European Journal of Clinical Nutrition (2015) 69, 282–284 © 2015 Macmillan Publishers Limited All rights reserved 0954-3007/15 www.nature.com/ejcn
SHORT COMMUNICATION
Taurolidine locks significantly reduce the incidence of catheter-related blood stream infections in high-risk patients on home parenteral nutrition J Saunders1, M Naghibi1, Z Leach2, C Parsons1, A King3, T Smith1 and M Stroud1 Emerging evidence suggests taurolidine reduces the risk of repeated episodes of catheter related blood stream infections (CRBSI) in a subgroup of patients receiving home parenteral nutrition (HPN). We defined 3 indications where taurolidine could be considered and retrospectively analysed data from patients who were treated over a 10 year period to examine the validity of these criteria. Twenty-two patients were identified from a total HPN population of 81, representing 33.2 years of experience. The overall CRBSI rate pre- and post-taurolidine usage was reduced from 5.71 to 0.99 infections per 1000 patient parenteral nutrition days (P-value o 0.0001), with reductions identified in each smaller subgroup, confirming previous reports of a significant reduction in infections when taurolidine is used as secondary prophylaxis and providing initial data suggesting the benefit of its use as primary prophylaxis. European Journal of Clinical Nutrition (2015) 69, 282–284; doi:10.1038/ejcn.2014.32; published online 19 March 2014
INTRODUCTION One of the most concerning complications of home parenteral nutrition (HPN) is the occurrence of catheter-related blood stream infections (CRBSI), which cause significant morbidity and are potentially life threatening. There is an evidence base in small studies that taurolidine line locks are useful treatments for secondary prophylaxis.1–3 Anecdotal evidence suggests that increasing numbers of patients are being treated with taurolidine but existing literature provides little guidance on specific indications or which patient groups may benefit. We developed the criteria for taurolidine use based on our own clinical experience (Table 1). These criteria were designed to treat three separate indications: (A) patients with recurrent episodes of CRBSI; (B) patients with a potential source of persistent intraabdominal sepsis who had been discharged form hospital on HPN to rehabilitate before undergoing definitive surgery to restore intestinal continuity (mostly patients with persistent enterocutaneous fistulae); and (C) patients with very limited vascular access, in whom the further loss of vascular access might prevent continuation of life-sustaining parenteral nutrition treatment. Patients were taught to instil a volume of the lock solution (taurolidine combined with citrate), TauroLock or Tauroline, depending on the individual home-care companies. This antimicrobial lock replaced the saline locks that were used previously, patients were not routinely anticoagulated and there were no other specific changes to intravenous access protocol in this period.
MATERIALS AND METHODS We undertook a retrospective study to examine the nature of patients we treated with taurolidine and considered the validity of our treatment criteria. Clinical information was collected retrospectively from the records of all adult patients receiving HPN from the University Hospital Southampton NHS Foundation Trust between 1 January 2001 to 31 December 2011. Data collected included demographics, primary diagnosis, indication for taurolidine, episodes of community-acquired CRBSI, successful catheter salvage, type of microorganism and duration of treatment before and after taurolidine. Taurolidine usage was considered to be either a primary or a secondary prophylaxis depending on the individual patient’s history of CRBSI.
Table 1. Category
Southampton criteria for use of taurolidine in HPN patients Inclusion criteria
Indication A The occurrence of two or more episodes of CRBSI acquired in the community (in a period of o12 months) Indication B The occurrence of one or more episodes of CRBSI (community or hospital acquired) in patients with a potential persistent source of intra-abdominal sepsis Indication C Patients with high-risk vascular access (e.g. chronic central venous occlusion in multiple vessels) Italic, modified post-data analysis from this study.
