用悬液试验法测定联苯苄唑的抗真菌作用

以Kimmig液体培养基稀释法测定了国产联苯苄唑对15种真菌的抑制作用。结果表明,该药具有广谱抗真菌作用,除对类星形念珠菌的MIC为32μg/ml外,对其余真菌的MIC均<8μg/ml。     

头孢美唑对产ESBLs肠杆菌科细菌的体外抗菌作用研究

目的 评价头孢美唑对产ESBLs肠杆菌科细菌的体外抗菌活性.方法 采用琼脂稀释法测定头孢美唑对临床分离大肠埃希菌、肺炎克雷伯菌、产酸克雷伯菌和奇异变形杆菌523株的体外抗菌作用.结果 523株细菌中产ESBLs 294株、产AmpC酶7株、同时产ESBLs和AmpC酶40株,非产ESBLs和AmpC酶182株.头孢美唑对上述4种肠杆菌科细菌中产ESBL-s菌株和非产ESBLs菌株均具有良好的抗菌作用,并较头孢西丁强2～4倍,但较头孢米诺为差.头孢美唑对ESBLLs高度稳定,但对AmpC酶稳定性差,产AmpC酶菌株对其多呈现耐药.头孢美唑对产ESBLs菌株的作用优于受试的半合成青霉素,第一、第二、第三和第四代头孢菌素,亦优于氨苄西林-舒巴坦、头孢哌酮-舒巴坦和哌拉西林-他唑巴坦,但差于亚胺培南、美罗培南和帕尼培南;较受试的氨基糖苷类和氟喹诺酮类抗菌药略强或相仿.结论 头孢美唑对ESBLs稳定,对产ESBLs菌株和非产ESBLs菌株均具有良好的抗菌作用.提示该药是治疗产ESBLs肠杆菌科细菌所致感染的可选药物之一.     

伊曲康唑治疗老年患者肺部侵袭性真菌感染42例分析

目的：评价伊曲康唑治疗老年患者侵袭性肺部真菌感染的临床疗效及不良反应。方法：对42例老年患者给予伊曲康唑抗真菌治疗，疗程6～12周以上。结果：42例老年患者痊愈11例，显效20例，总有效率为73．8％；共培养出真菌74株，治疗后清除43株，真菌总清除率58．1％；其中5例不良反应，占11．9％。结论：伊曲康唑治疗老年患者肺部侵袭性真菌感染疗效明确、不良反应少。     

国产伏立康唑对临床分离病原真菌体外抗菌活性研究

目的了解国产伏立康唑对北京和我国其他地区临床分离的常见病原真菌体外抗菌活性。方法分别参照CLSIM27-A2和M38-A方案测定伏立康唑对144株酵母和82株产孢丝状真菌的抗菌活性。受试菌株包括念珠菌114株（含氟康唑获得性耐药白念珠菌）、新型隐球菌20株、阿萨希毛孢子菌10株、曲霉62株（含伊曲康唑耐药曲霉及两性霉素B不敏感曲霉）、镰刀菌10株、尖端赛多孢菌10株。结果伏立康唑对念珠菌（不包括氟康唑耐药和剂量依赖敏感白念珠菌）、新型隐球菌、阿萨希毛孢子菌的MIC50≤0．5mg／L、MIC90≤1mg／L；而对氟康唑获得性耐药白念珠菌MIC50和MIC90均〉16mg／L。对曲霉、尖端赛多孢菌的MIC50≤1mg／L、MIC90≤2mg／L，对镰刀菌的MIC50和MIC90分别为4mg／L和〉16mg／L。结论伏立康唑对多数酵母有较强的体外抗菌活性，尤其是对克柔念珠菌和光滑念珠菌等氟康唑天然耐药菌株。该药对多数产孢丝状真菌也有较好的体外抗菌作用，包括伊曲康唑耐药及两性霉素B不敏感的曲霉以及对多种抗真菌药物耐药的尖端赛多孢菌；但其对氟康唑获得性耐药白念珠菌有一定交叉耐药。     

