Clinical Nutrition 34 (2015) 918e922

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Clinical Nutrition
journal homepage: http://www.elsevier.com/locate/clnu

Original article

A comparison of two methods of treatment for catheter-related

bloodstream infections in patients on home parenteral nutrition
Michał Ławin
ski a, *, Krystyna Majewska a, Łukasz Gradowski b, Iwona Fołtyn a,
Pierre Singer c
a _
Department of General Surgery and Clinical Nutrition, Medical University of Warsaw, Zwirki i Wigury 61, 02-091 Warsaw, Poland
b
Interdisciplinary Center for Applied Cognitive Studies, University of Social Sciences and Humanities, Chodakowska 19/31, 03-815 Warsaw, Poland
c
General Intensive Care Department and Institute for Nutrition Research, Rabin Medical Center, Beilinson Hospital, 49100 Petah Tikva, Israel

a r t i c l e i n f o s u m m a r y

Article history: Background & aims: Home parenteral nutrition (HPN) enables patients who cannot eat normally to
Received 10 February 2014 survive and function. Catheter-related bloodstream infections (CRBSIs) are the most dangerous
Accepted 22 September 2014 complication, which may be fatal if left untreated or if treatment is delayed. For over 20 years CRBSIs
were managed by catheter removal and implantation of a new one after completion of antibiotic
Keywords: treatment. However, frequent catheter replacements put the patient at risk of large vein thrombosis,
HPN
which may render parenteral nutrition impossible. The management of CRBSIs evolved into antibiotic
CRBSI
treatment without catheter removal. The effectiveness of this approach was, however, limited by the low
Antibiotic-ethanol lock therapy
penetration of the antibiotics into the biofilm. Filling catheters with concentrated ethanol destroys the
biofilm and does not result in the emergence of drug resistance. The aim of our study was to assess the
remote outcomes of CRBSI treatment using two approaches: antibiotic-ethanol lock therapy and catheter
replacement. Methods: We retrospectively analysed the treatment outcomes of CRBSI diagnosed and
managed in HPN patients. During the analysed period, a total of 428 patients between 13 and 96 years of
age were on HPN and a total of 181 of them suffered a total of 352 CRBSI episodes managed with one of
the two approaches.
Results: We showed no significant differences between the two approaches in terms of survival likeli-
hood or duration of catheter use after an episode of CRBSI caused by various bacterial species.
Conclusion: The use of antibiotic-ethanol lock therapy in the management of CRBSI is equally effective as
catheter replacement.
© 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

1. Introduction and lumen by microorganisms [2]. Catheter colonisation leads to

Parenteral nutrition involves the supply of all nutrients intra-
venously, thus bypassing the gastrointestinal tract [1]. The success
of long-term parenteral nutrition, which is often a lifetime inter-
vention, is conditional upon the avoidance of complications related
to access to the venous system and upon the selection of nutrients
that is appropriate to the patient's needs and metabolic capacity.
Everyday administration of a nutrient mixture into the venous
system requires at least two manipulations at the catheter end/
transfusion set interface. Following aseptic technique while per-
forming between 25 and 40 actions each day is a condition of
avoiding the contamination and colonisation of the catheter end
* Corresponding author. Tel.: þ48 501702899.

ski).
E-mail address: michal-lawinski@wp.pl (M. Ławin
catheter-related bloodstream infections (CRBSIs) with all the
possible sequelae of a systemic infection, which is fatal if left un-
treated or if treatment is delayed [3,4]. Although a number of
methods to reduce the risk of colonisation and infection have been
developed, it is not possible to avoid them completely. Recently, the
use of taurolidine 2% (taurolidine citrate) has shown to decrease
significantly the number of CRBI (5a Quarello F et al. Blood Purifi-
cation 2002) in hemodialyis catheter for haemodialysis patients.
Taurolidine citrate lock therapy reduced the CRBI's number from 1.3
to 0.3 infections per 1000 catheter days (J Hosp inf 2012). The
traditional approach to the management of CRBSI involves
removing the catheter which is the source of infection and
administering an appropriate antibiotic [5]. A new catheter is
implanted after the infection has been controlled. However, each
subsequent catheter implantation into a large vein is more difficult
and poses a risk of complications related to very catheter

http://dx.doi.org/10.1016/j.clnu.2014.09.013
0261-5614/© 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

