Taurolidine is effective in the treatment of central venous catheter-related bloodstream infections in cancer patients

https://doi.org/10.1016/j.ijantimicag.2004.06.006Get rights and content

Abstract

Taurolidine is an antimicrobial agent that was originally used in the local treatment of peritonitis and was shown to be effective in the prevention of catheter-related bloodstream infections (CR-BSI). In this pilot study, we used taurolidine solution as an intravenous (i.v.) lock into the totally implantable intravascular devices of 11 consecutive oncological patients with catheter-related bloodstream infections not responding to systemic antimicrobial chemotherapy. All patients recovered completely from the infection. No adverse drug effects were seen. Three patients were successfully retreated for a recurrent infection. Our data suggest a beneficial role of taurolidine i.v. lock for the therapy of catheter-related bloodstream infections in oncological patients. Taurolidine i.v. lock application is feasible and could especially be useful in infections resistant to antibiotic chemotherapy.

Introduction

Venous access is a critical issue in the care and management of many malignancies since these patients frequently require not only i.v. cytostatic chemotherapy but parenteral nutrition and hydration, analgesic therapy, treatment of infections and repetitive laboratory work up. Thus, the placement of indwelling central catheters such as Broviac and Hickman catheters or of port catheter systems enabling safe and permanent venous access is strongly recommended due to physical and psychological factors associated with repeated venepuncture secondary to the loss of peripheral venous access [1], [2]. The use of permanent central venous access systems has increased steadily in the last two decades but was accompanied by a simultaneous increase of complications, mainly by a variety of local and systemic catheter-related infections [3], [4], [5]. Catheter-related bacteraemia or septicaemia may be secondary to a local infection at the site of skin puncture, haematogenous seeding of bacteria from a distant focus or may be associated with contamination of the solution or administration set (fluids or parenteral nutrition mixtures). In about two-third of cases, the organisms causing catheter-related bloodstream infections (CR-BSI) are skin commensals such as coagulase negative staphylococci emphasising the relevance of proper skin care and hand washing for adequate prevention [6].

New approaches to make intravascular catheters more resistant to bacterial colonization are under investigation. These include antiseptic or antibiotic coating of the catheter surface, impregnation of cuffs with silver ions and antiseptic hubs [7]. The antiseptic agent taurolidine is a derivative of taurinamide, a naturally occurring aminosulphonic acid, and formaldehyde. Taurolidine has an exceptionally broad spectrum of antimicrobial activity including activity against Gram negative and Gram positive bacteria and fungi. Emergence of bacterial resistance to taurolidine has not been demonstrated. The antimicrobial properties of taurolidine have been ascribed to the biologically active methylol taurinamide which reacts with cell wall constituents of microbial pathogens via methylene iminium ions preventing bacterial adhesion to biological surfaces [8], [9]. Additional proposed mechanisms of action of taurolidine include the capability to reduce tumour necrosis factor (TNF)-α synthesis and activity [10], [11] and interaction with cell surface structure and function [12]. Taurolidine has been shown to be non-toxic to human and animals. It has a short half-live and is metabolised to taurine, carbon dioxide and water. The extent of its antimicrobial activity in vitro and in vivo is well documented in several studies [8], [13], [14], [15], [16], [17]. Recent clinical publications report that taurolidine is effective in the prevention of urinary tract infections subsequent to urinary catheterisation and haemodialysis catheter-related infections and that its intravenous and intraperitoneal administration is not associated with noteworthy side effects [18], [19], [20], [21], [22]. The efficacy of taurolidine in infected indwelling central venous catheters or port catheter systems has only been described in a few case reports and has not yet been analysed in a greater panel of patients within the scope of a randomised or non-randomised clinical study [23].

Section snippets

Patients and methods

Our trail was designed as an open non-randomised single centre pilot study and was conducted at the Department of Haematology, Oncology and Immunology, St. Johannes Hospital Duisburg, Germany. Hospitalised adult patients with proven CR-BSI related to totally implantable intravascular devices (TID) who did not respond to 48–72 h of i.v. antibiotic chemotherapy were eligible. Eleven consecutive patients (three male and eight female individuals) with a mean age of 64.5 years were enrolled in this

Assessment of CR-BSI

CR-BSI was diagnosed on the basis of typical clinical signs of bloodstream infection (temperature >38 °C, chills, arterial hypotension and a raised or lowered peripheral white blood count (WBC)) with the catheter as the only obvious source of infection. In addition, isolation of the same organism (identical species and antibiogram) from catheter culture and peripheral blood culture was regarded as direct evidence. In patients with clinically suspected CR-BSI repetitive, peripheral blood samples

Treatment of CR-BSI

Patients with proven CR-BSI who did not respond to i.v. antibiotic treatment received a taurolidine i.v. lock in addition to systemic antibiotic chemotherapy according to the antibiogram. We administered 3 ml taurolidine-ringer 0.5% into the devices and left them closed for 24 h. Hereafter, the device was flushed with 10 ml NaCl 0.9%. In order to evaluate the effect of repeated taurolidine administration, in two patients the treatment was repeated after 24 h and in three patients after 24 and 48 h.

Microbial isolates and treatment

Microbial isolates from peripheral blood and devices of patients with CR-BSI included coagulase negative Staphylococcus spp. (n = 4), Acinetobacter baumannii (n = 2), Stenotrophomonas maltophilia (n = 1), Staphylococcus aureus (n = 1), Escherichia coli (n = 1), Pseudomonas picketti (n = 1) and Pseudomonas aeruginosa (n = 1). Systemic antibiotic regimes following the antibiogram were initiated and taurolidine i.v. lock solutions were administered as described above.

Treatment response

Six patients received a single

Discussion

TID are frequently used in patients with oncological diseases. CR-BSI is a major complication of TID which often leads to hospital readmission. For the prevention of these infections, sterile handling of the catheter is crucial. Recent comparative studies have shown that the use of central venous catheters impregnated either with minocycline and rifampicin or with chlorhexidine and silver sulfadiazine is associated with lower rates of catheter colonization and bloodstream infection than the use

Acknowledgement

We would like to dedicate this article to Martin Westerhausen (Director of Medizinische Klinik II, St. Johannes Hospital Duisburg, Germany) on the occasion of his 70th birthday.

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