Taurolidine

The bactericidal and antiendotoxin activity of the taurolidine molecule is by the release of three active methylol (hydroxymethyl) groups as taurolidine is rapidly metabolized by hydrolysis via taurultam and methyloltaurultam to methyloltaurinamide and taurine. These labile methylol groups react with the bacterial cell-wall resulting in lysis, and by inter- and intramolecular cross-linking of the lipopolysaccharide-protein complex, neutralization of the bacterial endotoxins which is enhanced by enzymatic activation. This mechanism of action is accelerated and maximised when taurolidine is pre-warmed to 37°C.

Taurolidine inhibits the formation of postoperative peritoneal adhesions, and in vitro has been shown to reduce the adherence of micro-organisms to mucosal epithelium. The chemical mode of action of taurolidine via its reactive methylol groups confers greater potency in vivo than indicated by in vitro MIC (minimum inhibitory concentration) values, and also appears to preclude susceptibility to resistance mechanisms.

Whilst taurolidine is highly active against the common infecting pathogens associated with peritonitis, this activity extends across a wide-spectrum of aerobic/anaerobic bacteria and fungi (with no diminution of effect in the presence of biological fluids, eg blood, serum, pus) including:

Gram positive bacteria (MIC/MBC 1-2 mg/ml):

Staphylococci (including multiple-antibiotic resistant coagulase negative strains, Methicillin-resistant Staph. aureus), Streptococci, Enterococci, Pneumococci.

Gram negative bacteria (MIC/MBC 0.5-5 mg/ml):

Aerobacter species, Citrobacter species, Enterobacter species, Escherichia coli, Proteus species (in dole negative), Proteusmirabilis, Pseudomonas species (including Ps. aeruginosa). Salmonella species, Serratia marcescens, Klebsiella species.

Anaerobes (MIC/MBC 0.03-0.3 mg/ml):

Bacteroides species (including Bact.fragilis), Fusobacteria, Clostridium species, Peptostreptococcus anaerobius.

Fungi (MIC 0.3-5 mg/ml):

Candida albicans, Cryptococcus neoformans, Aspergillus species, Trichophyton rubrum, Epidermophyton floccosum, Pityrosporum ovale.

Taurolidine is metabolised with a short half-life to taurinamide, carbon dioxide and water. Absorption from the peritoneal cavity is rapid, with maximum concentrations of taurultam occurring between 10 and 15 minutes, and the half-life being less than one hour. Maximum plasma taurinamide concentration occurs between 0.5 and 2 hours, and the elimination half-life lies between 1.5 and 5.5 hours. The rate and extent of peritoneal absorption is not modified in the presence of peritonitis. Urinary estimations show excretion of taurinamide accounts for 25% of the taurolidine dose.

Since taurolidine is well-established for its proposed use, additional preclinical safety data are not provided.