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Anton Sculean - One of the best experts on this subject based on the ideXlab platform.
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Taurolidine Acts on Bacterial Virulence Factors and Does Not Induce Resistance in Periodontitis-Associated Bacteria—An In-Vitro Study
Antibiotics (Basel Switzerland), 2020Co-Authors: Sabrina Radakovic, Simon Schmid, Nicola Andreoli, Sandor Nietzsche, Jürg Zumbrunn, Anton Sculean, Sigrun EickAbstract:The aims of the present study were: (a) to determine the mechanism of action of Taurolidine against bacterial species associated with periodontal disease, and (b) to evaluate the potential development of resistance against Taurolidine as compared with minocycline. After visualizing the mode of action of Taurolidine by transmission electron micrographs, the interaction with most important virulence factors (lipopolysaccharide (LPS), Porphyromonas gingivalis gingipains, Aggregatibacter actinomycetemcomitans leukotoxin), was analyzed. Then, 14 clinical isolates from subgingival biofilm samples were transferred on agar plates containing subinhibitory concentrations of Taurolidine or minocycline up to 50 passages. Before and after each 10 passages, minimal inhibitory concentrations (MICs) were determined. Increasing MICs were screened for efflux mechanism. Taurolidine inhibited in a concentration-dependent manner the activities of LPS and of the arginine-specific gingipains; however, an effect on A. actinomycetemcomitans leukotoxin was not detected. One P. gingivalis strain developed a resistance against Taurolidine, which was probably linked with efflux mechanisms. An increase of MIC values of minocycline occurred in five of the 14 included strains after exposure to subinhibitory concentrations of the antibiotic. The present results indicate that: (a) Taurolidine interacts with LPS and gingipains, and (b) development of resistance seems to be a rare event when using Taurolidine.
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Taurolidine acts on bacterial virulence factors and does not induce resistance in periodontitis-associated bacteria
2019Co-Authors: Sabrina Radakovic, Simon Schmid, Nicola Andreoli, Sandor Nietzsche, Jürg Zumbrunn, Anton Sculean, Sigrun EickAbstract:Abstract Background Taurolidine is thought to be an alternative antimicrobial in periodontal therapy. The purpose of this follow-up Taurolidine study was to determine in more detail the mode of action of Taurolidine against bacterial species being associated with periodontal disease. Further, a potential development of resistance against Taurolidine in comparison with minocycline was to evaluate. Results Visualizing the mode of action of Taurolidine to Porphyromonas gingivalis by scanning and transmission electron micrographs showed in part pores and release of constituents from the cell wall. The interaction of taurolidin with bacterial cell wall is also supported by the finding that Taurolidine inhibited in a concentration-dependent manner the activities of LPS and of the P. gingivalis arginine-specific gingipains. However, an effect on A. actinomycetemcomitans leukotoxin was not found. When transferring 14 clinical isolates from subgingival biofilm samples (4 P. gingivalis, 2 A. actinomycetemcomitans, 2 Tannerella forsythia, 2 Fusobacterium nucleatum, 4 oral streptococci) on agar plates containing subinhibitory concentrations of Taurolidine up to 50 passages, one P. gingivalis strain developed a resistance against Taurolidine which was probably linked with efflux mechanisms. When antimicrobial pressure was removed, MIC reverted to baseline value. Testing development of resistance to minocycline in a similar way, an increase of MIC values occurred in five of the 14 included strains after exposure to subinhibitory concentrations of the antibiotic. Efflux might play a role in one A. actinomycetemcomitans strains, but obviously not in the other four strains. Removing antimicrobial pressure for a few passages did not revert the increased MIC values. Conclusion Taurolidine interacts with LPS and gingipains. Development of resistance seems to be a rare event when applying Taurolidine. A potential development of resistance might be associated with efflux mechanisms.
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Activity of Taurolidine on species associated with periodontitis
2019Co-Authors: Sabrina Radakovic, Simon Schmid, Nicola Andreoli, Sandor Nietzsche, Jürg Zumbrunn, Anton Sculean, Sigrun EickAbstract:Abstract Background Taurolidine is thought to be an alternative antimicrobial in periodontal therapy. The purpose of this follow-up Taurolidine study was to determine in more detail the mode of action of Taurolidine against bacterial species being associated with periodontal disease. Further, a potential development of resistance against Taurolidine in comparison with minocycline was to evaluate. Results Visualizing the mode of action of Taurolidine to Porphyromonas gingivalis by scanning and transmission electron micrographs showed in part pores and release of constituents from the cell wall. The interaction of taurolidin with bacterial cell wall is also supported by the finding that Taurolidine inhibited in a concentration-dependent manner the activities of LPS and of the P. gingivalis arginine-specific gingipains. However, an effect on A. actinomycetemcomitans leukotoxin was not found. When transferring 14 clinical isolates from subgingival biofilm samples (4 P. gingivalis, 2 A. actinomycetemcomitans, 2 Tannerella forsythia, 2 Fusobacterium nucleatum, 4 oral streptococci) on agar plates containing subinhibitory concentrations of Taurolidine up to 50 passages, one P. gingivalis strain developed a resistance against Taurolidine which was probably linked with efflux mechanisms. When antimicrobial pressure was removed, MIC reverted to baseline value. Testing development of resistance to minocycline in a similar way, an increase of MIC values occurred in five of the 14 included strains after exposure to subinhibitory concentrations of the antibiotic. Efflux might play a role in one A. actinomycetemcomitans strains, but obviously not in the other four strains. Removing antimicrobial pressure for a few passages did not revert the increased MIC values. Conclusion Taurolidine interacts with LPS and gingipains. Development of resistance seems to be a rare event when applying Taurolidine. A potential development of resistance might be associated with efflux mechanisms.