烟曲霉的微管蛋白基因鉴定及唑类抗真菌药物的耐药性研究

目的建立烟曲霉临床分离菌株的微管蛋白基因鉴定方法,并分析烟曲霉对唑类抗真菌药物的耐药性。方法对表型鉴定为烟曲霉的菌株,采用十六烷基三甲基溴化铵(CTAB)方法提取烟曲霉菌株DNA,并采用对微管蛋白基因进行PCR扩增和测序的方法对烟曲霉菌株进行分子生物学鉴定,采用琼脂稀释法检测烟曲霉菌株对伊曲康唑和伏立康唑的耐药性。结果 91株临床分离株表型鉴定为烟曲霉,这些菌株在35℃和48℃生长。其中88株(96.70%)经微管蛋白基因鉴定为烟曲霉。87株烟曲霉菌株对4μg/mL伊曲康唑和1μg/mL伏立康唑敏感,检出1株对4μg/mL伊曲康唑和1μg/mL伏立康唑耐药菌株。结论微管蛋白基因鉴定方法可以对烟曲霉进行准确鉴定。     

头孢美唑与异帕米星联合应用治疗ICU病房感染临床观察

目的 通过对头孢美唑与异帕米星联合应用治疗ICU病房患者感染的临床观察，探讨临床治疗耐药菌感染的新途径。方法 62例患者随机分为头孢美唑治疗组和头孢他啶治疗组，分别观察细菌学疗效、各系统细菌清除情况、细菌耐药性产生情况、真菌并发率以及各自的不良反应。结果 对两组患者的细菌学疗效、各系统细菌清除情况以及耐药菌产生的情况进行分析比较，先锋美他醇和依克沙联合应用其临床疗效优于头孢他啶与阿米卡星联合应用，统计学分析显示存在显著性差异。结论 头孢美唑与异帕米星联合应用能有效治疗各种耐药菌所致的感染，临床效果明确。     

2014年中段尿培养病原微生物分布及耐药性分析

目的:了解并分析2014年南京医科大学第一附属医院中段尿培养阳性标本的病原菌分布、构成及耐药状况,为临床合理使用抗菌药物提供实验依据。方法:细菌、真菌鉴定采用VITEK 2 Compact全自动微生物鉴定系统或API鉴定系统,细菌药物敏感性测定采用Kirby-Bauer纸片扩散法,真菌药物敏感性测定采用ATB FUNGUS 3板条,应用WHONET5.6软件进行统计分析。结果:2014年共送检5 172份中段尿标本,分离出1 326株病原微生物,阳性率25.6%。革兰阴性菌、革兰阳性菌、真菌分别占72.0%、19.6%、8.4%。革兰阴性杆菌对碳青霉烯类抗菌药、革兰阳性球菌对万古霉素和利奈唑胺仍高度敏感;真菌对两性霉素B、伏立康唑高度敏感。检出亚胺培南和美洛培南同时耐药的大肠埃希菌3株、肺炎克雷伯5株;检出5株万古霉素耐药屎肠球菌。结论:大肠埃希菌是泌尿系感染主要致病菌,多种病原菌对临床常用抗菌药物耐药性日趋严重。     

60株酵母样真菌的药敏试验分析

目的 对从老年病房中分离的60株酵母样真菌进行药敏分析，以指导临床用药。方法 用法国生物梅里埃公司全自动细菌分析鉴定仪进行真菌的分类鉴定．再用E试验药敏试条进行药敏试验。结果 共分离60株酵母样真菌，其中自念珠菌33株。占55％，热带念珠菌14株，占23．3％，其他还有光滑念珠菌，副热带念珠菌，近平滑念珠菌，无名念珠菌，克柔念珠菌，季也蒙念珠菌，皱落念珠菌和奥默毕赤酵母菌共10种酵母样真菌。其结果显示，60株酵母样真菌对两性霉素B均敏感，对氟康唑、酮康唑及伊曲康唑均有耐药株。结论 本试验结果表明，两性霉素B、5－氟胞嘧啶对深部真菌感染仍有效，而氟康唑和伊曲康唑治疗深部真菌感染疗程长，有一定的不良反应。而老年人肝、肾功能较差，应加强治疗过程的监测，避免不良反应。     

