| First part:Correlation between drug resistance of Pseudomonas aeruginosa causing pneumonia and mortalityObjective:To explore the drug resistance of Pseudomonas aeruginosa causing pneumonia and the related risk factors for mortality. Methods:This prospective cohort clinical study was conducted in a tertiary surgical intensive care unit(SICU) in Zhongshan Hospital, Fudan University. From Jan2007to Dec2010, a total of53patients who underwent endotracheal intubation and ventilated for more than48hours and were with positive culture of P. aeruginosa were enrolled in this study; the drug susceptibility testing was performed by KB method. The vital signs, ventilation parameters, treatment regiments of the patients were recorded, the follow-up of the mortality within28days was carried out.Results:Of8commonly used antibiotics against P. aeruginosa, amikacin was with the lowest resistance rate of15.1%, followed by cefoperazone/sulbactam, meropenem, ceftazidime, cefepime, and imipenem; the resistance rate to piperacillin/tazobactam was the highest (47.2%), the multidrug-resistant rate was32.1%; of53patients,17patients died and11patients died within28days; the drug resistance rates of P. aeruginosa to piperacillin/tazobactam and imipenem and the multidrug-resistance rate were much higher in death group than in the survival group (76.5%vs33.3%,58.8%vs27.8%, and58.8%vs19.4%, respectively)(P<0.05). There was significant difference between survivors and non-survivors for age (75.5vs56.0respectively)(P<0.05); of the patients in the death group, the survival days of the patients resistant to imipenem were less than those of the patients without imipenem-resistance (P=0.025); multivariate logistic regression analysis showed that there was significant correlation between the age, duration of mechanical ventilation, multidrug-resistance of P. aeruginosa, resistance to piperacillin/tazobactam and the mortality. Conclusion:For the dead patients, the survival days of imipenem-resistant patients are significantly shortened; the age, duration of mechanical ventilation, multidrug-resistance, and the resistance to piperacillin/tazobactam are the independent risk factors for P. aeruginosa infection in the SICU patients. Second part:Therapeutic effects of keratinocyte growth factor-2on pseudomonas aeruginosa-induced pneumonia and acute lung injury Objective:To build the model of pseudomonas aeruginosa-induced severe pneumonia in mice in vivo and to investigate therapeutic role of intravenous application and intratracheal instillation of keratinocyte growth factor-2in vivo against severe Pseudomonas aeruginosa pneumonia, including the impacts on the survival rates of mice, bacterial clearance from the air spaces and P. aeruginosa-induced acute lung injury.Methods:180specified-pathogens free male BALB/C were used for P. aeruginosa infection models. The mice instilled with5X106P. aeruginosa (Pa103and R4) intratracheally into the left lung were separately randomized into four group:control group:without any treatment; group rhKGF-2:treatment with rhKGF-25mg/kg intravenously immediately after modeling; group ceftazidime:injecting of; ceftazidime500mg/kg bid intraperitoneally immediately after modeling; group rhKGF-2+group ceftazidime:treatment with rhKGF-25mg/kg intravenously and injecting of ceftazidime500mg/kg bid intraperitoneally immediately after modeling. The survival of mice with severe pneumonia was observed within7days. Another mice were randomized into two group:control group:1×107PaOlwas used to instilled in the trachea;group rhKGF-2:when1×107PaOlwas used to instilled in the trachea, KGF was immediately administered by the intratracheal route and the dose was5mg/kg. The survival of mice was also observed within7days. The remaining mice were also randomized into two group:control group:5×106Pa01was used to instilled in the trachea group rhKGF-2:when5×106PaOlwas used to instilled in the trachea,5 mg/kg rhKGF-2was immediately administered by the intratracheal route. The curve of body temperature was recorded. The amount of P. aeruginosa, the levels of total proteins, the total cell count and the mononuclear macrophages count in bronchoalveolar lavage fluid(BALF)were examined. Furthermore, the pathological change of lung was observed under light microscope, and the lung injury score was also evaluated.Results:The mice with severe pneumonia caused by Pa103and R4were died within24h, the survival time of mice could prolong to48h when treated with rhKGF-2. However, there are no statistical difference in survival rate between group rhKGF-2and control group(P>0.05). Compared with control group, survival rate of those mice of group ceftazidime was significantly increased(P<0.05); However, no statistical difference between the group ceftazidime and group rhKGF-2+group ceftazidime (p>0.05). Some of the mice with severe pneumonia caused by1×107Paol were died, while all mice instilled with5X106Paolwere survived. The suivival rate of the mice with severe pneumonia caused by1×107Paol was significantly increased, Compared with ceftazidime group (P<0.05). After4h,24h,72h and7d treatment with rhKGF-2, colony forming units of rhKGF-2group were statistically decredsed, compared with colony forming units of control group in lung homogenates. There are no statistical difference in the numbers of total cells in the BALF between group rhKGF-2and control group(P>0.05), While the numbers of mononuclear macrophages in the BALF were significantly higher than those of the control group (P<0.05). The levels of total protins of group rhKGF-2were significantly lower than those of the control group in24h, while there are no statistical difference in4h and72h after intratracheal instillation of P. aeruginosa. Intratracheal instillation of rhKGF-2resulted in significantly decreased lung injury score in72h (P<0.05).Conclusion:Intravenous and topical instillation of rhKGF-2could not improve the survival rate of mice with letaral pneumonia caused by Pa103and R4, while the suivival rate of the mice with severe pneumonia caused byPaol are significantly increased. Topical administration of rhKGF-2accelerates the clearance of P. aeruginosa from the lungs, increase the number of mononuclear macrophages in the BALF and attenuates lung injury induced... |
PDF Full Text Request