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In vitro activity of Taurolidine gel on bacteria associated with periodontitis
Clinical oral investigations, 2015Co-Authors: Sigrun Eick, Jürg Zumbrunn, Nicoletta Gloor, Cecilia Püls, Anton SculeanAbstract:The purpose of this in vitro study was to determine the antimicrobial activity of two different Taurolidine gel formulations in comparison with minocycline microspheres. Three percent Taurolidine gel (TLG3) and 2 % Taurolidine gel (TLG2) were compared to minocycline microspheres (MINO) against single bacterial species and a 12-species-mixture. The antimicrobial activity was proven by determination of minimal inhibitory concentrations (MICs), killing assays, after exposure of the antimicrobials as well as within a biofilm. The MICs against the single species were between 0.5 and 2 mg/ml of Taurolidine. MICs of the used mixed microbiota were 1.5 mg/ml (TLG3) and 4 mg/ml (TLG2). Fusobacterium nucleatum and Porphyromonas gingivalis were completely killed by 10 % TLG3 and TLG2 (equivalent to 3 and 2 mg/ml Taurolidine) after 6 h. The mixture of 12 species was not completely killed by any of the test substances. Taurolidine gels showed a post-antimicrobial activity, however being less than that of MINO. On biofilms, Taurolidine gels reduced concentration dependently the colony forming unit (CFU) counts (multi-species biofilms by 3.63 log10 after 100 % (30 mg/ml) of TLG3), reductions were 2.12 log10 after MINO (1000 μg/ml minocycline). Taurolidine gel formulations exert antimicrobial activity against bacteria associated with periodontal disease. Nevertheless, a complete elimination of biofilms seems to be impossible and underlines the importance of mechanical removal of biofilms prior to application of the antimicrobial. Taurolidine gels may represent a potential alternative for adjunctive topical antimicrobial treatment in periodontitis and infectious peri-implant diseases.
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In-vitro activity of Taurolidine on single species and a multispecies population associated with periodontitis.
Anaerobe, 2014Co-Authors: Lilly Zollinger, Sandor Nietzsche, Anton Sculean, Simone Schnyder, Sigrun EickAbstract:The antimicrobial activity of Taurolidine was compared with minocycline against microbial species associated with periodontitis (four single strains and a 12-species mixture). Minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs), killing as well as activities on established and forming single-species biofilms and a 12-species biofilm were determined. The MICs of Taurolidine against single species were always 0.31 mg/ml, the MBCs were 0.64 mg/ml. The used mixed microbiota was less sensitive to Taurolidine, MIC and the MBC was 2.5 mg/ml. The strains and the mixture were completely killed by 2.5 mg/ml Taurolidine, whereas 256 μg/ml minocycline reduced the bacterial counts of the mixture by 5 log10 colony forming units (cfu). Coating the surface with 10 mg/ml Taurolidine or 256 μg/ml minocycline prevented completely biofilm formation of Porphyromonas gingivalis ATCC 33277 but not of Aggregatibacter actinomycetemcomitans Y4 and the mixture. On 4.5 d old biofilms, Taurolidine acted concentration dependent with a reduction by 5 log10 cfu (P. gingivalis ATCC 33277) and 7 log10 cfu (A. actinomycetemcomitans Y4) when applying 10 mg/ml. Minocycline decreased the cfu counts by 1-2 log10 cfu independent of the used concentration. The reduction of the cfu counts in the 4.5 d old multi-species biofilms was about 3 log10 cfu after application of any minocycline concentration and after using 10 mg/ml Taurolidine. Taurolidine is active against species associated with periodontitis, even within biofilms. Nevertheless a complete elimination of complex biofilms by Taurolidine seems to be impossible and underlines the importance of a mechanical removal of biofilms prior to application of Taurolidine.
Geert J A Wanten - One of the best experts on this subject based on the ideXlab platform.
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Clinical outcomes of home parenteral nutrition patients using Taurolidine as catheter lock: A long-term cohort study.
Clinical nutrition (Edinburgh Scotland), 2018Co-Authors: Yannick Wouters, Wietske Kievit, Britt Roosenboom, Erna Causevic, Hans Groenewoud, Geert J A WantenAbstract:Summary Background & aims Central venous access device (CVAD)-related complications, such as central-line associated bloodstream infections (CLABSIs), CVAD-related venous thromboses (CRVTs) and –occlusions frequently occur in home parenteral nutrition (HPN) patients. A preventive strategy to decrease the incidence of CLABSIs is the use of CVAD lock solutions, such as 2% Taurolidine. The aim of this study was to evaluate long-term clinical outcomes of our HPN cohort while using Taurolidine as lock solution. In addition, we explored risk factors associated with CVAD-related complications. Methods We conducted a retrospective analysis of complications (CLABSIs, CRVTs and CVAD occlusions) and adverse events in adult HPN patients while using Taurolidine as lock solution. Patients with a benign underlying disease leading to intestinal failure were included between 2006 and 2017 at our tertiary referral centre for intestinal failure. Primary outcome was the effectiveness of Taurolidine, as described by complication incidence rates. Secondary objectives were to assess adverse events of Taurolidine, complication rates of patients who subsequently discontinued Taurolidine and started using 0.9% saline alternatively, and risk factors associated with complications. Results In total, 270 HPN patients used Taurolidine during 338521 catheter days. CLABSIs, CRVTs and CVAD occlusions occurred at a rate of 0.60 (CI95% 0.52–0.69), 0.28 (CI95% 0.23–0.34), and 0.12 (CI95% 0.08–0.16) events per 1000 catheter days, respectively. In 24 (9%) patients, mild to moderate adverse events resulted in discontinuation of 2% Taurolidine. A subsequent switch to 0.9% saline resulted in an increased CLABSI rate (adjusted rate ratio 4.01 (95%CI 1.23–13.04), P = 0.02). Several risk factors were identified for CLABSIs (a lower age, nontunneled catheters, infusion frequency), CRVTs (site of vein insertion), and CVAD occlusions (type of CVAD). Conclusion Complication rates remained low in the long-term, and use of Taurolidine was generally safe. The identified risk factors may help to create new strategies to further prevent CVAD-related complications and improve HPN care in the future.
