B族链球菌不同侵袭性感染类型临床特征及药敏试验的多中心研究

Clinical characteristics and antibiotic susceptibility features of different types of invasive infections caused by group B Streptococcus: a multicenter prospective study

目的分析B族链球菌(group B Streptococcus, GBS)侵袭性早发型GBS感染(early-onset GBS disease, GBS-EOD)和晚发型GBS感染(late-onset GBS disease, GBS-LOD)的临床特征及药敏结果。方法前瞻性纳入2016年1月至2018年6月在由厦门市妇幼保健院等7家三级医院组成的闽西南GBS感染研究协作组住院治疗的96例GBS侵袭性感染患儿,其中,生后<7 d内发病患儿为GBS-EOD组(67例),生后7~89 d发病患儿为GBS-LOD组(29例)。记录GBS-EOD和GBS-LOD患儿的临床资料,对其临床表现、疾病谱、并发症及转归进行比较分析。同时采用纸片法对96株GBS菌株进行药敏试验分析。采用两独立样本t检验、Mann-Whitney U检验、χ2检验或Fisher精确概率法对数据进行统计学分析。结果(1)GBS-EOD组和GBS-LOD组患儿平均发病日龄分别为(15.8±6.7)h(0.5~142.0 h)及(25.0±8.1)d(9~89 d);气促、皮肤苍白、发热、抽搐的发生率分别为68.7%(46/67)与44.8%(13/29)、52.2%(35/67)与17.2%(5/29)、23.9%(16/67)与65.5%(19/29)、7.5%(5/67)与48.3%(14/29),χ2值分别为6.282、10.199、15.146及21.237,GBS-EOD组以气促、皮肤苍白为主,GBS-LOD组以发热、抽搐为主(P值均<0.05)。(2)GBS-EOD组和GBS-LOD组患儿的肺炎、败血症、脑膜炎、败血症+髋关节脓肿、肺炎+败血症、败血症+脑膜炎及肺炎+败血症+脑膜炎的发生率分别为43.3%(29/67)与20.7%(6/29)、9.0%(6/67)与17.2%(5/29)、0.0%(0/67)与3.4%(1/29)、0.0%(0/67)与6.9%(2/29)、31.3%(21/67)与13.8%(4/29)、6.0%(4/67)与31.0%(9/29)、10.4%(7/67)与6.9%(2/29),疾病谱比较差异有统计学意义(Fisher精确概率法,P值均<0.001),其中,GBS-EOD组肺炎的发生率高于GBS-LOD组[85.1%(57/67)与41.4%(12/29),χ2=19.116,P<0.001],但脑膜炎的发生率低于GBS-LOD组[16.4%(11/67)与41.4%(12/29),χ2=6.922,P=0.009]。GBS-EOD组患儿急性呼吸窘迫综合征(acute respiratory distress syndrome, ARDS)、肺出血、休克、新生儿持续肺动脉高压(persistent pulmonary hypertension of the newborn, PPHN)等并发症的发生率高于GBS-LOD组[分别为28.4%(19/67)与6.9%(2/29)、13.4%(9/67)与0.0%(0/29)、11.9%(8/67)与10.3%(3/29)、4.5%(3/67)与0.0%(0/29),χ2=13.683,P<0.001]。(3)96例中,23例(24.0%)脑膜炎患儿作为脑膜炎组,73例(76.0%)肺炎和败血症患儿作为肺炎败血症组。脑膜炎组患儿病死率高于肺炎败血症组[17.4%(4/23)与4.1%(3/73),χ2=4.564,P=0.035],且存活患儿平均住院时间较长[(37.2±12.6)与(14.1±5.3)d,t=7.831,P<0.001]。脑膜炎组患儿存活的19例中,7例发生颅内疾患。(4)GBS-EOD与GBS-LOD患儿病死率比较[7.5%(5/67)与6.9%(2/29),χ2=0.010,P=0.982],差异无统计学意义;总体病死率为7.3%(7/96)。GBS-EOD患儿中,58例(86.6%)24 h内发病,其中5例死亡;9例(13.4%)24 h后发病,无一例死亡。(5)共培养96株GBS均对青霉素、氨苄青霉素、头孢唑林、美罗培南100%敏感,对万古霉素敏感率约为97%,对克林霉素、红霉素的耐药率为79.3%~91.0%。结论GBS-LOD和GBS-EOD的临床特征有明显差异,脑膜炎患儿的预后较差,GBS对红霉素和克林霉素的耐药率较高。

