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1.
目的 研究耐药基因ermB、mefA、tetM与转座子整合酶基因intTn在携带肺炎链球菌的北京儿童中分布特点。方法对185株呼吸道感染患儿鼻咽部分离的肺炎链球菌进行以下检测:E-test、琼脂稀释或纸片扩散法测定对大环内酯类、四环素、β-内酰胺类及头孢类等15种抗生素的药物敏感性。PCR检测大环内酯类耐药基因ermB和mef/A,四环素耐药基因tetM以及转座子Tn1545的整合酶基因intTn。结果185株肺炎链球菌的药敏结果显示,对红霉素、克林霉素、四环素和复方磺胺甲基异嗯唑的耐药率较高,分别为78.9%、76.2%、86.0%和78.7%,对阿莫西林,克拉维酸、头孢克洛、头孢曲松和头孢呋辛耐药率较低,分别为2.2%、15.5%、2.8%和14.1%。所有红霉素耐药株均检出ermB和/或mefA,其中79.5%为ermB阳性,17.8%为ermB和mefA同时阳性,2.7%为mefA阳性。tetM基因在分离株中的阳性率是87%,四环素耐药组的tetM基因携带率是96.9%,高于敏感组(26.9%)。四环素耐药株的红霉素耐药率(90.0%)亦高于敏感株组(11.5%)。87.6%的肺炎链球菌存在intTn基因,intTn基因阳性组的红霉素、四环素、氯霉素、复方磺胺甲基异嗯唑和环丙沙星的耐药率较intTn基因阴性组高。分离株最常见的基因组合是intTn+terM+ermB,占58.4%。结论北京地区呼吸道感染儿童鼻咽部肺炎链球菌耐大环内酯类抗生素的主要原因是ermB编码的23S rRNA甲基化酶致靶位改变。tetM基因编码蛋白质的核糖体保护作用,是肺炎链球菌四环素耐药的重要机制。接合性转座子Tn1545的存在与菌株的红霉素和四环素耐药关系密切,可能是肺炎链球菌多重耐药的重要机制之一。  相似文献   

2.
目的了解儿童急性呼吸道感染(ARTIS)鼻咽部常见的病原菌及其耐药性.方法对285例取鼻咽拭子进行培养,分离鉴定病原菌,同时对肺炎链球菌和流感嗜血杆菌(Hi)进行耐药性监测.结果285例中共检出病原菌161株。肺炎链球菌、流感嗜血杆菌、卡他莫拉氏菌、金黄色葡萄球菌的分离率分别为20.4%、16.5%、13.0%、6.7%.肺炎链球菌对青霉素耐药率高达57.5%,同时对非B一内酰胺类抗生素复方新诺明、四环素、红霉素的耐药率已高达79.2%.89.5%,对头孢曲松、阿莫西林/棒酸尚具有较好的敏感性(85.1%-93.3%).Hi对氨苄西林的耐药率为13.3%。对头孢克洛、头孢曲松、头孢呋新、阿莫西林/棒酸均有很好的敏感性(96.4%-100%),对四环素、复方新诺明的耐药范围分别为25.3%-56.6%.结论肺炎链球菌、流感嗜血杆菌、卡他莫拉氏菌和金黄色葡萄球菌是广州地区儿童急性呼吸道感染的常见病原菌.肺炎链球菌和流感嗜血杆菌耐药形势严峻,抗生素合理应用尤为重要.  相似文献   

3.
79株肺炎链球菌的耐药性测定   总被引:38,自引:0,他引:38  
目的调查北京地区肺炎链球菌对青霉素等抗生素的耐药率。方法用Etest及琼脂稀释法测定临床分离的79株肺炎链球菌15种抗生素的最低抑制浓度(MIC)。结果Etest测得10株(12.7%)低耐青霉素(MIC0.125~1μg/ml),1株(1.3%)高耐青霉素(MIC4μg/ml);仅1株处于头孢曲松、头孢噻肟中介范围(MIC1μg/ml).琼脂稀释法测得阿莫西林、阿莫西林/棒酸、头孢呋肟、环丙沙星、氯霉素、四环素、红霉素的耐药率分别为1.3%、1.3%、2.5%、2.5%、16.5%、49.4%、40.5%,所有菌株对头孢曲松、万古霉素敏感。结论北京地区14%的肺炎链球菌耐青霉素,耐三代头孢菌素及多重耐药株罕见。  相似文献   

