Primary Klebsiella pneumoniae liver abscess complicated with metastatic meningitis or endophthalmitis is a globally emerging infectious disease. Its pathogenic mechanism remains unclear. The bacterial virulence factors were explored by comparing clinical isolates. Differences in mucoviscosity were observed between strains that caused primary liver abscess (invasive) and those that did not (noninvasive). Hypermucoviscosity correlated with a high serum resistance and was more prevalent in invasive strains (52/53 vs. 9/52; P < 0.0001). Transposon mutagenesis identified candidate virulence genes. A novel 1.2-kb locus, magA, which encoded a 43-kD outer membrane protein, was significantly more prevalent in invasive strains (52/53 vs. 14/52; P < 0.0001). The wild-type strain produced a mucoviscous exopolysaccharide web, actively proliferated in nonimmune human serum, resisted phagocytosis, and caused liver microabscess and meningitis in mice. However, magA⁻ mutants lost the exopolysaccharide web and became extremely serum sensitive, phagocytosis susceptible, and avirulent to mice. Virulence was restored by complementation using a magA-containing plasmid. We conclude that magA fits molecular Koch's postulates as a virulence gene. Thus, this locus can be used as a marker for the rapid diagnosis and for tracing the source of this emerging infectious disease.

Background. Since 1986, researchers have noted a syndrome of Klebsiella pneumoniae pyogenic liver abscess that is complicated by endophthalmitis or central nervous system infections. There are limited data regarding the role of bacterial genotype in the pathogenesis of this syndrome.

Nosocomial infections caused by antibiotic-resistantKlebsiella pneumoniaeare emerging as a major health problem worldwide, while community-acquiredK. pneumoniaeinfections present with a range of diverse clinical pictures in different geographic areas. In particular, an invasive form ofK. pneumoniaethat causes liver abscesses was first observed in Asia and then was found worldwide. We are interested in how differences in gene content of the same species result in different diseases. Thus, we sequenced the whole genome ofK. pneumoniaeNTUH-K2044, which was isolated from a patient with liver abscess and meningitis, and analyzed differences compared to strain MGH 78578, which was isolated from a patient with pneumonia. Six major types of differences were found in gene clusters that included an integrative and conjugative element, clusters involved in citrate fermentation, lipopolysaccharide synthesis, and capsular polysaccharide synthesis, phage-related insertions, and a cluster containing fimbria-related genes. We also conducted comparative genomic hybridization with 15K. pneumoniaeisolates obtained from community-acquired or nosocomial infections using tiling probes for the NTUH-K2044 genome. Hierarchical clustering revealed three major groups of genomic insertion-deletion patterns that correlate with the strains' clinical features, antimicrobial susceptibilities, and virulence phenotypes with mice. Here we report the whole-genome sequence ofK. pneumoniaeNTUH-K2044 and describe evidence showing significant genomic diversity and sequence acquisition amongK. pneumoniaepathogenic strains. Our findings support the hypothesis that these factors are responsible for the changes that have occurred in the disease profile over time.

To prospectively evaluate lung parenchyma on paired inspiration-expiration thin-section computed tomographic (CT) scans in patients recovering from severe acute respiratory syndrome (SARS). After the institutional review board approved the study and written consent was obtained from patients, 40 patients (25 female, 15 male; mean age, 42.8 years +/- 12.3 [standard deviation]) underwent thin-section CT at 51.8 days +/- 20.2 after onset of SARS symptoms. Twenty of the 40 patients underwent follow-up thin-section CT at 140.7 days +/- 26.7 after symptom onset. Lung findings were scored according to extent and then grouped in three categories (ground-glass opacity, interstitial opacity, and air trapping) for analysis. Mean CT scores for each finding in the various patient subgroups were compared by using the Mann-Whitney test. Clinical parameters and scores were evaluated for correlation by using Spearman rank correlation analysis. Mean scores for each finding were compared between the two serial examinations by using the Wilcoxon matched-pairs signed rank test. Air trapping, ground-glass opacity, and reticulation were found in 37 (92%), 36 (90%), and 28 (70%) of 40 patients, respectively, at initial thin-section CT examination and in 16 (80%), 14 (70%), and 10 (50%) of 20 patients, respectively, at follow-up examination. Scans from patients with adult respiratory distress syndrome (ARDS) had a significantly higher score for ground-glass opacity than did those from patients without ARDS (P = .009). A comparison of scores for the serial thin-section CT examinations indicated a significant reduction in the extent of ground-glass opacity (P < .001) and interstitial opacity (P < .001) but not in that of air trapping (P = .38) at follow-up examination. At initial thin-section CT, scores for ground-glass opacity, interstitial opacity, and air trapping correlated with age; those for ground-glass opacity and air trapping, with peak C-reactive protein level. At the second examination, scores for ground-glass opacity and interstitial opacity correlated with peak lactate dehydrogenase level; that for air trapping, with age and peak C-reactive protein level. Thin-section CT scores correlated with clinical and laboratory parameters in patients after SARS. Although ground-glass opacity and interstitial opacity resolve over time, air trapping persists.

Aortic dissection and aortic aneurysm are major life-threatening diseases worldwide.^1,2 Epidemiology studies show that mortality from aortic aneurysm and dissection has risen over the past decades in many developed countries including the United States, Britain, and Japan, with the rate of increase ranging from 1.2 to 24.8 fold.^3-6 In fact, aortic aneurysm has become the 13th leading cause of death, claiming an estimated 15 000 deaths annually in the United States.⁷ Aortic dissection is defined as separation of the layers within the aortic wall, while aortic aneurysm is defined as a localized or diffuse dilation of the aorta.^8,9 Both aortic aneurysm and dissection are caused by weakness of the aortic wall due to congenital defect, hypertension, or chronic inflammation.^8-11 Ruptured aortic aneurysm and dissection are associated with high morbidity and mortality rates.^10,12,13 Many patients even experience out-of-hospital cardiac arrest before the diagnosis of aortic aneurysm or dissection is made.