医院获得性铜绿假单胞菌肺炎死亡率相关性研究及角质细胞生长因子-2治疗铜绿假单胞菌肺炎的作用

发布时间：2018-04-22 05:27

本文选题：医院内肺炎 + 铜绿假单胞菌　；参考：《复旦大学》2013年硕士论文

【摘要】：第一部分医院铜绿假单胞菌性肺炎对抗菌药物耐药性及死亡率相关性研究目的探讨铜绿假单胞菌引起的医院内肺炎患者抗菌药物的耐药率及其可能的死亡相关危险因素。方法采用前瞻性队列临床研究,对中山医院外科重症监护病房(SICU)2007年1月—2010年12月气管插管和机械通气时间48h,且首次痰培养检出铜绿假单胞菌的53例患者,采用K-B法抗菌药物敏感试验,记录患者生命体征、通气参数、治疗方案,并随访28d死亡率。结果在8种常用的抗菌药物中阿米卡星耐药率最低,为15.1%,其次为头孢哌酮/舒巴坦、美罗培南、头孢他啶、头孢吡肟、亚胺培南,哌拉西林/他唑巴坦耐药率最高为47.2%,多药耐药率为32.1%；53例患者中,17例死亡,11例在28d内死亡；死亡组铜绿假单胞菌对哌拉西林/他唑巴坦、亚胺培南耐药率和多药耐药率分别为76.5%、58.8%和58.8%,非死亡组分别为33.3%、27.8%和19.4%(P0.05)；死亡患者中,耐亚胺培南患者的生存时间少于非耐药者(P0.05)；多因素分析年龄、机械通气时间、哌拉西林/他唑巴坦耐药、多药耐药和死亡率明显相关。结论死亡患者中,对亚胺培南耐药患者生存时间明显缩短；年龄、机械通气时间、多药耐药、哌拉西林/他唑巴坦耐药是住SICU患者铜绿假单胞菌感染后独立的危险因素。第二部分角质细胞生长因子-2对铜绿假单胞菌所致的肺部感染和急性肺损伤的治疗作用目的本实验通过建立小鼠铜绿假单胞菌肺炎模型,旨在研究全身和局部使用KGF-2治疗铜绿假单孢菌肺炎和急性肺损伤的作用。方法本实验选用SPF级BALB/C小鼠180只,铜绿假单胞菌标准株PA01、PA103和临床耐药株R4。经气道内分别给以PA103或RA,5×106CFU/只注入左肺内,造成小鼠重症肺炎模型,对照组无处理,实验组分别为头孢他啶治疗500mg/kgbid腹腔注射、尾静脉注射5mg/kg rhKGF-2治疗和两药物联合治疗,观察小鼠的生存情况,记录生存曲线。经气道内注入PA01,剂量分别为1×107CFU/只和5×106CFU/只,对照组无治疗,实验组rhKGF-2以5mg/kg体重同时经气道内给药治疗,高剂量PA01肺炎观察小鼠的生存情况；低剂量组观察rhKGF-2气道内注入后4h、1d、3d和7d,两组小鼠的体温曲线、肺组织细菌计数、支气管肺泡灌洗液(BALF)总蛋白浓度、BALF白细胞计数及分类计数和肺组织病理评分。结果实验结果显示,Pa103和R4感染所致的重症肺炎小鼠24h内死亡,仅用rhKGF-2治疗延长生存时间到48h,生存率与对照组相比无差异(P0.05)；头孢他啶治疗组与对照组相比,生存率差异有统计学意义(P0.05),改善小鼠的生存率；联合治疗组生存率较单用头孢他啶治疗组差异无统计学意义(P0.05)。高剂量Pa01菌株造成小鼠死亡的重症肺炎,rhKGF-2治疗组较对照组,生存率差异显著,有统计学意义(P0.05)。低剂量Pa01菌株造成小鼠生存的肺炎模型,rhKGF-2组较对照组比较,肺组织内细菌菌落计数明显降低,有统计学意义(P0.05)。两组BALF白细胞总数无明显差异,但rhKGF-2治疗后BALF巨噬细胞数量增多,差异明显(P0.05),中性粒细胞数量减少,差异明显(P0.05)rhKGF-2组BALF总蛋白浓度在24h降低,4h和72h无明显差异。病理提示对照组肺组织炎症细胞浸润、肺组织实变、间质水肿等损伤表现显著。rhKGF-2治疗组病理评分,在rhKGF-2治疗4h和24h时较对照组降低不明显(P0.05),在72h时较对照组显著降低(P0.05), 结论rhKGF-2全身治疗对Pa103和R4所致重症肺炎小鼠的生存率无改善作用,提高了Pa01菌株造成的重症肺炎小鼠的生存率。rhKGF-2局部给药对Pa01感染所致非重症肺炎和肺损伤有治疗作用,其作用可能与rhKGF-2增加肺内细菌的清除,及肺泡巨噬细胞的数目有关。
[Abstract]:Part one: correlation between antimicrobial resistance and mortality in patients with Pseudomonas aeruginosa pneumonia in hospital
Objective to investigate the antibiotic resistance rate and possible death related risk factors of nosocomial pneumonia caused by Pseudomonas aeruginosa.
Methods using prospective cohort clinical study, 53 patients with Pseudomonas aeruginosa from January 2007 to December 2010 in Zhongshan hospital surgical intensive care unit (SICU) were detected by 48h, and Pseudomonas aeruginosa was detected for the first time in sputum culture. The K-B method of antimicrobial susceptibility test was used to record the patient's vital signs, ventilation parameters, and treatment plan. Visit the 28d mortality rate.
Results the resistance rate of Amikacin was the lowest among the 8 commonly used antibiotics, followed by Cefoperazone / sulbactam, meropenem, ceftazidime, cefimetime, imipenem, piperacillin / tazobactam, 47.2% and 32.1%, 17 of the 53 patients, 11 in 28d, and the death group of aeruginosa. The rate of piperacillin / tazobactam, imipenem resistance and multidrug resistance were 76.5%, 58.8% and 58.8%, respectively, 33.3%, 27.8% and 19.4% (P0.05) in non death groups, and the survival time of imipenem resistant patients was less than that of non drug resistant patients (P0.05); multifactor analysis age, mechanical ventilation time, piperacillin / tazole The survival time of imipenem resistant patients was significantly shortened in the death patients; age, mechanical ventilation time, multidrug resistance, piperacillin / tazobactam resistance were independent risk factors for SICU patients after Pseudomonas aeruginosa infection.
The second part is the therapeutic effect of keratinocyte growth factor -2 on pulmonary infection and acute lung injury caused by Pseudomonas aeruginosa.