1 Southampton NIHR Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, University of Southampton, Southampton, UK; 2Department of Nutrition and Dietetics, University Hospital Southampton, Southampton, UK and 3Department of Surgery, University Hospital Southampton, Southampton, UK. Correspondence: Dr M Stroud, Southampton NIHR Nutrition, Diet and Lifestyle BRC, Mailpoint 113, Southampton general hospital, Tremona Road, Southampton SO16 6YD, UK. E-mail: [email protected] Contributors: JS conceived the study, carried out the study, data analysis and drafted the manuscript. MN carried out the study, data analysis and helped draft the manuscript. MN carried out the study, data analysis and helped draft the manuscript. ZL carried out data collection and helped draft the manuscript. CP carried out data analysis and performed statistical analysis. AK conceived the study, participated in its design and coordination and helped write the manuscript. TS conceived the study, participated in its design and coordination and helped write the manuscript. MS conceived the study, participated in its design and coordination and helped write the manuscript (guarantor of article). All authors approved the final version of the article including the authorship list. Received 18 June 2013; revised 30 December 2013; accepted 21 January 2014; published online 19 March 2014
Taurolidine reduces line infections in HPN patients J Saunders et al
283 Table 2.
Pre- and post-taurolidine CRBSI rates by indication n
All indications 22 Indication A 13 Indication B 6 Indication C 3
Median age (years)
Number of patient days pre-taurolidine
Number of patient days posttaurolidine
Number of infections pretaurolidine
Number of infections posttaurolidine
50 39 67.5 58
7351 6773 165 413
12121 7506 1698 2917
42 36 4 2
12 10 1 1
Pre-taurolidine Post-taurolidine CRBSI rate per 1000 CRBSI rate per 1000 patient PN days patient PN days
5.71 5.32 24.24 4.84
0.99 1.33 0.59 0.34
P-value
o0.0001 o0.0001 o0.0001 0.0042
Abbreviation: PN, parenteral nutrition.
RESULTS Complete data were available for 22 patients during the study period, representing 20.1 years pre-taurolidine and 33.2 years post-taurolidine. Pre- and post-taurolidine CRBSI rates are shown in Table 2. The overall CRBSI rate was significantly reduced from 5.71 per 1000 patient days pre-taurolidine to 0.99 per 1000 patient days post taurolidine (P-value o 0.0001) (Table 2). This compares to a CRBSI rate of 0.72 per 1000 patients days in our HPN cohort who did not receive taurolidine in the same time period. There were also reductions in CRBSI for each of our three indications but the number of patients in groups B and C was very small. The types of CRBSI-causative organisms pre and post taurolidine were fairly similar with Gram-positive bacteria 16 (38%) versus 5 (42%), Gram-negative bacteria 15 (36%) versus 2 (17%), fungal 4 (10%) versus 1 (8%) and culture-negative infections 7 (17%) versus 4 (33%). Catheter salvage was successful in 19 (45%) pre-taurolidine cases compared with 4 (33%) post-taurolidine cases. There was no statistical difference between the rates of catheter salvage pre- and post-taurolidine use (P = 0.46).
DISCUSSION To our knowledge, it is the first study to suggest specific criteria for the use of taurolidine locks and one of the largest reported series. However, this study was limited as it was retrospective with no control group and demonstrated the considerable inter-patient diversity that exists in those receiving HPN. The study was also limited by low numbers, a consequence of the low prevalence of HPN patients at risk of repeated line infections. The number of type A patients was small (n = 13) but in all likelihood adequate to confirm the validity of that indication. There was no limitation on the time period over which these infections had to have occurred, which is arguably an overcautious approach, as a patient who has two infections in 6 months is clearly at a greater risk than one with two infections 10 years apart. It may therefore be more appropriate to define the indication as having two infections in a period of o12 months and indeed, in this study, all type A patients had actually fulfilled this tighter criterion. Although it would seem logical that patients would be more likely to develop CRBSI in the first few months after starting HPN due to inexperience with the aseptic techniques needed, our type A group had a median duration of 303 patient days before commencing taurolidine, suggesting that this is not the case. The number of individuals who were type B (n = 6) and particularly type C (n = 3) were very small and hence it is not possible to really confirm their validity. Nevertheless, there were clear reductions in both these groups that would support further exploration of the validity of these treatment criteria in future studies. Four patients in our study cohort (three type B and one type C) received taurolidine as primary prophylaxis against community-acquired CRBSI. Three of the four patients did not develop subsequent infections, preventing the need for readmission and potential delays in undertaking definitive surgery. © 2015 Macmillan Publishers Limited
