Lysostaphin is an endopeptidase that kills Staphylococcus aureus, a predominant organism in catheterrelated infections. Lysostaphin-coated catheters prevented catheter colonization by several strains of S. aureus, and activity was maintained for at least 4 days. Prophylactic use of lysostaphin in catheters may help prevent the occurrence of catheter-related staphylococcal infections.Catheter-related infections continue to be a significant source of morbidity and mortality in patients requiring catheterization (6,10,12,15) and increase medical expenses by prolonging hospitalization (7). Catheter infections are most commonly caused by staphylococci, either coagulase-negative staphylococci (CoNS) or Staphylococcus aureus. Currently, six types of antiseptic catheters have been tested in clinical trials: cefazolin-, teicoplanin-, vancomycin-, silver-, chlorohexidinesilver sulfadiazine-, and minocycline-rifampin-coated catheters (3, 7). However, only the minocycline-rifampin-and chlorohexidine-silver sulfadiazine-coated catheters have been shown to reduce the incidence of catheter-related bloodstream infections, and long-term efficacy has not been shown (3,7,16). Lysostaphin is an endopeptidase that cleaves the cross-linking pentaglycine bridges of the cell wall of staphylococci (2,5,8,11,14,17). Lysostaphin is highly active against S. aureus because of the prevalence of pentaglycine cross-linking in the cell wall of S. aureus and has lesser activity against CoNS (2, 4). This study demonstrated that lysostaphin is readily adsorbed onto catheter surfaces while maintaining its staphylolytic activity and may have the potential to decrease the incidence of S. aureus-and CoNS-related catheter infections.Lysostaphin, obtained from AMBI, Inc., was coated onto two different plastic surfaces, polystyrene and FEP polymer, a Teflon-like material used in Angiocath catheters produced by Becton Dickinson. Twenty-four-well polystyrene plates were coated overnight at 4°C with 300 l of 10, 1, or 0.1 mg of lysostaphin/ml diluted in phosphate-buffered saline (PBS). The lumenal side of the catheters was coated for 1 h at room temperature with 0.1 mg of lysostaphin/ml. The coated surfaces were washed extensively with 50 ml of PBS, and the last aliquot of wash solution was tested to confirm the absence of unbound lysostaphin. The surfaces were challenged with an inoculum of about 10 4 S. aureus capsule type 5 organisms (SA5; clinical isolate) in tryptic soy broth, incubated for 1 to 2 h, and then streaked onto blood agar to enumerate surviving colonies (Table 1). On average, 610 CFU was recovered from the polystyrene control wells, whereas only 3 CFU remained in the lysostaphin-coated wells, a 99.5% reduction in bacterial counts. The lysostaphin-coated catheters were completely cleared of bacteria as compared to control catheters, from which an average of 493 CFU was recovered. The killing was not concentration dependent in the range of 10 to 0.1 mg/ml, as all three concentrations reduced bacterial titers to the same level. These results s...