肺炎链球菌对于大环内酯类抗生素的耐药

随着大环内酯类抗生素的广泛应用,肺炎链球菌对大环内酯类抗生素的耐药问题成为一个全球性问题,包括我国在内的亚洲地区尤为严重。从流行病学现况、耐药原因分析、耐药机制、耐药的临床意义,以及多重耐药问题等几个方面对肺炎链球菌的大环内酯类抗生素耐药进行了综述。     

肺炎链球菌对大环内酯类抗生素耐药的研究进展

肺炎链球菌是社区获得性肺炎（community Acquired pneumonia,CAP）的重要病原。由于大环内酯类抗生素对常见社区获得性呼吸道感染的病原体普遍有效,毒性低,过敏反应少,被广泛用于治疗CAP和其他呼吸道感染,随着肺炎链球菌对大环内酯类抗生素耐药情况的不断加重,目前对所有大环内酯类抗生素耐药及临床疗效的持续监测非常重要。     

肺炎链球菌对大环内酯类耐药机制研究进展

肺炎链球菌是导致高发病率、高致死率的最主要社区获得性感染致病菌。近年来,肺炎链球菌对红霉素等大环内酯的耐药性迅速增长,多重耐药菌株全球范围流行,在我国及周边一些国家,这一问题尤其严重。本文综述了大环内酯及相关的林可霉素、链阳性菌素的抗菌作用机制,肺炎链球菌对其耐药机制的研究进展,并简单介绍肺炎链球菌耐药株的实验室检测、流行情况及临床意义。     

肺炎支原体对大环内酯类抗生素的耐药分子机制研究

目的研究和分析肺炎支原体对大环内酯类抗生素的耐药分子机制。方法本次临床实践分析主要在2013年1月至2014年12月期间,选取了280例确诊为肺支原体感染的患者进行临床实践分析,从患者的咽部和鼻咽部获取标本,借助肺炎支原体分离培养技术和药物敏感试验,筛选出耐药株。结果在280例标本当中,分离阳性株为12例,12例患儿的临床表现、X线胸片等均符合支原体肺炎的特点,耐药株为8例,占66.67%,耐药株同时对阿齐霉素和交沙霉素耐药。结论肺炎支原体对大环内酯类抗生素的耐药分子机制研究能够产生积极的影响,对肺炎支原体进行研究,明确大环内酯类抗生素的耐药分子机制十分必要,值得在临床实践研究中广泛推广和应用。     

肺炎链球菌对抗生素耐药机制基因研究进展

随着抗生素广泛大量的使用,细菌的耐药性及耐药水平越来越高,病原菌对常用抗生素,如大环内脂类、β-内酰胺类、氨基糖苷类和喹诺酮类药物的耐药性尤为突出,给疾病的治疗和临床用药造成了诸多困难。肺炎链球菌（Streptococcus pneumoniae,sp）是社区获得性肺炎、中耳炎、菌血症、脑膜炎等感染的主要致病菌,尤其易感染儿童、老年人、居住拥挤的人群。自1967年在美国首次检测到耐红霉素肺炎链球菌以来,肺炎链球菌大环内酯耐药株迅速发展,耐药率也持续增加。多重耐药株不断涌现,并在全球范围流行,     

肺炎链球菌耐药性及其耐药机制研究

多重耐药肺炎链球菌全球瞩目。近年来，肺炎链球菌对β-内酰胺类、大环内酯类及氟喹诺酮类抗生素的耐药率呈上升趋势，对其耐药基因的研究引起广泛关注，现就肺炎链球菌对β-内酰胺类、大环内酯类及喹诺酮类抗生素耐药基因的研究进展进行综述。     

肺炎链球菌的耐药性和耐药机制

耐药性肺炎链球菌在世界范围内的广泛流行引起了医学界的普遍关注，肺炎链球菌对β－内酰胺类，大环内酯类抗生素的耐药率在世界各地以较快速度上升，不同地区差异较大，磺胺类，四环素类，氯霉素耐药率普遍较高，出现了氟喹诺酮药性临床菌株，肺炎链球菌的β－内酰胺耐药性主要由青霉素结合蛋白变异所致，非pbp基因突变也会导致β－内酰胺耐药性，大环内酯耐药性肺炎链球菌的耐药表型MLS型，M型分别由耐药基因ermB和mefA介导，23SrRNA和核糖体蛋白L4突变也是其耐药机制之一。DNA促旋酶和拓扑异构酶Ⅳ基因突变引起的靶位改变导致肺炎链球菌对氟喹诺酮类药物耐药。肺炎链球菌也存在氟喹诺酮耐药性主动排系统，pmrA基因编码了外排蛋白PmrA。     

