婴儿心内直视术后呼吸机相关性肺炎致病菌及耐药性分析
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摘要
研究背景
呼吸机相关性肺炎(Ventilator-associated Pneumonia，VAP)指原无肺部感染的患者，机械通气治疗48小时后发生肺部感染，或原有肺部感染，机械通气治疗48小时后发生新的肺部感染。根据机械通气后肺炎发生时间将呼吸机相关性肺炎分为早发型(early-onset VAP)和迟发型(later-onset VAP)。自从Lareau等从70年代开展研究有关引起VAP因素以来，历经20多年研究，积累了丰富的经验，但新问题仍层出不穷，VAP对病人威胁较大，处理棘手。
引起VAP发病的原因较多：重症监护病房(ICU)收治患者病情严重，免疫功能低下，接受的侵入性医疗手段较多；气管插管损害了气道防御功能；胃内容物返流；病室环境和医务人员手的交叉感染；频繁更换机械通气管道；机械通气时间延长等。
尽管目前十分重视对呼吸设施的有效消毒，以及在治疗呼吸机依赖等方面技术不断提高，但接受机械通气的病人中仍有约(8～28)％发生VAP。ICUs中肺炎发
浙江大学硕士学位论文
生率显著高于普通住院病房，而气管插管机械通气使病人发生肺炎的危险增加
(3一10)倍。有报道vAP总死亡率在11%左右，但一些特殊情况或高危险致病菌
引起VAP的死亡率可高达76%。
导致VAP的病原菌在不同情况下有很大的差异，比如ICU中病人种类，住院
和ICU留住时间等。许多研究报道绝大多数肺炎由革兰氏阴性菌引起。然而近年
来一些研究报道以金黄色葡萄球菌为主革兰氏阳性菌引起的VAP变得较为常见。
新生儿、婴儿先天性心脏病需适时合理纠治，绝大多数在心脏外科术后经有
效治疗可完全康复。在这部分群体中，vAP不仅严重影响其预后，而且大大增加
医疗费用。
有关婴儿心内直视术后VAP的发生及病原菌特征等国内外较少报道，而患儿
术前反复肺炎和抗生素应用使术后引起VAP的致病菌常多重耐药，给临床治疗带
来较大难度。作者总结分析我院1999年6月一2002年6月三年间连续婴儿先心病
体外循环心脏术后VAP相关致病菌分布特征及耐药性变化趋势，指导术后合理选
用抗生素，改善病人预后。
材料与方法
1研究对象
取自1999年6月~2002年6月三年间连续311例在浙江大学附属儿童医
院施行体外循环心脏手术的先天性心脏病(Congenital Heart Disease，cHD)
婴儿(年龄8天~12月)。呼吸机相关性肺炎的诊断标准:气管插管机械通气
48h后发生新或持续(>48hr)的浸润灶(排除感染以外的因素如ARDS、肺水
肿、肺梗塞等)，至少满足下面三条件中的两条:(l)体温大于38℃;(2)外
浙江大学硕士学位论文
周血白细胞计数>l 0xl09几;(3)可见气管内脓性分泌物，革兰氏染色可见1
种或1种以上的细菌。并根据肺炎发生时间，以应用机械通气后5天为界将
VAP分为早发型VAP(<5天)和迟发型VAP泛5天)。
2方法:
2.1痰标本的采集:以细的无菌吸痰管经气管插管达深部负压吸引采集下呼吸道
分泌物入无菌痰液收集器，送细菌学检查。
2.2细菌学检查:
细菌分离鉴定:将标本接种于血平板、巧克力平板、MacC平板，置于37℃5%
CO:孵育箱培养24一48h看结果.在培养基上生长出的优势菌和致病菌，进行
分离鉴定，根据菌株不同针对性做不同的药物敏感试验。
药物敏感试验:1.纸片扩散法(K一B法):挑选琼脂平板上形态相同的菌落移
种于M一H液体培养基中置35℃水箱中孵育4小时，校正浊度。用灭菌棉拭子
蘸取制备好的接种菌液于巧分钟内反复均匀涂布于整个培养基表面。待平板
上水分被琼脂完全吸收后再贴纸片。巧分钟内放35℃孵箱中孵育18一24小时
后，读取结果。2.仪器鉴定法:应用法国bioM合iex公司VITEK一60仪做细菌
鉴定，并用GPS一1 07卡行革兰氏阳性菌药敏试验，GNS一121卡行革兰氏阴性
菌药敏试验。
判定结果:均根据美国国家临床实验室标准化委员会(National Committce for
e一inieal Laborato叮standards，NCCLS)1999年制订的指南(Mloo·59版)和
各年NCCLS个别修订指南。
3数据的统计学处理方法
采用SPSS for windows 10.0版本进行数据统计分析。组间计数资料的比较
浙江大学硕士学位论文
采用犷检验，p<0.05认为差异有显著性意义。
结果
1.311例婴儿先心病手术中67例(2 1.5%)婴儿术后发生VAP。男51例，女16
例，年龄(7.2士3.3)月，其中单纯先心病39例，复杂先心病28例。复杂先
心病组vAP的发生率比单纯先心病组高(x切2.47，P<0.0。。l)，且迟发vAp
的构成比高(x2=6.02，p=0.014)。
2.分离出致病菌79株，革兰氏阴性(G〕菌为主，其次为真菌和革兰氏阳性(G+)菌。
G一菌中多见鲍曼不动杆菌、铜绿假单胞菌、脑膜炎败血黄色杆菌等。G+菌常
见金黄色葡萄球菌和表皮葡萄球菌。真菌以白色念珠菌为主。
3.耐药性:G一菌对亚胺培南/西司他丁、头抱呱酮嘟巴坦、呱拉西林地哇巴坦、
环丙沙星、阿米卡星、头抱他睫较敏感。但其中的嗜麦芽黄单胞菌、脑膜炎
败血黄色杆菌对亚胺培南/西司他丁耐药率高。产超广谱p一内酞胺酶菌主要为
肺炎克雷伯菌和大肠埃希菌，对一代、二代、三代
Ventilator-associated pneumonia(VAP) was considered ventilator-associated, if it developed 48 hours after mechanical ventilation, unless the clinical evidence strongly suggested otherwise. The time of onset of VAP after mechanical ventilation was used to define as early-onset VAP(< 5 d) or late-onset VAP (≥5 d). Although there have been many studies about VAP since Lareau et al analyzed factors associated with the onset of pneumonia in mechanical ventilated patients in the 1970s, new problem still emerges one after one and presents challenge to clinicians to treat with VAP.
