肺炎链球菌耐药性检测及其对大环内酯类抗生素耐药机制的研究

目的了解浙江地区肺炎链球菌临床菌株对临床常用抗生素耐药性以及肺炎链球菌对大环内酯类抗生素耐药机制。方法从浙江省不同地区病人临床标本中分离并鉴定肺炎链球菌138株。采用K-B纸片法和E-test检测上述肺炎链球菌临床菌株对9种抗生素的敏感性。采用PCR检测上述菌株中与大环内酯类抗生素耐药性密切相关的ermB和mefE基因携带情况。分析ermB和mefE基因携带、分布状况与红霉素耐药性关系。结果138株肺炎链球菌临床菌株中,对红霉素耐药率高达93.5%(129/138),对头孢噻肟、头孢呋辛、阿莫西林和左氧氟沙星的耐药率较低(2.9%~4.3%)。上述菌株er-mB基因检测阳性率(91.3%,126/138)明显高于mefE基因(33.3%,46/138)(P0.05),其中27.5%菌株(38/138)同时携带。不携带ermB和mefE基因菌株均对红霉素敏感,仅携带mefE基因菌株对红霉素耐药率(62.5%)明显低于同时携带两种基因菌株耐药率(100%)及仅携带ermB基因菌株耐药率(97.7%)(P0.05)。结论红霉素已不适合作为治疗肺炎链球菌感染性疾病的药物。ermB基因是肺炎链球菌临床菌株携带的红霉素耐药相关优势基因。ermB基因可使肺炎链球菌产生较mefE基因更强的红霉素耐药性。     

Penicillin resistance in Streptococcus pneumoniae in Isparta

OBJECTIVE: The first case reports of infection with penicillin-resistant pneumococci were made in Australia in 1967 and South Africa in 1977. Since this time the increasing emergence of penicillin- resistant strains of Streptococcus pneumoniae have been a serious therapeutic problem. Therefore, the aim of the present study was to determine the penicillin resistance of S. pneumoniae strains isolated in the laboratory. The effect of procaine penicillin treatment against these strains was also investigated. METHODS: Sensitivity testing was done by disc diffusion method using oxacillin discs. Minimal inhibitory concentration (MIC) values were determined in tests with penicillin by the use of E-test (AB Biodisc, Solna, Sweden). Patients were treated with 2 x 800,000 U of i.m. procaine penicillin every 12 h for 10 days. RESULTS: Thirty-seven strains of S. pneumoniae were isolated from the sputa of adult patients who had pneumonia. Moderately resistant (0.12-1.00 microg/mL) and penicillin-sensitive (< or = 0.06 microg/mL) strains were identified in nine (24.3%) and 28 (75.7%) isolates, respectively. There were no high-level penicillin-resistant strains in the study. There was no therapeutic failure. CONCLUSION: These results suggest that procaine penicillin may still be useful in the empirical therapy of pneumococcal pneumonia.     

肺炎患儿肺炎链球菌的分离及耐药性分析

目的 调查肺炎患儿肺炎链球菌的分离及耐药性.方法 通过对415例肺炎患儿痰及咽拭子标本培养,分离SP,予以细菌鉴定和药敏的试验.结果 415例标本中共分离出肺炎链球菌96株（23.13%）,炎链球菌对青霉素的耐药率为41.67%.在检测的β-内酰胺类抗菌药物中,头孢噻肟与头孢曲松较为敏感,分别为66.66%、79.16%.对青霉素敏感和不敏感的肺炎链球菌其对头孢噻肟、头孢曲松、头孢呋辛、红霉素、阿奇霉素及克林霉素的敏感性也各不相同,P〈0.01.结论 肺炎儿童SP分离率高,SP对万古霉素、左氧氟沙星敏感性高,对头孢噻肟、头孢曲松、头孢呋辛及氯霉素比较敏感,对青霉素耐药率比较严重.     

