本文選題：新生兒敗血癥 + 早發(fā)性敗血癥　； 參考：《重慶醫(yī)科大學》2015年碩士論文

【摘要】：目的新生兒敗血癥(Neonatal sepsis,NS)是新生兒時期嚴重的感染性疾病,具有較高的發(fā)病率和死亡率。NS病原菌及其藥敏的分析在治療及預防中起到重要的作用。明確其病原菌及其藥敏有助于及時、合理的選用抗菌治療,有效的降低NS的死亡率。而NS病原菌及藥敏情況存在地區(qū)性及時間性差異。本課題旨在研究中國西南地區(qū)NS病原菌及其藥敏的變遷。方法收集自1993年1月1日至2014年9月30日期間在重慶醫(yī)科大學附屬兒童醫(yī)院新生兒診治中心住院的共1245名NS患兒相關臨床資料�；仡櫺苑治鏊谢純旱囊话阈畔ⅰ⒉≡捌渌幟舻臉嫵杀燃白冞w。所有數(shù)據(jù)采用SPSS13.0版本進行統(tǒng)計分析和處理。結果本研究中共有596名患兒診斷為早發(fā)性敗血癥(early-onset sepsis, EOS),649名診斷為晚發(fā)型敗血癥(late-onset sepsis, LOS) o EOS主要的致病菌為葡萄球菌屬(53.6%,n=339),其次為腸桿菌屬(12.7%,n=80)及克雷伯氏菌屬(7.1%,n=45); LOS最主要的致病菌仍是葡萄球菌屬(50.8%,n=356),其次為腸桿菌(9.8%,n=69)、克雷伯氏菌(9.7%,n=68)以及真菌(7.4%,n=52)。在研究期間,對于EOS而言,其主要致病菌G+球菌的比例由71%下降至43%左右,位居第二位的G-桿菌則由14%上升至55%左右。與此同時,G+球菌中占絕大部分的葡萄球菌屬的比例由65%降至37%左右。而作為G-桿菌的主要病原菌,腸桿菌屬及克雷伯菌屬分別由4%升至36%左右、2%升至15%左右。對于LOS而言,G-桿菌的比例由10%升至38%左右,而作為LOS的主要致病菌,G+球菌則由80%降至47%左右。其中,在G+球菌中所占雖多的葡萄球菌屬的比例由68%降至35%左右,而G-桿菌中的腸桿菌屬及克雷伯氏菌屬分別由5%升至17%左右、2%升至18%左右。另外,我們發(fā)現(xiàn)真菌屬在EOS中所占比例不高,僅為0.5%(n=3),但在LOS中所占比例高達7.4%(n=52),且其在LOS中的比例在2005-2014年期間由3%逐年上升至20%左右。無論EOS還是LOS, G+球菌對萬古霉素、替考拉寧的敏感性均高達90%以上,其次是利奈唑胺、奎奴普汀及利福平,敏感性波動在80-90%。而對于紅霉素、部分頭孢類(頭孢噻肟、頭孢唑林及頭孢西丁)及部分青霉素類等國內外常用抗生素(青霉素、氨芐青霉素、苯唑青霉素),其敏感性僅波動在20%-40%之間；與G+球菌類似,G-桿菌對部分青霉素類及部分頭孢類抗生素(例如氨芐青霉素、頭孢唑林等)的敏感性僅為20%-40%。而對于亞胺培南、司帕沙星、環(huán)丙沙星及慶大霉素的敏感性均高于70%。另外,在部分常見病原菌藥敏分析中,我們發(fā)現(xiàn)無論EOS還是LOS,萬古霉素在葡萄球菌及腸球菌中的敏感性均高達80%以上。肺炎克雷伯氏菌及大腸埃希氏菌對碳青霉烯類及喹諾酮類抗生素的敏感性也明顯高于80%。而對于上述絕大多數(shù)細菌而言,大部分青霉素類(例如青霉素、氨芐青霉素、苯唑青霉素)及頭孢類(例如頭孢噻肟、頭孢噻吩以及頭孢唑林)等總體上的敏感性均低于30%。另外,真菌對目前臨床上使用的抗真菌的藥物例如兩性霉素B、伊曲康唑及5-氟胞嘧啶等的敏感性仍相對較高,均在70%以上。在病原菌藥敏的變遷的研究中,我們發(fā)現(xiàn)對于EOS G+球菌而言,近20多年來,部分敏感抗生素的敏感性有所下降,例如萬古霉素的敏感性由95%降至65%左右,而慶大霉素由70%降至40%左右,環(huán)丙沙星由80%降至50%左右。而對于G-桿菌,在研究期間敏感抗生素例如亞胺培南及環(huán)丙沙星的敏感性始終保持在80%以上。而氨芐青霉素的敏感性無論在G+球菌還是G-桿菌中均持續(xù)低于40%。同樣的變化趨勢在LOS中也被發(fā)現(xiàn),在G+球菌中萬古霉素及環(huán)丙沙星的敏感性均由100%下降至60%左右,而對于G-桿菌,亞胺培南、環(huán)丙沙星及慶大霉素的敏感性總體上保持在70%左右。部分青霉素類例如氨芐青霉素及苯唑青霉素敏感性總體上維持在30%以下。結論1.無論EOS還是LOS,最主要的致病菌為G+球菌,其主要構成是葡萄球菌屬及腸球菌屬。而G-桿菌為NS第二位常見致病菌,主要由腸桿菌屬、克雷伯氏菌屬及真菌屬構成。2.G+球菌及葡萄球菌屬的比例在EOS及LOS中均呈明顯的下降趨勢。G-桿菌在總體上則呈上升趨勢,但在EOS中表現(xiàn)為腸桿菌屬明顯升高,而在LOS中表現(xiàn)為多種G-桿菌如腸桿菌屬及克雷伯氏菌屬輕微上升。3.真菌屬在EOS中所占比例較小,而在LOS中所占比例明顯增加,且其比例自2005年有逐年上升趨勢。4.藥敏研究中發(fā)現(xiàn),無論是EOS還是LOS, G+球菌對萬古霉素、替考拉寧及利福平的敏感性均較高,而G-桿菌則對亞胺培南、司帕沙星、環(huán)丙沙星及慶大霉素相對比較敏感。5.類似的藥敏模式也表現(xiàn)在具體的病原菌藥敏分析中,例如葡萄球菌及腸球菌對萬古霉素的敏感性最高；而肺炎克雷伯氏菌及大腸埃希氏菌則對碳青霉烯類(例如亞胺培南、美洛培南)及喹諾酮類(例如環(huán)丙沙星、司帕沙星及莫西沙星)的敏感性普遍較高。大部分青霉素類例如青霉素、氨芐青霉素及頭孢類例如頭孢唑林、頭孢噻肟、頭孢西丁等,對絕大多數(shù)病原菌的敏感性均較低。此外,臨床上常用抗真菌藥物,例如兩性霉素-B、伊曲康唑及5-氟胞嘧啶等仍具有較高敏感性。6.與此同時,無論EOS還是LOS, G+球菌的大部分敏感抗生素例如萬古霉素、利福平、慶大霉素等的敏感性總體上均呈明顯下降趨勢,而這種藥敏變遷模式在G-桿菌中不明顯,均保持較高敏感水平。7.繼續(xù)動態(tài)的、長期的、多中心的針對該地區(qū)NS病原菌及其藥敏的研究,可以為臨床上合理的、適時的予以抗菌治療提供重要的依據(jù)。
[Abstract]:Objective neonatal sepsis (Neonatal sepsis, NS) is a serious infectious disease in the newborn period. The high incidence and mortality rate and mortality of.NS pathogens and their drug sensitivity analysis play an important role in the treatment and prevention. It is clear that the pathogenic bacteria and their drug sensitivity are helpful to the timely, rational selection of antibacterial treatment and the effective reduction of the death of NS. NS pathogenic bacteria and drug sensitivity have regional and temporal differences. This