ski et al. / Clinical Nutrition 34 (2015) 918e922
M. Ławin
implantation procedure and thrombotic complications which lead
to the loss of vena cava access [6]. The management of CRBSIs is of
dual nature and involves systemic management, including systemic
antibiotics, and catheter management [12]. The traditional man-
agement of CRBSIs involves administration of antibiotics, removal
of the catheter responsible for the infection, and implantation of a
new catheter after the infection has been cured. However, in pa-
tients with recurrent catheter-related infections, each subsequent
catheterization of a large vein is increasingly difficult and risky, and
may lead to the loss of venous access. Therefore, in patients
requiring parenteral nutrition, maintenance of venous access is as
important as controlling and curing the infection. Because of that,
attempts have been made to treat CRBSIs without catheter removal.
This method has been used in many modifications but it turned out
that its effectiveness is limited due to the low penetration of most
antibiotics into the biofilm formed by the microorganisms in the
catheter [7]. While the patients improved and the symptoms of
infection resolved during hospitalisation, the infection recurred
after the patients were discharged home [8,9]. In their search for
agents penetrating into the biofilm, Ball et al. suggested using
concentrated ethanol, previously used to restore catheter patency
[10,11]. The Infectious Disease Society of America does not un-
equivocally recommend ethanol lock therapy as a method for
endoluminal eradication of microorganisms in cases of catheter
colonisation [5]. It is, however, widely believed that the use of
ethanol to destroy the biofilm, followed by the use of antibiotic lock
therapy to completely cure catheter contamination, may be bene-
ficial. The aim of our study was to assess the remote outcomes of
CRBSI treatment in patients on long-term home parenteral nutri-
tion (HPN) using two approaches: antibiotic-ethanol lock therapy
and the traditional approach involving replacement of the
contaminated catheter with a new one.
2. Material and methods
2.1. Material
Between 1 January 2005 and 31 December 2010, HPN was
provided to 428 patients from our hospital outpatient clinic: 240
females (56%) aged 16e92 years (mean age: 56.5 ± 16 years) and
188 males (44%) aged 13e96 years (mean age: 54 ± 17 years). In-
dications for parenteral nutrition in this patient group included:
short bowel syndrome, multilevel bowel obstruction, postoperative
gastrointestinal fistulas, malabsorption syndrome, gastrointestinal
motility abnormalities, cachexia, radiation enteritis. The patients
were fed through 5 kind of permanent venous accesses: tunnelized
single lumen catheters the name of Broviac (n ¼ 305), Groshong
(n ¼ 67), Broviac-Lifecath Expert 19, Cook Redo TPN (n ¼ 29), ports
(n ¼ 8).
Data was obtained from the hospital database and retrospective
study was approved 20.09.2011 by the ethics committee of the
Medical University of Warsaw.
2.2. Management of suspected catheter-related infection
In each case of suspected catheter-related infection, the patient
was hospitalized for evaluation and treatment. Throughout that
period, the catheter was excluded from use and the patient was
being fed and hydrated via peripheral veins. In patients in grave
condition and patients with catheter exit-site or tunnel infection,
the catheter was removed. Cultures for microbial evaluation were
obtained from skin smears around the entry of the catheter,
hemocultures taken from CV catheter, peripheral vein. Final deci-
sion on the course of management was made after obtaining the
culture results for blood collected from the central catheter and
919
after the diagnosis of CRBSI was established. After confirming that
colonisation of the inner surface of the catheter was the source of
bacteraemia, the justifiability of using antibiotic and ethanol lock
with or without systemic antibiotic therapy to sterilize the catheter
was considered. This antibiotic-ethanol lock therapy was compared
to the group of patients in whom the catheter was removed if
contraindications for antibiotic-ethanol lock therapy was
identified.
The following were considered to be the contraindications to
antibiotic-ethanol lock therapy:
 a Groshong catheter (due to its design),
 a previously repaired catheter,
 a ruptured catheter hub,
 colonisation with fungi or bacterial strains of: Staphylococcus
aureus, Staphylococcus haemolyticus, Corynebacterium spp.,
Mycobacterium spp., Pseudomonas aeruginosa, Micrococcus spp.,
Bacillus spp.,
 colonisation with strains resistant to most antibiotics or strains
whose antibiotic susceptibility could not be established.
2.3. Establishment of the antibiotic-ethanol lock
The residual content and blood were aspirated from the cath-
eter, the catheter hub and lumen were flushed to remove the re-
sidual blood using a 0.9% saline solution and the catheter was filled
with a 95% ethanol solution. The solution was left in the catheter for
24 h. The next day blood was aspirated, the catheter lumen and hub
were flushed and the catheter was filled with ethanol again. Four
days later, the ethanol solution was replaced with an antibiotic
solution, which was administered according to the same procedure
for the next four days. The antibiotic was selected according to
culture results. Twenty-four hours after the last dose of the anti-
biotic, the patient was started on his/her nutrient mixture and the
next day blood from the central catheter was drawn for follow-up
culture. If the patient had remained asymptomatic for the past
48 h and the culture was negative, he/she was discharged home.
The following antibiotic solutions at the following concentrations
were used to fill the catheters: amikacin 100 mg/ml, teicoplanin:
40 mg/ml, vancomycin: 50 mg/ml. If the patient developed fever
and/or chills or if his/her condition deteriorated, the treatment was
discontinued, the catheter was removed and a new catheter was
implanted after completion of antibiotic treatment.
2.4. Statistical analysis
The antibiotic lock therapy group was compared to the catheter
removed group. Data were expressed as median with a 25the75th
percentile interquartile range. The median time of new catheter use
after catheter replacement and after antibiotic-ethanol lock ther-
apy was compared using the U ManneWhitney test. Time to
recurrence of infection and survival for each of the two analysed
treatments were compared with the KaplaneMeier method and
the significance of the results was assessed with the CoxeMantel
test. The rates of recurrent infections with the same strains were
assessed with the chi-square test and, for low number of cases, with
the Yates continuity correction. The mean follow-up time to
recurrence was assessed with the U ManneWhitney test. In order
to identify the effect of factors associated with infection recurrence,
multivariate logistic regression analysis of factors identified as
potentially relevant in univariate analysis was performed. The IBM
SPSS Statistic software package (version 21.0) was used for statis-
tical analysis.
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ski et al. / Clinical Nutrition 34 (2015) 918e922
M. Ławin

