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.
To investigate whether pericatheter tissue is an additional niche for bacteria potentially causing catheter-associated infections in humans.Postmortem patient study.Intensive care unit, autopsy room, and microbiological laboratory in a university hospital.Eighteen deceased patients from whom 35 catheters plus surrounding tissues were collected.Under axenic conditions catheters and surrounding tissue were excised from deceased intensive care unit patients. The excised parts of the catheters and samples of surrounding tissue were quantitatively cultured and bacteria identified, and tissue histology/immunohistochemistry was performed.Nine of the 35 (26%) pericatheter tissue samples tested were highly culture positive. The corresponding catheter segments were culture negative or yielded only low numbers of bacteria. Bacteria cultured from different sites of the catheter and surrounding tissues almost all were coagulase-negative staphylococci (predominantly Staphylococcus epidermidis) and Enterococcus faecalis. In histology, bacteria were seen in tissue, intercellularly and associated with host phagocytes.Tissue surrounding biomedical devices forms a niche for bacteria. This is an as yet nonrecognized element in the pathogenesis of catheter-associated infections, with possible consequences for strategies of prevention and treatment of these infections.
ABSTRACT 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.