儿童侵袭性肺炎链球菌感染的血清型和耐药性

 目的 了解某医院住院患儿侵袭性肺炎链球菌感染的临床特征以及菌株的血清型和耐药性,以期指导临床合理用药,寻找防治侵袭性肺炎链球菌感染的有效方法。方法 回顾性分析2014年1月—2018年12月该院明确诊断为侵袭性肺炎链球菌感染患儿的临床资料,肺炎链球菌的药敏结果、血清型,以及疫苗对其血清型覆盖情况。结果 74例侵袭性肺炎链球菌感染患儿主要为幼儿期患儿（55.4%）,感染部位主要以单部位血液为主（44.6%）。74株肺炎链球菌,其中22株分离自脑脊液标本,分为13种血清型,常见的血清型为19F、19A、14和23F。青霉素不敏感肺炎链球菌（PNSP）检出率为56.7%（42株）,未发现对利奈唑胺、万古霉素、莫西沙星和左氧氟沙星耐药的肺炎链球菌。不同血清型菌株的耐药率有明显差异,血清型19F和19A对青霉素、头孢噻肟、头孢吡肟和美罗培南的耐药率高于其他血清型。肺炎链球菌疫苗对肺炎链球菌的覆盖率：PCV7为63.5%,PCV13为97.3%。结论 该医院住院患儿侵袭性肺炎链球菌感染多见于婴幼儿,分离的肺炎链球菌血清型以19F、19A、14、23A为主,PCV13对这些血清型覆盖率高,可通过接种疫苗减少侵袭性肺炎链球菌感染的发生。流行率高的血清型往往表现出更高的耐药性,应根据药敏试验结果合理选用抗菌药物。     

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。     

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.     

马鞍山市肺炎链球菌血清型分布及耐药性分析

目的了解马鞍山地区肺炎链球菌临床分离株的血清型分布及药物敏感性。方法应用奥普脱欣试验及胆汁溶解试验鉴定肺炎链球菌;采用荚膜肿胀试验进行肺炎链球菌血清学分型,计算PPV23价疫苗及PCV7疫苗覆盖率;K-B法测定8种药物的耐药试验。结果 80株肺炎链球菌共鉴定13种血清型,有5株不能定型或群,马鞍山地区相对的优势血清型以19F、19A、23F为主,PPV23价疫苗可覆盖本次测试株的86.42%,PCV7疫苗可覆盖测试株的55.56%血清型;75株测试菌对青霉素等药物耐药率较高,耐受四种以上药物的菌株达60株,占测试菌株的80.00%,所有测试菌对左氧氟沙星和万古霉素全部敏感。结论马鞍山地区肺炎链球菌临床分离株以19F、19A、23F血清型为主,PPV23价疫苗的预防作用更显著;绝大多数肺炎链球菌呈多药耐药趋势,应注意合理用药。     

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。     

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.     

肺炎链球菌毒力基因表达差异性及对大环内酯类耐药性分析

目的探讨临床分离各表型肺炎链球菌毒力基因表达的差异性并分析其对青霉素和大环内酯类抗菌药物的耐药性。方法收集2012年12月-2016年12月不同来源的肺炎链球菌111株,分为侵袭性组和非侵袭性组,采用荚膜肿胀实验进行血清学分型,聚合酶链反应(PCR)和荧光定量PCR检测psaA、ply、lytA、cbpA、nanA毒力基因,最低抑菌浓度(MIC)法检测药物敏感性并用PCR检测相关耐药基因(PBP1A、PBP2B、PBP2X,ermB、mefA)。结果 111株肺炎链球菌共检出24个血清型/群,流行血清型为:19F、19A、14、23F、6A、6B。所有菌株5个毒力基因的携带率基本均接近100%;侵袭性菌株nanA、lytA、psaA、ply 4个毒力基因在转录水平高于非侵袭性菌株,此外19F和6A/B血清型中侵袭性菌株这4个毒力基因转录水平也高于非侵袭性组;nanA、psaA、cbpA和ply在3型中的转录水平高于其他血清型。血液与痰液标本来源的肺炎链球菌毒力基因转录水平有一定差异但无统计学意义,脑脊液来源与血液,痰液比较,转录水平增高;脑膜炎肺炎链球菌青霉素非敏感率为70.00%(7/10),非脑膜炎肺炎链球菌青霉素非敏感率为18.81%(19/101),90.09%(100/111)菌株同时对红霉素和克林霉素耐药,主要携带ermB基因。结论常见5种毒力基因在肺炎链球菌中普遍存在,但不同致病类型、不同血清型和不同来源菌株基因表达水平存在差异,侵袭性3型和脑脊液来源的菌株毒力较强,且该地区肺炎链球菌对青霉素、红霉素和克林霉素耐药率较高,尤其是脑膜炎肺炎链球菌,应引起临床重视。     

