2017-2019年苏州地区儿童肺炎链球菌血清分型及耐药特征

  目的  了解苏州大学附属儿童医院呼吸道感染儿童肺炎链球菌菌株的血清型分布及耐药特征,为制定肺炎链球菌相关疾病的治疗和预防接种策略提供参考。  方法  采用乳胶凝集和荚膜肿胀试验对肺炎链球菌菌株进行血清分型,采用E-test法检测菌株对多种抗生素的耐药性。  结果  2017年1月-2019年7月共收集3 652株肺炎链球菌,主要来自于6月龄~2岁年龄段儿童,男女性别比为1.5:1。常见血清型为19F、6B、23F、19A及6A,13价肺炎球菌结合疫苗(13-valent pneumococcal conjugate vaccine, PCV13)的血清型覆盖率为73.1%(95% CI:71.6%~74.5%)。肺炎链球菌菌株对青霉素的耐药率为1.9%。青霉素不敏感肺炎链球菌(penicillin-non susceptible streptococcus pneumoniae, PNSP)(含中介和耐药菌株)对阿莫西林、红霉素、阿奇霉素等抗菌药物的耐药率高于青霉素敏感肺炎链球菌(penicillin-susceptible streptococcus pneumoniae, PSSP)菌株;PCV13疫苗血清型菌株的耐药率高于非疫苗血清型菌株。  结论  苏州地区儿童肺炎链球菌分离株PCV13疫苗血清型覆盖较高,且青霉素不敏感菌株大多为PCV13疫苗血清型。     

健康6月龄内儿童肺炎链球菌携带状况及耐药特征分析

目的 了解济南地区健康6月龄内儿童鼻咽部肺炎链球菌携带血清型及耐药特征,为肺炎球菌疫苗推广接种提供数据。方法 2019年11月—2020年4月采集济南地区216例健康6月龄内儿童鼻咽拭子,经分离培养获得疑似肺炎链球菌菌株;利用基质辅助激光解吸电离飞行时间质谱和奥普托欣敏感试验鉴定后,采用多重PCR方法明确肺炎链球菌血清型;进一步采用微生物药敏分析仪进行药物敏感性检测。结果 216例健康6月龄内儿童肺炎链球菌携带率为5.1%(11/216),共携带7种血清型：15B、23F、6B、8、18C、19F和13。13价肺炎球菌多糖结合疫苗血清型覆盖率为54.5%,23价肺炎球菌多糖疫苗覆盖率为90.9%。19种抗生素中红霉素和阿奇霉素耐药率为100.0%;耐药率80.0%以上的有四环素、克林霉素、甲氧苄胺嘧啶/磺胺甲噁唑;头孢呋辛和青霉素(口服)的耐药率超过50.0%。万古霉素、利奈唑胺、左氧氟沙星、氯霉素和莫西沙星未发现耐药菌株。11例儿童鼻咽部肺炎链球菌分离株显示多重耐药,耐药种类3～6种。结论 济南地区健康6月龄内儿童鼻咽部定植的肺炎链球菌具有多种血清型,且抗生素耐药现象较严重。     

绍兴地区肺炎链球菌的血清型和耐药性

目的:调查绍兴地区流行肺炎链球菌的血清型和耐药性,对不同来源的菌株进行比较,计算PCV7的覆盖率,为临床用药提供指导。方法:收集105株不同样本来源的肺炎链球菌,使用Pneumotest-latex鉴定血清型,统计耐药性,并研究两者之间关系。结果:105株肺炎链球菌,青霉素不敏感仅1株咽拭子分离菌,红霉素、克林霉素耐药率为99.3%,未检到万古霉素、左氧氟沙星耐药株,复方SMZ、四环素、利福平、氯霉素的耐药率分别为77.9%、86.2%、5.1%、10.6%。主要检出的血清组/型为19和23,占所有菌株的47.6%(49/103),PCV疫苗覆盖率为62.1%。结论:不同样本来源的肺炎链球菌的流行血清型和耐药性差异有统计学意义,眼部分离肺炎链球菌较其他部位分离株耐药程度低,PCV7覆盖率低,需长期监测。     