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Randomised clinical trial: 2% Taurolidine versus 0.9% saline locking in patients on home parenteral nutrition
Alimentary pharmacology & therapeutics, 2018Co-Authors: Yannick Wouters, Miryam Theilla, Pierre Singer, Siri Tribler, Palle Jeppesen, Loris Pironi, Lars Vinter-jensen, Henrik Højgaard Rasmussen, Farooq Rahman, Geert J A WantenAbstract:Background The catheter lock solutions 2% Taurolidine and 0.9% saline are both used to prevent catheter-related bloodstream infections (CRBSIs) in home parenteral nutrition patients. Aims To compare the effectiveness and safety of Taurolidine and saline. Methods This multicentre double-blinded trial randomly assigned home parenteral nutrition patients to use either 2% Taurolidine or 0.9% saline for 1 year. Patients were stratified in a new catheter group and a pre-existing catheter group. Primary outcome was the rate of CRBSIs/1000 catheter days in the new catheter group and pre-existing catheter group, separately. Results We randomised 105 patients, of which 102 were analysed as modified intention-to-treat population. In the new catheter group, rates of CRBSIs/1000 catheter days were 0.29 and 1.49 in the Taurolidine and saline arm respectively (relative risk, 0.20; 95% CI, 0.04-0.71; P = 0.009). In the pre-existing catheter group, rates of CRBSIs/1000 catheter days were 0.39 and 1.32 in the Taurolidine and saline arm respectively (relative risk, 0.30; 95% CI, 0.03-1.82; P = 0.25). Excluding one outlier patient in the Taurolidine arm, mean costs per patient were $1865 for Taurolidine and $4454 for saline (P = 0.03). Drug-related adverse events were rare and generally mild. Conclusions In the new catheter group, Taurolidine showed a clear decrease in CRBSI rate. In the pre-existing catheter group, no superiority of Taurolidine could be demonstrated, most likely due to underpowering. Overall, Taurolidine reduced the risk for CRBSIs by more than four times. Given its favourable safety and cost profile, Taurolidine locking should be considered as an additional strategy to prevent CRBSIs. Trial registration Clinicaltrials.gov, identifier: NCT01826526.
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Taurolidine Lock Is Superior to Heparin Lock in the Prevention of Catheter Related Bloodstream Infections and Occlusions
2016Co-Authors: Evelyn D. Olthof, M W J Versleijen, Getty Huisman–de Waal, Ton Feuth, Wietske Kievit, Geert J A WantenAbstract:Background and Aims: Patients on home parenteral nutrition (HPN) are at risk for catheter-related complications; mainly infections and occlusions. We have previously shown in HPN patients presenting with catheter sepsis that catheter locking with Taurolidine dramatically reduced re-infections when compared with heparin. Our HPN population therefore switched from heparin to Taurolidine in 2008. The aim of the present study was to compare long-term effects of this catheter lock strategy on the occurrence of catheter-related bloodstream infections and occlusions in HPN patients. Methods: Data of catheter-related complications were retrospectively collected from 212 patients who received HPN between January 2000 and November 2011, comprising 545 and 200 catheters during catheter lock therapy with heparin and Taurolidine, respectively. We evaluated catheter-related bloodstream infection and occlusion incidence rates using Poisson-normal regression analysis. Incidence rate ratios were calculated by dividing incidence rates of heparin by those of Taurolidine, adjusting for underlying disease, use of anticoagulants or immune suppressives, frequency of HPN/fluid administration, composition of infusion fluids, and duration of HPN/fluid use before catheter creation. Results: Bloodstream infection incidence rates were 1.1/year for heparin and 0.2/year for Taurolidine locked catheters. Occlusion incidence rates were 0.2/year for heparin and 0.1/year for Taurolidine locked catheters. Adjusted incidence ratios of heparin compared to Taurolidine were 5.9 (95 % confidence interval, 3.9–8.7) for bloodstream infections and 1.9 (95
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Taurolidine Lock Is Superior to Heparin Lock in the Prevention of Catheter Related Bloodstream Infections and Occlusions
PloS one, 2014Co-Authors: Evelyn D. Olthof, M W J Versleijen, Ton Feuth, Wietske Kievit, Getty Huisman-de Waal, Geert J A WantenAbstract:BACKGROUND AND AIMS: Patients on home parenteral nutrition (HPN) are at risk for catheter-related complications; mainly infections and occlusions. We have previously shown in HPN patients presenting with catheter sepsis that catheter locking with Taurolidine dramatically reduced re-infections when compared with heparin. Our HPN population therefore switched from heparin to Taurolidine in 2008. The aim of the present study was to compare long-term effects of this catheter lock strategy on the occurrence of catheter-related bloodstream infections and occlusions in HPN patients. METHODS: Data of catheter-related complications were retrospectively collected from 212 patients who received HPN between January 2000 and November 2011, comprising 545 and 200 catheters during catheter lock therapy with heparin and Taurolidine, respectively. We evaluated catheter-related bloodstream infection and occlusion incidence rates using Poisson-normal regression analysis. Incidence rate ratios were calculated by dividing incidence rates of heparin by those of Taurolidine, adjusting for underlying disease, use of anticoagulants or immune suppressives, frequency of HPN/fluid administration, composition of infusion fluids, and duration of HPN/fluid use before catheter creation. RESULTS: Bloodstream infection incidence rates were 1.1/year for heparin and 0.2/year for Taurolidine locked catheters. Occlusion incidence rates were 0.2/year for heparin and 0.1/year for Taurolidine locked catheters. Adjusted incidence ratios of heparin compared to Taurolidine were 5.9 (95% confidence interval, 3.9-8.7) for bloodstream infections and 1.9 (95% confidence interval, 1.1-3.1) for occlusions. CONCLUSIONS: Given that no other procedural changes than the catheter lock strategy were implemented during the observation period, these data strongly suggest that Taurolidine decreases catheter-related bloodstream infections and occlusions in HPN patients compared with heparin.
