First Report World-Wide of Clinical Use of

Taurolidine 4% citrate Catheter Lock Solution To Treat an

Intravascular Catheter Colonised With A Mycobacteria; With A Highly
Successful Outcome
T. A. COLLYNS 1, A. YOUNG 1, C. Herdeis2, C. WEIS 2, G. ROBINSON 1, M. HUFTON 1, S. ROBERTS 3, J. CHESTER 1;
1Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom, 2TauroPharm GmbH, Waldbuttelbrunn, Germany, 3KIMAL plc,
Uxbridge,
United Kingdom.

Abstract
Background: Device removal is usually recommended for catheter infections by mycobacteria such
as Mycobacterium chelonae (Mermel 2001). Taurolidine is a unique cidal antimicrobial agent, active
against a wide range of bacteria & fungi. It is combined with 4% citrate in the catheter lock solution
TauroLockTM (TauroPharm GmbH). We describe the successful in vivo use of TauroLockTM (T/L) to
treat a patient with a catheter colonised by M. chelonae. This has not been reported before for any
mycobacteria (MedLine, PubMed search).
Methods: The patient was a 54 year old, with penile squamous cell carcinoma & inguinal lymph node
involvement. Post resection, 6 cycles of 5-FU/cisplatin chemotherapy (CRx) were planned, via a dual
lumen Hickman catheter. Post a CRx cycle, patient had febrile episode & luminal blood cultures
(LBCxs), using BD BACTECTM, grew an acid-fast bacillus. This was identified by the Reference unit
(HPA Laboratory, Newcastle, UK) as M chelonae, in vitro resistant to many systemic agents, as is
common for the organism (Brown-Elliott 2002), sensitive to macrolides & aminoglycosides. Patients
systemic symptoms resolved rapidly; and he remained clinically well on the clarithromycin initiated, but
the organism was consistently isolated from subsequent LBCxs. To try to keep the catheter to
complete CRx course, T/L was instilled.
Results:After 17 days in situ, LBCxs (including using Myco/F-Lytic bottles) were negative, as was line
tip culture on removal post successful completion of all planned CRx. In vitro sensitivity testing of
taurolidine against mycobacterial spp is in progress and will be presented.
Conclusions: This report suggests TauroLockTM may play a very useful salvage role in these difficult
to treat infections, and warrants further study.

Background
M chelonae is a species of rapidly growing mycobacteria (RGM); and in vitro is one of the most
antimicrobial resistant of pathogenic RGM species 2. It can cause a variety of infections; with that
related to catheters, such as intravascular or peritoneal, being the most common healthcare
associated type 2 . For the successful management of catheter related mycobacterial bloodstream
infections, catheter removal is usually recommended 2,4,5.However, removal / replacement of a
tunnelled silicone intravascular catheter, such as a Hickman line, may delay intravenous
chemotherapy administration; as well as there being the costs, and risk of an acute adverse event,
consequent to insertion of a new line 3.
Taurolidine [2 H-1,2,4-thiadiazine-4,4-methylenebis(tetrahydro-1,1,1,1-tetraoxide] is a derivative of
taurine, a naturally occurring amino acid, and formaldehyde 3,6. It has a very broad spectrum of
antimicrobial activity, including Gram positive & negative bacteria, and fungi; with a currently apparent
unique cidal mechanism of action, believed to relate to methylol derivatives interaction with microbial
cell walls 3,6,7. Mycobacterial species were not included in the recent published surveys of the
spectrum of organisms covered 6,7; and there is a lack of published data regarding its activity against
mycobacteria, however unpublished results had suggested taurolidine would also be active against
certain mycobacteria (TauroPharm GmbH on file)
TauroLockTM is a commercially available intravascular catheter locking solution containing
taurolidine and 4% citrate; the latter acting as an anticoagulant. It has shown both prophylactic and
therapeutic efficacy vs. catheter related infections 1,3. This report describes the use of TauroLockTM
to control M. chelonae isolated from a tunnelled intravascular catheter; and to conserve the affected
line, enabling the chemotherapy course to be delivered on schedule.