万古霉素和利奈唑胺联合对耐甲氧西林金葡菌的体外杀菌试验

许多临床医师尝试对经典治疗方案无效的耐甲氧西林葡萄球菌感染患者使用万古霉素联合利奈唑胺。本研究中万古霉素和利奈唑胺未显示协同作用,相反,万古霉素联合利奈唑胺对5株受试菌中的3株显示拮抗作用。作者推测拮抗原因可能是利奈唑胺抑制了细菌蛋白质合成,使万古霉     

苯唑西林耐药金黄色葡萄球菌的临床分离和药敏情况分析

目的分析苯唑西林耐药金黄色葡萄球菌的临床分离和药敏情况,并与苯唑西林敏感金黄色葡萄球菌的情况进行比较。方法回顾性分析84株金黄色葡萄球菌,依据苯唑西林分为耐药株和敏感株,采用χ2检验分析耐药株和敏感株的来源差异和对每种抗生素的敏感性差异。结果苯唑西林敏感株和耐药株的标本来源和病区分布差异无统计学意义,药敏分析结果显示敏感株和耐药株对呋西地酸、吗啉噁酮、奎奴普丁/达福普汀、替考拉宁和万古霉素的敏感性差异无统计学意义(P0.05),对阿米卡星、克林霉素、环丙沙星、红霉素、庆大霉素、妥布霉素、利福平、复方磺胺和四环素的敏感性差异有统计学意义(P0.05)。结论临床在确诊金黄色葡萄球菌感染时,应区别对待苯唑西林敏感株和耐药株,及时、合理使用抗生素预防和控制感染。     

两种植物挥发油体外抗菌作用试验观察

目的观察金银花和山楂果核挥发油体外抗菌效果,为实际应用提供科学依据。方法采用稀释法对两种植物挥发油体外最小抑菌浓度和最小杀菌浓度进行了测定。结果金银花挥发油对革兰阴性菌株的MIC50和MIC90值均≥128μg/ml,对金黄色葡萄球菌MIC90值≥128μg/ml、MIC50值为64μg/ml。山楂果核挥发油对所有试验菌株的MIC50值在16～64μg/ml范围;MIC90值在64～128μg/ml。山楂果核挥发油作用15 min,对大肠杆菌和金黄色葡萄球菌MBC值在32～64μg/ml范围;金银花挥发油作用60 min,对上述两种细菌MBC值为64μg/ml。结论两种植物挥发油对试验菌株都具有良好的体外抗菌效果,但其MIC和MBC值均明显高于两种对照药物。     

咔哒唑胺与利奈唑胺对艰难梭菌的敏感性实验

目的 比较咔哒唑胺与利奈唑胺对不同基因和毒素型别的艰难梭菌的抑菌效果，以及咔哒唑胺对艰难梭菌芽孢形成的影响。方法 采用咔哒唑胺与利奈唑胺对10株不同基因型别的艰难梭菌、1株产气荚膜梭菌和1株脆弱拟杆菌进行药物敏感性实验，获得各菌株测试药物对应的最低抑菌浓度（MIC）值。选取其中1株艰难梭菌ATCC BAA-1803，核糖体027型高毒株，试验咔哒唑胺对菌株芽孢形成的影响，从而对药物进行评价。结果 艰难梭菌咔哒唑胺MIC为0.25 g/ml（0.03~0.25 g/ml），利奈唑胺MIC为4.0 g/ml（0.5~16.0 g/ml），艰难梭菌咔哒唑胺MIC值低于利奈唑胺16倍。2种抗生素对不同基因型别与毒素型别的艰难梭菌均具有良好抑菌效果，同时对产气荚膜梭菌也具有抑菌效果。咔哒唑胺对脆弱拟杆菌不产生抑菌效果，利奈唑胺对其有抑菌效果。咔哒唑胺能抑制艰难梭菌芽孢形成。结论 临床常见的不同基因型和毒素型别的艰难梭菌对咔哒唑胺敏感，咔哒唑胺可用于治疗艰难梭菌感染。     