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Microbiocidal effects of various Taurolidine containing catheter lock solutions.
Clinical Nutrition, 2014Co-Authors: Evelyn D. Olthof, Reindert Nijland, A.f. Gülich, Geert J A WantenAbstract:Summary Background & aims We have recently shown that a catheter lock solution containing Taurolidine dramatically decreases catheter-related bloodstream infections (CRBSI) in patients on home parenteral nutrition (HPN) when compared to heparin. Since several Taurolidine formulations are commercially available, some of which also contain citrate or heparin, we were interested in the effect of these different locks on growth and biofilm formation of fungal, Gram-negative and Gram-positive pathogens that are known to impede HPN treatment. Methods Clinical isolates obtained during CRBSI of HPN patients were grown in the presence of catheter locks (2% Taurolidine, 1.34% Taurolidine–citrate, 1.34% Taurolidine–citrate–heparin, citrate and heparin) or phosphate buffered saline diluted in lysogeny broth medium for bacteria and sabouraud liquid medium for yeasts. Biofilm formation, assessed by crystal violet staining, and growth of clinical isolates were determined by optical density measurements. Results We found that 12.5× diluted solutions of all Taurolidine containing formulations completely prevented growth of Escherichia coli , Staphylococcus aureus and Candida glabrata . Growth of these microbes was detected earlier in 1.34% Taurolidine–citrate(–heparin) than in 2% Taurolidine, while citrate and heparin did not inhibit growth of clinical isolates compared to PBS. No differences in biofilm formation were found between Taurolidine containing solutions. Conclusion Taurolidine containing lock solutions prevent growth of fungal, Gram-negative and Gram-positive pathogens. While 2% Taurolidine appears to be the most potent in this respect in this in vitro setting, the relevance of the small differences in growth inhibition between the commercially available Taurolidine containing lock solutions for clinical practice remains to be established.
Chris Braumann - One of the best experts on this subject based on the ideXlab platform.
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prevention of disease progression in a patient with a gastric cancer re recurrence outcome after intravenous treatment with the novel antineoplastic agent Taurolidine report of a case
World Journal of Surgical Oncology, 2006Co-Authors: Chris Braumann, Goetz Winkler, P Rogalla, Charalambos Menenakos, C A JacobiAbstract:Background Taurolidine (TRD) is a novel agent with multimodal antineoplastic effects. We present the case of a tumor remission after intravenous administration of Taurolidine in a patient with gastric cancer re-recurrence.
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Effects of increasing doses of a bolus injection and an intravenous long-term therapy of Taurolidine on subcutaneous (metastatic) tumor growth in rats
Clinical & Experimental Metastasis, 2005Co-Authors: Chris Braumann, Charalambos Menenakos, Marco Schoenbeck, Maik Kilian, Christoph A. JacobiAbstract:Background experimental studies have shown that Taurolidine suppresses intraperitoneal tumor growth following local application in rats. In opposite, a single intravenous therapy affected neither intraperitoneal nor subcutaneous growth of malignancies. Thus, an intravenous long-term therapy with Taurolidine was investigated in rats after administration of a subcutaneous tumor load. VEGF and TNFα production and their effects on tumor growth have not been elucidated so far. Methods VEGF and TNFα levels of rat colon adenocarcinoma cells (DHD/K12/TRb) were analyzed in the supernatant undergoing treatment of increasing Taurolidine doses in vitro . Besides the cell experiments rats were treated intravenously. At the beginning of the operation, 10 000 colon adenocarcinoma cells were applied subcutaneously at the back of the rats. Then the animals ( n = 80, BD IX rats) were randomized into eight groups and underwent a standardized midline laparotomy for 30 min. At the end of the operation the animals were given either a bolus (1 ml Ringer’s solution) or a long-term intravenous therapy (7 days, eight-hourly 1 ml 1%, 2%, or 3% Taurolidine) were performed. For long-term therapy, a jugularis vein port catheter system was placed and left for 1 week. The influence on subcutaneous tumor growth, animal growth, general side effects and leukocyte/granulocyte levels were analyzed. Total tumor weights were determined 4 weeks after cell application. Results The VEGF and TNFα levels decreased rapidly after Taurolidine therapy with low doses in vitro . The subcutaneous tumor growth showed a downtrend of tumor weight ( P = 0.075) with a statistical significance in solid tumor counts ( P = 0.04) at the back of the animals. A slight and temporary depression in animal growth was observed only in long-term therapy groups. Independent of the therapeutic agents and the application forms, the operation itself caused a slight leukopenia shortly after the operation compensated by a moderate leukocytosis in the following course. Fast injections of Taurolidine led to a reduction of breathing rate. Conclusions Only the intravenous long-term therapy of 3% Taurolidine led to a slight downregulation in subcutaneous tumor growth. The changes of leukocyte counts were not affected by Taurolidine. Fast injections have to be avoided. The findings prompted us to start new experiments to determine the influence of increasing doses of Taurolidine on progressive tumor growth in rats.
