金黄色葡萄球菌母婴传播风险的前瞻性队列研究
发布时间：2018-07-28 15:50
【摘要】：目的探讨孕妇(阴道)及其新生儿(口腔、眼周、耳内及脐周)金黄色葡萄球菌(Staphylococcus aureus,以下简称SA)的携带率,探究SA的药物敏感性和分子学特征,研究母婴SA的同源性并预测母婴传播的风险,为有效的防控措施提供科学依据。方法本研究采用前瞻性队列研究和分子流行病学相结合的方法,方便抽样入院待产的孕妇为研究对象并进行随访。根据孕妇的阴道分泌物结果把孕妇分为暴露组(阴道分泌物分离鉴定出SA阳性)和非暴露组(阴道分泌物分离鉴定出SA阴性),观察结局为其新生儿出生时是否携带SA。比较两组中新生儿SA的携带率和计算相对危险比(relative risk,RR);SA的药物敏感性分析使用Kirby-Bauer test纸片扩散法,耐甲氧西林金黄色葡萄球菌(methicillin-resistant Staphylococcus aureus,MRSA)菌株的进一步鉴定使用纸片扩散法和mecA基因扩增法;用t检验、χ2检验或Fisher确切概率法比较不同组别人群情况的差异、探究新生儿携带SA和MRSA的危险因素和菌株药敏性的差别,单因素分析P0.05的影响因素纳入广义线性模型进行多因素分析;Kappa检验分析母婴SA的表型和毒素基因特征的一致性;应用PCR技术检测毒素基因(PVL、TST、ETA和ETB),MRSA菌株进一步SCCmec分子分型;使用多位点测序分型(multilocus sequencing typing,MLST)探究本地流行的SA类型并确定母婴SA的同源性。结果基本情况:本研究共纳入了1834名待产孕妇,其中暴露组孕妇(SA阳性)133人,非暴露组孕妇(SA阴性)1701人。随访后共获得1834个新生儿样本。SA及MRSA携带情况:1834名孕妇中,133人(7.25%)携带SA,31人(1.69%)携带MRSA。1834名新生儿中,60人(3.27%)携带SA,15人(0.82%)携带MRSA。暴露组新生儿SA携带率为15.79%,MRSA为2.26%;非暴露组新生儿SA携带率为2.29%,MRSA为0.71%。两人群新生儿SA携带率有差异,MRSA携带率无差异。暴露组新生儿携带SA的相对危险比是非暴露组的6.89倍(95%CI:4.18-11.36),调整新生儿的性别、分娩方式、是否胎膜早破及怀孕天数影响因素后,暴露组新生儿携带SA的相对危险比是非暴露组的6.90倍(95%CI:4.22-11.27)。共有21对母婴同时检出SA阳性。药敏试验:孕妇SA对克林霉素(41.35%)、红霉素(50.38%)、替考拉宁(81.20%)和青霉素(92.48%)的耐药率均较高;与甲氧西林敏感金黄色葡萄球菌(methicillin-susceptible Staphylococcus aureus,MSSA)菌株相比,MRSA是多重耐药的危险因素(OR=3.64;95%CI:1.23-13.02)。新生儿SA对克林霉素(28.33%)、红霉素(46.67%)和青霉素(93.33%)的耐药率较高;MRSA是多重耐药的危险因素(OR=12.36;95%CI:2.56-76.77)。暴露组与非暴露组新生儿中SA的药敏情况无差异。21对母婴配对子耐药谱一致性有统计学差异(P0.01),一致性程度为适中(Kappa=0.523)。毒素基因:孕妇中SA的PVL、ETA、ETB和TST基因携带率为2.26%、3.01%、0.00%和2.26%,新生儿分别为5.00%、3.33%、11.67%和0.00%。孕妇及新生儿中MRSA与MSSA携带PVL、TST、ETA基因的情况均无差异。21对母婴配对子中,母亲及其新生儿中的SA均检不出PVL和ETB基因,母婴配对子携带TST和ETA基因的一致性有统计学意义,一致性程度分别为最佳(Kappa=1.000)和适中(Kappa=0.462)。SCCmec分型:孕妇分离的MRSA菌株中,45.16%(14/31)属于医院相关MRSA(hospital-associated MRSA,HA-MRSA),29.03%(9/31)属于社区相关MRSA(community-associated MRSA,CA-MRSA),以SCCmecⅡ型(11/31)和Ⅳa型(7/31)占优。新生儿MRSA中,20.00%(3/15)属于HA-MRSA,26.67%(4/15)属于CA-MRSA,以SCCmecⅣa型(4/7)和Ⅱ型(2/7)占优。孕妇及新生儿中的HA-MRSA和CA-MRSA菌株对克林霉素、红霉素和青霉素等抗生素的耐药性均较高,对11种药物的耐药性和多重耐药无统计学差异。21对母婴配对子中,检出1对MRSA菌株,同为SCCmecⅡ型。MLST:孕妇及新生儿中SA主要的ST型别均为ST188(37/133;15/60)、ST7(18/133;7/60)和ST6(14/133;5/60);MRSA菌株的主要型别均为ST59(8/31;4/15)、ST6(6/31;2/15)和ST188(5/31;3/15)。孕妇及新生儿中SA的优势克隆群均为CC5(71/133;28/60),其次为CC7(18/133;7/60)。树状聚类分析中,21对母婴对子中共有19对各自聚成一类,与eBURST V3软件分析得出的结果相似。结论该区域孕妇及新生儿人群中SA的携带率略低,但孕妇中MRSA菌株携带率略高。孕妇及新生儿中约65%及38%的SA呈现多药耐药,耐药性严重,毒力基因的携带率较低。孕妇中MRSA以医院来源为主,新生儿以社区来源为主。孕妇及新生儿中SA流行的ST型别为ST188、ST7和ST6,MRSA主要为ST59、ST6和ST188,与我国流行菌株接近,也与国际流行菌株存在密切关系。调整其他影响因素后,母亲携带SA的新生儿携带SA的风险是母亲非携带的新生儿的6.90倍。
[Abstract]:Objective to explore the carrying rate of Staphylococcus aureus (Staphylococcus aureus, hereinafter referred to as SA) in pregnant women (vagina) and their neonates (oral, perinatal, ear and umbilical), to explore the drug sensitivity and molecular characteristics of SA, to study the homology of mother and infant SA and to predict the risk of maternal and infant transmission, and to provide a scientific basis for effective prevention and control measures. A prospective cohort study combined with molecular epidemiology was used to facilitate the sampling of pregnant women who were hospitalized and followed up. The pregnant women were divided into exposure groups according to the vaginal secretions of pregnant women (vaginal secretions separation and identification of SA positive) and non exposed groups (vaginal secretions isolated and identified SA negative). The outcome was the carrying rate of SA and relative risk ratio in the two groups of newborn babies born with SA. (relative risk, RR); the drug sensitivity analysis of SA using Kirby-Bauer test paper diffusion method and further identification of