儿童上呼吸道感染肺炎链球菌的血清分型及耐药性分析

目的调查上呼吸道感染儿童肺炎链球菌感染情况,并分析其耐药性及血清分型。方法选取2017—2019年在大邑县妇幼保健院就诊的676名上呼吸道感染患儿为研究对象,采集鼻咽拭子,采用全价血清凝集试验和optochin纸片试验鉴定肺炎链球菌,采用浓度梯度法(E-test)进行药敏试验,用棋盘式分型法与血清因子分型法鉴定血清型。结果 676例患儿的肺炎链球菌的感染率为23.08%,其中3岁儿童的携带率最高,高达36.36%,最高出现在4月。156株肺炎链球菌对左氧氟沙星和阿莫西林的敏感率高达100.00%,对红霉素的耐药率高达94.87%。血清分型主要为常见血清型,以肺炎链球菌结合疫苗(PCV7)、PPV13为主,其覆盖率为分别为64.10%、75.64%。结论上呼吸道感染患儿中肺炎链球菌的比例仍然较高,以常见血清型为主,对红霉素存在较高的耐药性。PCV13疫苗的覆盖率高,值得推广使用。     

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。     

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。     

Phenotype,genotype, and serotype distribution of macrolide resistant invasive and non-invasive Streptococcus pneumoniae strains,in Sousse,Tunisia

ObjectiveWe determined the macrolide resistance phenotypes and genotypes in Streptococcus pneumoniae isolates in Sousse and assessed the serotype distribution.MethodsWe included S. pneumoniae strains isolated at our laboratory (2010–2013). The antimicrobial susceptibility was tested according to CA-SFM specifications. Serotyping was performed by agglutination of latex particles, to identify a subset of serotypes included in pneumococcal conjugate vaccines. The presence of macrolide resistance genes (ermB, mefA, mel) was detected by PCR.ResultsA total of 52.8% of 140 S. pneumoniae isolates were macrolide-resistant: MLSB (89.2%) and M (10.8%). The MLSB phenotypes were genotypically confirmed by ermB gene presence. 62% had decreased susceptibility to penicillin. The serotypes were: 14, 1, 23F, and 19A. Serotype coverage by PCV7, PCV10 and PCV13 was 44.2%, 73.6%, and 75.6% respectively.Conclusion50% of S. pneumoniae isolates were macrolide resistant. The MLSB phenotype encoded by the ermB gene was the most frequent. Serotype coverage seems inadequate.     

Pneumococcal serotype distribution and antimicrobial resistance in Chinese children hospitalized for pneumonia

A prospective study was performed to determine serotype distribution and antimicrobial resistance in Streptococcus pneumoniae (S. pneumoniae) from Chinese children <5 years old meeting pneumonia criteria. A total of 3865 children were enrolled and 338 S. pneumoniae isolates were obtained. The most frequent serotypes were 19F (55.6%), 19A (13.9%), 23F (10.1%), 6B (4.7%), and 14 (3.6%). The 7-, 10- and 13-valent conjugate vaccines, respectively, covered 76.3%, 76.9%, and 92.3% of isolates. Out of the isolates, six (1.8%) were penicillin resistant. All except 1 of the isolates were resistant to erythromycin. Serotype 19A showed the highest drug resistance. The use of PCV7 has the potential to prevent a substantial number of pneumococcal infections. However, PCV13 is likely to prevent more episodes of pneumococcal disease in China because of the high rates of 19A.     

一所大型教学医院临床分离肺炎链球菌耐药性分析

目的了解一所大型教学医院临床分离的肺炎链球菌临床分布及耐药情况,为临床合理使用抗菌药物,预防和控制感染提供依据。方法收集中南大学湘雅医院2010年11月-2012年11月临床标本分离的肺炎链球菌192株,均经全自动细菌鉴定仪鉴定。采用K B法检测其对常用14种抗菌药物的敏感性,琼脂稀释法检测青霉素的最低抑菌浓度(MIC)。结果肺炎链球菌主要分离自儿科（36.98%）,标本主要为痰液（64.07%）;患者年龄呈双峰分布,以＜5岁和＞50岁的感染者较多。肺炎链球菌对红霉素、氯霉素、四环素、克林霉素耐药率均＞80%。192株肺炎链球菌青霉素MIC范围为0.015～≥32.0 μg/mL,其中MIC50为2.0 μg/mL,MIC90为16.0 μg/mL。非侵袭性肺炎链球菌耐药性高于侵袭性肺炎链球菌。结论该院肺炎链球菌耐药情况较为严重,在临床上对肺炎链球菌的治疗应重视青霉素耐药菌株的出现。     

Prevalence of antimicrobial resistant Streptococcus pneumoniae serotype 11A isolates in Korea,during 2004–2013, due to the increase of multidrug-resistant clone,CC166