4.
目的调查广州地区老年患者肺炎链球菌分离株对青霉素的敏感性,并分析其亲缘关系。方法K—B纸片法对33株分离自老年住院病人的肺炎链球菌进行青霉素药敏试验;应用PCR技术检测青霉素结合蛋白基因pbp1a,pbp2x,pbp2b;用盒式PCR(BOX—PCR)分析菌株间亲缘关系。用多位点测序分型技术(multilocus sequence typing,MLST)检测青霉素耐药菌株的分子分型。结果青霉素的耐药率为3.03%(1/33):用PCR方法鉴定PSSP的准确率为68.75%;BOX-PCR可将这33株肺炎链球菌分为21型。MIST分型显示,青霉素耐药菌株属ST271型。结论广州地区老年患者肺炎链球菌对青霉素耐药率较低.用PCR方法检测PSSP有一定的可行性。BOX—PCR显示了较高的分辨率,能快速可靠地检测菌株间的亲缘关系。广州地区流行的耐药克隆与Taiwan^19F-14株同源。  相似文献   

5.
目的 调查急慢性上颌窦炎及咽炎患者肺炎链球菌带菌及耐药情况。方法 用E—test法及纸片扩散法测定耐药情况.结果 86株肺炎链球菌中,对青霉素敏感64株(74.4%),低度耐药18株(20.9%),高度耐药4株(4.7%),青霉素耐药菌株对红霉索、氯霉素、复方新诺明及四环素的耐药率比青霉素敏感株高,所有菌株对万古霉素敏感.结论 了解细菌耐药性的变化是合理应用抗生素的重要依据。  相似文献   

6.
目的 监测青岛地区肺炎链球菌的耐药性,为临床合理应用抗菌药物提供依据.方法 采集青岛地区部分医院2005年1月到2008年12月门诊与住院感染患者呼吸道、血液、脑脊液等标本,培养、分离和鉴定肺炎链球菌.根据NCCLS的推荐,采用琼脂微茸稀释法测定分离出的231株肺炎链球菌对11种常用抗菌药物的耐药性,分析耐药趋势及年龄差异.结果 231株肺炎链球菌对青霉素不敏感率为23.38%[耐青霉素肺炎链球菌(PRSP):9.52%;低耐青霉素肺炎链球菌(PISP):13.85%].对头孢噻肟耐药率最低为9.96%(23/231),其次阿莫西林为12.55%(29/231).对红霉素耐药率最高为90.48%(209/231).14岁以下患者PRSP检出率为27.91%(12/43),明显高于成人的PRSP检出率5.38%(10/186).结论 本地区PRSP检出率较2004年前明显增加,并有逐年增加的趋势,肺炎链球菌的耐药性也有逐年上升的趋势.本地区对感染低耐青霉素肺炎链球菌的患者头孢噻肟、阿莫西林可为首选药物.  相似文献   

7.
目的了解儿童急性呼吸道感染(ARTIS)鼻咽部常见的病原菌及其耐药性.方法对285例取鼻咽拭子进行培养,分离鉴定病原菌,同时对肺炎链球菌和流感嗜血杆菌(Hi)进行耐药性监测.结果 285例中共检出病原菌161株,肺炎链球菌、流感嗜血杆菌、卡他莫拉氏菌、金黄色葡萄球菌的分离率分别为20.4%、16.5%、13.0%、6.7%.肺炎链球菌对青霉素耐药率高达57.5%,同时对非β-内酰胺类抗生素复方新诺明、四环素、红霉素的耐药率已高达79.2%~89.5%,对头孢曲松、阿莫西林/棒酸尚具有较好的敏感性(85.1%~93.3%).Hi对氨苄西林的耐药率为13.3%,对头孢克洛、头孢曲松、头孢呋新、阿莫西林/棒酸均有很好的敏感性(96.4%~100%),对四环素、复方新诺明的耐药范围分别为25.3%~56.6%.结论肺炎链球菌、流感嗜血杆菌、卡他莫拉氏菌和金黄色葡萄球菌是广州地区儿童急性呼吸道感染的常见病原菌.肺炎链球菌和流感嗜血杆菌耐药形势严峻,抗生素合理应用尤为重要.  相似文献   