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The tumor-suppressive reagent Taurolidine is an inhibitor of protein biosynthesis.
International journal of cancer, 2004Co-Authors: Chris Braumann, Wolfgang Henke, Christoph A. Jacobi, Wolfgang DubielAbstract:Taurolidine has been successfully used as a disinfectant and to prevent the spreading and growth of tumor cells after surgical excision. However, the underlying mechanisms regarding its effects remain obscure. Here, we show that Taurolidine treatment reduces endogenous levels of IκBα, p105, c-Jun, p53 and p27 in a dose-dependent manner in colon adenocarcinoma cells, which can be in part due to massive cell death. Because expression of tested proteins was affected by Taurolidine, its influence on protein expression was studied. In the coupled transcription/translation system, Taurolidine inhibited c-Jun expression with an IC50 value of 1.4 mM. There was no or little effect on transcription. In contrast, translation of c-Jun or p53 mRNA was completely inhibited by Taurolidine. To determine which step of translation was affected, prominent complexes occurring in the course of translation were analyzed by density gradient centrifugation. In the presence of Taurolidine, no preinitiation translation complex was assembled. Taurolidine also suppressed protein expression in bacteria. Based on our data, we conclude that Taurolidine blocks a fundamental early phase of translation, which might explain its effects as a disinfectant and inhibitor of tumor growth. © 2004 Wiley-Liss, Inc.
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Effects of Taurolidine and octreotide on tumor growth and lipid peroxidation after staging-laparoscopy in ductal pancreatic cancer
Prostaglandins leukotrienes and essential fatty acids, 2003Co-Authors: M. Kilian, Chris Braumann, Christoph A. Jacobi, I. Mautsch, Ingolf Schimke, H. Guski, F. A. WengerAbstract:Abstract Irrigation with Taurolidine after laparoscopy decreases tumor growth in colon carcinoma. In pancreatic cancer subcutaneous therapy with octreotide decreases oxidative stress and carcinogenesis as well. However, it is still unclear, whether irrigation with Taurolidine or octreotide after laparoscopic pancreatic biopsy reduces tumor growth in pancreatic cancer as well. In 60 Syrian hamsters ductal pancreatic adenocarcinoma was induced by weekly injection of 10mg/kg body weight N -nitrosobis-2-oxopropylamine s.c. for 10 weeks. In week 16 laparoscopic pancreatic biopsy by use of carbon dioxide was performed (gr. 1, n =20) with subsequent laparoscopic irrigation with Taurolidine (gr. 2, n =20) or octreotide (gr. 3, n =20). In week 25 hamsters were sacrificed. Our results show that macroscopic visible primary tumors were found in only one animal of the Taurolidine group (5.9%), compared to 42.1% in the saline and 62.5% in the octreotide group ( P 2 ) than after octreotide irrigation (70±120mm 2 , P In conclusion this study showed that laparoscopic irrigation with Taurolidine after pancreatic biopsy inhibited tumor growth in ductal pancreatic adenocarcinoma.
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effects of Taurolidine and octreotide on port site and liver metastasis after laparoscopy in an animal model of pancreatic cancer
Clinical & Experimental Metastasis, 2002Co-Authors: F. A. Wenger, Chris Braumann, M. Kilian, H. Guski, A Neumann, J Ridders, F J Peter, C A JacobiAbstract:Port site metastasis is a dreadful event following laparoscopy; however, the exact pathomechanism is still unknown. In order to prevent trocar metastasis we determined the effects of intraperitoneal lavage with either Taurolidine or octreotide on port site and liver metastasis after laparoscopy in a chemically induced, solid pancreatic adenocarcinoma. Pancreatic adenocarcinoma was induced in 60 Syrian hamsters by weekly injection of 10 mg/kg body weight N-nitrosobis-2-oxopropylamine s.c. for 10 weeks. Six weeks later, a laparoscopic pancreatic biopsy was performed by the use of a pneumoperitoneum with carbon dioxide (12 mm Hg), followed by an abdominal irrigation with 5 ml normal saline (group 1, n=20), 5 ml 0.5% Taurolidine (group 2, n=20) or 5 ml octreotide (20 mg/ml) (group 3, n=20). After 8 weeks, all hamsters were sacrificed and histopathologically examined. There was only one macroscopic visible primary tumor in the Taurolidine group (5.9%), compared to 42.1% in the saline group and 62.5% in the octreotide group (P<0.05). The size of carcinomas was smaller in the saline group than after octreotide irrigation (median 6, range 2–25 vs. median 70, range 40–160 mm2, P<0.05). The number of liver metastases per animal was increased after saline irrigation (median 4, range 2–6), compared to Taurolidine (median 2, range 1–3) or octreotide (median 2.5, range 2–4) (P<0.05). Port site metastases were found in 36.8% after saline, in 37.5% after octreotide and in 0% after Taurolidine irrigation (P<0.05). Thus port site metastasis was effectively prevented by Taurolidine irrigation after staging-laparoscopy in pancreatic cancer.
Christoph A. Jacobi - One of the best experts on this subject based on the ideXlab platform.
