摘要
背景1929年Fleming发现青霉素,随后Florey和Chain将其用于临床取得惊人效果,标志着抗生素时代的来临,使人类的平均寿命大大延长。但好景不长,随着青霉素等抗生素使用单位的逐渐上升,病原菌的耐药性问题越来越突出并日益引起人们的重视。现在,科学家们已经提出了“后抗生素时代”来形容这一问题的严重性。更严重的是,病原菌能同时产生对几种结构完全不同的抗生素的耐受性,即多重耐药性。当前,耐药性尤其是多重耐药性己经成为研究的热点之一。
意义Kollef.MH提出每一个ICU病房都应明确本地区内病原菌流行病学,以及药物敏感等感染资料,防止抗菌药物滥用,提高抗菌药物的抗菌活性;如果不清楚本区域的病原菌流行病学资料,经验性使用抗菌药物,不如不使用抗菌药物。ICU感染患者正处于生死存亡的紧急关头,被动的等待病原菌学资料和药敏结果,显然会贻误最佳救治时机而难以施行,所以了解本ICU病原菌流行病学及药物敏感资料,可帮助医生合理选用经验性抗菌药物,重拳猛击,迅速控制感染,提高抢救成功率。
目的建立重症监护病房抗生素使用和病原菌耐药的监测数据库,分析研究重症监护病房近3年来病原菌耐药的变化及耐药菌感染患者中医证候学研究,探索中医药降低细菌耐药水平和治疗耐药菌感染提供依据。
方法采用临床流行病学回顾性研究方法,收集2005年3月~2008年2月中国中医科学院广安门医院重症监护病房所有住院病人的病历,纳入符合细菌耐药标准的病例,将资料输入ACCESS数据库,通过SAS统计分析感染性疾病种类、细菌分布、耐药率及中医症候的变化。
结果ICU病房的住院患者大多合并多种基础疾病,病情危重、住院时间长,感染率较高;感染性疾病以下呼吸道感染为主,慢性阻塞性肺病占5成以上。感染细菌以革兰阴性菌为主,培养位居前三位的依次是铜绿假单胞菌(38.3%)、金黄色假单胞菌(18%)、鲍曼不动杆菌(17%);白色念珠菌(7%)三年均排在第四位,所占比率逐年下降;铜绿假单胞菌在2006年所占比率迅猛上升,2007年又回到2005年水平,2007年鲍曼不动杆菌所占比率有所上升,达到当年培养最多的菌株。
三年G+菌敏感率高的前三位是万古霉素(91.58%)、呋喃妥因(77.23%)、磺胺(64.85%),其余抗生素敏感率均不到20%;三年G-菌敏感率高的前三位是阿米卡星(71.89%)、哌拉西林/他唑巴坦(63.78%)、头孢哌酮/舒巴坦钠(61.89%),亚胺培南敏感率逐年下降、头孢吡肟未能在培养中体现出头孢四代的优势;三年真菌敏感率结果中临床常用的氟康唑、伏立康唑敏感率在80%以上。
在主要病原菌敏感率结果中,铜绿假单胞菌数量最多,阿米卡星、带有酶抑制剂的哌拉西林/他唑巴坦、头孢哌酮/舒巴坦钠敏感率均在70%以上,但三年监测发现阿莫西林/棒酸、头孢曲松、头孢呋肟、头孢噻肟、复方新诺明、呋喃妥因、氨曲南、四环素敏感性均不足5%,应尽量少用;头孢吡肟、呋喃妥因、氨曲南敏感度明显下降;金黄色葡萄球菌数量列第二位,对万古霉素、磺胺、呋喃妥因90%以上敏感,近两年MRSA培养率迅速增加,临床可选用药少;鲍曼不动杆菌近三年培养数量增长最快,2007年已经超过铜绿假单胞菌,成为临床培养阳性最多的病原菌。
我院克雷伯菌属敏感率较高,所有培养药物敏感率均在50%以上,对亚胺培南100%敏感,对头孢呋肟、头孢噻肟、环丙沙星、左氧氟沙星敏感度逐年下降,应注意临床药物的选择;对于大多数抗生素,大肠埃希菌近三年敏感度上升较快,但呋喃妥因,敏感度已经降至70%左右;万古霉素对粪肠球菌100%敏感,临床疗效好。但其他抗生素敏感度较低,除青霉素、氨苄西林磺胺、呋喃妥因外均在12%以下;我院培养的白色念珠菌对伏立康唑100%敏感,对5-氟胞嘧啶、氟康唑等敏感率也在80%,但近年出现天然耐氟康唑等药物的克柔氏假丝单胞菌等。
各病原菌感染,在中医证型上既有相似之处,也有自身的特点。从共性来讲,由于本研究统计的标本绝大多数为痰,且原发病多为重症肺炎或慢阻肺合并肺部感染。因此痰浊阻肺为基本证型,而且本次统计的多为气管插管病人,铜绿假单胞菌、金黄色葡萄球菌、肠杆菌科、鲍曼不动杆菌及真菌为最常见的院内感染病原体,病情危重,正气受损也相当常见,主要特点为气阴两伤。
结论细菌耐药性的出现和发展受到多种因素影响,本次研究发现,药物消耗量与细菌耐药有相当大的关系,但两者关系相当复杂,一般认为大量使用抗感染药物导致抗感染药物的选择性压力增大,增加病原菌对其产生耐药的机率;临床医生应合理使用抗生素,应该重视并提高感染性疾病细菌培养的送检率,重视细菌鉴定和药敏结果,并根据本地区既往的细菌流行情况进行经验用药,药敏结果报告后应及时调整使用敏感抗生素,避免因不合理使用抗生素而造成对耐药菌株的筛选;我们更要充分发挥中医的优势。鉴于感染者以痰浊内结证为主,我科率先根据细菌耐药机制与中医“伏邪”理论的相近性,根据齐文升教授临床经验,临床选用新加达原饮,以发散伏邪、破结解毒、扶正固本、对减少抗生素耐药和治疗耐药菌感染取得了一定疗效。
Background The advent of the“antibiotics era”came with two historical events--Fleming discovered penicillin in 1929 and it worked amazingly after applied clinically by Florey and Chain, which greatly prolonged human being's life. But soon, the units of penicillin and other antibiotics increased along with their wide use in clinic, which made people realize bacteria's resistance to drugs and paid more and more attention to this problem. Nowadays,“post-antibiotics era”has been used to underline the severity. Moreover,bacteria could produce resistance to several antibiotics structurally unrelate, that is, multiple antibiotics resistance (MAR). Bacteria's resistance especially multi-drug resistance has been a heated topic at present in the world.
