already treated with cephems were S. aureus and P. aeruginosa. From the patients who had already treated with macrolides, S. pneumoniae was the most frequently isolated while S. aureus was the most frequently isolated from the patients pre-treated with quinolones.