Taurolidine

# Overview
Taurolidine (
Taurolidine has been used to treat patients with peritonitis and as an antiendoxic agent in patients with systemic inflammatory response syndrome. It is a live-saving antimicrobial for severe abdominal sepsis and peritonitis.
For severe surgical infections and use in surgical oncology
Taurolidine is active against a wide range of micro- organisms that include gram positive bacteria, gram negative bacteria, fungi, mycobateria and also bacteria that are resistant to various antibiotics such as MRSA, VISA VRSA ORSA VRE. Additionally, taurolidine demonstrates some anti-tumor properties, with positive results seen in early-stage clinical investigations using the drug to treat gastrointestinal malignancies and tumors of the central nervous system.
Taurolidine is the active ingredient of anti-microbial catheter lock solutions for the prevention and treatment of catheter related blood stream infections (CRBSIs) and is suitable for use in all catheter based vascular access devices.
Bacterial resistance against taurolidine has never been observed in various studies.
Taurolidine acts by a non selective chemical reaction.
In aqueous solution, the parent molecule taurolidine forms equilibrium with taurultam and N-hydroxymethyl taurultam, with taurinamide being a downstream derivative.
The active principle of taurolidine are N-methylol derivatives of taurultam and taurinamide, which react with the bacterial cell wall, cell membrane, proteins as well as with the primary amino groups of endo- and exotoxins. Microbes are killed and the resulting toxins are inactivated; the destruction time in vitro is 30 minutes.
Pro-inflammatory cytokines and enhanced TNF- levels are reduced when used as a catheter lock solution.
Taurolidine decreases the adherence of bacteria and fungi to host cells by destructing the fimbriae and flagella and thus prevent the biofilm formation.
Dose of 5g over 2 hours every 4 hours for at least 48 hours were given intravenously for the treatment of various sepsis condition.

# Pharmacokinetic properties
Absorption 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
Taurolidine is metabolised with a short half-life to taurine, carbon dioxide and water. 
Elimination half-life lies between 5 and 5.5 hours. 
Urinary estimations show excretion of taurinamide accounts for 25% of the Taurolidine dose.

# Pharmacodynamic properties
Following administration of taurolidine, the bactericidal and antiendotoxin activity of the taurolidine molecule is conferred by the release of three active methylol (hydroxymethyl) groups as taurolidine is rapidly metabolized by hydrolysis via taurultam and methylol taurultam to methylol taurinamide and taurine. These labile methylol groups react with the bacterial cell-wall resulting in lysis of the bacteria, 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 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 vitroMIC (minimum inhibitory concentration) values, and also appears to preclude susceptibility to resistance mechanisms.
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, e.g. blood, serum, pus.
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 (indole negative), Proteus mirabilis, Pseudomonas species (including Ps. aeruginosa), Salmonella species, Serratia marcescans, 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, Pitosporom ovale.

# Contraindications
Taurolidine should not be used systemically in neonates, infants and children under 10 years of age.
Taurolidine should be used with caution in patients with renal impairment for systemic use.

## Pregnancy and Breastfeeding
Taurolidine has shown no evidence of teratogenicity in animal studies, but administration to pregnant women should only be undertaken if the clinician considers it essential.

# Side effects
No systemic side effects have been identified. The safety of taurolidine has also been confirmed in clinical studies with long-term intravenous administration of high doses (up to 20 g daily).
In the body, taurolidine is metabolized rapidly via the metabolites taurultam and methylol taurinamide, which also have a bactericidal action, to taurine, an endogenous aminosulphonic acid, CO2 and H2O.  Therefore, no toxic effects are known or expected in the event of accidental injection.

# Catheter lock solution in hemodialysis (HD)
The combination of taurolidine with the anticoagulant citrate (4%) and heparin (500IU/mL) may help to decrease the incidence and occurrence of catheter-related blood stream infections (CRBSI) in hemodialysis patients (HD).

# Catheter lock solution in oncology
Catheter-or port-a-cath-related bloodstream infections are a common problem in cancer patients. The use of taurolidine/citrate lock solution is associated with a significant reduction in bloodstream infections in immune compromised (pediatric) patients.

# Catheter lock solution in home parenteral nutrition (HPN) / total parenteral nutrition (TPN)
CRBSI remains the most common serious complication associated with long-term parenteral nutrition HPN/TPN. The use of taurolidine/citrate as a catheter lock solution shows a significant reduction of CRBSI in adult patients and in pediatric patients.