Abstract:
:Infection is a major complication of implantable medical devices, which provide a scaffold for biofilm formation, thereby reducing susceptibility to antibiotics and complicating treatment. Hematogenous implant-related infections following bacteremia are particularly problematic because they can occur at any time in a previously stable implant. Herein, we developed a model of hematogenous infection in which an orthopedic titanium implant was surgically placed in the legs of mice followed 3 wk later by an i.v. exposure to Staphylococcus aureus This procedure resulted in a marked propensity for a hematogenous implant-related infection comprised of septic arthritis, osteomyelitis, and biofilm formation on the implants in the surgical legs compared with sham-operated surgical legs without implant placement and with contralateral nonoperated normal legs. Neutralizing human monoclonal antibodies against α-toxin (AT) and clumping factor A (ClfA), especially in combination, inhibited biofilm formation in vitro and the hematogenous implant-related infection in vivo. Our findings suggest that AT and ClfA are pathogenic factors that could be therapeutically targeted against Saureus hematogenous implant-related infections.
journal_name
Proc Natl Acad Sci U S Aauthors
Wang Y,Cheng LI,Helfer DR,Ashbaugh AG,Miller RJ,Tzomides AJ,Thompson JM,Ortines RV,Tsai AS,Liu H,Dillen CA,Archer NK,Cohen TS,Tkaczyk C,Stover CK,Sellman BR,Miller LSdoi
10.1073/pnas.1703427114subject
Has Abstractpub_date
2017-06-27 00:00:00pages
E5094-E5102issue
26eissn
0027-8424issn
1091-6490pii
1703427114journal_volume
114pub_type
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