8.
目的调查急慢性上颌窦炎及咽炎患者肺炎链球菌带菌及耐药情况. 方法用E-test法及纸片扩散法测定耐药情况. 结果 86株肺炎链球菌中,对青霉素敏感64株(74.4%),低度耐药18株(20.9%),高度耐药4株(4.7%),青霉素耐药菌株对红霉素、氯霉素、复方新诺明及四环素的耐药率比青霉素敏感株高,所有菌株对万古霉素敏感. 结论了解细菌耐药性的变化是合理应用抗生素的重要依据.  相似文献   

9.
肺炎链球菌的耐药性和pbp2b基因扩增产物图谱的相关性   总被引:13,自引:1,他引:13  
目的 了解肺炎链球菌对青霉素和其它抗生素的耐药情况;对40株青霉素敏感菌株和30株青霉素不敏感菌株进行pbp2b基因扩增产物RFLP图谱相关性研究。方法 采用肉汤稀释法、E-试验和K-B纸片法进行抗生素药物敏感试验;通过用特异性引物pF和pR对肺炎链球菌进行PCR扩增,并对扩增产物进行限制性内切酶HaeⅢ消化反应。结果 肺炎链球菌对青霉素的不敏感率为9.9%~14.6%;40株青霉素敏感菌株(MICs≤0.094μg/ml)中的39株(97.5%)为s1、s2和s3三种之一,1株为r1;30株青霉素不敏感菌株(MICs≥0.12μg/ml)中的26株(86.7%)为r1-16六种之一,其余4株为s1。结论 青霉素和β-内酰胺酶类抗生素对北京地区的肺炎链球菌具有活性;肺炎链球菌的耐药性和pbp2b基因扩增产物图谱之间有相关性。  相似文献   

10.
儿童社区获得性呼吸道感染的病原学研究   总被引:2,自引:0,他引:2  
目的探讨儿童呼吸道感染的病原学特点,以期为临床治疗提供依据.方法采集1784名呼吸道感染患儿咽拭标本常规细菌培养和/或PCR法支原体,K-B法测定流感嗜血杆菌、肺炎链球菌耐药性,以套式-聚合酶链反应及PCR技术进行肺炎链球菌耐药基因TEM基因、ermB基因和mefA基因检测,加DAN测序分析.结果 129例细菌培养阳性,依次为流感嗜血杆菌、肺炎链球菌、肺炎克雷伯杆菌、金黄色葡萄球菌、阴沟肠杆菌、不动杆菌属;153例支原体阳性,以肺炎支原体、人型支原体为主,少数为肺炎衣原体.其中流感嗜血杆菌、肺炎链球菌对青霉素、克林霉素、红霉素、阿奇霉素、阿莫西林/克拉维酸、复方甲基异恶唑、头孢菌素及红霉素等10种常用抗生素均不同程度耐药,但对氯霉素和万古霉素均敏感;肺炎链球菌β内酰胺酶基因(TEM)、红霉素耐药基因(甲基化酶基因ermB)表达阳性,但未表达红霉素耐药基因(外排基因mefA).结论流血嗜血杆菌和肺炎链球菌本地区呼吸道感染儿童主要致病菌,对常用抗生素有不同程度耐药,肺炎支原体和人型支原体也是重要致病原;肺炎链球菌耐药可能是通过表达TEM基因和ermB基因实现的.  相似文献   

11.
This study determined nasopharyngeal (NP) carriage rates of Streptococcus pneumoniae among healthy Estonian children, aged 1-7 years, and characterised the serotype/serogroup distribution and antibiotic susceptibility rates. NP swabs were collected from 685 previously healthy children attending 29 day care centres during the winters of 1999-2000 and 2003. The NP carriage rate of S. pneumoniae was 44%. Rates of penicillin and erythromycin non-susceptibility were low (both 6%), but high (67%) rates of co-trimoxazole resistance were found. Among the pneumococcal serotypes identified, 64% were included in or cross-reacted with the licensed heptavalent pneumococcal vaccine.  相似文献   

