目的 分析鼻咽拭子细菌培养在儿童呼吸道感染病原诊断中的价值.方法 同时采集403例类百日咳综合征或肺炎住院患儿鼻咽拭子和口腔吸取物,以分区划种半定量法接种培养后进行菌种鉴定,"+++"及以上考虑有临床意义.对比2种类型样本培养结果及其与患儿临床表现和疾病转归的吻合程度.结果 403例患儿中,鼻咽拭子培养阳性率为31.5％(127/403),居前4位的病原分别为百日咳鲍德特菌(13.4％)、流感嗜血杆菌(7.9％)、卡他莫拉菌(4.0％)和肺炎链球菌(3.5％).口腔吸取物培养阳性率为12.4％(50/403),百日咳鲍德特菌、流感嗜血杆菌、卡他莫拉菌和肺炎链球菌的分离率分别为0.7％、4.5％、1.0％和1.2％.鼻咽拭子样本4种病原总阳性率均显著高于口腔吸取物样本(P<0.05).62.0％(31/50)的患儿鼻咽拭子样本病原培养结果与口腔吸取物样本培养结果一致.经鼻咽拭子样本确定的病原中,有98.4％(125/127)经抗菌药物治疗后细菌培养阴转,患儿临床症状有所改善.结论 鼻咽拭子样本细菌培养有助于提高儿童呼吸道病原菌的检出率,对临床病原判断有一定参考价值.

Objective:To investigate the distribution of pathogen species isolated from cerebrospinal fluid culture (CSF) in children and analyze the antibiotic-resistance of the main isolates in vitro, which provides reference for interpreting the pathogens and choosing antibiotics in empiric therapy for pediatric patients. Methods:The results of cerebrospinal fluid culture were collected by checking laboratory information system of the Children′s Hospital of Zhejiang University and the clinical characteristics of these children were analyzed retrospectively by checking electronic medical record system.Results:A total of 1 312 isolates were detected, including 1 294 isolates of bacteria and 18 isolates of fungi. A total of 497 (37.9%) isolates were pathogenic microorganisms, of which 288 (57.9%) isolates were gram-positive, 200 (40.3%) isolates were gram-negative, and 9 (1.8%) isolates were fungi. The top 5 pathogens were Escherichia coli (102 isolates, 20.5%), Streptococcus pneumoniae (64 isolates, 12.9%), Streptococcus agalactiae (52 isolates, 10.5%), Enterococcus faecium (33 isolates, 6.6%) and Staphylococcus aureus (28 isolates, 5.6%). Most of the Streptococcus pneumoniae strains were isolated from children more than 1 year old (76.6%, 49/64), while the other top 4 bacteria were mainly isolated from infants less than 1 year old, with the rate of 95.1%(97/102) for Escherichia coli, 98.1%(51/52) for Streptococcus agalactiae, 81.8%(27/33) for Enterococcus faecium and 71.4% (20/28) for Staphylococcus aureus. A total of 815 (62.1%) isolates were considered to be contaminated pathogens according to the analysis on clinical manifestations and other laboratory findings in CSF, and coagulase-negative Staphylococcus (680 isolates), Micrococcus (50 isolates), Corynebacterium (28 isolates) and Enterococcus faecium (23 isolates), which accounted for 41.1% (23/56) of the total detected Enterococcus faecium, were the top 4 contaminated bacteria. During the study period, the isolation rate of the pathogenic microorganisms increased year by year (χ2=34.84, P<0.001), while the isolation rate of the contaminated pathogens, which detected mainly in summer and autumn, decreased year by year (χ2=13.26, P<0.001). Conclusions:The predominant bacteria causing pediatric purulent meningitis were Escherichia coli, Streptococcus pneumoniae, Streptococcus agalactiae, Enterococcus faecium and Staphylococcus aureus. Coagulase-negative Staphylococcus, Micrococcus, Corynebacterium and Enterococcus faecium were common contaminated bacteria in CSF culture, therefore clinicians should interpret the results of CSF culture cautiously according to the bacterial species and clinical manifestations.

Background: Salmonella is a common pathogen for gastroenteritis, but it rarely causes intracranial infection in China. To improve the understanding of pediatric Salmonella meningitis, we report three cases of Salmonella meningitis in Chinese children. Case presentation: The patients were aged from 1 day to 14 months. Fever was the first symptom in two patients, while loose stool with a little mucus occurred in one patient during the course of disease. Peripheral white blood cell count, neutrophils count, and C-reactive protein were 20.08 - 25.2 *10 9 /L, 15.4 - 19.7 *10 9 /L, and 1.6 - >160 mg/L, respectively. CSF analysis showed that white blood cell count, glucose, and protein were 70 - 1473 *10 6 /L, 0.18 - 3.19 mmol/L, and 598.1 - 6639.0 mg/L, respectively. Three isolates of Salmonella were detected in cerebrospinal fluid cultures, including Salmonella newport, Salmonella paratyphi, and Salmonella typhimurium (one case per each). All strains were sensitive to ceftriaxone, ceftazidime, cefoperazone / sulbactam, meropenem, and imipenem, while one strain was resistant to ampicillin. The blood cultures were all negative. All patients were treated with carbapenems after failed therapies of cefotaxime or ceftriaxone, for a total duration of 3 - 5 weeks. One patient died, and subdural effusion occurred in one of the two survivors. Conclusions: Salmonella meningitis was rare, but the clinical conditions were serious. Carbapenems might be the first choice for treating Salmonella meningitis.

