肺炎链球菌对抗菌药物的耐药性调查及对大环内酯类抗生素耐药机制研究

目的：调查成都地区肺炎链球菌对抗菌药物的敏感性，研究成都地区肺炎链球菌对大环内酯类抗生素耐药机制。方法：收集2001年9月-2002年9月成都地区临床分离的肺炎链球菌，测定其对13种抗菌药物的耐药性及对大环内酯类抗生素的耐药表型；用聚合酶链反应(PCR)扩增耐药基因ermB和mefA，并对ermB和mefA进行基因序列分析。结果：82株肺炎链球菌中13株对青霉素低度耐药(占15．9％),肺炎链球菌对大环内酯类抗生素和克林霉素表现出较高的耐药率，对红霉素和克林霉素耐药率分别为80．5％(66／82)和68．3％(56／82)。耐大环内酯类肺炎链球菌中,96．4％菌株表现为内在型耐药。标准菌株ATCC49619及16株红霉素敏感菌株均未检测到ermB基因及mefA基因；ermB基因和；mefA基因分别在62和11株耐红霉素肺炎链球菌中检测到，其中7株菌同时检测到ermB基因和mefA基因。所测ermB和mefA基因序列与基因库收录序列高度一致。结论：成都地区临床分离的肺炎链球菌对青霉素耐药率较低，但对大环内酯类抗生素和克林霉素耐药却非常普遍。ermB基因介导的靶位改变是成都地区肺炎链球菌对大环内酯类抗生素的主要耐药机制。     

肺炎链球菌对大环内酯类抗生素耐药机制研究

目的了解肺炎链球菌对大环内酯类抗生素的耐药机制和转座子整合酶的流行情况。方法188株红霉素耐药肺炎链球菌，用E试验和K—B纸片扩散法检测其对11种抗菌药物的敏感性；用双纸片法（红霉素和克林霉素）确定其耐药表型；用PCR扩增这些菌株的耐药基因ermB、mefa、mefE、tetM及转座子整合酶基因intTn。结果188株红霉素耐药株中耐药基因ermB总检出率为91．5％（172／188），mefE总检出率为38．3％，未检出mefA基因。97．9Yoo的红霉素耐药株中存在转座子整合酶intTn。耐药基因组合ermB（＋）mefE（-）和ermB（＋）mef（＋），占91．5％，两者均呈cMLSB耐药表型。ermB（-）mefE（＋）占8．5％，耐药表型为M型。结论我院分离的肺炎链球菌大环内酯耐药以errnB介导的cMLS。耐药表型为主。转座子可能在本地区肺炎链球菌耐药基因的水平转移和克隆播散中起重要作用。     

肺炎链球菌对大环内酯类抗生素的耐药状况及耐药机制研究进展

社区获得性肺炎（CAP）是威胁人类健康的常见感染性疾病之一,尽管引起CAP的常见病原菌中,肺炎链球菌感染的比率存在下降趋势,但其仍然是CAP最为常见的病原菌之一。据文献报道,2002年在欧洲各国进行的关于CAP病原菌的41项前瞻性研究表明,门诊患者肺炎链球菌感染占19．3％,     

儿童肺炎链球菌对三种抗菌药物的耐药性及相关耐药基因的研究

目的了解南昌地区儿童肺炎链球菌（streptococus pnenurmoniae，SP）对青霉素、红霉素、四环素耐药状况。方法对呼吸道、血液标本、脑脊液标本中分离的31株SP进行青霉素、头孢噻肟E-test药敏试验及青霉素、红霉素和四环素耐药相关的PBP2B、ermB、ermA／B／C、mefA和Term基因PCR检测。结果①PBP2B基因突变30株，均为点突变，PBP2B同源性在80。85％之间。另有1株对青霉素敏感无突变；②含ermA／B／C耐药基因24株，含InerA耐药基因26株，含有erm或InefA耐药基因30株。结论PBP2B基因突变在对青霉素耐药的同时也对三代头孢表现为不同程度的耐药．SP的耐药性已严重影响青霉素．红霉素．四环素的疗效。     

儿童肺炎链球菌对三种抗菌药物的耐药性及相关耐药基因的研究

目的了解南昌地区儿童肺炎链球菌（streptococus pnenurmoniae，SP）对青霉素、红霉素、四环素耐药状况。方法对呼吸道、血液标本、脑脊液标本中分离的31株SP进行青霉素、头孢噻肟E-test药敏试验及青霉素、红霉素和四环素耐药相关的PBP2B、ermB、ermA／B／C、mefA和Term基因PCR检测。结果①PBP2B基因突变30株，均为点突变，PBP2B同源性在80。85％之间。另有1株对青霉素敏感无突变；②含ermA／B／C耐药基因24株，含InerA耐药基因26株，含有erm或InefA耐药基因30株。结论PBP2B基因突变在对青霉素耐药的同时也对三代头孢表现为不同程度的耐药．SP的耐药性已严重影响青霉素．红霉素．四环素的疗效。     