Objective the aim of this experiment was to establish a mouse model of Pseudomonas aeruginosa pneumonia in order to study the effect of KGF-2 on Pseudomonas aeruginosa pneumonia and acute lung injury in the whole body and local use. Methods 180 SPF BALB/C mice were selected, PA01 of Pseudomonas aeruginosa, PA103 and R4. in the airway were given PA103 or RA, respectively, in the airway. 5 * 106CFU/ was only injected into the left lung, causing severe pneumonia in mice and no treatment in the control group. The experimental group was treated with ceftazidime for 500mg/kgbid intraperitoneal injection, the tail vein injected with 5mg/kg rhKGF-2 and the combined treatment of two drugs. The survival conditions of the mice were observed and the survival curve was recorded. The injection of PA01 in the airway was 1 * 107CFU/, respectively. And 5 x 106CFU/ only, the control group had no treatment. The experimental group rhKGF-2 was treated with 5mg/kg body weight simultaneously through the airway administration and high dose of PA01 pneumonia to observe the survival of the mice; the low dose group observed the 4h, 1D, 3D and 7d after the injection of rhKGF-2 in the airway, the temperature curve of the two groups, the count of the lung tissue, the total protein concentration of the bronchoalveolar lavage fluid (BALF). BALF leucocyte count, classification count and lung histopathology score. Results the results showed that the severe pneumonia mice caused by Pa103 and R4 infection were dead in 24h, and the survival time was prolonged to 48h only with rhKGF-2 (P0.05), and the difference of survival rate in the ceftazidime group was statistically significant compared with the control group. Significance (P0.05), improve the survival rate of mice; the survival rate of the combined treatment group was no significant difference compared with the single ceftazidime group (P0.05). The high dose Pa01 strain caused severe pneumonia in mice and the rhKGF-2 treatment group was more significant than the control group. There was a significant difference in survival rate (P0.05). The low dose Pa01 strain caused the survival of mice. Compared with the control group, the bacterial colony count in the lung tissue was significantly lower in the rhKGF-2 group than in the control group (P0.05). There was no significant difference in the total number of BALF leukocytes in the two groups, but the number of BALF macrophages increased significantly after the rhKGF-2 treatment (P0.05), the number of neutrophils decreased, and the total BALF protein concentration in the group of rhKGF-2 group was significantly (P0.05) in the group of rhKGF-2. 24h decreased, and there was no significant difference between 4H and 72h. Pathological findings showed that the infiltration of inflammatory cells in lung tissue, pulmonary tissue change, interstitial edema and other injuries in the control group were significantly lower than those of the control group (P0.05) in the treatment of 4H and 24h in rhKGF-2 (P0.05), and significantly lower in 72h (P0.05) at 72h than those in the control group.
Conclusion rhKGF-2 systemic therapy has no effect on the survival rate of severe pneumonia in mice caused by Pa103 and R4, and improves the survival rate of severe pneumonia mice caused by Pa01 strain,.RhKGF-2 local administration has the therapeutic effect on the non severe pneumonia and lung injury caused by Pa01 infection. The effect may increase the clearance of the lung bacteria and the alveolar macrophage by rhKGF-2. The number of cells is related.

【学位授予单位】：复旦大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R563.1

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