OBJECTIVE:The purpose of the current study is to investigate the bactericidal effect of macrolides and β-lactams on Bordetella pertussis (B. pertussis) in the nasopharynx and provide guidance for treating macrolides-resistant B. pertussis infections. METHODS:Patients with whooping cough was diagnosed by culture of nasopharynx swabs between January 2016 to December 2018. B. pertussis was identified using specific antisera against pertussis and parapertussis. Drug susceptibility test was carried out using the E-test method. The clearance of B. pertussis in nasopharynx at 7 and 14 days into and posttreatment with macrolides, and β-lactams was compared. RESULTS:A total of 125 B. pertussis samples were collected from patients who received single antibiotic treatment. Among those isolates, 62.4% (78/125) had high resistance with minimum inhibitory concentrations greater than 256 mg/L for erythromycin and azithromycin. The MIC90 of piperacillin, cefoperazone-sulbactam, meropenem, ampicillin, ceftriaxone, ceftazidime and trimethoprim-sulfamethoxazole for these isolates was <0.016, 0.094, 0.094, 0.19, 0.19, 0.25 and 0.75 mg/L, respectively. The clearance rate with β-lactams treatment (68.8%, 44/64) was significantly higher than that with macrolides treatment at 14 days posttreatment (50.8%, 31/61) (χ2 = 4.18, P = 0.04). Macrolides had a better clearance rate at 7 days posttreatment than β-lactams (χ2 = 4.49, P = 0.03) for macrolides-sensitive isolates and a worse clearance rate for macrolides-resistant isolates. CONCLUSION:B. pertussis isolates had a high-resistant rate for macrolides in our study. Macrolides are the first choice for treating pertussis caused by macrolides-sensitive strains, and some β-lactams such as piperacillin should be considered as alternative antibiotics for treatment of macrolides-resistant B. pertussis infection.

Background: Salmonella is a common pathogen for gastroenteritis, but it rarely causes intracranial infection in China. To improve the understanding of pediatric Salmonella meningitis, we report three cases of Salmonella meningitis in Chinese children. Case presentation: The patients were aged from 1 day to 14 months. Fever was the first symptom in two patients, while loose stool with a little mucus occurred in one patient during the course of disease. Peripheral white blood cell count, neutrophils count, and C-reactive protein were 20.08 - 25.2 *10 9 /L, 15.4 - 19.7 *10 9 /L, and 1.6 - >160 mg/L, respectively. CSF analysis showed that white blood cell count, glucose, and protein were 70 - 1473 *10 6 /L, 0.18 - 3.19 mmol/L, and 598.1 - 6639.0 mg/L, respectively. Three isolates of Salmonella were detected in cerebrospinal fluid cultures, including Salmonella newport, Salmonella paratyphi, and Salmonella typhimurium (one case per each). All strains were sensitive to ceftriaxone, ceftazidime, cefoperazone / sulbactam, meropenem, and imipenem, while one strain was resistant to ampicillin. The blood cultures were all negative. All patients were treated with carbapenems after failed therapies of cefotaxime or ceftriaxone, for a total duration of 3 - 5 weeks. One patient died, and subdural effusion occurred in one of the two survivors. Conclusions: Salmonella meningitis was rare, but the clinical conditions were serious. Carbapenems might be the first choice for treating Salmonella meningitis.

目的 了解儿童单核细胞增生性李斯特菌(LM)感染的临床特点,为本病的经验诊治提供参考.方法 通过检索电子病历系统,回顾性分析2010年1月至2018年12月我院无菌来源标本培养结果为LM的患儿临床特点.结果 确诊为LM侵袭性感染患儿22例,男11例.年龄范围为2h～14y8m,中位数为3d,新生儿占68.2％.血培养阳性16例,脑脊液培养阳性11例,其中5例血液脑脊液培养同时分离到LM.16例诊断为化脓性脑膜炎,其中9例出现颅内并发症(颅内出血4例、硬膜下积液4例、脑积水3例、脑室管膜炎1例).临床表现新生儿主要为气促发绀、发热、状态反应差、末梢循环差、呻吟及黄疸等;非新生儿以发热、呕吐、精神状态改变、头痛、抽搐及颈强直常见.脑脊液检查白细胞数、蛋白、乳酸脱氢酶升高14例,糖降低12例,氯化物降低11例.药敏试验显示,LM对氨苄西林、万古霉素和利奈唑胺敏感率为100％.本组资料治愈好转率77.3％,病死率18.2％.结论 儿童LM感染以新生儿多见,化脓性脑膜炎发生率高,并发症多,死亡率高,氨苄西林可作为首选用药,而美罗培南联合万古霉素作为替代用药也值得考虑.