细菌对大环内酯类抗生素耐药机制的研究进展

细菌对大环内酯类抗生素的主要耐药机制为靶位改革,某些细菌产生的灭活酶也可导致细菌的耐药,近年来的研究发现主动外排系统在细菌对大环内酯类抗生素的耐药中也起了重要的作用。本文对上述３种耐药机制,着重对主动外排系统的近年研究情况作一综述。     

肺炎链球菌抗生素耐药的流行病学及机制的研究进展

肺炎链球菌是儿科社区获得性呼吸道感染常见病原菌，近年来，来自世界各地的多数文献报道肺炎链球菌对常用抗生素耐药性迅速增加，本文综述了肺炎链球菌对青霉素类、大环内酯类、氟哇诺酮类、四环素、氯霉素、及SMZ/TMP耐药和万古霉素的耐受的发生、发展及耐药机制的研究进展。同时，介绍了2000～2001年北京、上海、广州、西安四地急性上呼吸道感染儿童鼻咽部肺炎链球菌分离株对常用抗生素敏感性监测情况。     

肺炎链球菌流行基因型的细菌毒力及大环内酯类的耐药机制

目的研究分离的侵袭性肺炎链球菌(IPD)的流行血清基因型、致病毒力基因、大环内酯类耐药机制及与细菌毒力的关系。方法收集2013年6月~2016年6月分离鉴定的侵袭性肺炎链球菌共12株(观察组),同时收集10株携带肺炎链球菌(对照组);采用多重PCR扩增法进行血清基因型分型,PCR扩增6个致病毒力基因,包括荚膜(cps2A)、细菌素(bacteriocin)、表面黏附素A(psa A)、B组链球菌细胞壁分离蛋白(pcs B)、溶血素(ply)和酪蛋白水解蛋白酶P(clp P),分析其碱基序列的突变情况;采用MIC法测定青霉素、头孢吡肟、左氧氟沙星、红霉素和美罗培南的耐药性和最低抑菌浓度(MIC)值。结果基因型14、6A/6B和19F在2组中检出率比较差异无统计学意义(P>0.05),19A、6C和17F在观察组中检出率显著高于对照组(P<0.05)。2组对头孢吡肟、左氧氟沙星和美罗培南的敏感率比较差异无统计学意义(P>0.05)。观察组对青霉素和红霉素不敏感率和MIC值显著高于对照组(P<0.05)。结论分离的IPD血清型主要有19A、6C和17F,共有6种致病毒力基因,对青霉素和红霉素耐药。     

324株儿童感染肺炎链球菌耐药情况的分析

目的了解本院儿童感染肺炎链球菌(SP)的耐药情况。方法采集本院2007年1月至2008年6月324株SP,纸片扩散法(K-B法)进行抗菌药物敏感实验,E-test法测最低抑菌浓度(MIC)。结果324株肺炎链球菌耐药率,阿莫西林/棒酸为17.90%,万古霉素为3.09%,阿奇霉素为96.91%,复方新诺明为70.37%,美罗培南为0.62%,氨苄西林为25.31%,青霉素为94.75%,头孢曲松为10.19%,氧氟沙星为14.20%,头孢克洛为53.09%,氯霉素为3.70%,红霉素为95.37%。结论南京地区儿童感染SP,青霉素、阿奇霉素、红霉素耐药率高,耐药情况严峻。     