The onset of VAP may due to, the severity of patients admited to ICU, inhibition of immunologic function, respiratory tract defense mechanics impairment after tracheal intubation, reflux and aspiration of gastric contents, crossinfection, frequent ventilator circuit changes, prolonged mechanical ventilation etc.
Although great efforts have been made both on keeping the ventilation equipments sterilized and treatment with ventilator-depedent patients to decrease nosocomial infection, 8-28% patients who received mechanical ventilation developed VAP yet. The frequency of nosocomial pneumonia in ICUs is obviously higher than common ward. Furthermore, tracheal intubation and mechanical ventilation increase the risk of pneumonia onset by 3-10 fold. The overall mortality attributed to VAP had been estimated at 11 % , but in several special conditions or with dangerous pathogens infection, the mortality can reach as high as 76%.
The causative pathogens of VAP vary widely depending on different conditions such as, underlying diseases, the duration of ICU stay etc. Most pathogens of VAP include gram-negative bacilli(GNB). More recently , however, some investigators had reported that gram-positive bacteria have become increasingly more common , the percentage of gram-positive cocci especially methicillin-resistant Staphylococcus aureu (MRSA), methicillin-resistant Staphylococcus epidermidis(MRSE) and enterococci increased, meanwhile the percentage of GNB decreased, for example, former commonly seen GNB such as Pseudomonas aeruginosa was less frequent in several adult ICUs.
The newborns and infants with congenital heart defect should receive corrective cardiac surgery at proper time. The majority of them will, if successfully treated, return to a normal productive life. VAP represents an important cause of mortality in this population and increases hospitalization costs.
There was few reports about epidemiology of VAP in infants after cardiac surgery. The causative pathogens maybe multi-resistant because preoperative recurrent
pneumonia and prior administration of antibiotics in these patients. The primary aim of this study was to describe the epidemiology of VAP in infants after cardiac surgery from June 1999 to June 2002 in our hospital. Special emphasis will be directed towards the trend of the changing distribution of the pathogen and its antibiotic resistance pattern during the last 3 years.
Methods
Setting This was a retrospective study using prospectively collected data performed at
the pediatric cardiovascular surgical ICU, Affiliated Children's Hospital, Zhejiang
University,China.
Patients Data were collected on 311 consecutive infants (aged from 8 days to 12
months) with congenital heart defect(CHD) who underwent open-heart surgery in our
hospital between June 1999 and June 2002 .