Objective To study the clinical manifestations and antibiotic sensitivity features of early- and late-onset invasive infections caused by group B Streptococcus (GBS). Methods A total of 96 infants with invasive GBS infections were enrolled prospectively from seven tertiary hospitals of GBS Infection Research Cooperative Group in southwest Fujian, such as Xiamen Maternal and Child Care Hospital, etc., from January 2016 to June 2018. According to the onset time of infection after birth, they were divided into early-onset GBS disease (GBS-EOD) group (<7 d, n=67) and the late-onset GBS disease (GBS-LOD) group (7-89 d, n=29). Clinical manifestations, disease spectrum, complications and outcomes of the two groups were compared. Drug sensitivity test was carried out using disk diffusion test. Chi-square or Fisher's exact test, two independent sample t-test or Mann-Whitney U tests were used for statistical analysis. Results (1) The average ages at onset in GBS-EOD and GBS-LOD groups were (15.8±6.7) h (0.5-142.0 h) and (25.0±8.1) d (9-89 d), respectively. The incidence of tachypnea, pallor, fever and convulsion were noted in 68.7%(46/67) vs 44.8%(13/29), 52.2%(35/67) vs 17.2%(5/29), 23.9%(16/67) vs 65.5%(19/29) and 7.5%(5/67) vs 48.3%(14/29) of GBS-EOD and GBS-LOD groups with χ2 values of 6.282, 10.199, 15.146 and 21.237 (all P<0.05). The main clinical manifestations of GBS-EOD were tachypnea and pallor, while most of the patients in the GBS-LOD group developed fever and convulsions.(2) The incidence of pneumonia, sepsis, meningitis, sepsis complicated by septic joints, pneumonia complicated by sepsis, sepsis complicated by meningitis and pneumonia complicated by sepsis and meningitis were noted in 43.3%(29/67) vs 20.7%(6/29), 9.0%(6/67) vs 17.2%(5/29), 0.0%(0/67) vs 3.4%(1/29), 0.0%(0/67) vs 6.9%(2/29), 31.3%(21/67) vs 13.8%(4/29), 6.0%(4/67) vs 31.0%(9/29) and 10.4%(7/67) vs 6.9%(2/29) of GBS-EOD and GBS-LOD groups. There was a statistically significant difference in the disease spectrum between the two groups (Fisher's exact test, all P<0.001). Compared with the GBS-LOD group, the GBS-EOD group had a higher incidence of pneumonia [85.1%(57/67) vs 41.4%(12/29),χ2=19.116, P<0.001] and a lower incidence of meningitis [16.4%(11/67) vs 41.4%(12/29),χ2=6.922, P=0.009]. Complications such as acute respiratory distress syndrome (ARDS), pulmonary hemorrhage, shock and persistent pulmonary hypertension of the newborn (PPHN) occurred much more in the GBS-EOD group than the GBS-LOD group [28.4%(19/67) vs 6.9%(2/29), 13.4%(9/67) vs 0.0%(0/29), 11.9%(8/67) vs 10.3%(3/29), 4.5%(3/67) vs 0.0%(0/29),χ2=13.683, P<0.001].(3) Among the 96 patients, 23 (24.0%) had meningitis and 73 (76.0%) developed pneumonia and sepsis. Meningitis resulted in a higher fatality rate [17.4%(4/23) vs 4.1%(3/73),χ2=4.564, P=0.035] and longer average hospital stay [(37.2±12.6) vs (14.1±5.3) d, t=7.831, P<0.001] than pneumonia and sepsis. Seven out of the 19 meningitis survivors developed intracranial complications.(4) The overall fatality rate in this study was 7.3%(7/96) and no significant difference was found between GBS-EOD and GBS-LOD group [7.5%(5/67) vs 6.9%(2/29),χ2=0.010, P=0.982]. Among the 67 GBS-EOD infants, 58 (86.6%) occurred within 24 h and five of them died, but no death was reported in the other nine cases occurred after 24 h.(5) Totally 96 strains of GBS were isolated with 100% sensitivity to penicillin, ampicillin, cefazolin and meropenem, and 97% to vancomycin. Around 79.3%-91.0% of GBS isolates were resistant to clindamycin and erythromycin. Conclusions Clinial features vary greatly in GBS-LOD and GBS-EOD cases. Infants with meningitis have poor prognosis. The drug resistance rate of GBS to erythromycin and clindamycin are relatively high.