subject aims to study the changes of NS pathogens and their drug sensitivity in southwestern China. Methods the clinical data of 1245 children with NS were collected from January 1, 1993 to September 30, 2014 in the neonatal diagnosis and treatment center of the Affiliated Children's Hospital of Medical University Of Chongqing. A retrospective analysis of the general information of all children, the proportion and changes of the pathogenic bacteria and their drug sensitivity. All data were analyzed and processed by SPSS13.0 version. Results 596 children were diagnosed as early onset sepsis (early-onset sepsis, EOS), and 649 diagnosed as late onset sepsis (late-onset sepsis, LOS) o EOS The main pathogenic bacteria were Staphylococcus (53.6%, n=339), followed by Enterobacteriaceae (12.7%, n=80) and Klebsiella (7.1%, n=45); the main pathogenic bacteria of LOS were Staphylococcus (50.8%, n=356), followed by Enterobacteriaceae (9.8%, n=69), Klebsiella (9.7%, n=68) and fungi (7.4%, n=52). During the study, it was mainly for EOS. The proportion of the pathogenic bacteria G+ dropped from 71% to about 43%, and the second place G- bacilli increased from 14% to about 55%. At the same time, the proportion of the most Staphylococcus in the G+ coccus was reduced from 65% to 37%. As the main pathogen of the G- bacillus, the genus and Klebsiella were increased from 4% to 36%, 2% to 15%, respectively. For LOS, the proportion of G- bacilli increased from 10% to about 38%, and as the main pathogenic bacteria of LOS, the G+ coccus fell from 80% to about 47%. Among them, the proportion of Staphylococcus in G+ was reduced from 68% to 35%, while the genus and Klebsiella in G- bacilli increased from 5% to about 17%, 2% to 18% left. On the other hand, we found that the proportion of fungi in EOS was not high, only 0.5% (n=3), but the proportion in LOS was 7.4% (n=52), and the proportion in LOS increased from 3% to 20% year by year. No matter EOS or LOS, the sensitivity of G+ to vancomycin and teicoplanin was above 90%, followed by linezole. Amines, quetipine and Li Fuping, sensitive to erythromycin, some cefotaxime (cefotaxime, cefazolin and cefoxitin) and some penicillins, and some other common domestic and foreign antibiotics (penicillin, ampicillin, azolicillin) in 80-90%., and its sensitivity only fluctuates between 20%-40%; it is similar to G+ coccus, and G- bacilli The sensitivities of penicillins and some cephalosporins (such as ampicillin, cefazolin, etc.) were only 20%-40%. and for imipenem, sparfloxacin, ciprofloxacin and gentamicin were higher than 70%.. In some common pathogenic bacteria susceptibility analysis, we found that vancomycin was in Staphylococcus and EOS in Staphylococcus and LOS. The susceptibility of Enterococcus to more than 80%. Klebsiella pneumoniae and Escherichia coli are also more sensitive to carbapenems and quinolones than 80%.. For most of these bacteria, most penicillins (such as penicillin, ampicillin, azolicillin) and cefotaxime (e. g. cefotaxime) The sensitivities of cefathiophene and cefazolin were all lower than that of 30%., and the sensitivity of fungi to the current clinical antifungal