12.
At this time, many antibiotics have decreased activity against Streptococcus pneumoniae, a major agent of infectious disease. In this study, we evaluated antibiotic susceptibility and serogroups of strains isolated from bacteraemia, meningitis and acute otitis media in adults and children over the 1997-2003 period in Brittany, France. In 2003, 62% of the isolates were not susceptible to penicillin and 11% were fully resistant. The prevalence of erythromycin resistance was 63%. Resistance rates were higher among isolates recovered from children than adults. Serogroups 19 and 14 were the most frequently isolated, especially the 19 one among children. The emergence of this serogroup might be a consequence of the use of heptavalent conjugate vaccine introduced in 2001 in France. Future surveillance after vaccination will be needed to detect emerging serogroups and resistance among S. pneumoniae.  相似文献   

13.
To address the public health problem of antibiotic resistance, the European Union (EU) founded the European Antimicrobial Resistance Surveillance System. A network of 40 hospitals that serve approximately 30% of the Spanish population (about 12 million) participated. Each laboratory reported data on antimicrobial susceptibility testing using standard laboratory procedures that were evaluated by an external quality control program. The antibiotic consumption data were obtained from the National Health System. We compared the antibiotic susceptibility of Spanish isolates of invasive Streptococcus pneumoniae (2001 to 2003) with antibiotic consumption. Invasive S. pneumoniae was isolated from 1,968 patients, 20% of whom were children at or below the age of 14 years. Of non-penicillin-susceptible strains (35.6%; 95% confidence interval, 34 to 37.2), 26.4% were considered intermediate and 9.2% were considered resistant. Between 2001 and 2003, penicillin resistance decreased from 39.5 to 33% overall and from 60.4 to 41.2% in children at or below the age of 14 years (P = 0.002). Resistance to erythromycin was at 26.6%, and coresistance with penicillin was at 19.1%. Of total isolates, the ciprofloxacin MIC was >2 mug/ml for 2.1%, with numbers increasing from 0.4% (2001) to 3.9% (2003). Total antibiotic use decreased from 21.66 to 19.71 defined daily doses/1,000 inhabitants/day between 1998 and 2002. While consumption of broad-spectrum penicillins, cephalosporins, and erythromycin declined, use of amoxicillin-clavulanate and quinolones increased by 17.5 and 27%, respectively. The frequency of antibiotic resistance in invasive S. pneumoniae in Spain was among the highest in the EU. However, a significant decrease in penicillin resistance was observed in children. This decrease coincided with the introduction of a heptavalent conjugate pneumoccocal vaccine (June 2001) and with a global reduction in antibiotic consumption levels.  相似文献   

14.
We examined the penicillin and macrolide resistance of 496 strains of Streptococcus pneumoniae (S. pneumoniae) isolated at Showa University Hospital from November 2004 to May 2005. According to the classification established by the Clinical and Laboratory Standards Institute, the ratio of penicillin susceptible S. pneumoniae (PSSP) was 25.8%, penicillin intermediate S. pneumoniae was 35.9% and penicillin resistant S. pneumoniae (PRSP) was 38.3%. The ratios of macrolide resistant S. pneumoniae were 85.3% for erythromycin and 76.2% for clarithromycin. S. pneumoniae strains were isolated mainly from pediatric patients, and the ratios of PRSP were similar between outpatients (39.8%) and inpatients (45.6%). We screened for mutations in pbp1a, pbp2b and pbp2x, and the retention rate of the macrolide resistance genes, ermB and mefA in 90 strains isolated in the same period. Seventy two strains had at least one mutation in the pbp genes. Interestingly, some of the penicillin susceptible strains had one or two pbp mutations, suggesting a progressive genetic acquirement of penicillin resistance. In screening for retention of the macrolide resistance genes, we found that 42 strains(46.7%) had ermB, 19 strains (21.1%) had mefA and 13 strains (14.4%) had both ermB and mefA. The possession of resistance genes and the minimal inhibitory concentration indicate that the resistance to erythromycin and clarithromycin were induced by ermB or mefA, and the resistance to clindamycin was induced only by ermB. Among the 72 strains with pbps mutations, 65 strains (90.3%) had ermB or mefA or both. Together, these results show that the strains with pbp mutations were being selected and, after acquiring the macrolide resistance gene, transform to multidrug resistant S. pneumoniae.  相似文献   

