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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several studies have implicated a role of peptidoglycan (PepG) as a pathogenicity factor in sepsis and organ injury, in part by initiating the release of inflammatory mediators. We wanted to elucidate the structural requirements of PepG to trigger inflammatory responses and organ injury. Injection of native PepG into anesthetized rats caused moderate but significant increases in the levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and bilirubin (markers of hepatic injury and/or dysfunction) and creatinine and urea (markers of renal dysfunction) in serum, whereas PepG pretreated with muramidase to digest the glycan backbone failed to do this. In an ex vivo model of human blood, PepG containing different amino acids induced similar levels of the cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), IL-8, and IL-10, as determined by plasma analyses (enzyme-linked immunosorbent assay). Hydrolysis of the Staphylococcus aureus cross-bridge with lysostaphin resulted in moderately reduced release of TNF-alpha, IL-6, IL-8, and IL-10, whereas muramidase digestion nearly abolished the ability to induce cytokine release and IL-6 mRNA accumulation in CD14(+) monocytes compared to intact PepG. However, additional experiments showed that muramidase-treated PepG synergized with lipopolysaccharide to induce TNF-alpha and IL-10 release in whole blood, despite its lack of inflammatory activity when administered alone. Based on these studies, we hypothesize that the structural integrity of the glycan chain of the PepG molecule is very important for the pathogenic effects of PepG. The amino acid composition of PepG, however, does not seem to be essential for the inflammatory properties of the molecule.
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PMID:Organ injury and cytokine release caused by peptidoglycan are dependent on the structural integrity of the glycan chain. 1497 33

S. aureus is a significant cause of late-onset sepsis in neonates. Increasing antibiotic resistance, however, requires additional treatment options. Lysostaphin, an endopeptidase, has that potential. The objective of this study is to compare lysostaphin versus vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) in a neonatal mouse model. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against MRSA strain USA300 were determined using standard methods. To determine pharmacokinetics, neonatal pups received either vancomycin or lysostaphin intraperitoneal and serum samples were obtained. To evaluate efficacy, pups were infected s.c. and littermates randomized to receive either saline, vancomycin, or lysostaphin intraperitoneal. Pups were observed for survival and growth. Quantitative blood cultures were obtained 24 h after infection. The MIC/MBC for vancomycin and lysostaphin were 0.71/1.19 microg/mL and <0.008/0.015 microg/mL, respectively. Mean lysostaphin concentrations ranged from 2.34 to 8.92 microg/mL. Mean vancomycin concentrations ranged from 1.72 to 11.2 microg/mL. Lysostaphin improved survival compared with placebo (p < 0.00001) and vancomycin (p < 0.03). There was no significant difference in growth among the groups. All treatment regimens resulted in less bacteremia compared with placebo (p < 0.0001). Lysostaphin appears to be more effective than vancomycin in treating MRSA in a neonatal model.
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PMID:Treatment of methicillin-resistant Staphylococcus aureus in neonatal mice: lysostaphin versus vancomycin. 1912 12

Strain D958, a methicillin-resistant Staphylococcus aureus strain with reduced susceptibility to vancomycin, was isolated from a 69-year-old Saudi male patient presenting with severe sepsis immediately after admission. Despite high serum levels of vancomycin, the same S. aureus strain was isolated from five blood culture sets during 1 week. Treatment failure under therapeutic levels of vancomycin prompted us to investigate the resistance profile of this strain in further detail. The MIC values for vancomycin as determined by Etest and microdilution were 3.0 and 2.0 mg/liter, respectively, and remained unchanged during the treatment course. The macro-Etest method showed a MIC of 4 mg/liter. The strain showed liquid vancomycin and lysostaphin MBCs of 2.0 and 5.0 mg/liter, respectively. The isolates were confirmed as heterogeneously vancomycin-intermediate S. aureus (hVISA) by vancomycin population analysis profile. The areas under these curves were similar for Mu3 and D958 for vancomycin and teicoplanin (ratio values were 1 and 1.1 for vancomycin and teicoplanin, respectively). Extensive genotyping and molecular characterization demonstrated that the strain harbored a staphylococcal cassette chromosome mec element (SCCmec) type III cassette and was of sequence type ST241, a single-locus variant of the successful multiresistant clone ST239. Microarray results demonstrated that D958 contained numerous resistance determinants (generally plasmid or phage encoded). These results suggest that this strain is constitutively expressing an altered susceptibility to vancomycin. Further studies are warranted to assess the clonal distribution of such strains displaying reduced susceptibility to vancomycin prior to any antimicrobial therapy.
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PMID:First detection of an invasive Staphylococcus aureus strain (D958) with reduced susceptibility to glycopeptides in Saudi Arabia. 2039 6