[A multicentric clinical study on clinical characteristics and drug sensitivity of children with pneumococcal meningitis in China].

Objective: To understand clinical characteristics of children with pneumococcal meningitis (PM) in China and to analyze the drug sensitivity of Streptococcus pneumoniae isolates and associated impacts on death and sequelae. Methods: The clinical data, follow-up results and antimicrobial sensitivity of isolated strains of 155 children (including 98 males and 57 females, age ranged from 2 months to 15 years) with PM in 10 tertiary-grade A class hospitals of Infectious Diseases Surveillance of Pediatrics (ISPED) from 2013 to 2017 were collected and analyzed retrospectively. Patients were divided into different groups according to the following standards: ≤1 year old group,>1-3 years old group and >3 years old group according to age; death group and non-death group according to the death within 30 days after PM diagnosis; complication group and non-complication group according to the abnormal cranial imaging diagnosis; sequelae group and no-sequelae group according to the follow-up results. Bonfereoni chi-square segmentation and Kruskal-Wallis H test were used for statistical analysis. Results: There were 64 cases (41.3%) in the ≤1 year old group, 39 cases in the >1-3 years old group (25.2%), and 52 cases (33.5%) in the >3 years old group. The most common clinical manifestation was fever (151 cases, 97.4%). The mortality was 16.8% (26/155) during hospitalization. The neurological complication rate was 49.7% (77/155) during hospitalization, including the most common complication, subdural effusion and (or) empyema in 50 cases (32.3%) and hearing impairment in 6 cases. During follow-up after discharge, no death was found and focal neurological deficits were found in 47 cases (30.3%), including the frequent neurological sequelae: cognitive and mental retardation of different degree in 22 cases and hearing impairment in 14 cases (9.0%). The rate of cure and improvement on discharge was 74.8% (116/155) and the lost to follow-up rate was 8.4% (13/155). The proportions of died cases, neurological complications during hospitalization and proportions of peripheral white blood cell count <12 × 10(9)/L before admission in ≤1 year old group were significantly higher than those in >3 years old group (25.0% (16/64) vs. 5.8% (3/52), 75.0% (48/64) vs. 25.0% (13/52), 48.4% (31/64) vs. 15.4% (8/52), χ(2)=7.747, 28.767, 14.044; P=0.005, 0.000, 0.000). The proportions of headache, vomiting, neck resistance and high risk factors of purulent meningitis in >3 years old group were significantly higher than those in ≤ 1 year old group (67.3%(35/52) vs. 1.6%(1/64), 80.8% (42/52) vs. 48.4% (31/64), 69.2% (36/52) vs. 37.5% (24/64), 55.8% (29/52) vs. 14.1%(9/64), χ(2)=57.940, 12.856, 11.568, 22.656; P=0.000, 0.000, 0.001, 0.000). Streptococcus pneumoniae isolates were completely sensitive to vancomycin (100.0%, 152/152), linezolid (100.0%, 126/126), moxifloxacin (100.0%, 93/93) and ofloxacin (100.0%,41/41); highly sensitive to levofloxacin (99.3%, 142/143) and ertapenem (84.6%, 66/78); moderately sensitive to ceftriaxone (48.4%, 45/93), cefotaxime (40.0%, 44/110) and meropenem (38.0%, 38/100); less sensitive to penicillin (19.6%, 27/138) and erythromycin (4.2%, 5/120). The proportions of non-sensitive strains of penicillin (21/21) and meropenem (17/18) in the death group were significantly higher than those (90/117, 45/82) in the survived group(χ(2)=4.648 and 9.808, P=0.031 and 0.002). Conclusions: The children's PM is mainly found in infants under 3 years old in China. Death and neurological complications are more common in PM children under 1 year old. The clinical manifestations and peripheral blood inflammatory markers of PM patients under 1 year old are not typical. Fever is the most common clinical manifestation and subdural effusion and (or) empyema is the most common complication. Long-term hearing impairment is common in PM and the follow-up time must be prolonged. The dead PM cases had high in sensitive rates to penicillin and meropenem.目的：了解中国儿童肺炎链球菌脑膜炎（PM）的临床特征、分离菌株的药物敏感性并分析常用抗菌药物敏感情况及其对死亡、后遗症的影响。 方法：回顾性分析2013至2017年中国儿童感染性疾病病原学及细菌耐药监测协作组10家三级甲等儿童医院住院PM患儿155例的临床资料、随访结果及分离菌株药物敏感性。155例患儿中男98例，女57例，年龄范围为2月龄~15岁，按年龄分为≤1岁、>1~3岁和>3岁组；根据PM诊断明确后30 d内死亡、住院期间头颅影像学异常结果以及随访情况分别进行分组。组间比较采用Bonfereoni χ(2)分割及Kruskal-Wallis H检验。 结果：155例PM患儿中≤1岁组64例（41.3%），>1~3岁组39例（25.2%），>3岁组52例（33.5%）。临床表现以发热最常见（151例，97.4%）；住院期间死亡26例（16.8%）；神经系统并发症77例（49.7%），其中以硬膜下积液和（或）积脓最常见（50例，32.3%），听力损害6例；出院后随访未发现死亡，其中47例（30.3%）患儿有局灶性神经功能缺陷，以不同程度认知、精神发育迟缓最常见（22例），听力损害14例。治愈和好转出院率为74.8%（116/155），失访8.4%（13/155）。≤1岁组PM患儿死亡、住院期间神经系统并发症及入院前外周血白细胞计数<12×10(9)/L的比例均明显高于>3岁组[25.0%（16/64）比5.8%（3/52），75.0%（48/64）比25.0%（13/52），48.4%（31/64）比15.4%（8/52），χ(2)=7.747、28.767、14.044，P=0.005、0.000、0.000]；>3岁组患儿头痛、呕吐、颈抵抗及化脓性脑膜炎高危因素的比例均高于≤1岁组[67.3%（35/52）比1.6%（1/64）、80.8%（42/52）比48.4%（31/64）、69.2%（36/52）比37.5%（24/64）、55.8%（29/52）比14.1%（9/64），χ(2)=57.940、12.856、11.568、22.656，P=0.000、0.000、0.001、0.000]。肺炎链球菌对万古霉素（100.0%，152/152）、利奈唑胺（100.0%，126/126）、莫西沙星（100.0%，93/93）及氧氟沙星（100.0%，41/41）完全敏感；对左氧氟沙星（99.3%，142/143）、厄他培南（84.6%，66/78）敏感率高；对头孢曲松（48.4%，45/93）、头孢噻肟（40.0%，44/110）及美罗培南（38.0%，38/100）中等敏感；对青霉素（19.6%，27/138）、红霉素（4.2%，5/120）敏感率低。死亡组患儿青霉素、美罗培南非敏感菌株的比例明显高于非死亡组（21/21比90/117、17/18比45/82，χ(2)=4.648、P=0.031，χ(2)=9.808、P=0.002）。 结论：中国儿童PM主要见于3岁以下，PM出现死亡、神经系统并发症多见于≤1岁患儿，≤1岁PM患儿的临床表现及外周血炎症指标不典型。发热与硬膜下积液和（或）积脓分别是最常见的临床表现与并发症。PM存在远期听力损害，必须延长随访时间。PM死亡患儿青霉素和美罗培南非敏感率高。.