Since the introduction of the pneumococcal conjugate vaccine (PCV7) in Korea in 2003, the proportion of non-vaccine serotypes has increased. Among non-vaccine serotypes, serotype 11A is highly prevalent in Korea. We investigated the prevalence and characteristics of Streptococcus pneumoniae serotype 11A isolates in a Korean tertiary-care hospital, during 2004–2013. A total of 1579 non-duplicate clinical S. pneumoniae isolates, collected from 2004 to 2013, were included in this study. Serotype was determined by the capsular Quellung method, and in vitro susceptibility testing was performed by broth microdilution method. Multilocus sequence typing was performed to determine the genotypes of the S. pneumoniae isolates. We identified 90 serotype 11A isolates (5.7%). During this period, the proportion of serotype 11A has increased from 3.2% up to 13.2% (in 2012). Among the serotype 11A isolates, two main clonal complexes (CCs), CC166 and CC99, were identified. The increase of serotype 11A was mainly due to the increase of CC166 isolates, which have high antimicrobial resistance rates. In addition, we identified that 14 isolates, belonging to ST8279, ST9875, and ST3598 of CC166, were non-susceptible to all antimicrobial agents tested in this study. We identified the increase of S. pneumoniae serotype 11A in Korea, which mainly due to the expansion of a resistant clonal group, CC166.     

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.     

Nationwide surveillance of paediatric invasive and non-invasive pneumococcal disease in Japan after the introduction of the 13-valent conjugated vaccine, 2015–2017

Streptococcus pneumoniae is still one of the major causes of morbidity and mortality worldwide. In Japan, pneumococcal conjugate vaccine (PCV)7 and PCV13 were licensed in 2010 and 2013, respectively. We conducted a nationwide paediatric invasive pneumococcal disease (IPD) and non-IPD surveillance study in Japan between 2015 and 2017. We collected 498 IPD isolates and 231 non-IPD isolates from a total of 187 medical institutions in Japan. We performed serotyping, antimicrobial susceptibility testing and multi-locus sequencing typing (MLST) for the collected isolates. Among the 498 IPD isolates, the most prevalent serotype was 24F, followed by 12F, 15A and 15B/C. However, 12F increased and 24F significantly decreased during the study period (p < 0.001), resulting in 12F becoming the most prevalent serotype in 2017. Among the IPD isolates, the PCV7 and PCV13 coverage rates were 0.8% and 9.2%, respectively. The most prevalent serotype among the non-IPD isolates was 15A, followed by 35B, 15B/C and 19A. The overall resistance rates to penicillin (PG), cefotaxime (CTX), meropenem (MEM), erythromycin (EM) and levofloxacin (LFX) were 40.5%, 12.2%, 19.4%, 91.8% and 0.5%, respectively. PG, CTX and MEM resistance rates were significantly higher in non-IPD isolates than in IPD isolates (p < 0.001). Serotype 15A-CC63 and serotype 35B-CC558 tended to be multi-drug resistant. In conclusion, the PCV13 coverage rate was significantly lower than that in a previous surveillance study in Japan between 2012 and 2014, and IPD cases attributable to serotype 19A also decreased. We should note the rapid increase in the prevalence of serotype 12F in IPD cases and the spread of the multi-drug resistant serotype 15A-CC63 and 35B-CC558 lineages.     

Invasive Streptococcus pneumoniae in children, Malawi, 2004-2006

Of 176 invasive Streptococcus pneumoniae isolates from children in Malawi, common serotypes were 1 (23%), 6A/B (18%), 14 (6%), and 23F (6%). Coverage with the 7-valent pneumococcal conjugate vaccine (PCV) was 39%; PCV10 and PCV13 increased coverage to 66% and 88%, respectively. We found chloramphenicol resistance in 27% of isolates and penicillin nonsusceptibility in 10% (by using meningitis breakpoints); all were ceftriaxone susceptible.     

Emergence of antimicrobial-resistant serotype 19A Streptococcus pneumoniae--Massachusetts, 2001-2006

Streptococcus pneumoniae (pneumococcus) is a leading cause of otitis, sinusitis, pneumonia, and meningitis worldwide. Treatment of the most serious type of pneumococcal infection, invasive pneumococcal disease (IPD), is complicated by antimicrobial resistance. Widespread introduction in 2000 of heptavalent pneumococcal conjugate vaccine (PCV7) against serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F resulted in a decline in antimicrobial-nonsusceptible IPD in the United States, including in Massachusetts. However, development of antimicrobial resistance in serotypes not covered by PCV7 is a growing concern. In Massachusetts during 2001-2006, IPD surveillance identified an increased number of cases in children caused by pneumococcal serotypes (most notably 19A) not covered by PCV7 and an associated increase in antimicrobial resistance among these isolates. This report examines these trends and clinical characteristics of Massachusetts patients with antimicrobial-nonsusceptible, non-PCV7-type IPD. The findings indicated that, despite increases in incidence of antimicrobial-nonsusceptible IPD, overall rates of IPD remained stable during 2001-2006. In addition, persons with IPD caused by antimicrobial-nonsusceptible S. pneumoniae had clinical outcomes comparable to persons with IPD caused by antimicrobial-susceptible serotypes. Although PCV7 is effective in preventing IPD, these results confirm that antimicrobial resistance among serotypes not covered by PCV7 remains a concern.