Sampling
Surveillance Samples: All patients were monitored for VAP after cardiac surgery by clinical standards and also by cultures of endotracheal aspirate. The technique of endotracheal aspiration was a simplified nonbronchoscopic diagnostic procedure(a blind procedure via a sterile suction catheter).
Diagnostic Samplings: Ventilator-associated pneumonia (VAP) was considered ventilator- associated, if it developed 48 hours after mechanical ventilation, unless the clinical evidence strongly suggested otherwise. VAP was defined as the presence of a
new or progressive roentgenographic infiltrate developed 48h after m
呼吸机相关性肺炎(Ventilator-associated Pneumonia，VAP)指原无肺部感染的患者，机械通气治疗48小时后发生肺部感染，或原有肺部感染，机械通气治疗48小时后发生新的肺部感染。根据机械通气后肺炎发生时间将呼吸机相关性肺炎分为早发型(early-onset VAP)和迟发型(later-onset VAP)。自从Lareau等从70年代开展研究有关引起VAP因素以来，历经20多年研究，积累了丰富的经验，但新问题仍层出不穷，VAP对病人威胁较大，处理棘手。
引起VAP发病的原因较多：重症监护病房(ICU)收治患者病情严重，免疫功能低下，接受的侵入性医疗手段较多；气管插管损害了气道防御功能；胃内容物返流；病室环境和医务人员手的交叉感染；频繁更换机械通气管道；机械通气时间延长等。
尽管目前十分重视对呼吸设施的有效消毒，以及在治疗呼吸机依赖等方面技术不断提高，但接受机械通气的病人中仍有约(8～28)％发生VAP。ICUs中肺炎发
浙江大学硕士学位论文
生率显著高于普通住院病房，而气管插管机械通气使病人发生肺炎的危险增加
(3一10)倍。有报道vAP总死亡率在11%左右，但一些特殊情况或高危险致病菌
引起VAP的死亡率可高达76%。
导致VAP的病原菌在不同情况下有很大的差异，比如ICU中病人种类，住院
和ICU留住时间等。许多研究报道绝大多数肺炎由革兰氏阴性菌引起。然而近年
来一些研究报道以金黄色葡萄球菌为主革兰氏阳性菌引起的VAP变得较为常见。
新生儿、婴儿先天性心脏病需适时合理纠治，绝大多数在心脏外科术后经有
效治疗可完全康复。在这部分群体中，vAP不仅严重影响其预后，而且大大增加
医疗费用。
有关婴儿心内直视术后VAP的发生及病原菌特征等国内外较少报道，而患儿
术前反复肺炎和抗生素应用使术后引起VAP的致病菌常多重耐药，给临床治疗带
来较大难度。作者总结分析我院1999年6月一2002年6月三年间连续婴儿先心病
体外循环心脏术后VAP相关致病菌分布特征及耐药性变化趋势，指导术后合理选
用抗生素，改善病人预后。
材料与方法
1研究对象
取自1999年6月~2002年6月三年间连续311例在浙江大学附属儿童医
院施行体外循环心脏手术的先天性心脏病(Congenital Heart Disease，cHD)
婴儿(年龄8天~12月)。呼吸机相关性肺炎的诊断标准:气管插管机械通气
48h后发生新或持续(>48hr)的浸润灶(排除感染以外的因素如ARDS、肺水
肿、肺梗塞等)，至少满足下面三条件中的两条:(l)体温大于38℃;(2)外
浙江大学硕士学位论文
周血白细胞计数>l 0xl09几;(3)可见气管内脓性分泌物，革兰氏染色可见1
种或1种以上的细菌。并根据肺炎发生时间，以应用机械通气后5天为界将
VAP分为早发型VAP(<5天)和迟发型VAP泛5天)。
2方法:
2.1痰标本的采集:以细的无菌吸痰管经气管插管达深部负压吸引采集下呼吸道
分泌物入无菌痰液收集器，送细菌学检查。
2.2细菌学检查:
细菌分离鉴定:将标本接种于血平板、巧克力平板、MacC平板，置于37℃5%
CO:孵育箱培养24一48h看结果.在培养基上生长出的优势菌和致病菌，进行
分离鉴定，根据菌株不同针对性做不同的药物敏感试验。
药物敏感试验:1.纸片扩散法(K一B法):挑选琼脂平板上形态相同的菌落移
种于M一H液体培养基中置35℃水箱中孵育4小时，校正浊度。用灭菌棉拭子
蘸取制备好的接种菌液于巧分钟内反复均匀涂布于整个培养基表面。待平板
上水分被琼脂完全吸收后再贴纸片。巧分钟内放35℃孵箱中孵育18一24小时
后，读取结果。2.仪器鉴定法:应用法国bioM合iex公司VITEK一60仪做细菌
鉴定，并用GPS一1 07卡行革兰氏阳性菌药敏试验，GNS一121卡行革兰氏阴性
菌药敏试验。
判定结果:均根据美国国家临床实验室标准化委员会(National Committce for
e一inieal Laborato叮standards，NCCLS)1999年制订的指南(Mloo·59版)和
各年NCCLS个别修订指南。
3数据的统计学处理方法
采用SPSS for windows 10.0版本进行数据统计分析。组间计数资料的比较
浙江大学硕士学位论文
采用犷检验，p<0.05认为差异有显著性意义。
结果
1.311例婴儿先心病手术中67例(2 1.5%)婴儿术后发生VAP。男51例，女16
例，年龄(7.2士3.3)月，其中单纯先心病39例，复杂先心病28例。复杂先
心病组vAP的发生率比单纯先心病组高(x切2.47，P<0.0。。l)，且迟发vAp
的构成比高(x2=6.02，p=0.014)。
2.分离出致病菌79株，革兰氏阴性(G〕菌为主，其次为真菌和革兰氏阳性(G+)菌。
G一菌中多见鲍曼不动杆菌、铜绿假单胞菌、脑膜炎败血黄色杆菌等。G+菌常
见金黄色葡萄球菌和表皮葡萄球菌。真菌以白色念珠菌为主。
3.耐药性:G一菌对亚胺培南/西司他丁、头抱呱酮嘟巴坦、呱拉西林地哇巴坦、
环丙沙星、阿米卡星、头抱他睫较敏感。但其中的嗜麦芽黄单胞菌、脑膜炎
败血黄色杆菌对亚胺培南/西司他丁耐药率高。产超广谱p一内酞胺酶菌主要为
肺炎克雷伯菌和大肠埃希菌，对一代、二代、三代