184例儿童感染肺炎链球菌的血清型分布及其耐药性分析

目的分析184例儿童感染肺炎链球菌的血清型分布及其耐药性情况。方法选取2014年1月至2017年12月我院呼吸道感染患儿2828例,进行痰液培养,分析病原菌检出情况,肺炎链球菌分布情况、血清分型以及对抗生素耐药性情况。结果2828例患儿的痰标本共检出674株病原菌(23.83%),其中肺炎链球菌184例,检出率为6.51%。年龄1个月~1岁患儿感染肺炎链球菌发生率为52.17%,明显高于1~3岁、3~6岁患儿的25.54%、22.28%(P<0.05);冬季患儿感染肺炎链球菌发生率为53.26%,明显高于春季、夏季、秋季的19.02%、13.05%、14.67%(P<0.05);184株肺炎链球菌共涉及11个血清型/群,主要分布于19F、19A、14型、9V、23F、6B、8型、7F、7A、其他等,另有11株未能分型。青霉素(脑膜炎)的不敏感率高达83.33%,明显高于青霉素(非脑膜炎)的63.24%(P<0.05);而头孢曲松对感染肺炎链球菌脑膜炎或非脑膜炎患儿的敏感率比较,无统计学意义(P>0.05)。患儿感染肺炎链球菌的青霉素(脑膜炎)、红霉素、四环素、复方新诺明、头孢克罗、克林霉素耐药检出率分别为72.91%、86.96%、89.13%、79.89%、80.43%、77.23%;而万古霉素、氯霉素、左氧氟沙星、氧氟沙星、莫西沙星、头孢曲松敏感率分别为100.00%、95.65%、98.38%、91.85%、92.94%、91.85%。结论儿童感染肺炎链球菌存在明显的年龄、季节、血清分布与耐药性差异,此研究结果对儿童肺炎抗感染治疗经验性抗生素选择有指导意义。     

Serotype distribution and antibiotic susceptibility of invasive and nasopharyngeal isolates of Streptococcus pneumoniae among children in rural Mozambique

Objective To describe and compare serotype distribution and antibiotic susceptibility of invasive and nasopharyngeal isolates of Streptococcus pneumoniae from children in rural Mozambique. Methods From August 2002 to July 2003, we prospectively obtained invasive pneumococcal isolates from children <15 years of age admitted to the paediatric ward of Manhiça District Hospital. During a cross‐sectional study of children <5 years of age with mild illnesses, attending the outpatient department of the hospital in March and April 2003, we collected nasopharyngeal isolates. Serotypes and antibiotic susceptibilities were determined using standardized methods. Results The two most common pneumococcal serotypes among invasive isolates were types 1 (40% of 88 isolates serotyped) and 5 (10%), but these types were rare among nasopharyngeal isolates. Compared with invasive isolates, nasopharyngeal isolates were more likely to be serotypes in the licensed seven‐valent conjugate vaccine (49%vs. 20%, P < 0.01), to have intermediate‐level penicillin resistance (52%vs. 14%, P < 0.01) and to be non‐susceptible to trimethoprim–sulfamethoxazole (61%vs. 45%, P < 0.01). Recent receipt of antibiotics or sulfadoxine/pyrimethamine were associated with carriage of antibiotic non‐susceptible isolates. Conclusions These data indicate that a pneumococcal conjugate vaccine containing serotypes 1 and 5 could substantially reduce pneumococcal invasive disease among young children in rural Mozambique. Carriage surveys can overestimate potential coverage of the seven‐valent pneumococcal conjugate vaccine in settings where serotypes 1 and 5 predominate.     

A comparative clinical study of pneumonia by penicillin-resistant and -sensitive Streptococcus pneumoniae in a community hospital