肺炎链球菌对大环内酯类抗生素耐药及传播机制研究

目的 研究上海3所医院临床分离肺炎链球菌对大环内酯类抗生素的耐药机制及传播方式。方法收集上海市3所医院临床分离的红霉素耐药肺炎链球菌共118株，用E试验和K-B纸片扩散法检测对12种抗菌药的敏感度；用双纸片法（D试验）确定大环内酯类耐药表型；用PCR扩增检测耐药基因ermB、mefA、mefE、msrD及Tn1545-Tn916家族转座子整合酶基因intTn；用转化试验证实耐药传播方式。结果①118株肺炎链球菌对红霉素的MIC范围为4-256mg／L，其中5．9％对克林霉素敏感，对青霉素不敏感率达72．7％。左氧氟沙星、阿莫西林-克拉维酸对红霉素耐药的肺炎链球菌仍有较好的体外活性；②该组细菌耐药基因ermB检出率为88．1％，mefE、msrD检出率各为50％，未检出，mefA基因，转座子整合酶基因intTn检出率达97．5％。耐药基因组合模式以ermB（＋）reefE（＋）msrD（＋）intTn（＋）和ermB（＋）mefE（-）msrD（-）intTn（＋）为主，两者均为cMLSB型耐药。ermB（-）mefE（＋）msrD（＋）intTn（＋）模式占5．9％，耐药表型为M型。③cMLSB型耐药代表菌株ET37和M型耐药代表菌株RJ324基因组DNA均成功转化敏感株，使之表现红霉素耐药性并可传代。结论上海地区肺炎链球菌对大环内酯抗生素耐药以ermB介导的cMLSB耐药表型为主；大环内酯外排基因有流行趋势，但仅限于起源于肺炎链球菌的，mefE。耐药基因可以转化方式进行传播，转座子可能在本地区肺炎链球菌耐药基因的传播中起重要作用。     

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（CAP）的重要病原菌。大环内酯类抗生素对敏感的革兰阳性菌有效，且对非典型病原体也有较好疗效，被广泛用于治疗CAP和其他呼吸道感染的经验性治疗。肺炎链球菌对大环内酯类抗生素耐药问题也随之成为全球性问题，近10年来逐年加重，以亚洲国家（地区）的肺炎链球菌对大环内酯类抗生素耐药最为严重。本文就肺炎链球菌对大环内酯类抗生素耐药现状、     

肺炎链球菌对大环内酯类抗生素耐药的研究进展

肺炎链球菌对大环内酯类抗生素耐药情况不断加重,所以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。不同国家地区对大环内酯类抗生素的耐药率和耐药机制上存在差异,提示我国在制定指南、选择抗生素和应用疫苗时不能照搬国外。目前为止,单一大环内酯类抗生素仍是治疗门诊患者和没有耐药危险因素的住院患者的替代药物。对菌血症和更严重的住院患者的感染,怀疑和证实有耐大环内酯类抗生素肺炎链球菌感染者需要小心,推荐β-内酰胺类与大环内酯类或喹诺酮类药物联合应用。此外,新型抗生素(如酮内酯类抗生素)的开发,以及根据当地血清型流行情况合理应用疫苗,也可以达到防治大环内酯类抗生素耐药肺炎链球菌(MRSP)感染的目的。     

肺炎链球菌对大环内酯类抗生素耐药的研究进展

肺炎链球菌是儿童社区获得性感染的主要病原菌。作为一种条件致病菌,它常定植于鼻咽部黏膜,3岁以内的婴幼儿携带率最高。随着机体免疫力下降,有致病力的肺炎链球菌乘机侵入,引起儿童中耳炎、肺炎、脑膜炎和菌血症等疾病。据估计,发展中国家每年约有814000名5岁以下的儿童死于肺炎链球菌感染。20世纪90年代以来,由于肺炎链球菌对8内酰胺类抗生素,主要是青霉素的耐药逐年增加,再加上大环内酯类抗生素对非典型病原体也有效,因此大环内酯类抗生素被广泛应用于治疗肺炎链球菌感染的疾病。     

