Community-acquired pyogenic liver abscess caused by Klebsiella pneumoniae is an emerging infectious disease. We explored the capsular polysaccharide synthesis (cps) regions of three non-K1, non-K2 K. pneumoniae strains, A1142, A7754, and A1517, from Taiwanese patients experiencing pyogenic liver abscess. Two of the strains, A1142 and A7754, belonged to capsular serotype K57, while the third belonged to a new capsular serotype, different from the previously reported 77 serotypes. Deletion and complementation experiments suggested that a unique K57 gene, a homologue of wzy, was essential for K57 capsular synthesis and confirmed that this gene cluster was a genetic coding region for K57. Compared to K1 and K2 strains, the three strains were all serum sensitive, suggesting that host factors might also be involved in the three patients. PCR using primers from specific genes for K57 was more sensitive and specific than traditional serotyping. The remaining strain, A1517, did not react to the antisera from any of the 77 serotypes, and none of the 77 reference strains reacted to the serum against this strain. Moreover, PCR analyses using various primer pairs from the serotype-specific open reading frames did not reveal cross-reactivity to any of the 77 reference strains, suggesting that this strain likely represents a new capsular type. We conclude that sequences from these two cps regions are very useful in detecting K57 and the new cps genotype.
The purpose of this study was to increase awareness, gain insight into acquisition, and assess the virulence of the hypervirulent (hypermucoviscous) clinical variant (hvKP) that is entrenched in the Pacific Rim but emerging in Western countries. A case of community-acquired liver abscess with metastatic spread to the spleen is described. Comparative in vitro and in vivo virulence studies on this isolate (hvKP1) and four randomly chosen blood isolates of "classic" K. pneumonia strains (cKP1-4) were performed. Cases of hvKP infection are occurring in Western countries and are under-recognized. A hypermucoviscous phenotype is a surrogate laboratory marker for this variant. The propensity of hvKP strains for metastatic spread in non-compromised hosts is both a defining and unusual trait. The mode of acquisition in the described case was unclear but potential means are discussed. hvKP1 was more resistant to complement and neutrophil-mediated bactericidal activity and was more virulent in a rat subcutaneous abscess model than cKP1-4. Recognition of the hypermucoviscous phenotype, defined by a positive "string-test", will alert the microbiologist or clinician that the infecting strain may be a hvKP, which is hypervirulent compared to cKP. This will improve our understanding of the epidemiology and clinical spectrum of infection, which may be more extensive than appreciated.
Vancomycin is one of the older antibiotics that has been now in clinical use close to 60 years. Earlier on, vancomycin was associated with many side effects including vestibular and renal, most likely due to impurities contained in early vancomycin lots. Over the years, the impurities have been removed and the compound has now far less vestibular adverse effects, but still possesses renal toxicity if administered at higher doses rendering trough serum levels of >15 mcg/mL or if administered for prolonged periods of time. Vancomycin is effective against most Gram-positive cocci and bacilli with the exception of rare organisms as well as enterococci that became vancomycin resistant, mostly Enterococcus faecium. The major use of vancomycin today is for infections caused by methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE) and amoxicillin-resistant enterococci. In its oral form, vancomycin is used to treat diarrhea caused by Clsotridium difficile. With S. aureus, there are only a handful of vancomycin-resistant strains. Nevertheless, a “vancomycin creep” that is slow upward trending of vancomycin MIC from <1 mcg/mL to higher values has been noted in several parts of the world, but not globally, and strains that have MIC’s of 1.5–2 mcg/mL are associated with high therapeutic failure rates. This phenomenon has also been recently recognized in methicillin-susceptible S. aureus (MSSA). While vancomycin is relatively a safe agent adverse events include the “red man” syndrome, allergic reactions, and various bone marrow effects as well as nephrotoxicity. Vancomycin has been a very important tool in our therapeutic armamentarium that remained effective for many years, it is likely remain effective as long as resistance to vancomycin remains controlled.
Natural killer T cells (NKT cells) represent a subset of T lymphocytes that express natural killer (NK) cell surface markers. A subset of NKT cells, termed invariant NKT cells (iNKT), express a highly restricted T cell receptor (TCR) and respond to CD1d-restricted lipid ligands. iNKT cells are now appreciated to play an important role in linking innate and adaptive immune responses and have been implicated in infectious disease, allergy, asthma, autoimmunity, and tumor surveillance. Advances in iNKT identification and purification have allowed for the detailed study of iNKT activity in both humans and mice during a variety of chronic and acute infections. Comparison of iNKT function between non-pathogenic simian immunodeficiency virus (SIV) infection models and chronic HIV-infected patients implies a role for iNKT activity in controlling immune activation. In vitro studies of influenza infection have revealed novel effector functions of iNKT cells including IL-22 production and modulation of myeloid-derived suppressor cells, but ex vivo characterization of human iNKT cells during influenza infection are lacking. Similarly, as recent evidence suggests iNKT involvement in dengue virus pathogenesis, iNKT cells may modulate responses to a number of emerging pathogens. This Review will summarize current knowledge of iNKT involvement in responses to viral infections in both human and mouse models and will identify critical gaps in knowledge and opportunities for future study. We will also highlight recent efforts to harness iNKT ligands as vaccine adjuvants capable of improving vaccination-induced cellular immune responses.
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