15.
Objective: To undertake a survey of nasopharyngeal carriage of Streptococcus pneumoniae , which reflects strains causing infection, in 100 children under 3 years of age attending day-care centers in Frosinone, a city near Rome.
Methods: Fifty-three unique isolates of S. pneumoniae , isolated from 41 of the children tested, were tested for antimicrobial susceptibility to penicillin, cefotaxime, erythromycin, clindamycin, tetracycline, chloramphenicol and trimethoprim-sulfamethoxazole.
Results: Resistance rates were as follows: penicillin, 20.7% (15% intermediate; 5.7% resistant); trimethoprim-sulfamethoxazole, 64.2%; erythromycin, 64.2%; clindamycin, 30.2%; tetracycline, 32.1%; and chloramphenicol, 3.8%. Except for three intermediate strains, all strains were susceptible to cefotaxime. Only five strains were susceptible to all of the antibiotics tested. An unusual finding of this study was that 23 of the 34 erythromycin-resistant strains were penicillin susceptible, whereas erythromycin-resistant strains found in other countries are predominantly penicillin resistant as well. In addition, 18 of the 34 erythromycin-resistant strains were susceptible to clindamycin. Serogroups 6, 14, 19 and 23 accounted for 84.9% of the isolates.
Conclusions: These data show that carriage of antibiotic-resistant pneumococci in children under 3 years of age is high in Frosinone, Italy. Information on resistance rates in pneumococcal disease in different age groups and on prevalence of drug resistance in other parts of the country is urgently needed.  相似文献   

16.
手术切口感染病原菌分析及管理策略   总被引:2,自引:0,他引:2  
目的探讨手术切口感染的病原菌及药物敏感性,制定相应的管理策略,为控制医院感染提供参考。方法回顾性分析某院4335例外科手术患者切口感染情况,收集伤口分泌物进行细菌培养及鉴定,对培养细菌进行药物敏感性分析,并制定相应的手术室管理策略。结果4335例外科手术患者发生切口感染189例次检出致病菌162株,其中G+杆菌占79.0%,其中主要为大肠埃希菌占29.6%、肺炎克雷伯杆菌占22.2%、铜绿假单胞菌占19.8%;G+球菌占15.4%;真菌占5.56%。药敏分析发现G+菌对亚胺培南最为敏感,而对青霉素、庆大霉素、头孢氨苄、克林霉素等的耐药率均超过50%。G+菌对亚胺培南、万古霉素敏感性强,对其他抗生素均有较高的耐药性。结论手术切口感染病原菌多以G-菌为主,并且具有较高的耐药性,必须采取合理的管理策略,预防感染发生。  相似文献   

17.
The prevalence of resistance to antibiotics was examined among 318 Streptococcus pneumoniae strains isolated during 1998 and 1999 in a children's hospital in Athens. The rate of resistance to penicillin was 25.8% (intermediate 22%, resistant 3.8%); 42.5% of the strains were resistant to > or = 1 antibiotic and 20% were multidrug resistant. Resistance to penicillin was lowest in invasive strains (8.3%) and highest in ear isolates (31%). A review of the same microbiology laboratory's records revealed that there has been a gradual increase in penicillin resistance since 1988-1989, when it was 5%. Capsular types were determined for 77 strains resistant to > or = 1 antibiotic, and 69 (90%) of them belonged to the following five serotypes: 19F, 14, 9V, 23F, and 6B. Seventy-five strains were analyzed by pulsed-field gel electrophoresis (PFGE) and 59/75 (79%) shared five electrophoretic types. The largest cluster consisted of 19 serotype 19F strains, of which 18 were nonsusceptible to penicillin and most were multidrug resistant and shared a common and distinct electrophoretic pattern not resembling any known clone. A group of 17 strains that were nonsusceptible to penicillin belonged to serotypes 9V (10), 14 (6), and 19F (1) and shared a common PFGE type similar to the international clone Spain9V-3. Seven serotype 23F strains, of which five were multidrug resistant, belonged to the international clone Spain23F-1. Among the strains susceptible to penicillin but resistant to non-beta-lactam antibiotics, the largest cluster consisted of 13 isolates resistant to erythromycin that belonged to serotype 14 and shared an electrophoretic pattern characteristic of the clone England14-9. Finally, three serotype 6B strains were penicillin susceptible and multidrug resistant and had features similar to the Mediterranean 6B clone. The introduction and spread of several antibiotic-resistant international clones accounts at least in part for the increase in pneumococcal resistance observed in recent years in the Athens metropolitan area.  相似文献   

