The development and characterization of a mouse model of chronic Staphylococcus epidermidis foreign body infection was done with two clinical isolates that differed in degree of extracellular slime production. Segments of Silastic catheters bearing preformed S. epidermidis biofilms were implanted intraperitoneally, and mice were assessed after 3 and 6 months. Both test strains of S. epidermidis persisted at the implant site through the 6-month follow-up in 80% of the mice, regardless of the degree of slime production. There was no evidence of overt animal morbidity, and microbiologic assessment of other peritoneal sites did not reveal dissemination of bacteria from the infected focus. In comparison with control mice, animals harboring chronic foreign body infection presented marked peripheral neutrophilia and mild anemia.

The incidence of wound infection following surgery on the colon is reduced by the preoperative adminstration of appropriate antibiotics. Quantitative bacteriologic studies raise the fundamental question as to whether effective antibiotic prophylaxis results from reduction of the bacterial content of the gut prior to surgery or whether effective tissue levels of the antibiotic is the key factor. Oral neomycin and metronidazole have been shown to markedly reduce the incidence of wound infection following colon surgery. A prospective randomized double-blind clinical trial was undertaken to compare the effectiveness of intravenous metronidazole (high tissue level) with oral administration (tissue and gut activity) on the incidence of wound infection. There was no difference in wound infection rates between the two groups of patients. Surprisingly, there was a significant reduction in the bacteroides content in the colon of patients who received intravenous metronidazole one hour before operation to a level almost equal to that achieved by the administration of the drug for two days by mouth before operation. Metronidazole levels in the colon at the time of surgery were comparable for both groups. The median time for recolonization of the colon was six days for the oral group, and four days for the intravenous group. Although peritoneal fluid contained significant numbers of coliforms and enterococci, clinical infection did not occur. These data suggest that systemic antibiotics effective against anerobic flora of the colon markedly reduce postoperative septic complications.

Rifampin has been noted to exhibit exceptional antimicrobial activity against Staphylococcus epidermidis biofilms as compared to commonly used antibiotics. To further explore this unique effect of rifampin, we evaluated the antimicrobial activity of three commercially available preparations of rifampin, two rifampin analogs (CGP29861 and rifapentine) and the parent compound rifamycin SV. These were tested against standardized S. epidermidis biofilms in various milieus. All six members of the rifamycin group tested demonstrated marked antimicrobial activity but with minor foci of resisters when tested in a peptone water environment. The microscopy of the exposed biofilms showed profound lysis and morphological distortion of the remaining cells. The synergistic elimination of the foci of resistance was achieved in an environment of fresh peritoneal dialysis (PD) solution or by the addition of vancomycin. Neither vancomycin nor fresh PD solution demonstrated significant antimicrobial activity when tested alone with biofilm preparations. Spent PD fluid markedly antagonized the activity of the rifamycins with the exception of the rifampin analogs, an effect primarily of pH. The synergistic effect of vancomycin with the rifamycins was not affected either by protein content or pH, leaving the antagonistic properties of spent PD fluid unexplained. The variable activity of the different members of the rifamycin group underlines the importance of structural differences in determining their interaction with bacterial biofilms. Further precision of the nature of these structural interactions is seen to have considerable potential for therapeutic advancement of catheter-associated sepsis.