疫苗引入前苏州地区儿童肺炎链球菌的分子流行病学特征研究

目的 了解苏州地区在7价肺炎链球菌结合疫苗(7 heptavalent pneumococcal conjugate vaccine,PCV7)引入前,不同临床治疗压力下肺炎链球菌分离株的耐药特征、血清分型及国际流行耐药克隆株(pneumococcal molecular epidemiology network,PMEN)的流行情况.方法 收集2006年3月～2007年3月期间苏州大学附属儿童医院住院治疗的呼吸道感染儿童(病例组)和非呼吸道感染儿童(对照组)中分离的肺炎链球菌134株,进行抗生素敏感性分析和血清型分型,并对其中86株大环内酯类药物菌株进行基因分型.结果 病例组抗生素的使用率高于对照组(x2=111.19,P＜0.001).病例组分离的菌株血清型以19F、19A和14为主,对照组菌株常见的血清型为6B、19F和23F,两组PCV7血清型覆盖率分别为58.3％和68.1％.对照组菌株对常用抗生素的敏感性均高于病例组(均有P ＜0.05).菌株基因分型共检测出10种PMEN克隆株,最常见的为Taiwan19F-14克隆株.PMEN克隆株对常用抗菌药物的不敏感率高于非PMEN克隆株.结论 在我国引入PCV7前,在抗生素等治疗压力下,苏州地区肺炎链球菌的耐药情况严重,以Taiwan19F-14克隆株流行为主,多种PMEN克隆株并存.     

肺炎链球菌疫苗在不同年龄组儿童中应用价值分析

目的根据感染患儿来源的肺炎链球菌血清型分布特征,初步评价不同肺炎链球菌疫苗在相对应年龄组儿童中的应用价值。方法参考文献对2014年收集到的182株肺炎链球菌菌株提取DNA,应用多重PCR方法进行分型,分析不同疫苗血清型比例。结果从河北省儿童医院的182株肺炎链球菌菌株中19F和19A型数量最多,分别为68株(占37.36%)和33株(占18.13%),其次较多的型别有6B、35B型、14型、23F型、15B/15C型等。7价、10价、13价肺炎链球菌结合疫苗所含血清型在2岁以下儿童来源菌株中分别占61.33%、61.33%、82.67%。所有2岁以上儿童来源菌株中81.25%属于23价肺炎链球菌多糖疫苗血清型。结论本研究中肺炎链球菌血清型分布存在以19F、19A型为主同时兼有多样性的特点。针对不同年龄组儿童应用结合疫苗或多糖疫苗都将取得一定的免疫效果。     

呼吸道感染住院患儿鼻腔及口咽部位肺炎链球菌定植状况与耐药性分析

目的探索某院住院呼吸道感染儿童鼻腔及口咽部位肺炎链球菌定植状况与耐药性。方法选取2016年12月-2017年12月于医院接受治疗的184例呼吸道感染住院患儿为研究对象,采集患儿鼻咽拭子分离肺炎链球菌。统计呼吸道感染住院患儿不同月份肺炎链球菌的阳性率。采用荚膜肿胀试验对分离菌株进行血清分型,并对13价肺炎链球菌结合疫苗(PCV13)覆盖率进行计算,同时按照PCV13是否覆盖分为PCV13覆盖菌株与非PCV13覆盖菌株,比较菌株对抗菌药物的不敏感性。结果 184例呼吸道感染住院患儿共分离出肺炎链球菌45株,分离率为24.46%(45/184)。呼吸道感染住院患儿主要血清分型包括19F(17/45,37.78%)、6A(11/45,24.45%)、14(7/45,15.56%)、19A(5/45,11.11%)。肺炎链球菌对青霉素(静脉)、头孢曲松、亚胺培南、左氧氟沙星、万古霉素、泰利霉素、利奈唑胺等抗菌药物敏感率较高。PCV13覆盖菌株对口服青霉素、头孢呋辛、亚胺培南等抗菌药物的不敏感率(中介+耐药)高于非PCV13覆盖菌株(P<0.05)。结论住院呼吸道感染患儿鼻腔及口咽部位肺炎链球菌分离率较高,主要血清分型为19F、6A、14和19A,同时PCV13覆盖菌株对青霉素(静脉)、头孢曲松、亚胺培南、左氧氟沙星等抗菌药物的不敏感率高于非PCV13覆盖菌株。     

