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Query: UMLS:C0014118 (endocarditis)
 15,629 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cultured endothelial cells phagocytize Staphylococcus aureus, but the resultant effects are unknown. Monolayers of cultured bovine endothelial cells with or without [3H]adenine label were exposed to 100, 10, or 1 S. aureus organism per endothelial cell for 3.5 h. Lysostaphin was then applied to all cultures to destroy extracellular but not phagocytized S. aureus. In cultures treated for only 20 min with lysostaphin, S. aureus multiplied exponentially after a 9- to 12-h lag period. In cultures treated continuously with lysostaphin, numbers of S. aureus remained constant or decreased. These results indicate that S. aureus became extracellular and multiplied but did not multiply intracellularly. In parallel experiments, the release of 3H-adenine from prelabeled endothelial cell monolayers was assayed to indicate cytotoxicity. Results indicated that the loss of 3H-adenine from endothelial cell monolayers depended on the following: (i) the size of the S. aureus inoculum, (ii) the strain of S. aureus, and (iii) the length of time after exposure to S. aureus. S. aureus endocarditis and persistent septicemia could arise, at least in part, from ingestion of S. aureus by host endothelium. The intracellular location would afford S. aureus protection from host defenses and antibiotics. Eventual damage to endothelial cells could expose collagen, thus resulting in platelet adherence and vegetation formation. Intracellular S. aureus would be continuously released into the circulation, possibly accounting for the persistent bacteremia that is found in S. aureus endovascular infections.
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PMID:Ingestion of Staphylococcus aureus by bovine endothelial cells results in time- and inoculum-dependent damage to endothelial cell monolayers. 362 96

The emergence of clinical isolates of methicillin-resistant Staphylococcus aureus with reduced susceptibility to vancomycin has prompted a search for new and novel therapeutic agents active against S. aureus. Lysostaphin, a peptidase produced by Staphylococcus simulans, specifically cleaves the glycine-glycine bonds unique to the interpeptide cross-bridge of the S. aureus cell wall. The effectiveness of various regimens of dosing with intravenous lysostaphin was compared to that of vancomycin in the rabbit model of aortic valve endocarditis caused by a clinical methicillin-resistant S. aureus isolate. All animals were treated for a total of 3 days. The most active regimen, lysostaphin given three times daily, produced sterile vegetations in 10 of 11 treated rabbits, with a mean reduction in vegetation bacterial counts of 8.5 log10 CFU/g compared to the counts in the untreated controls. In contrast, vancomycin given twice daily sterilized no vegetations and reduced vegetation bacterial counts by only 4.8 log10 CFU/g. Lysostaphin given once daily was less effective, reducing mean vegetation bacterial counts by only 3.6 log10 CFU/g, but the combination of lysostaphin once daily and vancomycin twice daily reduced the mean vegetation bacterial density by 7.5 log10 CFU/g, a result that was significantly better than that for either regimen alone (P < 0.05). Lysostaphin was well tolerated by the rabbits, with no evidence of immunological reactions following up to 9 weeks of intravenous administration. We conclude that lysostaphin given alone or in combination with vancomycin is more effective in the treatment of experimental methicillin-resistant S. aureus aortic valve endocarditis than vancomycin alone.
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PMID:Lysostaphin treatment of experimental methicillin-resistant Staphylococcus aureus aortic valve endocarditis. 962 75