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Effects of increasing doses of a bolus injection and an intravenous long-term therapy of Taurolidine on subcutaneous (metastatic) tumor growth in rats
Clinical & Experimental Metastasis, 2005Co-Authors: Chris Braumann, Charalambos Menenakos, Marco Schoenbeck, Maik Kilian, Christoph A. JacobiAbstract:Background experimental studies have shown that Taurolidine suppresses intraperitoneal tumor growth following local application in rats. In opposite, a single intravenous therapy affected neither intraperitoneal nor subcutaneous growth of malignancies. Thus, an intravenous long-term therapy with Taurolidine was investigated in rats after administration of a subcutaneous tumor load. VEGF and TNFα production and their effects on tumor growth have not been elucidated so far. Methods VEGF and TNFα levels of rat colon adenocarcinoma cells (DHD/K12/TRb) were analyzed in the supernatant undergoing treatment of increasing Taurolidine doses in vitro . Besides the cell experiments rats were treated intravenously. At the beginning of the operation, 10 000 colon adenocarcinoma cells were applied subcutaneously at the back of the rats. Then the animals ( n = 80, BD IX rats) were randomized into eight groups and underwent a standardized midline laparotomy for 30 min. At the end of the operation the animals were given either a bolus (1 ml Ringer’s solution) or a long-term intravenous therapy (7 days, eight-hourly 1 ml 1%, 2%, or 3% Taurolidine) were performed. For long-term therapy, a jugularis vein port catheter system was placed and left for 1 week. The influence on subcutaneous tumor growth, animal growth, general side effects and leukocyte/granulocyte levels were analyzed. Total tumor weights were determined 4 weeks after cell application. Results The VEGF and TNFα levels decreased rapidly after Taurolidine therapy with low doses in vitro . The subcutaneous tumor growth showed a downtrend of tumor weight ( P = 0.075) with a statistical significance in solid tumor counts ( P = 0.04) at the back of the animals. A slight and temporary depression in animal growth was observed only in long-term therapy groups. Independent of the therapeutic agents and the application forms, the operation itself caused a slight leukopenia shortly after the operation compensated by a moderate leukocytosis in the following course. Fast injections of Taurolidine led to a reduction of breathing rate. Conclusions Only the intravenous long-term therapy of 3% Taurolidine led to a slight downregulation in subcutaneous tumor growth. The changes of leukocyte counts were not affected by Taurolidine. Fast injections have to be avoided. The findings prompted us to start new experiments to determine the influence of increasing doses of Taurolidine on progressive tumor growth in rats.
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The tumor-suppressive reagent Taurolidine is an inhibitor of protein biosynthesis.
International journal of cancer, 2004Co-Authors: Chris Braumann, Wolfgang Henke, Christoph A. Jacobi, Wolfgang DubielAbstract:Taurolidine has been successfully used as a disinfectant and to prevent the spreading and growth of tumor cells after surgical excision. However, the underlying mechanisms regarding its effects remain obscure. Here, we show that Taurolidine treatment reduces endogenous levels of IκBα, p105, c-Jun, p53 and p27 in a dose-dependent manner in colon adenocarcinoma cells, which can be in part due to massive cell death. Because expression of tested proteins was affected by Taurolidine, its influence on protein expression was studied. In the coupled transcription/translation system, Taurolidine inhibited c-Jun expression with an IC50 value of 1.4 mM. There was no or little effect on transcription. In contrast, translation of c-Jun or p53 mRNA was completely inhibited by Taurolidine. To determine which step of translation was affected, prominent complexes occurring in the course of translation were analyzed by density gradient centrifugation. In the presence of Taurolidine, no preinitiation translation complex was assembled. Taurolidine also suppressed protein expression in bacteria. Based on our data, we conclude that Taurolidine blocks a fundamental early phase of translation, which might explain its effects as a disinfectant and inhibitor of tumor growth. © 2004 Wiley-Liss, Inc.
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Effects of Taurolidine and octreotide on tumor growth and lipid peroxidation after staging-laparoscopy in ductal pancreatic cancer
Prostaglandins leukotrienes and essential fatty acids, 2003Co-Authors: M. Kilian, Chris Braumann, Christoph A. Jacobi, I. Mautsch, Ingolf Schimke, H. Guski, F. A. WengerAbstract:Abstract Irrigation with Taurolidine after laparoscopy decreases tumor growth in colon carcinoma. In pancreatic cancer subcutaneous therapy with octreotide decreases oxidative stress and carcinogenesis as well. However, it is still unclear, whether irrigation with Taurolidine or octreotide after laparoscopic pancreatic biopsy reduces tumor growth in pancreatic cancer as well. In 60 Syrian hamsters ductal pancreatic adenocarcinoma was induced by weekly injection of 10mg/kg body weight N -nitrosobis-2-oxopropylamine s.c. for 10 weeks. In week 16 laparoscopic pancreatic biopsy by use of carbon dioxide was performed (gr. 1, n =20) with subsequent laparoscopic irrigation with Taurolidine (gr. 2, n =20) or octreotide (gr. 3, n =20). In week 25 hamsters were sacrificed. Our results show that macroscopic visible primary tumors were found in only one animal of the Taurolidine group (5.9%), compared to 42.1% in the saline and 62.5% in the octreotide group ( P 2 ) than after octreotide irrigation (70±120mm 2 , P In conclusion this study showed that laparoscopic irrigation with Taurolidine after pancreatic biopsy inhibited tumor growth in ductal pancreatic adenocarcinoma.