91株肺炎链球菌的血清型分布及耐药性分析

目的 了解重庆地区肺炎链球菌临床分离株的血清型分布及药物敏感性.方法 采用荚膜肿胀试验进行肺炎链球菌血清学分型,并计算疫苗(PVC7、PVC11、PVC13)覆盖率;肉汤稀释法测定抗菌药物的最低抑菌浓度(MIC).结果 91株肺炎链球菌的临床分离患者年龄呈典型双峰分布,以＜5岁婴幼儿与＞50岁中老年人群为主,占51.7％、27.5％;90株肺炎链球菌共鉴定出20个血清型,1株未能血清分型,常见的肺炎链球菌血清型为19F、19A、6B,PVC13覆盖率为74.4％;91株肺炎链球菌均表现出较高的耐药率,在67株β-内酰胺类抗菌药物不敏感株(BLAs)中,青霉素不敏感菌株(PNSP)占53.8％.结论 重庆地区肺炎链球菌临床分离株以19F、19A、6B血清型为主,PVC13的预防作用更显著;肺炎链球菌耐药性高尤其是大多数菌株呈多药耐药趋势,临床应注意合理选择用药.     

接种13价肺炎球菌结合疫苗对就诊儿童肺炎链球菌血清型和耐药性的影响

  目的  了解就诊儿童肺炎链球菌(Streptococcus pneumoniae, Spn)血清型分布和耐药特征,探索接种13价肺炎球菌结合疫苗(13-valent pneumococcal conjugate vaccine, PCV13)对Spn的影响。  方法  收集2017—2019年苏州大学附属儿童医院疫苗接种信息明确的就诊儿童的Spn菌株,根据疫苗接种情况进行分组,并采用荚膜肿胀法进行血清分型,E-test法检测菌株抗生素的耐药性,比较是否接种PCV13对Spn血清型和耐药性的差别。  结果  共收集692株Spn,其中20株分离自接种PCV13儿童。接种组中常见的血清型为19F、6B、19A、23F,对照组中常见的血清型为19F、6B、23F、19A、14,两组血清型分布差别无统计学意义(P=0.868),PCV13血清型覆盖率分别为70.0% 和72.4%(P=0.491)。所有菌株对红霉素、四环素、克林霉素高度耐药,且多重耐药率达98.5%。接种组和对照组的Spn菌株对青霉素的不敏感率分别为5.0%和9.1%(P=0.804)。  结论  苏州大学附属儿童医院监测就诊儿童Spn血清型以PCV13覆盖的血清型为主,菌株对β-内酰胺类抗生素的耐药性有所下降,但对红霉素等其他常用抗菌药物的耐药性依旧严峻,并存在大量的多重耐药情况。尚未观察到接种PCV13对菌株血清型分布及降低抗生素耐药性的明显效果。     

河北省肺炎链球菌疫苗在不同年龄组儿童中应用价值分析

目的：根据感染患儿来源的肺炎链球菌血清型分布特征,初步评价不同肺炎链球菌疫苗在相对应年龄组儿童中的应用价值。方法：参考文献对2014年收集到的182株肺炎链球菌菌株提取DNA,应用多重PCR方法进行分型,分析不同疫苗血清型比例。结果：所有菌株中19F和19A型数量最多,分别为68株（占37.36%）和33株（占18.13%）,其次较多的型别有6群、35B型、14型、23F型、15B/15C型等。7价、10价、13价肺炎链球菌结合疫苗所含血清型在2岁以下儿童来源菌株中分别占61.33%、61.33%、82.67%。所有2岁以上儿童来源菌株中81.25%属于23价肺炎链球菌多糖疫苗血清型。结论：本研究中肺炎链球菌血清型分布存在以19F、19A型为主同时兼有多样性的特点。针对不同年龄组儿童应用结合疫苗或多糖疫苗都将取得一定的免疫效果。     