目的:了解儿童副百日咳鲍特菌感染的临床特点和药物敏感性，为经验治疗提供参考。方法:纳入2017年1月1日至2018年12月31日浙江大学医学院附属儿童医院收治的5例副百日咳鲍特菌感染患儿，均经鼻咽拭子培养确诊。收集患儿临床资料，菌株鉴定采用副百日咳血清凝集试验，并经质谱分析验证。药物敏感试验采用E-test法，检测副百日咳鲍特菌株对11种抗菌药物的最低抑菌浓度(minimal inhibit concentration，MIC)范围。结果:5例确诊患儿中，男2例，年龄范围为4月龄至5岁4月龄，3例患儿的家庭中有出现较剧烈咳嗽的成员。患儿就诊时咳嗽持续7～90 d，所有患儿均无发热，均为阵发性痉挛性咳嗽，夜间加重，2例伴有咳嗽末鸡鸣样回声。1例患儿采样前口服过阿奇霉素。5株菌株对红霉素、阿奇霉素、克林霉素、甲氧苄啶-磺胺甲基异 唑、氨苄西林、氨苄西林舒巴坦、头孢呋辛、头孢曲松、头孢哌酮舒巴坦、哌拉西林和美罗培南的MIC范围分别为0.250～6.000 μg/mL、0.125～0.500 μg/mL、128～>256 μg/mL、0.047～0.190 μg/mL、2～>256 μg/mL、3～>256 μg/mL、>256 μg/mL、3～>256 μg/mL、0.500～2.000 μg/mL、0.023～0.250 μg/mL和0.016～0.064 μg/mL。经阿奇霉素、红霉素或克拉霉素治疗好转4例，1例合并肺炎链球菌感染，经甲氧苄啶-磺胺甲基异 唑治疗后好转。 结论:儿童副百日咳鲍特菌对大环内酯类抗菌药物和甲氧苄啶-磺胺甲基异 唑较敏感，可作为该菌感染的经验用药。

目的 了解化脓性链球菌(Streptococcus pyogenes,sP)在儿童中的致病谱及其耐药特点.方法 回顾性分析我院2013-2017年细菌培养为SP的患儿的临床特点.结果 分离到SP的患儿514例,其中6例同时在咽拭子和阴道分泌物中培养出SP.407株(79.2％)来自阴道分泌物,91株(17.7％)来自呼吸道标本,无菌标本10株(1.9％),其他标本12株(2.3％).患儿年龄(7.02±2.26)岁.侵袭性感染10例.所有菌株对青霉素、头孢曲松和万古霉素敏感,青霉素MIC50和MIC90分别为0.023和0.048μg/mL;98.4％的菌株对左氧氟沙星敏感,对红霉素、克林霉素耐药率分别为94.6％和93％.2例化脓性脑膜炎患儿发生脑梗塞、脑瘫后遗症.结论 SP主要引起儿童呼吸道和外阴阴道感染,青霉素和头孢曲松可作为该菌感染的首选用药,局部使用左氧氟沙星可作为SP外阴阴道炎的基础治疗.

目的:探讨小儿急性白血病使用不同剂量甲氨蝶呤(MTX)的毒副反应,指导制定个体化治疗方案.方法:收集因患有急性白血病住院治疗的患儿237例,根据使用甲氨蝶呤的不同剂量分为2组.低危组:甲氨蝶呤的给药剂量为3 g·m-2,共153例.高危组:甲氨蝶呤的给药剂量为5 g·m-2,共84例.首次使用甲氨蝶呤36 h后使用四氢叶酸钙(CF)解救,监测24 h、48 h血药浓度,48 h后若＞1 μmol·L-1,则加大剂量继续解救,直至达到安全浓度(＜0.1 mmol·L-1);若48 h后＜1μmol·L-1,则继续常规解救.对比分析2组24 h、48 h血药浓度;毒副反应的发生率.结果:2组患儿在24 h后血药浓度有差异,高危组明显高于低危组,差异具有统计学意义(P＜0.05).2组患儿在48 h后血药浓度的差异不具有统计学意义(P＞0.05).甲氨蝶呤化疗的毒副反应主要表现为消化道反应、肝肾功能损害等.2组的各毒副反应发生率不存在差异(P＞0.05).结论:大剂量的甲氨蝶呤治疗小儿急性白血病24 h、48 h后血药浓度达到较高水平,经四氢叶酸钙解救后均有不同程度地下降,给药剂量大可降低解救的效果.治疗过程中会出现各类毒副反应,给药剂量较大更易导致消化道反应毒副反应的出现.