Significance Kollef .MH proposed each ICU ward should be cleared about the infection materials of bacterium epidemiology in this area,as well as medicine sensitive and so on for preventing the antibiotics abusiveness and enhancing the activeness of antibiotics; If not clear the bacterium epidemiology material this region and use antibiotics by empirical, we should not use the antibiotics. It is in the critical moment for the infected patients in ICU, If wait passively the bacteriology material and the medicine sensitive result, It can be delayed for the opportunity of treating and executes with difficulty best. therefore understood bacterium epidemiology and the medicine sensitive material in ICU may help doctor to select the empirical antibiotics reasonably. By attacking fiercely, we can control the infection rapidly and enhance the rescue success ratio.
Objective Establish critically the monitor database of ICU ward usage and the nosocomial bacterial infection and analysis the research of the change of the bearing bacteria and syndrome differentiation of TCM in ICU ward near 3 years, It provides the evidence of reducing the level of bearing the medicine and selecting the antibiotic reasonably.
Methods By using the investigation method of reviewing clinical epidemiology, collect all in-patient's medical record during March 2005 to February 2008 in ICU of Chinese Medicine Academy of Science Guang'an Men Hospital and integrate the antibiotic cases of illness, which have the history of infective medical and (or) used the antibiotic in the courtyard, and then the material is input the ACCESS database, and analysis infectious disease type, the bacterium distribution, the rate of bearing the medicine and the Chinese medicine symptom change.
Results The patients in ICU mostly merge many kinds of foundation disease and live in hospital for a long time , the conditions are seriously injured. So the infection percentage is high and the infectious disease mostly belong to the respiratory tract infection. The chronic blocking pulmonary tuberculosis occupies above 5 tenths. The infection bacterium, situated the pseudomonas aeruginosa (38.3%), staphylococcus aureus(18%), acinetobacter baumannii(17%)in turn, are G- primarily. Candida albicans yearly arrange at fourth, but the infective ratio is dropping year by year; The ratio of Pseudomonas aeruginosa rises violently in 2006 and returns to the level of 2005 in 2007; In 2007 the ratio of the acinetobacter baumannii rises, and achieves the most bacterium.