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Influence of intraperitoneal and systemic application of Taurolidine and Taurolidine/heparin during laparoscopy on intraperitoneal and subcutaneous tumour growth in rats
Clinical & Experimental Metastasis, 2000Co-Authors: Chris Braumann, Jürgen Ordemann, Peer Wildbrett, Christoph A. JacobiAbstract:Background : Recent clinical and experimental studies investigated the problem and possible pathomechanisms of port-site metastases after laparoscopic resection of malignant tumours. A generally accepted approach to prevent these tumour implantations does not exist so far. Methods : After subcutaneous and intraperitoneal injection of 10^4 cells of colon adenocarcinoma (DHD/K12/TRb) the influences of either Taurolidine or Taurolidine/heparin on intraperitoneal and subcutaneous tumour growth were investigated in 105 rats undergoing laparoscopy with carbon dioxide. The animals were then randomised into seven groups. A pneumoperitoneum was established using carbon dioxide for 30 min (8 mmHg). Three incisions were used: median for the insufflation needle, and a right and left approach in the lower abdomen for trocars. To investigate the intraperitoneal (local) influence of either Taurolidine and heparin on tumour growth the substances were instilled intraperitoneally. Systemic effects were expected when the substances were applied intravenously (iv). Synergistic influences were tested when both application forms were combined. The number and the weight of tumours as well as the incidence of abdominal wall and port-site metastases were determined four weeks after intervention. Blood was taken to evaluate the influences of Taurolidine and heparin on systemic immunologic reactions: seven days before laparoscopy, two hours, two days, seven days, and four weeks after operation, and the peripheral lymphocytes were determined. Results : Intraperitoneal (ip) tumour weight in rats receiving Taurolidine (median 7 mg) and Taurolidine/heparin (0 mg) intraperitoneally was significantly reduced when compared to the control group (52 mg) ( P =0.001). There was no difference of subcutaneus tumour growth among the groups ( P =0.4). Trocar recurrences were decreased when Taurolidine was applied ip (3/15), ipiv (4/15), and ip in combination with heparin (4/15) in comparison to the control group (10/15). Immediately after intervention treated and untreated groups showed a peripheral lymphopenia. Conclusions : The intraperitoneal therapy with Taurolidine and the combination with heparin inhibits the intraperitoneal tumour growth and trocar recurrences. Neither the intraperitoneal nor the systemic application or the combination of Taurolidine and heparin did reduce the subcutaneous tumour growth. The intervention caused a lymphopenia which was compensated on day two.
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Taurolidine Acts on Bacterial Virulence Factors and Does Not Induce Resistance in Periodontitis-Associated Bacteria—An In-Vitro Study
Antibiotics (Basel Switzerland), 2020Co-Authors: Sabrina Radakovic, Simon Schmid, Nicola Andreoli, Sandor Nietzsche, Jürg Zumbrunn, Anton Sculean, Sigrun EickAbstract:The aims of the present study were: (a) to determine the mechanism of action of Taurolidine against bacterial species associated with periodontal disease, and (b) to evaluate the potential development of resistance against Taurolidine as compared with minocycline. After visualizing the mode of action of Taurolidine by transmission electron micrographs, the interaction with most important virulence factors (lipopolysaccharide (LPS), Porphyromonas gingivalis gingipains, Aggregatibacter actinomycetemcomitans leukotoxin), was analyzed. Then, 14 clinical isolates from subgingival biofilm samples were transferred on agar plates containing subinhibitory concentrations of Taurolidine or minocycline up to 50 passages. Before and after each 10 passages, minimal inhibitory concentrations (MICs) were determined. Increasing MICs were screened for efflux mechanism. Taurolidine inhibited in a concentration-dependent manner the activities of LPS and of the arginine-specific gingipains; however, an effect on A. actinomycetemcomitans leukotoxin was not detected. One P. gingivalis strain developed a resistance against Taurolidine, which was probably linked with efflux mechanisms. An increase of MIC values of minocycline occurred in five of the 14 included strains after exposure to subinhibitory concentrations of the antibiotic. The present results indicate that: (a) Taurolidine interacts with LPS and gingipains, and (b) development of resistance seems to be a rare event when using Taurolidine.
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Taurolidine acts on bacterial virulence factors and does not induce resistance in periodontitis-associated bacteria
2019Co-Authors: Sabrina Radakovic, Simon Schmid, Nicola Andreoli, Sandor Nietzsche, Jürg Zumbrunn, Anton Sculean, Sigrun EickAbstract:Abstract Background Taurolidine is thought to be an alternative antimicrobial in periodontal therapy. The purpose of this follow-up Taurolidine study was to determine in more detail the mode of action of Taurolidine against bacterial species being associated with periodontal disease. Further, a potential development of resistance against Taurolidine in comparison with minocycline was to evaluate. Results Visualizing the mode of action of Taurolidine to Porphyromonas gingivalis by scanning and transmission electron micrographs showed in part pores and release of constituents from the cell wall. The interaction of taurolidin with bacterial cell wall is also supported by the finding that Taurolidine inhibited in a concentration-dependent manner the activities of LPS and of the P. gingivalis arginine-specific gingipains. However, an effect on A. actinomycetemcomitans leukotoxin was not found. When transferring 14 clinical isolates from subgingival biofilm samples (4 P. gingivalis, 2 A. actinomycetemcomitans, 2 Tannerella forsythia, 2 Fusobacterium nucleatum, 4 oral streptococci) on agar plates containing subinhibitory concentrations of Taurolidine up to 50 passages, one P. gingivalis strain developed a resistance against Taurolidine which was probably linked with efflux mechanisms. When antimicrobial pressure was removed, MIC reverted to baseline value. Testing development of resistance to minocycline in a similar way, an increase of MIC values occurred in five of the 14 included strains after exposure to subinhibitory concentrations of the antibiotic. Efflux might play a role in one A. actinomycetemcomitans strains, but obviously not in the other four strains. Removing antimicrobial pressure for a few passages did not revert the increased MIC values. Conclusion Taurolidine interacts with LPS and gingipains. Development of resistance seems to be a rare event when applying Taurolidine. A potential development of resistance might be associated with efflux mechanisms.
