No abstract

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.

NCT00803595.

genospecies 2 of the A. baumannii complex was associated with greater resistance to antibiotics and higher mortality among bacteremic patients, compared with other genospecies, especially genospecies 13TU. These findings emphasize the need to focus on genospecies to better understand the pathogenesis and epidemiology of infections caused by the A. baumannii complex.

BackgroundRisk factors and outcomes in hematological patients who acquire invasive fungal sinusitis (IFS) are infrequently reported in the modern medical era.MethodA retrospective study of hospitalized patients with hematological disease was conducted at National Taiwan University Hospital between January 1995 and December 2009.ResultsClinical characteristics and outcomes with their associated radiographic and microbiological findings were analyzed. Forty-six patients with IFS and 64 patients with chronic non-invasive sinusitis were enrolled as comparsion. IFS developed more commonly in patients with acute myeloid leukemia (AML) and with prolonged neutropenia (absolute neutrophil count less than 500/mm3 for more than 10 days) (p < 0.001). Aspergillus flavus was the most common pathogen isolated (44%). Serum Aspergillus galactomannan antigen was elevated in seven of eleven patients (64%) with IFS caused by aspergillosis but negative for all three patients with mucormycosis. Bony erosion and extra-sinus infiltration was found in 15 of 46 (33%) patients on imaging. Overall, 19 of 46 patients (41.3%) died within 6 weeks. Patients with disease subtype of AML (p = 0.044; Odds Ratio [OR], 5.84; 95% confidence interval [95% CI], 1.02-30.56) and refractory leukemia status (p = 0.05; OR, 4.27; 95% CI, 1.003-18.15) had worse prognosis. Multivariate analysis identified surgical debridement as an independent good prognostic factor (p = 0.047) in patients with IFS.ConclusionsPatients of AML with prolonged neutropenia (> 10 days) had significantly higher risk of IFS. Early introduction of anti-fungal agent and aggressive surgical debridement potentially decrease morbidity and mortality in high risk patients with IFS.

Antibody response correlates with severity of infection.

Klebsiella pneumoniae liver abscess with metastatic complications is an emerging infectious disease in Taiwan. To identify genes associated with liver infection, we used a DNA microarray to compare the transcriptional profiles of three strains causing liver abscess and three strains not associated with liver infection. There were 13 clones that showed higher RNA expression levels in the three liver infection strains, and 3 of these 13 clones contained a region that was absent in MGH 78578. Sequencing of the clones revealed the replacement of 149 bp of MGH 78578 with a 21,745-bp fragment in a liver infection strain, NTUH-K2044. This 21,745-bp fragment contained 19 open reading frames, 14 of which were proven to be associated with allantoin metabolism. The K2044 (⌬allS) mutant showed a significant decrease of virulence in intragastric inoculation of BALB/c mice, and the prevalence of this chromosomal region was significantly higher in strains associated with liver abscess than in those that were not (19 or 32 versus 2 of 94; P ‫؍‬ 0.0001 [ 2 test]). Therefore, the 22-kb region may play a role in K. pneumoniae liver infection and serve as a marker for rapid identification.

The number of adult patients with CA-MRSA bacteremia increased with time, and the disease was associated with more necrotizing pneumonia and cutaneous abscess but less endovascular infection than was CA-MSSA bacteremia. Patients with CA-MRSA bacteremia did not have higher mortality than did patients with CA-MSSA, even though most of the patients with CA-MRSA bacteremia did not receive empirical glycopeptide therapy.