Ventilator-associated pneumonia(VAP) was considered ventilator-associated, if it developed 48 hours after mechanical ventilation, unless the clinical evidence strongly suggested otherwise. The time of onset of VAP after mechanical ventilation was used to define as early-onset VAP(< 5 d) or late-onset VAP (≥5 d). Although there have been many studies about VAP since Lareau et al analyzed factors associated with the onset of pneumonia in mechanical ventilated patients in the 1970s, new problem still emerges one after one and presents challenge to clinicians to treat with VAP.
The onset of VAP may due to, the severity of patients admited to ICU, inhibition of immunologic function, respiratory tract defense mechanics impairment after tracheal intubation, reflux and aspiration of gastric contents, crossinfection, frequent ventilator circuit changes, prolonged mechanical ventilation etc.
Although great efforts have been made both on keeping the ventilation equipments sterilized and treatment with ventilator-depedent patients to decrease nosocomial infection, 8-28% patients who received mechanical ventilation developed VAP yet. The frequency of nosocomial pneumonia in ICUs is obviously higher than common ward. Furthermore, tracheal intubation and mechanical ventilation increase the risk of pneumonia onset by 3-10 fold. The overall mortality attributed to VAP had been estimated at 11 % , but in several special conditions or with dangerous pathogens infection, the mortality can reach as high as 76%.
The causative pathogens of VAP vary widely depending on different conditions such as, underlying diseases, the duration of ICU stay etc. Most pathogens of VAP include gram-negative bacilli(GNB). More recently , however, some investigators had reported that gram-positive bacteria have become increasingly more common , the percentage of gram-positive cocci especially methicillin-resistant Staphylococcus aureu (MRSA), methicillin-resistant Staphylococcus epidermidis(MRSE) and enterococci increased, meanwhile the percentage of GNB decreased, for example, former commonly seen GNB such as Pseudomonas aeruginosa was less frequent in several adult ICUs.
The newborns and infants with congenital heart defect should receive corrective cardiac surgery at proper time. The majority of them will, if successfully treated, return to a normal productive life. VAP represents an important cause of mortality in this population and increases hospitalization costs.
There was few reports about epidemiology of VAP in infants after cardiac surgery. The causative pathogens maybe multi-resistant because preoperative recurrent
pneumonia and prior administration of antibiotics in these patients. The primary aim of this study was to describe the epidemiology of VAP in infants after cardiac surgery from June 1999 to June 2002 in our hospital. Special emphasis will be directed towards the trend of the changing distribution of the pathogen and its antibiotic resistance pattern during the last 3 years.