甲磺酸左氧氟沙星对耐青霉素肺炎链球菌的体外抗菌活性

目的 观察甲磺酸左氧氮沙星对耐青霉素肺炎链球菌(PRSP)的药敏及疗效。方法 对6株临床分离的耐青霉素肺炎链球菌，采用E—test方法，测定甲磺酸左氧氮沙星等6种抗生素的抗菌活性。同时观察甲磺酸左氧氮沙星单药治疗取SP临床疗效及不良反应。结果6株取SP均为低耐药菌株，对甲磺酸左氧氮沙星敏感。6例患者经治疗后，5例痊愈，l例显效，无明显副反应发生。结论 甲磺酸左氧氮沙星可有效治疗耐青霉素肺炎链球菌性肺炎。     

成都地区肺炎链球菌对抗菌药物的耐药性调查

目的 了解成都地区临床分离的肺炎链球菌的耐药性，为肺炎链球菌感染临床合理应用抗菌药物提供理论依据。方法 二倍琼脂稀释法测定11种抗菌药物对肺炎链球菌的最低抑菌浓度(MIC)。结果 91．94％菌株对青霉素敏感，8．06％中度耐药；88．71％菌株对SMZ／TMP敏感，11．29％中度耐药；肺炎链球菌对头孢呋辛、头孢噻肟、头孢毗肟、氧氟沙星、司帕沙星、美洛培南、万古霉素敏感率为100％；对红霉素、克林霉素耐药率相当高，分别达到62．90％和74．19％。结论 成都地区肺炎链球菌对青霉素耐药率较低，而对大环内酯类和克林霉素类耐药率较高。     

48株儿童侵袭性肺炎链球菌血清型分布

目的了解南京地区临床分离的侵袭性肺炎链球菌血清型分布情况。方法用荚膜肿胀实结果检测2007年1月-2010年12月临床分离的48株侵袭性肺炎链球菌的血清型别。结果 48株侵袭性肺炎链球菌常见的血清型别为19F(27.1%)、19A(22.8%)、14(18.7%)和9v(8.3%),有2株用丹麦抗血清无法确定血清型。结论南京地区儿童临床分离的侵袭性肺炎链球菌的常见血清型为19F、19A、14和9v,与其它地区报道有一定差别。     

肺炎球菌外膜蛋白A的分离纯化及免疫原性

培养肺炎球菌FY06，采用表面活性剂从菌泥抽提外膜蛋白，依次用硫酸铵盐析法和DEAE-纤维素离子交换法对肺炎球菌外膜蛋白进行分离和纯化。免疫原性实验表明：所制备的外膜蛋白A具有优良的免疫原性，对5种血清型肺炎球菌均有较广泛的交叉免疫效果。可作为新．代的肺炎球菌疫苗成分。     

阿莫西林与红霉素对肺炎链球菌的体外抗菌效果

目的研究阿莫西林(β内酰胺类抗生素)和红霉素(大环内酯类抗生素)联合应用体外对肺炎链球菌的相互作用,并验证红霉素对肺炎链球菌的杀菌作用。方法用琼脂平板二倍稀释法测定阿莫西林和红霉素对肺炎链球菌的最低抑菌浓度(MIC),用影印培养法测定最低杀菌浓度(MBC)。用棋盘微量稀释法和时间-杀菌曲线分析测定两药对肺炎链球菌的联合作用效果。结果阿莫西林对44株菌株的MIC为≤0.004～2mg·L-1,MBC≤0.004～4mg·L-1;红霉素对其的MIC值为0.008～≥256mg·L-1,MBC为0.016～≥256mg·L-1。阿莫西林的MBC/MIC为1～2;红霉素的MBC/MIC的为1～4。对阿莫西林和红霉素均敏感的肺炎链球菌株联合用药时,大部分菌株较单用时相同或略下降,其FICI在1～2。结论红霉素在体外对肺炎链球菌有杀菌作用;与阿莫西林体外联合应用时,阿莫西林杀菌效果不会被减弱。     

Drug-resistant Streptococcus pneumoniae in the Lebanon: implications for presumptive therapy.

