Background: The major impact of alcohol on the host is impairment of T-cell mediated immunity, such as impairment of transduction pathway, impaired lymphocyte migration, and suppress of IL-2, IL-12, and INF-γ response to infection. In the infected site of lung caused by Klebsiella pneumoniae, inadequate lymphocyte recruitment links to weaken clearance of K. pneumoniae from lung infections, thus leading to severe pneumonia. The compensatory activation of TNF-α-producing T cell could further cause life-threatening sepsis. Therefore, alcoholic patients with K. pneumoniae pneumonia are highly fatal. However, the virulence nature of the pathogenic K. pneumoniae in alcoholic patients has not been elucidated. The goals of the study were to investigate the virulence factors of hypermucoviscosity phenotype and rmpA gene among the K. pneumoniae isolates causing alcoholic pneumonia and to evaluate the clinical characteristics of these patients. Material and Methods: The alcoholic patients admitted to intensive care units (ICUs) with K. pneumoniae pneumonia were enrolled. The hypermucoviscosity phenotype was defined positive as a viscous string of > 5 mm of the colony on blood agar plate. Genomic DNA was extracted for screening the K capsule serotype genes and plasmid DNA was also extracted for detection of rmpA gene. The K capsule serotype and rmpA genes were identified by PCR and were confirmed by DNA sequencing. The virulence of K. pneumoniae for mouse lethality was determined by the medium lethal dose (LD50). Results: The age of the 14 alcoholic patients ranged from 40 to 81 years, with 3 patients > 65 years. Twelve patients were man. Six patients were diabetic and 2 patients had liver cirrhosis. Five patients had initial fever. Five patients had concurrent K. pneumoniae bacteremia. All patients needed mechanical ventilator for respiratory support. Complications were acute respiratory distress syndrome (n = 9), lung abscesses (n = 3), and pneumothorax (n = 3). The initial white blood cell counts ranged from 500/μL to 37,000/μL (mean + SD, 12,360 + 12,200/μL) and 6 patients had leukopenia. Eight patients had thrombocytopenia. The K capsule types were K2 (n = 3), K1 (n = 2) and others (n = 9). Ten isolates had the hypermucoviscosity phenotype and 12 isolates had rmpA gene. However, isolates with the virulence factors were not significantly associated with severity and mortality of the infected patients. Four representative strains with virulence factors showed the LD50 ranging between 102 to 103 CFU, and one isolate without virulence factors showed a LD50 of > 107 CFU. Six patients died in the hospital including 5 in the ICUs on the 1st, 3rd, 4th, 13th, and 14th day, respectively. Mortality patients were significantly associated with initial presentation of high TISS score, high SOFA score, low platelet count, low PaO2/FiO2 ratio, APACHE II score > 25, thrombocytopenia, septic shock, ARDS, and PaO2/FiO2 ratio < 100 mm Hg. The platelet count and PaO2/FiO2 ratio established the best model of hazard ratios for in-hospital mortality. Conclusion: We confirmed that the virulence factors were highly prevalent in the K. pneumoniae isolates causing alcoholic pneumonia. Isolates with virulence factors might be highly virulent with low LD50 in mouse lethality experiments. However, these virulence factors of the causative organisms did not further contribute to the disease severity and mortality of alcoholic patients with K. pneumoniae pneumonia.
|主出版物標題||Klebsiella Infections: Epidemiology, Pathogenesis and Clinical Outcomes|
|出版狀態||已發佈 - 2013|