多重耐药肺炎链球菌研究进展及防治策略

肺炎链球菌是引起儿童社区获得性感染的主要病原菌之一，也是脑膜炎、菌血症、中耳炎和鼻窦炎的主要病原菌。近年来，肺炎链球菌对β内酰胺类、大环内酯类抗生素耐药率在世界各地不断增加，且不同地区差异较大。对磺胺类、四环素类、氯霉素耐药率也普遍较高，甚至有耐氟喹诺酮类菌株出现。多重耐药肺炎链球菌已逐渐成为全球性问题。本文就肺炎链球菌的耐药现状、耐药机制和防治策略作一综述。     

肺炎链球菌对红霉素耐药机制的研究

目的 研究北京地区肺炎链球菌对红霉素的耐药机制。方法 收集本院1998－1999年分离的对红霉素耐药的肺炎链球菌116株,采用“荚膜肿胀”技术进行血清分型,聚合酶链反应（PCR）检测对红霉素耐药的基因erm/mef,脉冲场凝胶电泳（PFGE)客青霉素结合蛋白（PBP）基因印迹技术追踪菌株之间的同源性。结果 116株红霉素耐药株的血清型主要为23F（30.0%),6A（19.0%),19F（13.8%),15（7.8%),23A（5.2%)。95.7%的青霉素不敏感株同时也耐红霉素;85％的菌株表现为MLS表型,即同时耐克林霉素;86．4％的红霉素耐药株具有erm基因,6％的菌株同时有erm和mef基因,1．7％的菌株只有mef基因,4．2％未能检测到erm或mef基因。PFGE发现2种耐药克隆：1个是青霉素耐药的血清型为23F的克隆株,另1个是青霉素敏感而红霉素耐药的、血清型为6A的克隆株。结论 核糖体突变（erm基因编码）是北京地区肺炎链球菌耐红霉素的主要机制,2种耐药克隆值得关注。     

Nasal carriage in Vietnamese children of Streptococcus pneumoniae resistant to multiple antimicrobial agents

Resistance to antimicrobial agents in Streptococcus pneumoniae is increasing rapidly in many Asian countries. There is little recent information concerning resistance levels in Vietnam. A prospective study of pneumococcal carriage in 911 urban and rural Vietnamese children, of whom 44% were nasal carriers, was performed. Carriage was more common in children <5 years old than in those >/=5 years old (192 of 389 [49.4%] versus 212 of 522 [40.6%]; P, 0.01). A total of 136 of 399 isolates (34%) had intermediate susceptibility to penicillin (MIC, 0.1 to 1 mg/liter), and 76 of 399 isolates (19%) showed resistance (MIC, >1.0 mg/liter). A total of 54 of 399 isolates (13%) had intermediate susceptibility to ceftriaxone, and 3 of 399 isolates (1%) were resistant. Penicillin resistance was 21.7 (95% confidence interval, 7.0 to 67.6) times more common in urban than in rural children (35 versus 2%; P, <0.001). More than 40% of isolates from urban children were also resistant to erythromycin, trimethoprim-sulfamethoxazole, chloramphenicol, and tetracycline. Penicillin resistance was independently associated with an urban location when the age of the child was controlled for. Multidrug resistance (resistance to three or more antimicrobial agent groups) was present in 32% of isolates overall but in 39% of isolates with intermediate susceptibility to penicillin and 86% of isolates with penicillin resistance. The predominant serotypes of the S. pneumoniae isolates were 19, 23, 14, 6, and 18. Almost half of the penicillin-resistant isolates serotyped were serotype 23, and these isolates were often multidrug resistant. This study suggests that resistance to penicillin and other antimicrobial agents is common in carriage isolates of S. pneumoniae from children in Vietnam.     

In-vitro activity of ten antimicrobial agents against penicillin-resistant Streptococcus pneumoniae.

The minimum inhibitory concentrations (MICs) of ten antibiotics were determined by the agar dilution method for 40 strains of penicillin-resistant Streptococcus pneumoniae, all of which were clinical isolates from this laboratory. The antibiotics tested were clarithromycin, erythromycin, teicoplanin, vancomycin, ceftriaxone, cefodizime, azithromycin, ramoplanin, ciprofloxacin and MDL 62873. Of these agents, clarithromycin, vancomycin, teicoplanin, ceftriaxone, ramoplanin and MDL 62873 were the most active. The role of these antibiotics as alternatives to penicillin for the treatment of infections caused by penicillin-resistant S. pneumoniae is discussed.     