A total of 50 consecutive clinical isolates of Streptococcus pneumoniae, collected between 1996 and 1998, were tested against six antimicrobial agents using the E-test. The percentages of fully resistant (R) and intermediately-R strains, respectively, were: benzyl penicillin 18 and 38%, amoxycillin-clavulanate 6 and 12%, cefuroxime 22 and 16%, ceftriaxone 2 and 16%, and clarithromycin 10%. Fully and or intermediately multidrug-resistance (two or more drugs) was seen in 44% of the isolates, 18% being fully resistant. The MIC breakpoint for cefaclor is not defined by the National Committee for Clinical Laboratory Standards (NCCLS) but MICs showed that: 76% of the isolates had an MIC of ≤8 mg/l, 4% had an MIC of 16 mg/l and 20% had an MIC of ≥32 mg/l. There was agreement between the E-test Pen MIC results and the 1 μg oxacillin (oxa) disk diffusion screen test for the 22 susceptible and the nine fully R strains but not for the 19 strains with Pen MICs between 0.1 and 1 mg/l; this shows the importance of MIC determination in such isolates. Penicillin and multiply antibiotic-resistant pneumococci are spreading in Lebanon, emphasizing the necessity to reconsider current treatment regimens in this country.     

Linezolid, levofloxacin, and vancomycin against vancomycin-tolerant and fluoroquinolone-resistant Streptococcus pneumoniae in an in vitro pharmacodynamic model

STUDY OBJECTIVE: To compare the pharmacodynamic profiles of linezolid, levofloxacin, and vancomycin against clinical strains of Streptococcus pneumoniae, including vancomycin-tolerant and fluoroquinolone-resistant isolates. DESIGN: In vitro pharmacodynamic model. SETTING: Biosafety level 2, university research laboratory. BACTERIAL STRAINS: Ciprofloxacin-susceptible (79), ciprofloxacin-resistant (R921), and vancomycin-tolerant (P9802-020) clinical strains of S. pneumoniae. INTERVENTION: An in vitro pharmacodynamic model was used to simulate standard dosing regimens of linezolid, levofloxacin, and vancomycin against the isolates 79, R921, and P9802-020. MEASUREMENTS AND MAIN RESULTS: Bacterial density was profiled over 48 hours. Minimum inhibitory concentrations (MICs) for linezolid, levofloxacin, and vancomycin, respectively were 1, 1, 0.5 microg/ml for isolate 79; 1, 4, 0.5 microg/ml for R921; and 0.5, 0.5, 0.5 microg/ml for P9802-020. Vancomycin minimum bactericidal concentration (MBC) values varied across large ranges for the tested strains. Linezolid achieved 99.9% kill against 79 and R921 by 24 and 28 hours, respectively. Levofloxacin achieved 99.9% kill against 79 and P9802-020 by 28 and 4 hours, respectively. Vancomycin achieved 99.9% kill against 79 and R921 by 8 and 24 hours, respectively. Levofloxacin did not demonstrate activity against R921 at the 48-hour end point. Minimal kill (< 2 log) at 48 hours was noted for vancomycin and linezolid against P9802-020. Conclusion. Vancomycin tolerance appeared to be more reliably characterized by persistent viability in time-kill analyses than by MBC:MIC ratios. Vancomycin exhibited bactericidal activity against the non-vancomycin-tolerant strains of S. pneumoniae. Linezolid exhibited both bactericidal and bacteriostatic activity against all three strains tested, whereas levofloxacin demonstrated bactericidal activity against the fluoroquinolone-susceptible isolates. Further investigation of treatment alternatives for infections due to vancomycin-tolerant S. pneumoniae are needed.     

Antimicrobial resistance and serotype distribution of Streptococcus pneumoniae isolates from Crete, Greece

Susceptibility to 14 antibiotics was determined for 125 clinical isolates of Streptococcus pneumoniae collected over a 3-year period in Crete, Greece. Twenty-three isolates (18.4%) showed intermediate resistance and 15 (12%) high-level resistance to penicillin. Erythromycin, chloramphenicol, tetracycline, trimethoprim-sulphamethoxazole and sparfloxacin resistance rates were 16.8, 10.4, 19.2, 24.8 and 9.6%, respectively. Multiple resistance was observed in 22 strains. Vancomycin and levofloxacin were the most active agents tested. The most prevalent serotype among penicillin-susceptible pneumococci was 14, followed by 9, 7 and 1, while among penicillin-intermediate or -resistant strains serotype 23 was predominant followed by 19 and 9. These results show that as well as a high level of penicillin resistance in this region, some strains are also resistant to other antibiotics and may show multi-drug resistance.