Activities of Taurolidine In Vitro and in Experimental Enterococcal Endocarditis

Abstract

In vitro, the antimicrobial agent taurolidine inhibited virtually all of the bacteria tested, including vancomycin-resistant enterococci, oxacillin-resistant staphylococci, and Stenotrophomonas maltophilia, at concentrations between 250 and 2,000 g/ml. Taurolidine was not effective in experimental endocarditis. While it appears unlikely that this antimicrobial would be useful for systemic therapy, its bactericidal activity and the resistance rates found (<10 ؊9 ) are favorable indicators for its possible development for topical use.With the continuing emergence of multiply antibiotic-resistant organisms, the need to develop new therapeutic agents remains evident. Taurolidine [bis-(1,1-dioxoperhydro-1,2,4-thiadiazinyl-4)methane], a derivative of the amino acid taurine, is an antimicrobial agent which inhibits and kills a broad range of microorganisms in vitro, albeit at high concentrations (3,4,9,11,13). This compound acts through mechanisms unlike those described for other currently available antimicrobials. Specifically, it is believed that methylol derivatives interact with components of bacterial cell walls resulting in irreparable injury (4). Taurolidine also appears to have immunoregulatory properties, blunting lipopolysaccharide-induced tumor necrosis factor and interleukin-1 release from human peripheral blood mononuclear cells (2) and also reducing adherence of bacteria to human epithelial cells in vitro (5). The compound has been given to humans both intravenously (i.v.) and by peritoneal lavage (1, 12).The purpose of the present study was to examine the in vitro activity of taurolidine against a broad variety of bacterial species, including antibiotic-resistant strains. We also evaluated the activity of taurolidine in vivo in experimental endocarditis using two strains of enterococci, one of which was a vancomycin-resistant strain of Enterococcus faecium.Most of the bacterial strains used in this study were routine isolates collected by our clinical microbiology laboratory during 1997. Additional strains from our collection were included based upon specific resistance traits. Taurolidine was provided by Wallace Laboratories, Cranbury, N.J. Antimicrobial reference standards of ciprofloxacin, imipenem, and cefotaxime were provided by Bayer Corporation, West Haven, Conn.; Merck & Co., Inc., West Point, Pa.; and Hoechst Marion Roussel, Inc., Kansas City, Mo., respectively. Vancomycin was obtained from Eli Lilly & Co., Indianapolis, Ind. MICs were determined by agar dilution (7, 8) on Mueller-Hinton II agar (BBL Microbiology Systems, Cockeysville, Md.) except as noted otherwise. Agar was supplemented with 5% sheep blood for streptococci and diphtheroids. Inocula were ca. 10 4 (10 5 for anaerobes) CFU/spot. Plates were incubated in room air and read at 18 to 20 h, except for lactobacilli, Leuconostoc spp., Pediococcus spp., and pneumococci, which were incubated in 5% CO 2 and examined for growth at 24 h. Anaerobes were incubated for 48 h on brucella agar in an atmosphere produced by Gas-Pak Plus (BBL). Time-...

Antimicrobial Activity of a Novel Catheter Lock Solution

“…The results of our in vitro susceptibility studies confirm the observations of previous investigators (25,26,27).…”

“…It is hypothesized that these methylol groups bind irreversibly to bacterial or fungal cell wall constituents and exert their cidal actions (27). There was no evidence of resistance to taurolidine when it was tested against a broad range of microbial pathogens (25). Citrate solutions have been demonstrated to maintain patency by preventing blood coagulation and platelet aggregation (2,3).…”

“…It is a unique, nontoxic substance with antiadherence and immunomodulatory properties (9,28). Taurolidine has antimicrobial activity against a broad range of bacteria and fungi (25,26; L. A. Mermel, N. Magill, and S. Zinner, Abstr. 38th Intersci.…”

Comparative In Vitro Efficacies of Various Catheter Lock Solutions

“…MEDTA, when used in concentrations similar to that used in our study, was undetectable in serum (25). Taurolidine has novel activity, making resistance unlikely (5,8,16,17,45). It is bactericidal with broad-spectrum activity (38).…”

“…Traditional lock solutions minocycline (M), rifampin (R), ciprofloxacin (C), and vancomycin, except pharmacologic concentrations of C and R and of M and R, were less effective than MEDTA and T/PVP. Minocycline-edetate calcium disodium (MEDTA) (7,11,25,27,30), taurolidine-polyvinylpyrolidine (T/PVP) (2,6,33,38,45), and ethanol (E) (14, 21, 23) are promising lock solutions. We examined the relative efficacies of vancomycin (V), ciprofloxacin (C), minocycline (M), minocycline-rifampin (M/R), ciprofloxacin-rifampin (C/R), vancomycin-rifampin (V/R), E, EDTA, MEDTA, and T/PVP at killing Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Candida albicans growing in biofilms.…”