Multiple methicillin-resistant Staphylococcus aureus (MRSA) clones carrying type IV staphylococcal cassette chromosome mec were identified in the community-acquired MRSA strains of both the United States and Australia. They multiplied much faster than health-care-associated MRSA and were resistant to fewer nonbeta-lactam antibiotics. They seem to have been derived from more diverse S. aureus populations than health-care-associated MRSA strains.
Staphylococcal cassette chromosome mec (SCCmec) is a mobile genetic element composed of the mec gene complex, which encodes methicillin resistance, and the ccr gene complex, which encodes the recombinases responsible for its mobility. The mec gene complex has been classified into four classes, and the ccr gene complex has been classified into three allotypes. Different combinations of mec gene complex classes and ccr gene complex types have so far defined four types of SCCmec elements. Now we introduce the fifth allotype of SCCmec, which was found on the chromosome of a community-acquired methicillin-resistant Staphylococcus aureus strain (strain WIS [WBG8318]) isolated in Australia. The element shared the same chromosomal integration site with the four extant types of SCCmec and the characteristic nucleotide sequences at the chromosome-SCCmec junction regions. The novel SCCmec carried mecA bracketed by IS431 (IS431-mecA⌬mecR1-IS431), which is designated the class C2 mec gene complex; and instead of ccrA and ccrB genes, it carried a single copy of a gene homologue that encoded cassette chromosome recombinase. Since the open reading frame (ORF) was found to encode an enzyme which catalyzes the precise excision as well as site-and orientation-specific integration of the element, we designated the ORF cassette chromosome recombinase C (ccrC), and we designated the element type V SCCmec. Type V SCCmec is a small SCCmec element (28 kb) and does not carry any antibiotic resistance genes besides mecA. Unlike the extant SCCmec types, it carries a set of foreign genes encoding a restriction-modification system that might play a role in the stabilization of the element on the chromosome.
The references given here (excluding some of low credibility) attest the increasing awareness of the two conspicuous problems concerning methicillin-resistant S. aureus infection. One is the increasing trend of glycopeptide-resistance, making difficult the successful treatment of multi-drug-resistant methicillin-resistant S. aureus infection in the hospital. On the other hand, non-multi-drug-resistant methicillin-resistant S. aureus strains are emerging as novel threats in the community, the genetic analysis of which indicates that they are independent clones from those found in hospitals.
Granulocytapheresis (GCAP) therapy is a newly developed therapeutic modality for inflammatory bowel diseases such as ulcerative colitis and Crohn's disease. Pyoderma gangrenosum (PG) is a chronic inflammatory skin disease characterized by the appearance of erythematous macules and plaques with pustules or nodules that rapidly progress to ragged, undermined multiple ulcers. We attempted GCAP therapy in a patient with PG resistant to prednisolone and various other immunosuppressants. GCAP therapy was initiated at three- to four-day intervals and a good response from all skin lesions, with eventual total epithelialization, was observed after 10 sessions of this therapy. Furthermore, circulating levels of inflammatory cytokines such as interleukin-8 (IL-8) and granulocyte colony stimulating factor (G-CSF) also decreased after the GCAP therapy. Our results suggest that GCAP is a safe and useful tool for the treatment of intractable PG, and that IL-8 and G-CSF are likely to be involved in the pathogenesis of PG.
Psoriatic arthritis (PsA), a chronic inflammatory arthropathy associated with psoriasis, is an intractable immune disorder and refractory to pharmacological intervention. We assessed efficacy of selective depletion of myeloid lineage leukocytes in patients with PsA in a multicenter setting. A total of 20 patients with moderate to severe PsA refractory to conventional and biological disease-modifying antirheumatic drugs were included. Eligible patients had 3 points or more in the classification criteria for PsA. Each patient received five sessions, once a week, of adsorptive granulocyte and monocyte apheresis (GMA) with the Adacolumn . The primary efficacy outcome was 20% or more decrease in the American College of Rheumatology score 20 (ACR20). Partial responders could receive an additional five GMA sessions. Of 20 patients, two did not complete the study, nine responded to five GMA sessions and nine received 10 sessions. At the first evaluation 2 weeks after the last GMA session, 13 of the 20 (65.0%) patients achieved ACR20. ACR20 was maintained in seven of 10 (70%) and five of 10 (50%) patients at the follow-up evaluation points 8 and 20 weeks after the last GMA session, respectively. GMA was well tolerated without any safety concern. This study demonstrates that GMA with the Adacolumn was effective with good safety profile in patients with PsA refractory to pharmacologicals. The results indicate a major role for myeloid leukocytes in the immunopathogenesis of PsA. A large controlled study is warranted to fully evaluate the efficacy of Adacolumn GMA in patients with PsA.
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