肺炎链球菌的耐药性及其血清型分布调查

目的 了解中山市肺炎链球菌的耐药性及其血清型分布情况，比较正常人群肺炎链球携带株与临床分离株的耐药性与血清型分布关系，探讨肺炎链球菌的耐药性和血清型分布特点。方法 肺炎链球菌的培养、分离和鉴定按《全国临床检验操作规程》进行；药敏试验根据美国临床实验室标准委员会(NCCLS)有关抗生素敏感性试验法规进行试验并对结果进行判定；肺炎链球菌分型使用Quellung反应方法。结果 266株肺炎链球菌中耐青霉素肺炎链球菌占26．7％；耐青霉素肺炎链球菌对红霉素、四环素、氯霉素、克林霉素、利福平和复方新诺明的耐药率高达97．1％、100％、56．3％、84．5％、42．5％、78．9％；在所有菌株中排在前9位(占所有血清型的65．9％)的常见血清型是23F(13．2％)、6A(12．4％)、19F、(10．9％)、6B(7．1％)、14(6．4％)、1．5B(5．3％)、NT(5．3％)、19A(3．0％)、22F(2．3％)。而71株对青霉素不敏感的菌株中排在前9位的常见血清型分别为19F、23F、14型、不能分型、6B、22F、、9V、19B和33F。目前推荐使用的23价肺炎球菌多糖疫苗(1，2，3，4，5，6B，7F，8，9N，9V，10A，11A，12F，14，15B，17F，18C，19A，19F，20，22F，23F，33F、)能覆盖所有分离菌株血清型71．9％。结论 在携带者中，肺炎链球菌对青霉素耐药率已处于较高水平，耐青霉素肺炎链球菌同时对其它常用抗生素普遍耐药，且已发现对三代头孢菌素耐药菌株，对红霉素、四环素、氯霉素、克林霉素材复方新诺明耐药已非常严重；建议对小儿和体弱老人使用23价肺炎球菌多糖疫苗预防接种以减少抗生素的使用和降低耐药菌株出现的压力。     

Vaccine-driven serotype-rearrangement is seen with latency in clinical isolates: Comparison of carried and clinical pneumococcal isolates from the same time period in Hungary

Young children – the main asymptomatic carriers of pneumococcus – are often the source of pneumococcal infections. PCV13 replaced PCV7 in 2010 in Hungary and it became a mandatory vaccine in 2014. In this work we surveyed the effect of vaccination in three groups: in healthy children under 7?years; in children of the same age but infected with pneumococcus (P1); in older patients (P2) who were very likely not vaccinated.Nasal swabs were taken from 522 healthy children to screen pneumococcal carriage between March 2015 and May 2016. In the same time period, 146 clinical isolates were collected, mainly from mucosal infections. Serotypes, antibiotic susceptibility and clonality of the isolates was determined and compared.The carriage rate was 39.1%. Regarding carriage, the serotype distribution showed the total disappearance of serotypes 3 and 6A compared to former Hungarian studies. The prevalence of PCV13 serotypes was only 5.8% represented by three serotypes (19F, 19A, 9V). Of note, serotype 19A (a very resistant and invasive type) also decreased significantly. In the patient groups, PCV13 prevalence was higher: 17.5% (P1) and 32.6% (P2). Although serotype 3 was present in P1 (7.9%), the leading serotype was 23B (22.2%), a non-vaccine type (NVT). P2 showed the most diverse serotype distribution, but serotype 3 was predominant here (15.7%). Pneumococcal isolates from the patients were more resistant towards the tested antibiotics compared to those from carriers.PCV13 seems to be highly successful in reducing the prevalence of vaccine serotypes. The serotype-rearrangement can be seen also among clinical isolates, albeit somewhat later in time. Fortunately, the replacing serotypes are less invasive and less resistant, but, most worrisome, serotype 19F can be found again with increased frequency among carriage isolates and mucosal infections. Further surveillance is needed to carefully monitor such successful, antibiotic resistant “refugees”.     

