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Research On Risk Factors For Pathogen And The Development Of Infections In Patients With Liver Cirrhosis And Antibiotic Resistence, Drug Resistence Gene Of Bacteria

Posted on:2014-02-09Degree:DoctorType:Dissertation
Country:ChinaCandidate:T S GuoFull Text:PDF
GTID:1224330398456645Subject:Laboratory Diagnosis
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BACKGROUNDThere were500,000individuals in the world die each year from liver cirrhoses and the numbers are increasing steadily. Liver cirrhosis is now the fifth most common cause of death after heart disease, stroke, chest disease and cancer. However, unlike other major causes of mortality, liver cirrhosis rates are increasing rather than declining. For hepatologists worldwide, there have never been more challenges faced. Cirrhosis is considered an immunocompromised state that leads to a variety of infections, which then account for an approximate30%-50%mortality. Bacterial infections occer in32%to34%of admitted patients with cirrhosis. Apart from early recognition and better treatment of spontaneous bacterial peritonitis (SBP) leading to better survival, there has been little improvement in overall survival rates in recent decades:infections still account for a4-fold increase in mortality among patients with cirrhosis. There are many data about the infections risk factors, independent risk facters, distrabution of pathogens, antibiotics resistence spectrum of patients with cirrhosis in different countries and parts worldwide. But the data were not same. But there were no data on distribution fo infections, pathogen and bacterial resistence spectrum of bloodstream infection, and E. coli bacterimia in patients with cirrhosis in China. These data are necessary to help docters prevention, early diagnosis, and proper management of these infections to improve survival.AIM1. To investigate the infection rate in hospitalized patients with liver cirrhosis and to assess the risk facors of infections. 2. To analyze the spectrum of bacteria and bacterial resistence in hospitalized patients with liver cirrhosis. To find changes by comparing the data from2001to2004.3. To identify the risk factors for bloodstream infections caused by extended-spectrum beta-lactamase(ESBLs)-producing Escherichia coli in hospitalized patients with liver cirrhosis and the associated clinical outcomes of bacteremia..METHODS1. The prospective study was performed to assess the risk of bacterial infection in420hospitalized patients with liver cirrhosis. The data collected included age, gender, etiology of liver disease, reason for admission, admission site, origin of admission, endoscopic sclerotherapy or banding, variables of the Child-Pugh score (serum bilirubin and albumin, prothrombin time, degree of ascites, and encephalopathy), timing of bacterial infection after hospitalization, duration of hospitalization, and discharge status (alive vs dead). Univariate Analysis and logistic regression were used to analyse the risk fachors and independent risk factors of infections.2. Auto bacterial culture system and identification system were performed to analyze the spectrum of1017bacteria and the antibiotic resistence. The changes of spectrum of bacteria and bacterial resistence were found by comparing with the data of2001to2004.3.62ESBLs-producing E coli were genotyped by multi-PCR, PCR, sequancing and blast. Case control research was performed. Risk facters and independent risk factors were analyzed by univariate analysis, multivariate analysis, and logistic regression between research group and control group.RESULTS1. Twenty-eight (20%) patients developed an infection during their hospitalization. of Spontaneous bacterial peritonitis (32%) were the most common infections. Univariate analysis showed that patients who developed an infection were more likely to have a low serum albumin level, gastrointestinal bleeding, to stay in the intensive care unit, and to undergo therapeutic endoscopy. Logistic regression identified gastrointestinal bleeding (OR=4.3,95%CI=1.7-10.9) and a low serum albumin (OR=1.3,95%CI=1.03-1.22) as the only two variables independently associated with the development of an infection..2.30genera,88species and1017strains were obtained from the blood cultures in patients with liver cirrhosis, including1014-strain aerobic isolates (99.7%),0anaerobic isolates (0.0%) and3fungi (0.3%). The most common pathogens were Escherichia coli(308strains), coagulase-negative Staphylococcus(245strains), and Klebsiella spp.(102strains), streptotococcus spp.(78strains), and staphylococcus aus(36strains). Compared with the data of2001-2004, there was a big decrease of the rate of gram-negtive bacteria(P=0.0469). ESBLs-producing rate in E coli had an markable increase (P<0.0001)3. A total of123non-duplicate clinical isolates of E coli were consecutively collected from liver cirrhosis patients with bloodstream infection.62clinical isolates were detected to produce CTX-M type ESBLs. there were31CTX-M-1group and37CTX-M-9group, including6stains habouring both CTX-M-1and CTX-M-9group. Eight CTX-M genotypes were confirmed by sequencing of the PCR products, including CTX-M-3, CTX-M-14, CTX-M-15, CTX-M-24, CTX-M-28, CTX-M-31, CTX-M-65and CTX-M-79. Previous antibiotic treatment, previous beta-lactamase antibiotic treatment,and nosco were the independent risk factor for bacteremia due to ESBLs-producing E coli (OR=4.184,95%CI=1.697-10.3, OR=4.365,95%CI=1.611-11.83, and OR=5.333,95%CI=1.850-15.37, respectively). nosocomial infection, septic shock, encephalopathy, and renal impired t reatment were the independent risk factors for higher mortality rate (OR=9.128,95%CI=1.850-15.37, OR=14.55,95%CI=4.428-14.78, OR=5.143,95%CI=1.913-13.82, and OR=4.136,95%CI=1.374-12.46, respectively).CONCLUSIONS:1. Our present study indicates that patients with liver cirrhosis who are admitted for gastrointestinal bleeding and low serum albumin level have a higher risk of developing a infection during their hospitalization than other cirrhotic patients.2. The most common pathogens isolated from blood cultures in patients with liver cirrhosis were gram-negtive bacteria. But the rate of ESBLs-producing E coli was higher than the data of2001-2004.3. The dominant genotype of ESBLs produced by E coli isolated from bloodstream infection in patients with liver cirrhosis were CTX-M. Quick detection and early appropriate antibiotic treatment and prevention are urgently needed for ESBLs-producing E coli bacterimia in patients with cirrhosis.
Keywords/Search Tags:Liver Cirrhosis, Infection, Bloodstream, pathogen, extended-spectrumbeta-lactamase
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