methicillin resistant Staphylococcus aureus (methicillin-resistant Staphylococcus aureus, MRSA) strains. Using the paper diffusion method and mecA gene amplification method, t test, x 2 test or Fisher exact probability were used to compare the difference of other groups in different groups, the difference between the risk factors of SA and MRSA and the drug sensitivity of the newborn were explored. The factors of the single factor analysis of P0.05 were integrated into the generalized linear model for multi factor analysis; the Kappa test score was used. Analysis of the consistency between the phenotype of mother and baby SA and the characteristics of the toxin gene; using the PCR technique to detect the toxin gene (PVL, TST, ETA and ETB), and the further SCCmec molecular typing of the MRSA strain; use the multipoint sequencing (multilocus sequencing typing, MLST) to explore the local epidemic type and determine the homology of the mother and child. 1834 pregnant women, 133 of the exposure group (SA positive) and 1701 in the non exposed group (SA negative), were followed up for a total of 1834 newborn samples of.SA and MRSA: 1834 pregnant women, 133 (7.25%) carrying SA, 31 (1.69%) carrying MRSA.1834 name neonates, 60 (3.27%) carrying SA, 15 (0.82%) carrying MRSA. exposure. The carrying rate of SA in the group of newborn infants was 15.79%, MRSA was 2.26%, the rate of SA carrying in the non exposed group was 2.29%, the SA carrying rate of newborn infants in 0.71%. two was different, the MRSA carrying rate was no difference. The relative risk ratio of SA in the exposed group was 6.89 times as much as that of the non exposed group (95%CI: 4.18-11.36), adjusting the sex of the newborn, the mode of delivery, and whether the fetus was born. The relative risk of premature rupture of membrane and the number of pregnant days was 6.90 times higher than that of the non exposed group (95%CI:4.22-11.27). A total of 21 pairs of mothers and infants detected SA positive at the same time. Drug sensitivity test: the resistance rate of SA to clindamycin (41.35%), erythromycin (50.38%), teicorin (81.20%) and penicillin (92.48%) was higher in pregnant women. Compared to the strains of methicillin-susceptible Staphylococcus aureus (MSSA), MRSA was a risk factor for multidrug resistance (OR=3.64; 95%CI:1.23-13.02). The resistance rate of neonatal SA to clindamycin (28.33%), erythromycin (46.67%) and penicillin (93.33%) was higher; MRSA was a risk factor for multidrug resistance (OR=12.36; 95). %CI:2.56-76.77). There was no difference in the drug sensitivity of SA in the exposed and non exposed neonates. The consistency of.21 to mother to child was statistically significant (P0.01), and the consistency was moderate (Kappa=0.523). The gene carrying rate of SA in pregnant women was 2.26%, 3.01%, 0% and 2.26%, and 5% and 3.33% in newborn infants. 11.67% and 0.00%. pregnant women and neonates with MRSA and MSSA carrying PVL, TST, ETA genes were not different from.21 to mother and baby, and the SA in mother and newborn was not detected in PVL and ETB genes. The consistency of mother and baby with TST and ETA genes was statistically significant. (0.462).SCCmec typing: among MRSA isolates from pregnant women, 45.16% (14/31) belong to hospital related MRSA (hospital-associated MRSA, HA-MRSA), and 29.03% (9/31) belong to community related MRSA (community-associated MRSA, CA-MRSA). RSA was dominated by SCCmec IV A (4/7) and type II (2/7). The resistance of HA-MRSA and CA-MRSA strains to clindamycin, erythromycin and penicillin were higher in pregnant women and neonates, and there was no statistical