Serotype changes in adult invasive pneumococcal infections in Portugal did not reduce the high fraction of potentially vaccine preventable infections

We determined the serotype and antimicrobial susceptibility of 1100 isolates responsible for adult invasive pneumococcal infections (IPD) in Portugal between 2006 and 2008. Serotypes 3 (13%), 1 (12%), 7F (11%), 19A (10%) and 14 (7%) were the most frequent causes of IPD and the two later serotypes accounted for the majority of erythromycin and penicillin nonsusceptible isolates. Serotype 1 was associated with younger adults whereas serotype 3 was associated with older adults. Despite the availability of the 23-valent polysaccharide vaccine (PPV23) in Portugal since 1996, the proportion of PPV23 preventable IPD remained stable and above 80%. Comparing with previous data from Portugal, we showed a continued decline of the serotypes included in the 7-valent conjugate vaccine (PCV7) in adult IPD and a rise of serotypes included in the 13-valent conjugate vaccine, increasing its potential coverage of adult IPD to 70% in 2008. Penicillin non-susceptibility remained stable (17%) whereas erythromycin resistance (18%) has continued to rise in the post-PCV7 years.     

Immunogenicity for 16 serotypes of a unique schedule of pneumococcal vaccines in a high-risk population

BACKGROUND: A unique schedule of 7-valent pneumococcal conjugate vaccine (7PCV) at 2, 4 and 6 months of age and 23-valent pneumococcal polysaccharide vaccine (23PPV) at 18 months commenced for Australian Aboriginal infants in 2001. METHODS: Anti-capsular IgG concentrations in vaccinated and non-vaccinated (historic control) infants were determined (blinded) by (22F absorbed) ELISA. RESULTS: One month after dose 3 of 7PCV, geometric mean concentrations (GMCs) were >1.95 microg/ml and at least 89% of infants had IgG >0.35 microg/ml to all 7PCV serotypes. One month post-23PPV, IgG to 7PCV serotypes was >0.35 microg/ml for more than 96% infants (>1.3 microg/ml for at least 70%), and IgG to non-7PCV serotypes was >0.35 microg/ml for more than 50% infants (including serotype 6A, but not 12F (17%) or 19A (44%). CONCLUSION: 7PCV and 23PPV are immunogenic in this population.     

Comparison of the immunogenicity and safety of polysaccharide and protein-conjugated pneumococcal vaccines among the elderly aged 80 years or older in Japan: An open-labeled randomized study

An open-labeled randomized study was conducted to compare the immunogenicity and safety of polysaccharide (PPV23) or protein-conjugated pneumococcal vaccine (PCV7) among the elderly aged 80 years or older. A total of 105 nursing home residents were enrolled in this study. We analyzed the geometric mean concentration (GMC) of serotype-specific immunoglobulin G (IgG) and the geometric mean titer (GMT) of the opsonization index (OI) for serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. The GMCs of serotype-specific IgG and the GMTs of the OI significantly increased one month after vaccination in both groups for all seven serotypes evaluated. In the PCV7 group, study subjects with serotypes 4, 9V, 18C, and 23F exhibited statistically significant elevations in both serotype-specific IgGs and OIs compared to those of the PPV23 group. Both vaccines were tolerated without any severe adverse events, and no differences in systemic adverse events were observed between the two groups, although adverse reactions such as redness and localized swelling were more common in the PCV7 group. Our data demonstrated that the GMCs of serotype-specific IgG and the GMTs of the OI were higher in the PCV7 group compared to those in the PPV23 group. Our study also confirmed the safety of both the PCV7 and PPV23 vaccines in elderly people aged 80 years or older.     