drugs such as amphotericin B, itraconazole, and 5- fluorcytosine were still relatively high, both above 70%. In the study of the changes in drug sensitivity of pathogenic bacteria, we found that for EOS G+ cocci In the past 20 years, sensitivity to some sensitive antibiotics has declined, such as vancomycin sensitivity from 95% to about 65%, and gentamicin from 70% to about 40%, and ciprofloxacin from 80% to 50%. For G-, sensitive antibiotics, such as amienem and ciprofloxacin, remained in 80% for the period of study. The susceptibility to ampicillin was also found in LOS, both in G+ and G- bacilli, and in LOS, and the sensitivity of vancomycin and ciprofloxacin in G+ decreased from 100% to about 60%, while the sensitivity to G-, imipenem, ciprofloxacin and gentamicin was generally maintained. About 70%. Some penicillins, such as ampicillin and azolicillin, are generally less than 30%. Conclusion 1. of the main pathogenic bacteria, whether EOS or LOS, are G+ coccus, which are mainly composed of Staphylococcus and Enterococcus, and G- bacilli are common pathogens of NS second, mainly from the genus Enterobacter and Klebsiella. The proportion of.2.G+ and Staphylococcus and Staphylococcus in EOS and LOS showed a significant downward trend in EOS and LOS, while.G- showed an upward trend in general, but in EOS, the Enterobacteriaceae increased significantly, while in LOS, a variety of G- bacilli, such as Enterobacteriaceae and Klebsiella, were slightly higher in EOS than in EOS. The proportion of the cases was smaller and the proportion of LOS increased significantly, and the proportion of them increased from year to year in 2005. In the.4. drug sensitivity study, the sensitivity of G+ to vancomycin, teicoplanin and rifampicin was higher in both EOS and LOS, while G- was relatively sensitive to imipenem, ciprofloxacin, ciprofloxacin and gentamicin. Similar drug sensitivity patterns are also shown in specific antimicrobial susceptibility tests, such as Staphylococcus and Enterococcus with the highest susceptibility to vancomycin, while Klebsiella pneumoniae and Escherichia coli are against carbapenems (such as imipenem, meropenem) and quinolones (such as ciprofloxacin, sparfloxacin and moxifloxacin) Most penicillins such as penicillins such as penicillin, ampicillin and cefazoxime, cefotaxime, cefoxitin, and so on, have low sensitivity to most pathogenic bacteria. In addition, clinical antifungal agents such as amphotericin -B, itraconazole and 5- fluorine cytosine still have high sensitivity.6.. At the same time, the sensitivity of most of G+'s sensitive antibiotics, such as vancomycin, rifampicin and gentamicin, was obviously decreased in both EOS and LOS, and the drug sensitivity change mode was not obvious in G- bacilli, and all of them maintained high sensitivity,.7., continued dynamic, long and multicenter of NS disease in the region. The study of the original bacteria and its drug sensitivity can provide important evidence for clinical rational and timely antibacterial treatment.
【學位授予單位】：重慶醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R446.5

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