Pharmacodynamics of razupenem (PZ601) studied in an in vitro pharmacokinetic model of infection

Simulations of administration of razupenem at 1 g every 12 h by 1-h intravenous (i.v.) infusion were performed in an in vitro pharmacokinetic model of infection. The antibacterial effect of this razupenem dosing regimen against six strains of Staphylococcus aureus (one methicillin-sensitive S. aureus [MSSA] strain [MIC, 0.015 μg/ml] and five methicillin-resistant S. aureus [MRSA] strains [MIC range, 0.09 to 3 μg/ml]) and five strains of Enterobacteriaceae (three Escherichia coli strains [two containing extended-spectrum β-lactamases {ESBLs}] and two Enterobacter sp. strains [one with an AmpC enzyme and the other with a raised razupenem MIC; MIC range, 0.09 to 6 μg/ml]) was assessed. Against the MSSA and MRSA strains, razupenem produced a >3.5-log-unit reduction in viable count after 24 h. There were no changes in population profiles. In a second series of experiments, over 5 days there was rapid initial clearance of MRSA from the model followed by regrowth after 48 h. MRSA colonies appeared on 2× MIC recovery medium after 72 h with strain 33820 (MIC, 3.0 μg/ml) and at 120 h with strain 27706 (MIC, 1.5 μg/ml). Against E. coli and Enterobacter spp., razupenem produced a >3.5-log-unit reduction in bacterial counts for all strains except that with an MIC of 6 μg/ml, where razupenem had a notably poorer antibacterial effect. Population profiles were unchanged after 48 h of exposure to razupenem except for Enterobacter strain 34425 (MIC, 6.0 μg/ml), where colonies were recovered from media containing 2×, 4×, and 8× MIC. In dose-ranging studies with MRSA strains, the percentage of the dosing interval that the free drug concentration remained higher than the pathogen MIC (fT>MIC) for a 24-h bacteriostatic effect was 5.0% ± 1.4%, and that for a 1-log-unit reduction in count was 12.5% ± 5.8%. Population profiles indicated growth on 2× MIC recovery medium at fT>MIC values of 1 to 35% but not at a value of >35%. In a similar set of experiments with Enterobacteriaceae, the fT>MIC for a 24-h bacteriostatic effect was 34.2% ± 7.6% and that for a 1-log-unit reduction in count was 42.5% ± 7.8%. Population analysis profiles indicated growth on recovery media with 2×, 4×, and 8× MIC at fT>MICs in the range of 1 to 69% but rarely at values of ≥ 70%. In conclusion, razupenem at simulated human doses of 1 g i.v. every 12 h has a marked antibacterial effect on MSSA and MRSA strains with MICs of ≤ 3.0 μg/ml and Enterobacteriaceae with MICs of ≤ 0.4 μg/ml. fT>MIC targets of ≥ 35% for MRSA and ≥ 70% for Enterobacteriaceae should provide significant antibacterial effects combined with low risks of changing pathogen antibiotic population profiles.     

