BACKGROUND: The use of central venous catheters impregnated with either minocycline and rifampin or chlorhexidine and silver sulfadiazine reduces the rates of catheter colonization and catheter-related bloodstream infection as compared with the use of unimpregnated catheters. We compared the rates of catheter colonization and catheter-related bloodstream infection associated with these two kinds of antiinfective catheters. METHODS: We conducted a prospective, randomized clinical trial in 12 university-affiliated hospitals. High-risk adult patients in whom central venous catheters were expected to remain in place for three or more days were randomly assigned to undergo insertion of polyurethane, triple-lumen catheters impregnated with either minocycline and rifampin (on both the luminal and external surfaces) or chlorhexidine and silver sulfadiazine (on only the external surface). After their removal, the tips and subcutaneous segments of the catheters were cultured by both the roll-plate and the sonication methods. Peripheral-blood cultures were obtained if clinically indicated. RESULTS: Of 865 catheters inserted, 738 (85 percent) produced culture results that could be evaluated. The clinical characteristics of the patients and the risk factors for infection were similar in the two groups. Catheters impregnated with minocycline and rifampin were 1/3 as likely to be colonized as catheters impregnated with chlorhexidine and silver sulfadiazine (28 of 356 catheters [7.9 percent] vs. 87 of 382 [22.8 percent], P CONCLUSIONS: The use of central venous catheters impregnated with minocycline and rifampin is associated with a lower rate of infection than the use of catheters impregnated with chlorhexidine and silver sulfadiazine.

OBJECTIVE: Use of central venous catheters (CVCs) impregnated with minocycline and rifampin reduces the density of bacterial growth on catheters and decreases the incidence of catheter-related bloodstream infections. Questions have been raised over the possibility that the use of these catheters will lead to the emergence of antibiotic-resistant organisms. In this study, we sought to determine if in vitro exposure of four test organisms to catheter segments impregnated with minocycline and rifampin would lead to the development of antibiotic resistance. METHODS: Catheter segments (1.0 cm) were placed on the surface of agar plates previously inoculated with bacterial suspensions, such that a subconfluent lawn of colony growth would be apparent after 24 h incubation at 35 degrees C in air. Test organisms included American Type Culture Collection strains of Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Escherichia coli, and Pseudomonas aeruginosa. Zones of inhibition of colony growth surrounding catheters were measured at 24-h intervals up to 7 days (two catheter segments per test). Colonies on agar surfaces located at varying distances from catheter segments were examined for minocycline and rifampin resistance following various periods of exposure (six catheter segments per test). In addition, selected colonies were subsequently exposed to minocycline and rifampin in broth and examined for selection of minocycline and rifampin resistance (> 28 colonies per selection test). RESULTS: Inhibitory zones of 14 to 47 mm were observed with S aureus, S epidermidis, E faecalis, and E coli. Growth of P aeruginosa was not inhibited by CVC segments. Testing of colonies of the first four organisms at various distances from CVC segments after varying periods of exposure revealed only a single instance of the emergence of resistance (eg, S aureus vs rifampin). Recovery of resistant clones was enhanced with minocycline and rifampin broth selection; however, a direct link between CVC exposure and the emergence of resistance was not established. CONCLUSIONS: Our in vitro data suggest that the exposure of Gram-positive cocci to either rifampin or minocycline can lead to the development of resistance. However, exposure of bacteria to these antibiotics in combination does not directly lead to resistance. Clinical investigations will be required to determine the true risk and implications of the development of resistance.

Protein Arginine Deiminase 4 (PAD4) has emerged as a leading target for the development of a Rheumatoid Arthritis (RA) pharmaceutical. Herein, we describe the development of a novel screen for PAD4 inhibitors that is based on a PAD4-targeted Activity-Based Protein Profiling reagent, denoted Rhodamine-conjugated F-Amidine (RFA). This screen was validated by screening 10 Disease Modifying Anti-Rheumatic Drugs (DMARDs) and identified streptomycin, minocycline, and chlortetracycline as micromolar inhibitors of PAD4 activity.