In this cohort the types of organism causing CRBSI before treatment with taurolidine appear to be different from those reported in other studies evaluating infections in all HPN patients.4,5 When compared with data from Santarpia et al.,4 we identified a lower proportion of infections caused by Grampositive organisms (38% versus 76%), a higher proportion of cases caused by Gram-negative organisms (36 versus 16%), and a higher proportion caused by fungi (10% versus 3%). If frequency of catheter access or poor technique were the mechanism of infection, the assumption would be that the proportion of infections due to skin organisms would be high and therefore this study shows that alternative pathogenic mechanisms and patientspecific factors need to be considered, observations that certainly need further research. The increased proportions of Gram-negative organisms and fungi before taurolidine treatment in this cohort may explain the reduced rate of successful line salvage, which in this cohort of patients was only 45%, much lower than the 74–100% seen in other studies.6–8 There was no statistical difference in catheter salvage rates following taurolidine use, suggesting that in this cohort medical therapy should still be the first-line treatment. Interestingly, treatment with taurolidine did not seem to select out more pathogenic microorganisms with, if anything, fewer Gramnegative organisms identified after taurolidine use, 36% versus 17%, in addition to a slight reduction in fungal infections. In conclusion, this study has contributed to the growing evidence base that taurolidine line locks appear to be an effective treatment in reducing CRBSI in higher-risk subgroups of patients, and we have suggested three different clinical indications where taurolidine appears to have a role. Our data also suggest that, in these high-risk populations, the pathogenic organisms involved in CRBSI may be different than in other HPN cohorts. In the future a large multicentre trial is needed to clarify the role of taurolidine in primary and secondary prevention, standardise the definition of CRBSI and provide cost-effectiveness data. CONFLICT OF INTEREST The authors declare no conflict of interest.
REFERENCES 1 Toure A, Lauverjat M, Peraldi C, Boncompain-Gerard M, Gelas P, Barnoud D et al. Taurolidine lock solution in the secondary prevention of central venous catheter-associated bloodstream infection in home parenteral nutritionpatients. Clin Nutr 2012; 31: 567–570. 2 Bisseling TM, Willems MC, Versleijen MW, Hendriks JC, Vissers RK, Wanten GJ. Taurolidine lock is highly effective in preventing catheter-related bloodstream infections in patients on home parenteral nutrition: a heparin-controlled prospective trial. Clin Nutr 2010; 29: 464–468. 3 Cullis PS, McKee RF. Taurolidine lock - experience from the West of Scotland. Clin Nutr 2011; 30: 399–400; author reply 1. 4 Santarpia L, Alfonsi L, Tiseo D, Creti R, Baldassarri L, Pasanisi F et al. Central venous catheter infections and antibiotic therapy during long-term home parenteral nutrition: an 11-year follow-up study. JPEN J Parenter Enteral Nutr 2010; 34: 254–262.
European Journal of Clinical Nutrition (2015) 282 – 284
Taurolidine reduces line infections in HPN patients J Saunders et al
284 5 Ugur A, Marashdeh BH, Gottschalck I, Brobech Mortensen P, Staun M, Bekker Jeppesen P. Home parenteral nutrition in Denmark in the period from 1996 to 2001. Scand J Gastroenterol 2006; 41: 401–407. 6 Benoit JL, Carandang G, Sitrin M, Arnow PM. Intraluminal antibiotic treatment of central venous catheter infections in patients receiving parenteral nutrition at home. Clin Infect Dis 1995; 21: 1286–1288.
European Journal of Clinical Nutrition (2015) 282 – 284
7 Fortun J, Grill F, Martin-Davila P, Blazquez J, Tato M, Sanchez-Corral J et al. Treatment of long-term intravascular catheter-related bacteraemia with antibioticlock therapy. J Antimicrob Chemother 2006; 58: 816–821. 8 Fernandez-Hidalgo N, Almirante B, Calleja R, Ruiz I, Planes AM, Rodriguez D et al. Antibiotic-lock therapy for long-term intravascular catheter-related bacteraemia: results of an open, non-comparative study. J Antimicrob Chemother 2006; 57: 1172–1180.