Methods
Setting This was a retrospective study using prospectively collected data performed at
the pediatric cardiovascular surgical ICU, Affiliated Children's Hospital, Zhejiang
University,China.
Patients Data were collected on 311 consecutive infants (aged from 8 days to 12
months) with congenital heart defect(CHD) who underwent open-heart surgery in our
hospital between June 1999 and June 2002 .
Sampling
Surveillance Samples: All patients were monitored for VAP after cardiac surgery by clinical standards and also by cultures of endotracheal aspirate. The technique of endotracheal aspiration was a simplified nonbronchoscopic diagnostic procedure(a blind procedure via a sterile suction catheter).
Diagnostic Samplings: Ventilator-associated pneumonia (VAP) was considered ventilator- associated, if it developed 48 hours after mechanical ventilation, unless the clinical evidence strongly suggested otherwise. VAP was defined as the presence of a
new or progressive roentgenographic infiltrate developed 48h after m
引文
[1]Rello J, Jubert P. Pneumonia in intubated patients: role of respiratory airway care. Am J Respir Crit care Meal, 1996, 154(1):111-5.
[2]American Thoracic Society. Hospital-acquired pneumonia in adults: diagnosis, assessment of severity, initial antimicrobial therapy, and preventive strategies. A consensus statement, American Thoracic Society, November 1995. Am J Respir Crit Care Meal, 1996, 153: 1711-1725.
[3]Luyt CE, Chastre J, Fagon JY. Value of the clinical pulmonary infection score for the identification and management of ventilator-associated pneumonia. Intensive Care Med, 2004,30:844-52.
[4]Chastre J, Fagon JY. Pneumonia in the ventilator-dependent patient. In: Tobin MJ, editor. Principles and practice of mechanical ventilation..New York: McGraw-Hill, 1994. p. 857-890.
[5]Pennington JE. Nosocomial respiratory infection. In: Mandell GL, Douglas RG Jr, Bennet JE, editors. Principles and practice of infectiousdiseases. St. Louis, MO: Churchill Livingstone, 1990. p. 2199-2205.
[6]Rello J, Valles J, Jubert P, et al. Lower respiratory tract infections following cardiac arrest and cardiopulmonary resuscitation. Clin Infect Dis, 1995, 21:310-314.
[7]Richards M J, Edwards JE, Culver DH, et al. Nosocomial infections in medical ICUs in the United States. National Nosocomial Infections Surveillance System. Crit Care Med, 1999, 27:887-892.
[8]Brown RB, Stechenberg B, Sands M. Infections in a pediatric intensive care unit. Am J Dis Child, 1987,141: 267-270.
[9]Craven DE, Stager KA. Epidemiology of nosocomial pneumonia: new perspectives on an old disease. Chest, 1995,108:1S-16S.
[10]Torres A, Aznar R, Gatell JM, et al. Incidence, risk, and prognosis factors of nosocomial pneumonia in mechanically ventilated patients. Am Rev Respir Dis, 1990,142:523-528.
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[12]谈林华，朱雄凯，张泽伟，等．小儿先天性心脏病术后呼吸机相关性肺炎及危险因素．中华胸心血管外科杂志，2001，17(6)：337-339．
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[15]Craven DE. Epidemiology of ventilator-associated pneumonia. Chest, 2000, 117:186S-187S.
[16]Bonten M J, Bergmans DC, Speijer H, Stobberingh EE. Characteristics of polyclonal endemicity of Pseudomonas aeruginosa colonization in intensive care
units. Implications for infection control. Am J Respir Crit Care Med, 1999;160:1212-1219.
[17]Trouillet JL, Chastre J, Vuagnat A, et al. Ventilator-associated pneumonia caused by potentially drag-resistant bacteria. Am J Respir Crit Care Med, 1998, 157: 531-539.
[18]Singh N, Falestiny MN, Rogers P, Reed MJ, Pularski J, Norris R, Yu VL. Pulmonary infiltrates in the surgical ICU: prospective assessment of predictors of etiology and mortality. Chest, 1998;114:1129-1136.
[19]Einhom AE, Neuhauser MM, Bearden DT, et al. Extended-spectrum beta-lactamases: frequency, risk factors, and outcomes. Pharmacotherapy, 2002, 22:14-20.
[20]Gonzalez C, Rubio M, Romero-Vivas J, et al. Bacteremic pneumonia due to Staphylococcus aureus: A comparison of disease caused by methicillin-resistant and methicillin-susceptible organisms.Clin Infect Dis, 1999,29:1171-1177.