Takashi Uno, Takumi Sato, Mariko Yagi, Ryota Ito, Masato Kawamura, Shigeru Fujimura
Biofilm-forming Staphylococcus aureus makes it difficult to treatment for prosthetic joint infection. To improve the outcome of treatment, rifampicin is used combined with several antimicrobial agents. However, the evidence is not clear that the sterilization effect of antimicrobial agents with the concentration in bone tissue when the usual dose against biofilm-formed staphylococci. Using 10 isolates of S. aureus, we made a biofilm formation model on the washer surface which assumed a medical device in this study. The sterilization effect by combined treatment rifampicin and other antimicrobial agents (cefazolin, vancomycin, or clarithromycin) was considered against these models. All biofilm-formed S. aureus was not sterilized by 120 hours of exposure with a single antimicrobial agent. Besides, four strains were not sterilized by the exposure of a combination of rifampicin and cefazolin, and these strains acquired rifampicin resistance 8 hours later. Similarly, in rifampicin and vancomycin or and clarithromycin, 2 strains and 3 strains were not sterilized, respectively. Therefore, by all combinations including rifampicin, the biofilm-formed S. aureus were not completely sterilized. It was shown that the acquired rifampicin- resistant in 50% out of clinical isolates occurred 8 hours after the exposure of combined antimicrobial agents. Furthermore, with 4 of these 9 strains that were not sterilized, biofilm production was rather promoted. One of the reasons that these strains were not sterilized, probably is reduced the bactericidal effect of other antimicrobial agents due to increased biofilm formation by rifampicin-resistant acquisition. When rifampicin is selected for the treatment of prosthetic joint infection, the acquisition of rifampicin-resistance should be confirmed 24 hours after administration.