© 2015 Macmillan Publishers Limited
SHORT COMMUNICATION
Taurolidine locks significantly reduce the incidence of catheter-related blood stream infections in high-risk patients on home parenteral nutrition J Saunders1, M Naghibi1, Z Leach2, C Parsons1, A King3, T Smith1 and M Stroud1 Emerging evidence suggests taurolidine reduces the risk of repeated episodes of catheter related blood stream infections (CRBSI) in a subgroup of patients receiving home parenteral nutrition (HPN). We defined 3 indications where taurolidine could be considered and retrospectively analysed data from patients who were treated over a 10 year period to examine the validity of these criteria. Twenty-two patients were identified from a total HPN population of 81, representing 33.2 years of experience. The overall CRBSI rate pre- and post-taurolidine usage was reduced from 5.71 to 0.99 infections per 1000 patient parenteral nutrition days (P-value o 0.0001), with reductions identified in each smaller subgroup, confirming previous reports of a significant reduction in infections when taurolidine is used as secondary prophylaxis and providing initial data suggesting the benefit of its use as primary prophylaxis. European Journal of Clinical Nutrition (2015) 69, 282–284; doi:10.1038/ejcn.2014.32; published online 19 March 2014
INTRODUCTION One of the most concerning complications of home parenteral nutrition (HPN) is the occurrence of catheter-related blood stream infections (CRBSI), which cause significant morbidity and are potentially life threatening. There is an evidence base in small studies that taurolidine line locks are useful treatments for secondary prophylaxis.1–3 Anecdotal evidence suggests that increasing numbers of patients are being treated with taurolidine but existing literature provides little guidance on specific indications or which patient groups may benefit. We developed the criteria for taurolidine use based on our own clinical experience (Table 1). These criteria were designed to treat three separate indications: (A) patients with recurrent episodes of CRBSI; (B) patients with a potential source of persistent intraabdominal sepsis who had been discharged form hospital on HPN to rehabilitate before undergoing definitive surgery to restore intestinal continuity (mostly patients with persistent enterocutaneous fistulae); and (C) patients with very limited vascular access, in whom the further loss of vascular access might prevent continuation of life-sustaining parenteral nutrition treatment. Patients were taught to instil a volume of the lock solution (taurolidine combined with citrate), TauroLock or Tauroline, depending on the individual home-care companies. This antimicrobial lock replaced the saline locks that were used previously, patients were not routinely anticoagulated and there were no other specific changes to intravenous access protocol in this period.
MATERIALS AND METHODS We undertook a retrospective study to examine the nature of patients we treated with taurolidine and considered the validity of our treatment criteria. Clinical information was collected retrospectively from the records of all adult patients receiving HPN from the University Hospital Southampton NHS Foundation Trust between 1 January 2001 to 31 December 2011. Data collected included demographics, primary diagnosis, indication for taurolidine, episodes of community-acquired CRBSI, successful catheter salvage, type of microorganism and duration of treatment before and after taurolidine. Taurolidine usage was considered to be either a primary or a secondary prophylaxis depending on the individual patient’s history of CRBSI.
Table 1. Category
Southampton criteria for use of taurolidine in HPN patients Inclusion criteria
Indication A The occurrence of two or more episodes of CRBSI acquired in the community (in a period of o12 months) Indication B The occurrence of one or more episodes of CRBSI (community or hospital acquired) in patients with a potential persistent source of intra-abdominal sepsis Indication C Patients with high-risk vascular access (e.g. chronic central venous occlusion in multiple vessels) Italic, modified post-data analysis from this study.
