RESUMO
Gram-positive bacterial pathogens that secrete cytotoxic pore-forming toxins, such as Staphylococcus aureus and Streptococcus pneumoniae, cause a substantial burden of disease. Inspired by the principles that govern natural toxin-host interactions, we have engineered artificial liposomes that are tailored to effectively compete with host cells for toxin binding. Liposome-bound toxins are unable to lyse mammalian cells in vitro. We use these artificial liposomes as decoy targets to sequester bacterial toxins that are produced during active infection in vivo. Administration of artificial liposomes within 10 h after infection rescues mice from septicemia caused by S. aureus and S. pneumoniae, whereas untreated mice die within 24-33 h. Furthermore, liposomes protect mice against invasive pneumococcal pneumonia. Composed exclusively of naturally occurring lipids, tailored liposomes are not bactericidal and could be used therapeutically either alone or in conjunction with antibiotics to combat bacterial infections and to minimize toxin-induced tissue damage that occurs during bacterial clearance.
Assuntos
Infecções Bacterianas/prevenção & controle , Toxinas Bacterianas/química , Exotoxinas/química , Engenharia Genética , Lipossomos/química , Animais , CamundongosRESUMO
BACKGROUND: The aim of this study was to identify intraoperative risk factors for surgical site infections (SSIs), which are accessible to interventions. We evaluated the effect of extensive intraoperative antiseptic measures and the impact of the behavior of members of the surgical team on SSIs. METHODS: Standard versus extensive antiseptic measures were randomly assigned in 1,032 surgical patients. The adherence to principles of asepsis by members of the surgical team was assessed prospectively. RESULTS: The rate of SSI was 14% with standard antiseptic measures and 15% with extensive measures (P = .581). Multivariate analysis identified following independent risk factors: lapses in discipline (odds ratio [OR] 2.02, confidence interval [CI] 1.05-3.88), intestinal anastomosis (OR 6.74, CI 3.42-13.30), duration of operation more than 3 hours (OR 3.34, CI 1.82-6.14), and body mass index >30 kg/m2 (OR 1.98, CI 1.22-3.20). CONCLUSION: Extensive measures of antisepsis did not reduce the incidence of SSI. A lapse to adhere to principles of asepsis was identified as an independent risk factor for the development of SSI (ClinicalTrials.gov number, NCT00555815).