18.
The aim of this study was to describe the frequency of antimicrobial-resistance and serotypes of nasopharyngeal pneumococcal isolates from adolescents. Clinical data and nasopharyngeal specimens for culture were collected from 1,013 adolescents as a part of a population-based study. A total of 83 isolates of Streptococcus pneumoniae were identified (8.2%). Seventy-four of the 83 isolates were serotyped. The median age of the 83 adolescents colonized by pneumococci was 14 years (mean 14 +/- 2.2 yrs); 55.4% were males. Intermediate resistance to penicillin was detected in 7.2% (6/83). No strain showed high resistance to penicillin. All isolates were susceptible to clindamycin, chloramphenicol, rifampin, and vancomycin; 37.3%, 18.1%, and 4.8% were resistant to trimethoprim-sulfamethoxazole, tetracycline, and erythromycin, respectively. The most frequent serotypes (5-10% of strains each) were 6B, 6A, 23F, and 18C among 28 serotypes/serogroups identified; 18.9% of the strains were nontypeable (NT). Intermediate resistance to penicillin was detected in serotypes 6B, 14, and NT. The rate of resistance to penicillin of nasopharyngeal isolates is low considering data from other studies about invasive strains recovered from children in Brazil. Serotype patterns are similar, except for type 14, which was unusually infrequent.  相似文献   

19.
目的了解目前从中国住院治疗肺炎患儿分离到的肺炎链球菌的血清型分布,及几种蛋白多糖结合疫苗的覆盖率,评估应用蛋白多糖结合疫苗预防肺炎链球菌感染的价值。方法选择2006年2月16日至2007年2月16日在首都医科大学附属北京儿童医院、复旦大学附属儿科医院、广州市儿童医院和深圳市儿童医院呼吸科住院治疗的肺炎患儿为研究对象,采用一次性吸痰管收集全部病例的呼吸道分泌物标本分离肺炎链球菌,部分患儿进行脑脊液、血液和胸腔积液中肺炎链球菌的分离。采用荚膜肿胀实验进行血清型分析。对4家儿童医院肺炎链球菌分离率和血清型进行分析,率的比较采用χ2检验或Fisher精确概率法。结果研究期间共纳入2865例肺炎患儿,2865例呼吸道吸取物标本中分离到肺炎链球菌279株,其中有2株不同血清型菌株分离自同一病例,分离阳性率为9.7%(278/2865)。3/8例胸腔积液中分离到肺炎链球菌,其中2例同时从呼吸道分泌物分离到肺炎链球菌,取其一进行血清分型,另1株从胸腔积液中分离的肺炎链球菌复苏失败,未进行血清分型。脑脊液和血液标本中未分离到肺炎链球菌。共有279株肺炎链球菌进行了血清型分析,以19F型最常见(60.6%,169/279),其次为19A(9.7%,27/279)、23F(9.3%,26/279)和6B(5.4%,15/279),上述4种血清型占全部菌株的84.9%(237/279)。肺炎链球菌7价结合疫苗(PCV7)覆盖率为81.0%,但在北京仅为46.0%,明显低于上海(80.0%)、广州(98.4%)和深圳(94.4%)。9价、10价和11价疫苗的覆盖率与PCV7相比并没有明显增加。13价疫苗的覆盖率(92.8%)较PCV7明显升高。结论4家儿童医院肺炎住院患儿分离的肺炎链球菌以19F、19A、23F和6B型常见。PCV7覆盖率为87%。  相似文献   

20.
The serogroup/serotypes (SGTs) and antimicrobial susceptibilities to 10 antimicrobial agents of 110 clinical strains of Streptococcus pneumoniae were determined. Strains intermediately resistant or highly resistant to penicillin G (80 of 110) belonged predominantly to SGTs 23 (45.0%), 19 (13.7%), 6 (10.0%), 9 (6.2%), and 14 (3.7%). The MICs of all cephalosporins, tetracycline, trimethoprim-sulfamethoxazole, and chloramphenicol increased along with the MICs of penicillin G. However, erythromycin resistance and clindamycin resistance were observed more frequently among the intermediately penicillin-resistant strains. Multiple resistance was observed for 32 strains, of which 25 were highly resistant to penicillin G and belong to SGT 23F. All strains were susceptible to vancomycin.  相似文献   

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