Prevention of dialysis catheter-related sepsis with a citrate–taurolidine-containing lock solution

Michiel G. H. Betjes 0 1 Madelon van Agteren 0 1 0 PhD, Erasmus Medical Center, Dijkzigt Rotterdam, Department of Internal Medicine, Division of Nephrology , Dr Molewater plein erasmusmc.nl 1 Department of Internal Medicine, Division of Nephrology, Erasmus Medical Center , Dijkzigt Rotterdam , The Netherlands Background. The use of haemodialysis catheters is complicated by catheter-related sepsis. Intraluminal colonization of the catheter with bacteria is important in the pathogenesis of catheter-related sepsis. The use of a catheter lock solution containing the antimicrobial taurolidine might prevent bacterial colonization, thereby reducing the incidence of catheter-related sepsis. Methods. In a randomized prospective trial, patients receiving a dialysis catheter were included and catheters were locked with either heparin or a citrate-taurolidine-containing solution. Blood cultures drawn from the catheter lumen were routinely taken every 2 weeks and at time of removal of the catheter to detect bacterial colonization. Catheter-related sepsis and exit-site infections were registered for both groups. Results. A total of 76 catheters were inserted in 58 patients. The incidence of catheter colonization progressed slowly over time with no differences between dialysis catheters filled with heparin or citratetaurolidine-containing solution. The number of exitsite infections was also similar between both groups. In the heparin group, four cases of catheter-related sepsis occurred as opposed to no sepsis episodes in the patients with catheters locked with the citrate-taurolidinecontaining solution (P<0.5). No side effects with the use of citrate-taurolidine catheter lock solution were noted. Conclusions. This study shows that catheter filling with a solution containing the antimicrobial taurolidine may significantly reduce the incidence of catheterrelated sepsis. Taurolidine appears to be effective and safe and does not carry the risk for side effects that have been reported for other antimicrobial lock solutions containing gentamicin or high concentrations of citrate. Introduction The use of central venous catheters for haemodialysis is restricted by complications like thrombosis and infection. The catheter-related sepsis (CRS) incidence varies per dialysis unit, type of catheter used and site of insertion. An average CRS incidence of 23 episodes per 1000 catheter days is considered good, but most studies report a CRS incidence of 46 episodes per 1000 catheter days [1,2]. About half of all infections in haemodialysis patients are related to central venous catheters and CRS is causing significant morbidity and mortality [3]. Bacterial colonization of the intraluminal surface of the catheter with biofilm formation occurs in a high percentage of catheters and precedes peripheral bacteraemia and septic symptoms [4]. Several catheter fillings, such as highly concentrated citrate solutions and gentamicin, have been tested for their efficacy in reducing bacterial colonization and thereby lowering the incidence of CRS. Although effective, their use is restricted by undesirable side effects, such as the risk for hypocalcaemia and high trough levels of gentamicin [5,6]. Taurolidine, a derivative of the amino acid taurine, is an antimicrobial agent that inhibits and kills a broad range of micro-organisms [7,8]. The high concentrations that are needed to exert its antibacterial effect limits the use of taurolidine for parenteral use, but can be easily achieved intraluminal in a dialysis catheter. A catheter lock solution containing citrate and taurolidine has been developed and a low CRS incidence was observed when this lock solution was used in combination with subcutaneous catheter devices and tunnelled catheters [911]. In a single centre open label randomized trial, we tested the efficacy of citrate taurolidine lock solution compared with heparin in the prevention of CRS. Subjects and methods The study design was a single centre randomized controlled trial comparing the efficacy of citratetaurolidine lock solution vs the standard heparin catheter filling in the prevention of CRS. All patients were recruited in a teaching hospital between May 2002 and June 2003. Patients were eligible for the study if they needed a haemodialysis catheter for starting or continuing haemodialysis treatment. Patients were excluded if the dialysis catheter was used on the intensive care unit or for reasons other than haemodialysis. Patients using antibiotics were also excluded. Experienced nephrologists inserted all catheters and catheter placement was controlled for by a radiograph of the thorax. The choice of catheter was guided by the expected duration for the catheter to be in use. A non-tunnelled precurved single lumen catheter (Medcomp, Harleysville, PA, USA) was placed in the right jugular vein if the expected duration of use was <4 weeks and a double or single lumen tunnelled catheter was inserted for prolonged use (Tesio Cath and Ash Split Cath; Medcomp, Harleysville, PA, USA). The femoral vein was only used for catheters expected to be in place for <1 week. Catheters were placed under strict aseptic conditions and the exit site was covered with a transparent, oxygenpermeable dressing. Patients were administered nasal mupirocin on a weekly basis, because this may reduce the number of catheter-related infections [5]. Exit-site care involved inspection of the catheter exit site at each dialysis, cleaning with chlorhexidine or iodine and covering with a new transparent dressing. Connecting and disconnecting of the dialysis catheter to the bloodlines was done under strict aseptic conditions, with nurses wearing facial masks, sterile gloves and a sterile gown. Before the catheter was opened, the catheter hub was wrapped for 5 min in gauzes soaked in iodine or chlorhexidine. Patients were allocated to receive either heparin (5000 U/ml) or citratetaurolidine (1.35% taurolidine and 4% sodium citrate; NeutrolinTM, Biolink, Norwell, MA, USA) as a catheter lock solution using a computer-generated table of random numbers. The randomization procedure was done independent of type of catheter or place of insertion. The lock solution was withdrawn before each dialysis and the catheter was locked after dialysis with a volume equivalent to the lumen volume plus 0.1 ml. Patients clinical characteristics are shown in Table 1. Catheter-related infection Blood cultures were taken every 2 weeks until positive for bacteria and at the time of removal of the catheter. From each catheter lumen, the first 5 ml of aspirated blood was discarded and then 10 ml of blood was aspirated and inoculated in culture bottles for anaerobic and aerobic culture. The primary end-point was CRS. This was defined as a symptomatic patient with a positive bacterial blood culture drawn from the dialysis catheter with no other apparent source of infection. Clinical exit-site infection was defined according to the Centers for Disease Co (...truncated)