醋酸氯己定体外抗菌作用的实验观察

目的观察醋酸氯己定体外抗菌作用。方法采用肉汤稀释法,测定了醋酸氯己定对4种条件致病菌和一种厌氧菌的抗菌效果。结果醋酸氯己定对脆弱拟杆菌MIC为4μg/ml,MBC为8μg/ml;对产气荚膜梭菌的MIC为1μg/ml,MBC为2μg/ml。醋酸氯己定对金黄色葡萄球菌MIC为0.0625μg/ml,MBC为0.125μg/ml;对大肠埃希菌MIC为2μg/ml,MBC为4μg/ml;对铜绿假单胞菌MIC为4μg/ml,MBC为4μg/ml;奇异变形杆菌MIC为8μg/ml,MBC为8μg/ml。结论醋酸氯己定对常见条件致病菌和厌氧菌都有良好的体外抗菌作用。     

抗真菌药物对丝状真菌的体外抗菌活性研究

目的 了解两性霉素B(AMB)、伊曲康唑(ICZ)、伏立康唑(VRC)和卡泊芬净(CBF)对72株丝状真菌的体外抗菌活性,指导临床合理应用抗真菌药物.方法 MIC检测采用美国临床和实验室标准协会(CLSI)制订的用于产丝孢状真菌的体外药敏方案(M38-P)和(M38-A).AMB、VRC、ICZ在单独用药时分别取100%、100%、≥80%的生长抑制为MIC值,CBF在单独用药时取明确改变真菌菌丝形态的最低浓度作为最小有效浓度.分数抑菌浓度(FIC)评价体外联合效果,FIC=MIC<,联合>/MICA单独+MIC联合/MICB单独.结果 AMB、ICZ、CBF、VRC对72株丝状真菌的MIC90分别为8、4、2、8 μg/ml,AMB+ICZ、AMB+VRC、ICZ+VRC联合用药MIC的范围分别为0.125～16.97、0.245 2～1.25、0.062 5～8.25μg/ml.AMB+VRC对丝状真菌产生协同作用为20.0%～88.9%,优于AMB+ICZ的10.0%～62.5%和ICZ+VRC的20.0%～44.4%(P=0.007<0.05).结论 72株丝状真菌对4种常用抗真菌药物的体外抗菌活性有差异,AMB+VRC优于AMB+ICZ与ICZ+VRC,同样可作为直症感染治疗的联合用药.     

In vitro activity of JPC 2067 alone and in combination with sulfamethoxazole against nocardia species

JPC 2067 is a novel dihydrotriazine dihydrofolate reductase inhibitor that is being developed as an antimalarial therapeutic. We evaluated the in vitro activity of JPC 2067 alone and in combination with sulfamethoxazole (SMX) against a panel of nocardia isolates. The MIC(50)s and MIC(90)s for JPC 2067, SMX, and the combination were 0.125 μg/ml and 4 μg/ml, 16 μg/ml and 32 μg/ml, and 0.03 μg/ml and 2 μg/ml, respectively. JPC 2067 alone and in combination with SMX should be evaluated further to understand its clinical potential.     

Investigation of the potential for mutational resistance to XF-73, retapamulin, mupirocin, fusidic acid, daptomycin, and vancomycin in methicillin-resistant Staphylococcus aureus isolates during a 55-passage study

XF-73 is a dicationic porphyrin drug with rapid Gram-positive antibacterial activity currently undergoing clinical trials for the nasal decolonization of Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA). In multistep (55-passage) resistance selection studies in the presence of subinhibitory concentrations of XF-73, retapamulin, mupirocin, fusidic acid, and vancomycin against four Network on Antimicrobial Resistance in Staphylococcus aureus MRSA strains, there was no >4-fold increase in the MIC for XF-73 after 55 passages. In contrast, there was an increase in the MICs for retapamulin (from 0.25 μg/ml to 4 to 8 μg/ml), for mupirocin (from 0.12 μg/ml to 16 to 512 μg/ml), for fusidic acid (from 0.12 μg/ml to 256 μg/ml), and for vancomycin (from 1 μg/ml to 8 μg/ml in two of the four strains tested). Further investigations using S. aureus NRS384 (USA300) and daptomycin demonstrated a 64-fold increase in the MIC after 55 passages (from 0.5 μg/ml to 32 μg/ml) with a >4-fold increase in the MIC obtained after only five passages. Sequencing analysis of selected isolates confirmed previously reported point mutations associated with daptomycin resistance. No cross-resistance to XF-73 was observed with the daptomycin-resistant strains, suggesting that whereas the two drugs act on the bacterial cell membrane, their specific site of action differs. XF-73 thus represents the first in a new class of antibacterial drugs, which (unlike the comparator antibiotics) after 55 passages exhibited a ≤4-fold increase in MIC against the strains tested. Antibacterial drugs with a low propensity for inducing bacterial resistance are much needed for the prevention and treatment of multidrug-resistant bacteria both within and outside the hospital setting.     