difference between the resistance and multidrug resistance of the 11 drugs. In the mother infant pair, 1 pairs of MRSA strains were detected and the same as SCCmec II.MLST: pregnant women. The main ST types of SA in the newborn were ST188 (37/133; 15/60), ST7 (18/133; 7/60) and ST6 (14/133; 5/60). A total of 19 pairs of child pairs were divided into one class, which was similar to the results obtained by eBURST V3 software analysis. Conclusion the carrying rate of SA in pregnant women and newborns in this region is slightly lower, but the carrying rate of MRSA strains in pregnant women is slightly higher. The SA of pregnant women and newborns about 65% and 38% of SA presents multidrug resistance, the drug resistance is serious and the carrying rate of virulence genes is low. MRSA is mainly hospital source, and the newborn is mainly community source. The ST types of SA in pregnant women and newborns are ST188, ST7 and ST6, MRSA mainly ST59, ST6 and ST188, which are close to the epidemic strains in our country, and are closely related to the international epidemic strains. 6.90 times as much as non - carrying newborns.
【学位授予单位】：广东药科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R714.251
本文编号：2150781
[Abstract]:Objective to explore the carrying rate of Staphylococcus aureus (Staphylococcus aureus, hereinafter referred to as SA) in pregnant women (vagina) and their neonates (oral, perinatal, ear and umbilical), to explore the drug sensitivity and molecular characteristics of SA, to study the homology of mother and infant SA and to predict the risk of maternal and infant transmission, and to provide a scientific basis for effective prevention and control measures. A prospective cohort study combined with molecular epidemiology was used to facilitate the sampling of pregnant women who were hospitalized and followed up. The pregnant women were divided into exposure groups according to the vaginal secretions of pregnant women (vaginal secretions separation and identification of SA positive) and non exposed groups (vaginal secretions isolated and identified SA negative). The outcome was the carrying rate of SA and relative risk ratio in the two groups of newborn babies born with SA. (relative risk, RR); the drug sensitivity analysis of SA using Kirby-Bauer test paper diffusion method and further identification of methicillin resistant Staphylococcus aureus (methicillin-resistant Staphylococcus aureus, MRSA) strains. Using the paper diffusion method and mecA gene amplification method, t test, x 2 test or Fisher exact probability were used to compare the difference of other groups in different groups, the difference between the risk factors of SA and MRSA and the drug sensitivity of the newborn were explored. The factors of the single factor analysis of P0.05 were integrated into the generalized linear model for multi factor analysis; the Kappa test score was used. Analysis of the consistency between the phenotype of mother and baby SA and the characteristics of the toxin gene; using the PCR technique to detect the toxin gene (PVL, TST, ETA and ETB), and the further SCCmec molecular typing of the MRSA strain; use the multipoint sequencing (multilocus sequencing typing, MLST) to explore the local epidemic type and determine the homology of the mother and child. 