OBJECTIVE: This study aimed to determine the clinical difference of pneumonia between penicillin-resistant and penicillin-sensitive Streptococcus pneumoniae. METHODOLOGY: Forty-nine cases in 46 patients of pneumococcal pneumonia were studied from December 1992 to May 1997. There were 24 cases (in 22 patients) of penicillin-resistant pneumococci (PRSP) pneumonia which were compared with 25 cases (in 24 patients) with penicillin-sensitive pneumococci (PSSP). RESULTS: Both the mean age and the underlying disease states did not differ between the two groups. However, hospital-acquired pneumonia and previous use of antibiotics were observed in eight (33.3%) and 12 (50.0%) patients in PRSP compared with three (12.0%) and two (8.0%) in PSSP, respectively. The clinical efficacy rate and bacteriological eradication rates were 87.5 and 87.5% in PRSP compared with 87.5 and 87.0% in PSSP, respectively. Minimum inhibitory concentration (MIC) of antibiotics against 30 pneumococcal isolates was examined, and 10 strains ranged from 0.10-0.78 microg/mL and five strains were more than 1.56 microg/mL against penicillin G, while the MIC showed higher resistance to other antibiotics except for the carbapenems. Serotyping of the isolates by antiserum revealed differences in the predominant types PRSP (19F) and PSSP (6A,9V) [corrected]. CONCLUSIONS: We must care for not only community-acquired infection but also nosocomial transmission of PRSP pneumonia. Most patients with infections due to PRSP tended to have a milder illness with a good outcome (no patient died). As such it appears that empiric therapy for pneumococcal pneumonia does not require modification from what is recommended at present. However, in patients with infection due to highly resistant strains, and who are not responding to conventional therapy should have their treatment modified according to subsequent susceptibility testing.     

猪链球菌9型分离株的耐药性及耐药基因分析

目的 了解猪链球菌9型(Streptococcus suis serotype 9,SS9)的耐药性和耐药基因情况。方法 采用药敏纸片扩散法检测15株SS9菌株对9类21种不同抗生素的耐药性,并通过PCR方法检测其大环内酯类及四环素类耐药基因的携带情况。结果 被检菌株对大环内酯类及林可胺类耐药率都为100%,对四环素及链霉素的耐药率都为93.3%,对头孢类、氯霉素类、阿莫西林、糖肽类以及庆大霉素较为敏感。所有菌株均耐7种及以上抗菌药物,最高可耐16种,其中以8重耐药的菌株数量最多。不同地区SS9分离株对抗生素耐药情况不同,健康猪分离株耐药情况较病猪分离株更为严重。100%的菌株具有ermB基因,93.33%的菌株具有tetO基因,表明ermB和tetO分别可能是介导SS9对大环内酯类及四环素产生耐药性的主要原因之一。结论 本研究为猪链球菌9型的预防和临床治疗、耐药性及耐药机制的研究提供了参考依据。     

The impact of penicillin resistance on the outcome of invasive Streptococcus pneumoniae infection in children

Background: Invasive infections caused by Streptococcus pneumoniae with reduced susceptibility to penicillin are increasing in prevalence in Australia. Aims: To determine the impact of reduced susceptibility of S. pneumoniae to penicillin on morbidity, mortality and treatment of invasive infection. Methods: Retrospective case note review of children with invasive S. pneumoniae infection over a 26 month period. Penicillin minimum inhibitory concentrations (MIC) were determined by E test. Primary clinical outcome measures included days to defervescence, duration of hospital stay, complication rates and mortality. The secondary outcome of financial cost was examined. Comparisons between outcomes of patients with infections caused by susceptible and non‐susceptible strains were performed with Student's t test. Pearson χ², Mann‐Whitney U tests and multiple logistic regression. Results: Sixty‐eight episodes of invasive pneumococcal disease were reviewed: 14 isolates (21.1%) had reduced susceptibility or resistance to penicillin (PNSSP, MIC 0.125 mg/L‐1.5 mg/L). Ten patients had meningitis, 21 had pneumonia, 22 had bacteraemia with another focus and 15 had bacteraemia without an obvious focus. PNSSP were more common in patients with meningitis and pneumonia. No patients died. Overall, patients with infections caused by PNSSP had significandy longer hospitalisation and longer time to defervescence. Complication rates were not significantly different between groups. Outcome differences were no longer significant when meningitis patients were excluded from the analysis. The PNSSP group received more expensive intravenous antibiotics and their infections were significandy more costly to treat. Conclusions: Infections widi penicillin non‐susceptible S. pneumoniae are associated with higher morbidity than infections with penicillin susceptible strains, and treatment of diese infections is more expensive, due to higher drug costs and longer hospital stay.     