Dynamics of Streptococcus pneumoniae nasopharyngeal carriage with high heptavalent pneumococcal conjugate vaccine coverage in Central Greece

In order to study whether the use of the heptavalent pneumococcal conjugate vaccine (PCV7) led to a shift in the Streptococcus pneumoniae serotypes distribution and whether it modified the resistance to antibiotics, 2649 nasopharyngeal samples were obtained between 2005 and 2009, from children attending day-care centers in Central Greece. The percentage of attendees vaccinated with ≥1 dose of PCV7 increased from 12.9% (2005) to 95.5% (2009). Non-PCV7 serotypes replaced those belonging to PCV7. In 2009, 19F was virtually the only PCV7 serotype that continued to circulate. A significant increase in the frequency of penicillin-intermediate (oral penicillin V breakpoints) isolates coincided with a marked reduction in isolates with high resistance to penicillin. Several non-PCV7 serotypes colonized the children, but their frequency varied substantially from year to year. Each one of 14 specific non-PCV7 serotypes, i.e. 6A, 11A, 15B, 23A, 10A, 16F, 38, 22F, 15C, 19A, 35F, 24F, 6C, and 7F, accounted for ≥2% of pneumococcal isolates in at least 2 annual surveillances. An increase in non-PCV7 serotypes with antibiotic resistance, beyond 6A and 19A, occurred. Intermediate resistance to penicillin was observed in serotype 23B, 15B, 15C, 15A, 35F, 6C, and 24F pneumococci. Their exact role in invasive and non-invasive disease remains to be seen in the years ahead.     

Incidence of childhood pneumonia and serotype and sequence-type distribution in Streptococcus pneumoniae isolates in Japan

The 7-valent pneumococcal conjugate vaccine (PCV7) is reported to decrease the incidence of community-acquired pneumonia (CAP) in children. To determine the annual incidence of CAP before the introduction of PCV7, we counted the number of children hospitalized with CAP between 2008 and 2009 in Chiba City, Japan. We investigated serotype and multilocus sequence typing (MLST) for Streptococcus pneumoniae isolates in CAP cases. The annual incidence of hospitalized CAP in children aged <5 years was 17.6 episodes/1000 child-years. In 626 episodes, S. pneumoniae was dominant in 14.7% and 0.8% of sputum and blood samples, respectively. The most common serotypes were 6B, 23F and 19F. The coverage rates of PCV7 were 66.7% and 80% in sputum samples and blood samples, respectively. MLST analysis revealed 37 sequence types. Furthermore, 54.1% of the sputum isolates and 40% of the blood isolate were related to international multidrug-resistant clones.     

Safety and immunogenicity of 15-valent pneumococcal conjugate vaccine in pneumococcal vaccine-naïve adults ≥50 years of age

BackgroundPneumococcal disease remains a public health priority in adults. Safety and immunogenicity of 15-valent pneumococcal conjugate vaccine (PCV15) containing 13 serotypes included in 13-valent pneumococcal conjugate vaccine (PCV13) plus 2 additional serotypes (22F and 33F) was evaluated in adults ≥50 years old (NCT01513551).Methods691 adults received one dose of PCV15, PCV13, or 23-valent pneumococcal polysaccharide vaccine (PPV23) and were followed 14 days for safety. Serotype-specific IgG geometric mean concentrations (GMCs) and opsonophagocytic activity (OPA) geometric mean titers (GMTs) were measured immediately prior and 1-month postvaccination.ResultsSafety profiles were comparable across vaccination groups. PCV15 induced comparable levels of IgG GMCs and OPA GMTs to PCV13 and PPV23 for shared serotypes. Serotype-specific antibodies were numerically higher among recipients of PCV15 than PCV13 and PPV23 for 7 and 12 shared serotypes, respectively; and lower for 4 and 1 serotype(s), respectively. PCV15 induced higher IgG and OPA antibodies than PCV13 or PPV23 for serotypes unique to PCV15 (22F and 33F not in PCV13; 6A not in PPV23).ConclusionsPCV15 displayed an acceptable safety profile and induced IgG and OPA to all 15 serotypes included in the vaccine, at levels comparable to PCV13 and PPV23 for shared serotypes with these vaccines.Study identification: V114-002.CLINICALTRIALS.GOV identifier: NCT01513551.© 2018 Merck & Co., Inc.