Oritavancin activity against vancomycin-susceptible and vancomycin-resistant Enterococci with molecularly characterized glycopeptide resistance genes recovered from bacteremic patients, 2009-2010

Oritavancin exhibited potent activity against vancomycin-susceptible (MIC(50) and MIC(90), 0.015/0.03 μg/ml) and vanB-carrying E. faecalis isolates (MIC(50) and MIC(90), 0.015 and 0.015 μg/ml). Higher (16- to 32-fold) MIC(50)s and MIC(90)s for vanA-harboring E. faecalis were noted (MIC(50) and MIC(90), 0.25 and 0.5 μg/ml), although oritavancin inhibited all strains at ≤ 0.5 μg/ml. Vancomycin-susceptible and vanB-carrying E. faecium strains (MIC(50) and MIC(90), ≤ 0.008 and ≤ 0.008 μg/ml for both) were very susceptible to oritavancin, as were VanA-producing isolates (MIC(50) and MIC(90), 0.03 and 0.06 μg/ml). Oritavancin exhibited good in vitro potency against this collection of organisms, including vancomycin-resistant enterococci.     

In vitro activity of naftifine, a new antifungal agent.

Naftifine exhibits an interesting in vitro spectrum of activity against dermatophytes (38 strains; minimal inhibitory concentration [MIC] range 0.1 to 0.2 microgram/ml), aspergilli (6 strains; MIC range, 0.8 to 12.5 microgram/ml), Sporothrix schenckii (2 strains; MICs, 0.8 and 1.5 microgram/ml), and yeasts of the genus Candida (77 strains; MIC range, 1.5 to greater than 100 microgram/ml). Its degree of efficacy is unaffected by the organism density in the test medium, and it is primarily fungicidal against dermatophytes as well as yeasts. Its in vitro efficacy is pH dependent and rises with increasing pH values.     

In vitro activities of the novel cephalosporin LB 11058 against multidrug-resistant Staphylococci and Streptococci

LB 11058 is a novel parenteral cephalosporin with a C-3 pyrimidinyl-substituted vinyl sulfide group and a C-7 2-amino-5-chloro-1,3-thiazole group. This study evaluated the in vitro activity and spectrum of LB 11058 against 1,245 recent clinical isolates, including a subset of gram-positive strains with specific resistant phenotypes. LB 11058 was very active against Streptococcus pneumoniae. The novel cephalosporin was 8- to 16-fold more potent than ceftriaxone, cefepime, or amoxicillin-clavulanate against both penicillin-intermediate and -resistant S. pneumoniae. LB 11058 was also very active against both beta-hemolytic streptococci (MIC at which 90% of isolates were inhibited [MIC(90)], 64 micro g/ml) and Corynebacterium spp. (MIC(50), 32 micro g/ml). Against gram-negative pathogens, LB 11058 showed activity against Haemophilus influenzae (MIC(90), 0.25 to 0.5 micro g/ml) and Moraxella catarrhalis (MIC(90), 0.25 micro g/ml), with MICs not influenced by beta-lactamase production. In conclusion, LB 11058 demonstrated a broad antibacterial spectrum and was highly active against gram-positive bacteria, particularly against multidrug-resistant staphylococci and streptococci.