Streptococcus pneumoniae carriage and penicillin/ ceftriaxone resistance in hospitalised children in Darwin

Background: The prevalence of resistant Streptococcus pneumoniae (SP) is increasing worldwide. Pneumococcal prevalence and susceptibility patterns are not known for children in the Top End of the Northern Territory.
Aims: To determine the prevalence of nasopharyngeal carriage of pneumococci in children hospitalised in Darwin, and the extent of penicillin and ceftriaxone resistance in these isolates.
Methods: Nasopharyngeal swabs were collected on admission from 85 children who had not received antimicrobials for their admission illness. Antimicrobial resistance was determined following selective culture for SP isolates. Minimal inhibitory concentrations (MICs) for penicillin and ceftriaxone were determined using the E-test method.
Results: The overall prevalence of nasopharyngeal SP carriage was 44%. Carriage occurred more often in Aboriginal children from rural areas (56%) than in urban children (24%) (OR 3.94, 95% CI 1.35 - 11.78, p <0.01). Thirty per cent of isolates were penicillin resistant, 35% were ceftriaxone resistant, and 49% were resistant to at least one of these. One isolate showed high-level resistance to both antimicrobials; all other resistant isolates were of intermediate-level resistance. For the same isolate, MICs for ceftriaxone were more often higher than those for penicillin. Five isolates had intermediate resistance to ceftriaxone whilst remaining sensitive to penicillin.
Conclusions: The prevalence of pneumococcal resistance to penicillin and ceftriaxone in hospitalised children in Darwin is much higher than previously reported in Australia. This has implications for future antimicrobial management and highlights the need for regular regional surveillance of SP resistance. The development of conjugate pneumococcal vaccines for children under two years is a priority.     

331株肺炎链球菌的耐药性及基因分型

目的 了解杭州地区肺炎链球菌临床株的耐药性及青霉素耐药株的分子流行病学特征。方法 用Etest法测定菌株对青霉素的最低抑菌浓度(MIC)，用纸片扩散法测定肺炎链球菌对其他8种抗生素的耐药情况。并以盒式聚合酶链反应(PCR)和青霉素结合蛋白(PBP)基因指纹等分子生物学方法分析菌株间的亲缘关系。结果临床分离得到肺炎链球菌331株，Etest法测得55株(16．6％)青霉素高度耐药株(PRSP)，127株(38．4％)青霉素中度耐药株(PISP)。纸片扩散法测得氨苄西林、复方新诺明、红霉素、四环素、利福平、氯霉素的耐药率分别为1．2％、47．7％、90％、84．3％、0．3％及13％。所有菌株对氧氟沙星、万古霉素敏感。保存存活的35株PRSP可分为17种盒式-PCR谱型，PBP2X、PBP2B、PBP1A的指纹各为5种、7种、5种。盒式谱型A、H的菌株其耐药谱、MIC值和PBP基因指纹高度一致。结论杭州地区肺炎链球菌临床株的青霉素耐药率较高，非β-内酰胺类红霉素、四环素、复方新诺明的耐药率亦较高。杭州地区可能有耐药克隆的流行。     

肺炎链球菌对红霉素的耐药性及耐药表型

目的 调查上海地区肺炎链球菌对红霉素，克林霉素的耐药率及红霉素耐药菌的耐药表型。方法 以琼脂稀释法测定345株肺炎链球菌对红霉素，克林霉素的最低抑菌浓度，以双纸片法测定红霉素耐药菌的耐药表型。结果 肺炎链球菌对红霉素及克林霉素及克林霉素的耐药率分别为53.0%（183/345）及49.6%(171/345)。对红霉素耐药菌中，内在型耐药（cMLS)占90.3%(159/176)，诱导型耐药（iMLS)占5.7%(10/176)，M型耐药占4.0%(7/176)。结论 上海地区肺炎链球菌对红霉素的耐药率高，其耐药表型以cMLS为主。     