Methods
The patient was a 54 year old man who presented with a penile lesion that was shown to be
squamous cell carcinoma on histology. A partial penectomy was performed; however subsequently
there was local disease recurrence while CT and MRI scans showed bilateral regional
lymphadenopathy. After further surgical resection, a course of chemotherapy in the form of six cycles
of intravenous cisplatin and 5-fluorouracil was planned. A Hickman line was inserted.

After 3 cycles of chemotherapy, the patient presented to hospital with a febrile episode. He was not
neutropenic, and there was no clinical evidence of the Hickman line exit site being infected. The
symptoms abated overnight and the patient was discharged home on oral ciprofloxacin. Luminal blood
cultures taken on admission subsequently yielded a beaded Gram positive bacillus which was also
acid and alcohol fast. There was no growth from concurrent peripheral venous blood cultures. On the
basis of provisional in vitro susceptibility results, the patient was started on oral clarithromycin, and
systemically the patient remained well and apyrexial.
The organism was subsequently identified by the Regional Mycobacterial Reference Unit (Health
Protection Agency Laboratory, Newcastle upon Tyne, England) as M. chelonae; and reported in vitro
susceptible to clarithromycin & azithromycin, and tobramycin; while resistant to isoniazid,
rifampicin, ciprofloxacin, tetracycline, imipenem, co-trimoxazole, linezolid, teicoplanin &
vancomycin.
When the patient received his next cycle of chemotherapy, repeat luminal blood cultures again yielded
an acid and alcohol fast bacillus. In view of the patient remaining clinically well, and the desire to give
the complete intravenous chemotherapy course in the optimum timeframe, the affected line remained
in situ. Each lumen was instilled with 2mls TauroLockTM which was changed after one week, and then
left for a further 10 days until the last cycle of chemotherapy was due, when the TauroLockTM was
changed and alternated with the chemotherapy. Luminal blood cultures were taken post flushing, after
17 days of TauroLockTM being present, as well as peripheral blood cultures. After completion of the
last planned chemotherapy cycle, the Hickman line was removed and the tip cultured on standard
solid media.
Subsequently, the patient received local radiotherapy. He has remained systemically well, has had no
further reported febrile episodes, and no mycobacteria have been isolated subsequently.

Results
Luminal blood cultures taken on initial presentation and after various systemic antimicrobials including
clarithromycin yielded M. chelonae.
Luminal blood cultures taken after 19 days instillation of TauroLockTM were sterile on the basis of BD
BACTECTM cultures (including using Myco/F Lytic bottles). No bacteria were recovered from the line
tip after it was inoculated onto standard solid media.
No organism was isolated from peripheral venous blood cultures (including using Myco/F Lytic
bottles).
The MIC to taurolidine for M. avium complex strain was determined by diluting T/L as 630 mg/l; whilst
for M. terrae 1250 mg/l (L & S AG, Bad Bocklet, Germany). These results are comparable to the
published susceptibilities of other bacterial species 6,7.
In vitro studies of the activity of taurolidine against local recent intravascular catheter associated
RGMs, including this strain of M. chelonae, are in progress.
The literature search revealed no previous title, abstract or article reporting the use of taurolidine vs.
mycobacterial species in vivo ; and very limited data for in vitro activity.
Luminal blood cultures taken on initial presentation and after various systemic antimicrobials including
clarithromycin yielded M. chelonae.

Conclusions
The use of taurolidine in a catheter lock solution, such as TauroLockTM , may be a very useful
adjunctive therapy for mycobacterial catheter infections in cases where line salvage is considered
highly desirable.
In this particular case, one should note that the patient did not have a detected peripheral
mycobacteraemia; and that he remained clinically well with respect to infection throughout his
treatment course, after the initial presentation.
Additional studies are indicated to determine the in vitro spectrum of taurolidine against relevant
mycobacterial species, as well as to investigate further its apparent in vivo topical efficacy.

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