1834 pregnant women, 133 of the exposure group (SA positive) and 1701 in the non exposed group (SA negative), were followed up for a total of 1834 newborn samples of.SA and MRSA: 1834 pregnant women, 133 (7.25%) carrying SA, 31 (1.69%) carrying MRSA.1834 name neonates, 60 (3.27%) carrying SA, 15 (0.82%) carrying MRSA. exposure. The carrying rate of SA in the group of newborn infants was 15.79%, MRSA was 2.26%, the rate of SA carrying in the non exposed group was 2.29%, the SA carrying rate of newborn infants in 0.71%. two was different, the MRSA carrying rate was no difference. The relative risk ratio of SA in the exposed group was 6.89 times as much as that of the non exposed group (95%CI: 4.18-11.36), adjusting the sex of the newborn, the mode of delivery, and whether the fetus was born. The relative risk of premature rupture of membrane and the number of pregnant days was 6.90 times higher than that of the non exposed group (95%CI:4.22-11.27). A total of 21 pairs of mothers and infants detected SA positive at the same time. Drug sensitivity test: the resistance rate of SA to clindamycin (41.35%), erythromycin (50.38%), teicorin (81.20%) and penicillin (92.48%) was higher in pregnant women. Compared to the strains of methicillin-susceptible Staphylococcus aureus (MSSA), MRSA was a risk factor for multidrug resistance (OR=3.64; 95%CI:1.23-13.02). The resistance rate of neonatal SA to clindamycin (28.33%), erythromycin (46.67%) and penicillin (93.33%) was higher; MRSA was a risk factor for multidrug resistance (OR=12.36; 95). %CI:2.56-76.77). There was no difference in the drug sensitivity of SA in the exposed and non exposed neonates. The consistency of.21 to mother to child was statistically significant (P0.01), and the consistency was moderate (Kappa=0.523). The gene carrying rate of SA in pregnant women was 2.26%, 3.01%, 0% and 2.26%, and 5% and 3.33% in newborn infants. 11.67% and 0.00%. pregnant women and neonates with MRSA and MSSA carrying PVL, TST, ETA genes were not different from.21 to mother and baby, and the SA in mother and newborn was not detected in PVL and ETB genes. The consistency of mother and baby with TST and ETA genes was statistically significant. (0.462).SCCmec typing: among MRSA isolates from pregnant women, 45.16% (14/31) belong to hospital related MRSA (hospital-associated MRSA, HA-MRSA), and 29.03% (9/31) belong to community related MRSA (community-associated MRSA, CA-MRSA). RSA was dominated by SCCmec IV A (4/7) and type II (2/7). The resistance of HA-MRSA and CA-MRSA strains to clindamycin, erythromycin and penicillin were higher in pregnant women and neonates, and there was no statistical difference between the resistance and multidrug resistance of the 11 drugs. In the mother infant pair, 1 pairs of MRSA strains were detected and the same as SCCmec II.MLST: pregnant women. The main ST types of SA in the newborn were ST188 (37/133; 15/60), ST7 (18/133; 7/60) and ST6 (14/133; 5/60). A total of 19 pairs of child pairs were divided into one class, which was similar to the results obtained by eBURST V3 software analysis. Conclusion the carrying rate of SA in pregnant women and newborns in this region is slightly lower, but the carrying rate of MRSA strains in pregnant women is slightly higher. The SA of pregnant women and newborns about 65% and 38% of SA presents multidrug resistance, the drug resistance is serious and the carrying rate of virulence genes is low. MRSA is mainly hospital source, and the newborn is mainly community source. The ST types of SA in pregnant women and newborns are ST188, ST7 and ST6, MRSA mainly ST59, ST6 and ST188, which are close to the epidemic strains in our country, and are closely related to the international epidemic strains. 6.90 times as much as non - carrying newborns.
【学位授予单位】：广东药科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R714.251
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