呼吸道感染肺炎链球菌分离株的耐药性分析

目的研究呼吸道感染患者肺炎链球菌分离株的耐药情况。方法通过细菌培养获得肺炎链球菌，对获得的肺炎链球菌进行药敏实验。结果呼吸道分离肺炎链球菌中青霉素耐药(PRSP)占39．3％，对头孢哌酮／舒巴坦、头孢克洛、头孢呋辛、头孢噻肟、头孢曲松、环丙沙星、左氧氟沙星、红霉素、克林霉素、复方新诺明、万古霉素、利福霉素的耐药率分别为39．3％，13．8％，36．6％，17．2％，35．9％，16．6％，40．0％，36．6％．51．7％，38．6％，60．0％，0和17．2％。结论吉林省肺炎链球菌对青霉素的耐药率已经处于较高水平，耐青霉素菌株对其他抗生素普遍耐药．已经发现对三代头孢菌素耐药菌株，未发现万古霉素耐药菌株。     

国内耐药肺炎链球菌的流行现状

肺炎链球菌可引起细菌性肺炎、中耳炎和脑膜炎等疾病,是当今发达国家和发展中国家共有的一个重要病原.由于抗生素长期的过度使用,许多肺炎链球菌菌株能够同时耐受多种常用的抗生素,使得临床可应用的有效抗生素越来越少.耐药肺炎链球菌正在朝着"超级细菌"方向发展.这种现状值得我们关注并寻求近期和长期的解决方法.本文对国内肺炎链球菌耐...     

Epidemiology and clinical manifestations of children with macrolide‐resistant Mycoplasma pneumoniae pneumonia in Taiwan

Mycoplasma pneumoniae accounts for 10–30% of community‐acquired pneumonia (CAP) in children. This study reveals the epidemiology and clinical manifestations of children with macrolide‐resistant (ML^r) M. pneumoniae pneumonia in Taiwan. Respiratory tract specimens were collected from children hospitalized with CAP for evaluation via PCR followed by DNA sequencing for several point mutations related to the ML^r character. Of the 412 specimens collected during the study period, 60 (15%) were positive for M. pneumoniae, 14 (23%) of which presented point mutation (all A2063G) in 23S rRNA. Clinical symptoms and chest X‐ray findings between the ML^s and ML^r groups were not significantly different. However, the ML^r group had longer mean duration of fever after azithromycin treatment (3.2 days vs. 1.6 days, P = 0.02) and significantly higher percentage of changing antibiotics for suspected ML^r strain (42% vs. 13%, P = 0.04). Although 58% of children in the ML^r group did not receive effective antibiotics, all children were discharged without sequelae. In conclusion, 15% of CAP in children is caused by M. pneumoniae and the macrolide‐resistance rate is 23% in Taiwan. Despite ineffective antibiotics, children with ML^r M. pneumoniae pneumonia recover completely. Pediatr Pulmonol. 2013; 48:904–911. © 2012 Wiley Periodicals, Inc.     

猪2型链球菌安徽分离株的毒力基因、溶血性及耐药性分析

目的 了解猪2型链球菌(S. suis 2)安徽分离株的毒力基因分布特征以及溶血性和耐药性。方法 对19株S. suis 2安徽分离株,采用PCR方法检测cps2J、mrp、epf、sly 4种毒力基因,PA法和micro-ELISA法检测溶血类型和溶血价,K-B法检测对25种抗生素的敏感性。结果 11株毒力基因型为cps2J+/mrp+/epf+/sly+,占总菌株的57.9%,为毒力优势基因型;19株均呈α或β溶血,溶血价为1∶4～1∶128;对利福平、头孢他啶、氟苯尼考、头孢唑啉的敏感率较高,平均为84.2%,对强力霉素、四环素、杆菌肽和磺胺异恶唑的耐药率较高,平均为82.9%,且对该4种抗生素的多重耐药率为63.2%。结论 安徽猪群中流行的S. suis 2毒力基因的分布特征与国内相似,与国外存在一定差异,CPS、MRP、EPF和SLY是重要的毒力因子;S. suis 2的溶血类型与其SLY有关,但sly基因的不完整性并不一定改变S. suis 2的溶血性;S. suis 2安徽分离株的多重耐药性严重,耐药谱与其他地区存在一定差异。     

