Minocycline-
EDTA (M-
EDTA) flush
solution has been shown to prevent
catheter-related infection and colonization in a rabbit model and in
hemodialysis patients. We undertook this study in order to determine the activities of M-
EDTA against organisms embedded in fresh biofilm (in vitro) and mature biofilm (ex vivo). For the experiment with the in vitro model, a modified Robbin's device (MRD) was used whereby 25
catheter segments were flushed for 18 h with 10(6) CFU of biofilm-producing Staphylococcus epidermidis, Staphylococcus aureus, and Candida albicans per ml. Subsequently, each of the
catheter segments was incubated in one of the following solutions: (i)
streptokinase, (ii)
heparin, (iii) broth alone, (iv)
vancomycin, (v)
vancomycin-
heparin, (vi)
EDTA, (vii)
minocycline (high-dose alternating with low-dose), or (viii) M-
EDTA (low-dose
minocycline alternating with high-dose
minocycline were used to study the additive and synergistic activities of M-
EDTA). All segments were cultured quantitatively by scrape sonication. For the experiment with the ex vivo model, 54
catheter tip segments removed from patients and colonized with bacterial organisms by roll plate were longitudinally cut into two equal segments and exposed to either saline,
heparin,
EDTA, or M-
EDTA (with high-dose
minocycline). Subsequently, all segments were examined by confocal
laser electron microscopy. In the in vitro MRD model, M-
EDTA (with a low concentration of
minocycline) was significantly more effective than any other agent in reducing colonization of S. epidermidis, S. aureus, and C. albicans (P < 0.01). M-
EDTA (with a high concentration of
minocycline) eradicated all staphylococcal and C. albicans organisms embedded in the biofilm. In the ex vivo model, M-
EDTA (with a high concentration of
minocycline) reduced bacterial colonization more frequently than
EDTA or
heparin (P < 0.01). We concluded that M-
EDTA is highly active in eradicating microorganisms embedded in fresh and mature biofilm adhering to
catheter surfaces.