Moxifloxacin: a comparison with other antimicrobial agents of in-vitro activity against Streptococcus pneumoniae

Two hundred representative isolates, including 26 strains of Streptococcus pneumoniae with intermediate resistance to penicillin, were selected from a collection obtained from blood cultures of patients with bacteraemic pneumococcal pneumonia. The MICs of moxifloxacin (BAY 12-8039), grepafloxacin, sparfloxacin, levofloxacin, ofloxacin, ciprofloxacin, erythromycin, tetracycline and penicillin G were determined by a standard agar dilution technique. Moxifloxacin had the highest in-vitro activity against S. pneumoniae (MIC90 = 0.25 mg/L; MIC range 0.06-0.25 mg/L). The MIC90 values were one dilution lower than those obtained with sparfloxacin and grepafloxacin, three dilutions lower than those obtained with levofloxacin, and four dilutions lower than those of ofloxacin and ciprofloxacin.     

In-vitro activity of 29 antimicrobial agents against penicillin-resistant and -intermediate isolates of Streptococcus pneumoniae.

Antibiotic resistance among isolates of Streptococcus pneumoniae is increasing worldwide. Optimal therapy, though unknown, should be guided by in-vitro susceptibility testing. Currently, vancomycin is the only approved antibiotic that is universally active against multiresistant S. pneumoniae. In-vitro activities were determined for 29 antimicrobial agents against 22 penicillin-intermediate S. pneumoniae (PISP) and 16 penicillin-resistant S. pneumoniae (PRSP) isolates. MICs were determined in cation-adjusted Mueller-Hinton broth with 3% lysed horse blood in microtitre trays. Antimicrobial classes tested included cephalosporins, penicillin, aminopenicillins, macrolides, quinolones, carbapenems and other antimicrobial agents. Among the classes of antimicrobial agents tested, wide differences in susceptibility were demonstrated for both PISP and PRSP. Of the cephalosporins, ceftriaxone and cefotaxime demonstrated the best in-vitro activity for both PISP and PRSP. Of the quinolones, clinafloxacin and trovafloxacin showed the greatest in-vitro activity. Rifampicin and teicoplanin demonstrated excellent in-vitro activity. Promising in-vitro results of newer agents, such as quinupristin/dalfopristin, ramoplanin, teicoplanin and linezolid may justify further evaluation of these agents in clinical trials.     

Activity of moxifloxacin and twelve other antimicrobial agents against 216 clinical isolates of Streptococcus pneumoniae

BACKGROUND: An increased incidence of macrolide resistance in penicillin-resistant Streptococcus pneumoniae has been described. METHODS: With this in mind, 216 S. pneumoniae isolates were evaluated for their in vitro susceptibility to a new fluoroquinolone, moxifloxacin, which was compared with penicillin, amoxicillin, cefuroxime, cefotaxime, ceftriaxone, erythromycin, clarithromycin, ciprofloxacin, sparfloxacin, ofloxacin, vancomycin and teicoplanin. A broth microdilution assay was performed in cation- adjusted Mueller-Hinton broth with 5% (v/v) lysed horse blood according to NCCLS guidelines. RESULTS: Erythromycin resistance was observed in all the 22 penicillin-resistant S. pneumoniae (10.1%). All the penicillin- susceptible S. pneumoniae were susceptible to cephalosporins, whereas all the penicillin-resistant ones showed resistance to cefuroxime and only intermediate susceptibility to cefotaxime and ceftriaxone. The 216 tested strains were inhibited by sparfloxacin and moxifloxacin at concentrations of 0.12-0.5 mg/l and 0.06-0.25 mg/l, respectively, regardlesss of whether the strain was penicillin and/or erythromycin resistant. Seven penicillin-resistant strains displayed resistance to ofloxacin. All isolates were susceptible to vancomycin; teicoplanin MIC values ranged from 0.03 to 0.12 mg/l. The excellent in vitro activity of moxifloxacin against S. pneumoniae was not affected by penicillin and/or macrolides. CONCLUSION: Moxifloxacin appears to be a promising choice for the treatment of pneumococcal infections, including situations where therapeutic choices are limited due to penicillin and macrolide resistance.     

In vitro activities of five fluoroquinolone compounds against strains of Streptococcus pneumoniae with resistance to other antimicrobial agents.

Ciprofloxacin, clinafloxacin, PD 131628, sparfloxacin, and trovafloxacin were tested against 236 strains of Streptococcus pneumoniae, most of which were resistant to other agents. Resistance to multiple antibiotics did not affect the organism's susceptibility to the fluoroquinolones. The fluoroquinolones with in vitro antipneumococcal activity might be particularly useful against strains that are resistant to the more traditional therapeutic agents.