肺炎克雷伯菌体外耐药监测

目的 探讨肺炎克雷伯菌（KP）的分布、感染特点及其体外对抗生素的耐药情况。方法 采用纸片扩散法K-B法对武汉大学人民医院临床分离的130株KP进行耐药性检测，并用双纸片协同法初筛、确证法检测产超广谱β-内酰胺酶（ESBLs）菌。结果 130株KP主分布于呼吸内科，并以第二季度最多；对氨苄西林的耐药率高达95．31％，对第三代头孢菌素类抗生素的耐药率为41．27％～52．46％；最敏感抗生素为亚胺培南。产ESBLs肺炎克雷伯菌检出率为29．23％。结论 肺炎克雷伯菌对抗生素的耐药性日趋严重，临床实验室应常规检测其是否产ESBLs。     

102株侵袭性肺炎链球菌血清型分布特征及耐药谱分析

目的 了解侵袭性肺炎链球菌菌株血清群/型分布特征和菌株耐药性情况。方法 选用本科室保存的102株侵袭性肺炎链球菌菌株(来自内蒙古、宁夏、四川及辽宁)。合成23种肺炎链球菌血清群/型特异性引物,采用多重PCR方法扩增进行初筛,扩增阳性的用荚膜肿胀方法进行复核验证。并选用24种抗生素进行药物敏感性实验。结果 102株侵袭性肺炎链球菌共分为21个血清群,主要流行血清群/型(株数由高到低)依次为19、6、14、23、35/42、34、3、22A、15、1、18、4、5、7B、8、10A、11A、13、17A、20、33F。含10株以上的是19群、6群、14群。24种抗生素中,莫西沙星、吉米沙星、头孢曲松、多西环素未发现耐药菌株。其余20种抗生素均有耐药菌株出现。耐药率大于90%的抗生素从高到低依次为:阿奇霉素、地红霉素、克拉霉素、红霉素;耐药率小于10%的依次为:万古霉素、青霉素(注射)、利奈唑胺、美罗培南、利福平、左氧氟沙星、阿莫西林/克拉维酸、头孢吡肟。结论 我国侵袭性肺炎链球菌分离株以19群、6群、14群最多见;23价肺炎疫苗覆盖血清群但不包含的血清型(6A、6C、6D、15C、23B、22A、18A、7B、17A)和非疫苗相关的13群、34群、35/42群也占有一定比例。治疗由肺炎链球菌引起的感染首选吉米沙星、莫西沙星、头孢曲松、多西环素等抗生素。     

Trends in mortality and antibiotic resistance among HIV-infected patients with invasive pneumococcal disease

Objectives The aim of the study was to describe trends and risk factors for mortality and changes in antibiotic resistance, serotypes and clones among HIV‐infected patients with invasive pneumococcal disease (IPD). Methods A prospective study of 199 episodes of IPD occurring in a cohort of 4011 HIV‐infected patients was carried out. Predictors of mortality included clinical and microbiological data. The 7‐valent pneumococcal conjugate vaccine (PCV7) for children was introduced in late 2001. Time periods were classified for mortality studies as pre‐ (1986–1996), early (1997–2001) and late (2002–2007) highly active antiretroviral therapy (HAART) era, and for serotype studies as pre‐PCV7 (1986–2001) and PCV7 (2002–2007) era. Results Of 199 IPD episodes, 71 (36%) occurred in HIV‐infected patients with associated comorbidities (mainly liver cirrhosis; 52 of 71), which increased in recent years. The incidence of IPD decreased from the pre‐HAART era to the early HAART era and then remained stable in the late HAART era (24.1, 8.4 and 7.4 episodes per 1000 patient‐years, respectively). Rates of 30‐day mortality have risen over the three periods (8, 19 and 25%, respectively; P=0.017). In multiple logistic regression analysis, predictors of mortality were shock at presentation [odds ratio (OR) 7.01; 95% confidence interval (CI) 2.05–23.87] and associated comorbidities (OR 4.27; 95% CI 1.53–11.92). In the PCV7 era, IPD caused by non‐PCV7 serotypes increased, and resistance to betalactams decreased. The most frequent genotypes were Spain^9V‐ST156, Spain^23F‐ST81, ST88^19F, Sweden¹‐ST304 and Spain^6B‐ST90. Conclusions In the late HAART era, the incidence of IPD has not significantly decreased. Mortality from IPD has risen in association with an increase in comorbidities such as liver cirrhosis. New vaccination strategies are needed to diminish the burden of IPD in the HIV‐infected population.