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Activity of Taurolidine on species associated with periodontitis
2019Co-Authors: Sabrina Radakovic, Simon Schmid, Nicola Andreoli, Sandor Nietzsche, Jürg Zumbrunn, Anton Sculean, Sigrun EickAbstract:Abstract Background Taurolidine is thought to be an alternative antimicrobial in periodontal therapy. The purpose of this follow-up Taurolidine study was to determine in more detail the mode of action of Taurolidine against bacterial species being associated with periodontal disease. Further, a potential development of resistance against Taurolidine in comparison with minocycline was to evaluate. Results Visualizing the mode of action of Taurolidine to Porphyromonas gingivalis by scanning and transmission electron micrographs showed in part pores and release of constituents from the cell wall. The interaction of taurolidin with bacterial cell wall is also supported by the finding that Taurolidine inhibited in a concentration-dependent manner the activities of LPS and of the P. gingivalis arginine-specific gingipains. However, an effect on A. actinomycetemcomitans leukotoxin was not found. When transferring 14 clinical isolates from subgingival biofilm samples (4 P. gingivalis, 2 A. actinomycetemcomitans, 2 Tannerella forsythia, 2 Fusobacterium nucleatum, 4 oral streptococci) on agar plates containing subinhibitory concentrations of Taurolidine up to 50 passages, one P. gingivalis strain developed a resistance against Taurolidine which was probably linked with efflux mechanisms. When antimicrobial pressure was removed, MIC reverted to baseline value. Testing development of resistance to minocycline in a similar way, an increase of MIC values occurred in five of the 14 included strains after exposure to subinhibitory concentrations of the antibiotic. Efflux might play a role in one A. actinomycetemcomitans strains, but obviously not in the other four strains. Removing antimicrobial pressure for a few passages did not revert the increased MIC values. Conclusion Taurolidine interacts with LPS and gingipains. Development of resistance seems to be a rare event when applying Taurolidine. A potential development of resistance might be associated with efflux mechanisms.
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In vitro activity of Taurolidine gel on bacteria associated with periodontitis
Clinical oral investigations, 2015Co-Authors: Sigrun Eick, Jürg Zumbrunn, Nicoletta Gloor, Cecilia Püls, Anton SculeanAbstract:The purpose of this in vitro study was to determine the antimicrobial activity of two different Taurolidine gel formulations in comparison with minocycline microspheres. Three percent Taurolidine gel (TLG3) and 2 % Taurolidine gel (TLG2) were compared to minocycline microspheres (MINO) against single bacterial species and a 12-species-mixture. The antimicrobial activity was proven by determination of minimal inhibitory concentrations (MICs), killing assays, after exposure of the antimicrobials as well as within a biofilm. The MICs against the single species were between 0.5 and 2 mg/ml of Taurolidine. MICs of the used mixed microbiota were 1.5 mg/ml (TLG3) and 4 mg/ml (TLG2). Fusobacterium nucleatum and Porphyromonas gingivalis were completely killed by 10 % TLG3 and TLG2 (equivalent to 3 and 2 mg/ml Taurolidine) after 6 h. The mixture of 12 species was not completely killed by any of the test substances. Taurolidine gels showed a post-antimicrobial activity, however being less than that of MINO. On biofilms, Taurolidine gels reduced concentration dependently the colony forming unit (CFU) counts (multi-species biofilms by 3.63 log10 after 100 % (30 mg/ml) of TLG3), reductions were 2.12 log10 after MINO (1000 μg/ml minocycline). Taurolidine gel formulations exert antimicrobial activity against bacteria associated with periodontal disease. Nevertheless, a complete elimination of biofilms seems to be impossible and underlines the importance of mechanical removal of biofilms prior to application of the antimicrobial. Taurolidine gels may represent a potential alternative for adjunctive topical antimicrobial treatment in periodontitis and infectious peri-implant diseases.
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In-vitro activity of Taurolidine on single species and a multispecies population associated with periodontitis.
Anaerobe, 2014Co-Authors: Lilly Zollinger, Sandor Nietzsche, Anton Sculean, Simone Schnyder, Sigrun EickAbstract:The antimicrobial activity of Taurolidine was compared with minocycline against microbial species associated with periodontitis (four single strains and a 12-species mixture). Minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs), killing as well as activities on established and forming single-species biofilms and a 12-species biofilm were determined. The MICs of Taurolidine against single species were always 0.31 mg/ml, the MBCs were 0.64 mg/ml. The used mixed microbiota was less sensitive to Taurolidine, MIC and the MBC was 2.5 mg/ml. The strains and the mixture were completely killed by 2.5 mg/ml Taurolidine, whereas 256 μg/ml minocycline reduced the bacterial counts of the mixture by 5 log10 colony forming units (cfu). Coating the surface with 10 mg/ml Taurolidine or 256 μg/ml minocycline prevented completely biofilm formation of Porphyromonas gingivalis ATCC 33277 but not of Aggregatibacter actinomycetemcomitans Y4 and the mixture. On 4.5 d old biofilms, Taurolidine acted concentration dependent with a reduction by 5 log10 cfu (P. gingivalis ATCC 33277) and 7 log10 cfu (A. actinomycetemcomitans Y4) when applying 10 mg/ml. Minocycline decreased the cfu counts by 1-2 log10 cfu independent of the used concentration. The reduction of the cfu counts in the 4.5 d old multi-species biofilms was about 3 log10 cfu after application of any minocycline concentration and after using 10 mg/ml Taurolidine. Taurolidine is active against species associated with periodontitis, even within biofilms. Nevertheless a complete elimination of complex biofilms by Taurolidine seems to be impossible and underlines the importance of a mechanical removal of biofilms prior to application of Taurolidine.
