ABSTRACT
Biomaterial-associated infection (BAI) is a major problem in modern medicine, and is often caused by Staphylococcus epidermidis. We aimed to raise monoclonal antibodies (mAbs) against major surface protein antigens of S. epidermidis, and to assess their possible protective activity in experimental BAI. Mice were vaccinated with a cell wall protein preparation of S. epidermidis. A highly immunodominant antigen was identified as Accumulation-associated protein (Aap). mAbs against Aap and against surface-exposed lipoteichoic acid (LTA) were used for passive immunization of mice in experimental biomaterial-associated infection. Neither anti-Aap nor anti-LTA mAbs showed protection. Either with or without antibodies, tissue surrounding the implants was more often culture positive than the implants themselves, but bacterial adherence to the implants was significantly increased in mice injected with anti-LTA. In vitro, anti-Aap and anti-LTA did show binding to S. epidermidis, but no opsonic activity was observed. We conclude that antibodies against S. epidermidis LTA or Aap showed no opsonic activity and did not protect mice against BAI. Moreover, the increase in binding to implanted biomaterial suggests that passive immunization may increase the risk for BAI.
Subject(s)
Antibodies, Monoclonal/administration & dosage , Coated Materials, Biocompatible/adverse effects , Povidone/adverse effects , Silicone Elastomers/adverse effects , Staphylococcal Infections/etiology , Staphylococcal Infections/immunology , Staphylococcus epidermidis/drug effects , Animals , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/immunology , Cell Adhesion , Coated Materials, Biocompatible/chemistry , Materials Testing , Mice , Mice, Inbred C57BL , Povidone/chemistry , Silicone Elastomers/chemistry , Staphylococcal Infections/prevention & controlABSTRACT
Infections associated with implanted biomedical devices (BAI) are predominantly caused by Staphylococcus epidermidis. We previously observed in murine experimental BAI that S. epidermidis persists in peri-implant tissue rather than on the implanted biomaterial itself (Boelens et al., J Infect Dis 2000;181:1337-1349; Broekhuizen et al., Infect Immun 2007;75:1129-1136). To investigate the efficacy of rifampicin/vancomycin to clear S. epidermidis from implants and peri-implant tissues, mice with two implants were challenged with 10(7) cfu S. epidermidis per implant and received daily injections of rifampicin (25 mg/kg) and vancomycin (50 mg/kg). On the day of termination, implants and peri-implant tissue were collected and processed for culture and histology. After 1 and 8 days, implants of control mice were culture positive in 14/18 and 5/16 cases, respectively, and tissue biopsies were all culture positive. In the antibiotic-treated mice, bacteria were recovered from only 1/18 and 1/16 implants after 1 and 8 days, respectively, whereas the tissues were culture positive in 14/18 and 7/16 biopsies, respectively. In microscopy, bacteria were seen in the tissue at a distance of several cell layers from the tissue-implant interface, colocalized with host cells. Thus, although a regimen of rifampicin/vancomycin sterilized the implants, S. epidermidis persisted in peri-implant tissue, which might be an as yet unrecognized reservoir in the pathogenesis of BAI.
Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Prostheses and Implants/microbiology , Rifampin/pharmacology , Staphylococcal Infections/drug therapy , Staphylococcus epidermidis , Vancomycin/pharmacology , Animals , Biopsy , Colony Count, Microbial , Female , Mice , Staphylococcal Infections/microbiology , Staphylococcal Infections/pathology , Time Factors , Treatment FailureABSTRACT
Biomaterial-associated infections (BAI), which are predominantly caused by Staphylococcus epidermidis, are a significant problem in modern medicine. Biofilm formation is considered the pivotal element in the pathogenesis, but in previous mouse studies we retrieved S. epidermidis from peri-implant tissue. To assess the kinetics and generality of tissue colonization, we investigated BAI using two S. epidermidis strains, two biomaterials, and two mouse strains. With small inocula all implants were culture negative, whereas surrounding tissues were positive. When higher doses were used, tissues were culture positive more often than implants, with higher numbers of CFU. This was true for the different biomaterials tested, for both S. epidermidis strains, at different times, and for both mouse strains. S. epidermidis colocalized with host cells at a distance that was >10 cell layers from the biomaterial-tissue interface. We concluded that in mouse experimental BAI S. epidermidis peri-implant tissue colonization is more important than biofilm formation.