1 Southampton NIHR Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, University of Southampton, Southampton, UK; 2Department of Nutrition and Dietetics, University Hospital Southampton, Southampton, UK and 3Department of Surgery, University Hospital Southampton, Southampton, UK. Correspondence: Dr M Stroud, Southampton NIHR Nutrition, Diet and Lifestyle BRC, Mailpoint 113, Southampton general hospital, Tremona Road, Southampton SO16 6YD, UK. E-mail: [email protected] Contributors: JS conceived the study, carried out the study, data analysis and drafted the manuscript. MN carried out the study, data analysis and helped draft the manuscript. MN carried out the study, data analysis and helped draft the manuscript. ZL carried out data collection and helped draft the manuscript. CP carried out data analysis and performed statistical analysis. AK conceived the study, participated in its design and coordination and helped write the manuscript. TS conceived the study, participated in its design and coordination and helped write the manuscript. MS conceived the study, participated in its design and coordination and helped write the manuscript (guarantor of article). All authors approved the final version of the article including the authorship list. Received 18 June 2013; revised 30 December 2013; accepted 21 January 2014; published online 19 March 2014
Taurolidine reduces line infections in HPN patients J Saunders et al
283 Table 2.
Pre- and post-taurolidine CRBSI rates by indication n
All indications 22 Indication A 13 Indication B 6 Indication C 3
Median age (years)
Number of patient days pre-taurolidine
Number of patient days posttaurolidine
Number of infections pretaurolidine
Number of infections posttaurolidine
50 39 67.5 58
7351 6773 165 413
12121 7506 1698 2917
42 36 4 2
12 10 1 1
Pre-taurolidine Post-taurolidine CRBSI rate per 1000 CRBSI rate per 1000 patient PN days patient PN days
5.71 5.32 24.24 4.84
0.99 1.33 0.59 0.34
P-value
o0.0001 o0.0001 o0.0001 0.0042
Abbreviation: PN, parenteral nutrition.
RESULTS Complete data were available for 22 patients during the study period, representing 20.1 years pre-taurolidine and 33.2 years post-taurolidine. Pre- and post-taurolidine CRBSI rates are shown in Table 2. The overall CRBSI rate was significantly reduced from 5.71 per 1000 patient days pre-taurolidine to 0.99 per 1000 patient days post taurolidine (P-value o 0.0001) (Table 2). This compares to a CRBSI rate of 0.72 per 1000 patients days in our HPN cohort who did not receive taurolidine in the same time period. There were also reductions in CRBSI for each of our three indications but the number of patients in groups B and C was very small. The types of CRBSI-causative organisms pre and post taurolidine were fairly similar with Gram-positive bacteria 16 (38%) versus 5 (42%), Gram-negative bacteria 15 (36%) versus 2 (17%), fungal 4 (10%) versus 1 (8%) and culture-negative infections 7 (17%) versus 4 (33%). Catheter salvage was successful in 19 (45%) pre-taurolidine cases compared with 4 (33%) post-taurolidine cases. There was no statistical difference between the rates of catheter salvage pre- and post-taurolidine use (P = 0.46).
DISCUSSION To our knowledge, it is the first study to suggest specific criteria for the use of taurolidine locks and one of the largest reported series. However, this study was limited as it was retrospective with no control group and demonstrated the considerable inter-patient diversity that exists in those receiving HPN. The study was also limited by low numbers, a consequence of the low prevalence of HPN patients at risk of repeated line infections. The number of type A patients was small (n = 13) but in all likelihood adequate to confirm the validity of that indication. There was no limitation on the time period over which these infections had to have occurred, which is arguably an overcautious approach, as a patient who has two infections in 6 months is clearly at a greater risk than one with two infections 10 years apart. It may therefore be more appropriate to define the indication as having two infections in a period of o12 months and indeed, in this study, all type A patients had actually fulfilled this tighter criterion. Although it would seem logical that patients would be more likely to develop CRBSI in the first few months after starting HPN due to inexperience with the aseptic techniques needed, our type A group had a median duration of 303 patient days before commencing taurolidine, suggesting that this is not the case. The number of individuals who were type B (n = 6) and particularly type C (n = 3) were very small and hence it is not possible to really confirm their validity. Nevertheless, there were clear reductions in both these groups that would support further exploration of the validity of these treatment criteria in future studies. Four patients in our study cohort (three type B and one type C) received taurolidine as primary prophylaxis against community-acquired CRBSI. Three of the four patients did not develop subsequent infections, preventing the need for readmission and potential delays in undertaking definitive surgery. © 2015 Macmillan Publishers Limited