G+ sensitive rate of the top three is vancomycin (91.58%), nitrofurantoin result (77.23%), sulfonamides (64.85%), and the remaining antibiotics do not reach the rate of 20 percent for three years; G- sensitive rate of the top three is amikacin (71.89%), piperacillin /tazobactam(63.78%), cefoperazone /sulbactam(61.89%), The sensitive rate of imipenem decreased year after year, cefepime failed to reflect the effectiveness of four generations of cephalosporins; The sensitive rates of the fluconazole and voriconazole were more than 80 per cent better and have the clinical effect in the result of fungi.
Pseudomonas aeruginosa are the largest number of all Pathogens, The sensitive rates of amikacin、the enzyme inhibitor with penicillin and cephalo-sporins are above 70%, but three years monitoring results discovered that the sensitive rates of amoxicillin /clavulanic acid, ceftriaxone, ceftazidime, ceftiofur oxime, cefotaxime, co-trimoxazole, nitrofurantoin, aztreonam and tetracycline are less than 5%, So we should use less; The sensitive rates of cefepime, nitrofurantoin because and aztreonam decreased. The number of Staphylococcus aureus was second, and the sensitive rate to vancomycin, sulfonamides, nitrofurantoin was more than 90% for the last two years, with the rapid growing rate of MRSA training, Clinical drug is used less; the past three years ,the number of the acinetobacter baumanni is the fastest-growing. in 2007 it is more than Pseudomonas aeruginosa and the most positive pathogens. Since 2007 ICU producd ESBLs-ing strains of acinetobacter baumannii, almost all antibiotics are resistant for it. therefore, it should be aroused our full attention. In ICU the sensitive rate of Klebsiella was higher than other pathogens. All sensitivity rates of drug were more than 50%, and 100% sensitive to imipenem. The rates of cephalosporins ceftiofuroxime, cefotaxime, ciprofloxacin and levofloxacin decreased year after year, it should be noticed the clinical choice. For the majority of antibiotics, the rate of colon Escherichia coli nearly three years was rapid increased in sensitivity. However, the sensitivity rate of nitrofurantoinhas reduced to around 70%; vancomycin on the Enterococcus faecalis was 100% sensitive, The clinical effect was good. But other antibiotics were less sensitive, which, with the exception of penicillin, ampicillin sulfonamides and nitrofurantoin, were due to below 12%; The sensitive rate of candida albicans on voriconazole was 100% sensitive, and on 5-fluorocytosine, fluconazole and other were above 80% sensitive. but in recent years, ICU was found the sophie's candida aeromonas jundeng with natural resistance to drugs such as fluconazole grams. Sophie's candida aeromonas Jundeng should arouse attention!
The TCM-syndrome of the pathogen, infected, was similar, but also has their own characteristics. From the general speaking, the statistics of this research was used for the vast majority of sputum specimens, and the incidence is severe pneumonia or COPD with pulmonary infection. Therefore phlegm pulmonary resistance is the basic syndrome type, but this statistics had many patients of the tracheal intubation, So the Pseudomonas aeruginosa, Staphy-lococcus aureus, Enterobacteriaceae, and Acinetobacter baumannii are the most common fungal nosocomial pathogens. with critical condition and upright ness damaged, the main characteristics of Qi-Yin injury is quite common.
Conclusions The emergence and development of the bacteria-resistance are influencd by a variety of factors. The study found that consumption of drug had a large and complex relationship with the resistant-bacteria. Most reports indicated that the multiple antibiotics rate has been increasing in the domestic clinical isolates of bacterial. For reducing the rate of bacterial resistance, clinicians should rationally use of antibioticsand pay attention to the inspection rate of bacterial culture and identification and susceptibility to bacterial result, We should use drug experiencely according to the results of previous years and then timely adjust programme after the results coming, for avoiding the irrational use of antibiotics. In addition we should give fully play to the advantages of TCM.In view of the syndrome of infected persons was syndrome of phlegm heat retention mainly, We create the syndrome of Yu programme at first. According to the similar between bacterial resistance mechanism and "Fuxie" theory of TCM, we make "Fuxie" as a breakthrough point, with the clinical experience of Pro. Qi Wen-sheng, We use Xin Jia Da Yuan decoction in ICU, and make efforts for reducing the advantages of antibiotic resistance by cure Yu, strengthen the body and centralizer.
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