In this cohort the types of organism causing CRBSI before treatment with taurolidine appear to be different from those reported in other studies evaluating infections in all HPN patients.4,5 When compared with data from Santarpia et al.,4 we identified a lower proportion of infections caused by Grampositive organisms (38% versus 76%), a higher proportion of cases caused by Gram-negative organisms (36 versus 16%), and a higher proportion caused by fungi (10% versus 3%). If frequency of catheter access or poor technique were the mechanism of infection, the assumption would be that the proportion of infections due to skin organisms would be high and therefore this study shows that alternative pathogenic mechanisms and patientspecific factors need to be considered, observations that certainly need further research. The increased proportions of Gram-negative organisms and fungi before taurolidine treatment in this cohort may explain the reduced rate of successful line salvage, which in this cohort of patients was only 45%, much lower than the 74–100% seen in other studies.6–8 There was no statistical difference in catheter salvage rates following taurolidine use, suggesting that in this cohort medical therapy should still be the first-line treatment. Interestingly, treatment with taurolidine did not seem to select out more pathogenic microorganisms with, if anything, fewer Gramnegative organisms identified after taurolidine use, 36% versus 17%, in addition to a slight reduction in fungal infections. In conclusion, this study has contributed to the growing evidence base that taurolidine line locks appear to be an effective treatment in reducing CRBSI in higher-risk subgroups of patients, and we have suggested three different clinical indications where taurolidine appears to have a role. Our data also suggest that, in these high-risk populations, the pathogenic organisms involved in CRBSI may be different than in other HPN cohorts. In the future a large multicentre trial is needed to clarify the role of taurolidine in primary and secondary prevention, standardise the definition of CRBSI and provide cost-effectiveness data. CONFLICT OF INTEREST The authors declare no conflict of interest.
REFERENCES 1 Toure A, Lauverjat M, Peraldi C, Boncompain-Gerard M, Gelas P, Barnoud D et al. Taurolidine lock solution in the secondary prevention of central venous catheter-associated bloodstream infection in home parenteral nutritionpatients. Clin Nutr 2012; 31: 567–570. 2 Bisseling TM, Willems MC, Versleijen MW, Hendriks JC, Vissers RK, Wanten GJ. Taurolidine lock is highly effective in preventing catheter-related bloodstream infections in patients on home parenteral nutrition: a heparin-controlled prospective trial. Clin Nutr 2010; 29: 464–468. 3 Cullis PS, McKee RF. Taurolidine lock - experience from the West of Scotland. Clin Nutr 2011; 30: 399–400; author reply 1. 4 Santarpia L, Alfonsi L, Tiseo D, Creti R, Baldassarri L, Pasanisi F et al. Central venous catheter infections and antibiotic therapy during long-term home parenteral nutrition: an 11-year follow-up study. JPEN J Parenter Enteral Nutr 2010; 34: 254–262.
European Journal of Clinical Nutrition (2015) 282 – 284
Taurolidine reduces line infections in HPN patients J Saunders et al
284 5 Ugur A, Marashdeh BH, Gottschalck I, Brobech Mortensen P, Staun M, Bekker Jeppesen P. Home parenteral nutrition in Denmark in the period from 1996 to 2001. Scand J Gastroenterol 2006; 41: 401–407. 6 Benoit JL, Carandang G, Sitrin M, Arnow PM. Intraluminal antibiotic treatment of central venous catheter infections in patients receiving parenteral nutrition at home. Clin Infect Dis 1995; 21: 1286–1288.
European Journal of Clinical Nutrition (2015) 282 – 284
7 Fortun J, Grill F, Martin-Davila P, Blazquez J, Tato M, Sanchez-Corral J et al. Treatment of long-term intravascular catheter-related bacteraemia with antibioticlock therapy. J Antimicrob Chemother 2006; 58: 816–821. 8 Fernandez-Hidalgo N, Almirante B, Calleja R, Ruiz I, Planes AM, Rodriguez D et al. Antibiotic-lock therapy for long-term intravascular catheter-related bacteraemia: results of an open, non-comparative study. J Antimicrob Chemother 2006; 57: 1172–1180.
© 2015 Macmillan Publishers Limited