3. Results Table 2
The treatment of catheter-related infections (median and IQR e Inter Quartile
Range).
The total duration of parenteral nutrition in 428 patients on HPN
between 1 January 2005 and 31 December 2010 was 404,808 days. Duration of using the catheter U Manne p Value
During the follow-up period, 34 (7.9%) patients discontinued the after treatment Whitney
value
treatment due to regained nutritional autonomy, 214 (50.0%) Antibiotic-ethanol Catheter
continued treatment, 178 (41.6%) died and 2 (0.5%) transferred to lock removal

other facilities. Gram Positive Me ¼ 292 Me ¼ 353 5177.0 0.379

247 (57.5%) patients did not suffer any CRBSI episode, while 181 IQR 136 to 695 IQR 163 to 611
Staph Epidermitis Me ¼ 290 Me ¼ 261 1094.0 0.949
(42.5%) suffered a total of 352 CRBSI episodes. The demographic
IQR 126 to 516 IQR 159 to 567
date are presented in Table 1. The number of patients who suffered Staph Con Me ¼ 341 Me ¼ 366 476.5 0.467
1, 2, 3, 4, and more than 4 episodes was 98, 43, 17, 13, and 10, IQR 212 to 935 IQR 140 to 616
respectively. The incidence rate of CRBSIs was 0.87 per 1000 days, Gram Negative Me ¼ 182 Me ¼ 314 740.0 0.254
which corresponds to 0.31 episode of CRBSI per year of treatment. IQR 114 to 547 IQR 135 to 569

A total of 335 CRBSIs were cured. In 331 cases parenteral

nutrition was continued and in 4 cases parenteral nutrition was
terminated, as the patient regained nutritional autonomy or enteric
nutrition was sufficient. Catheter-related infection was attributable
to the death in 16 of the hospitalised patients.
3.1. Remote outcomes of treatment of catheter-related infections
Among the 331 episodes after which patients continued
parenteral nutrition after successful treatment, 100 had been
managed with antibiotic and ethanol lock and 231 had their cath-
eter replaced. The outcomes of treatment of catheter-related in-
fections is expressed in Table 2, showing the duration of using the
catheter after treatment, occurrence of recurrences of infection
with the same microbial species and patient survival after treat-
ment of a CRBSI episode relative to the management approach
used.
Recurrence of infection with the same microbial species was
observed in 33 patients: in 17 patients (17%) managed with
antibiotic-ethanol lock therapy (83% success) and 16 patients
(6.93%) after catheter replacement (93% success) (p < 001 in chi-
squared test). The mean time from completion of antibiotic-
ethanol lock therapy or catheter replacement to recurrence of
infection with the same microbial species was Me ¼ 265 IQR
110e516 days after antibiotic-ethanol lock therapy and Me ¼ 330
IQR 162e591 days after catheter replacement (U ¼ 6233.00;
p ¼ 0.051 in the U ManneWhitney test) (Fig. 1).
The antibiotic most commonly used for antibiotic lock therapy
was amikacin. Recurrences of infection with the same microbial
species were observed in 5 (8.47%) of the 59 patients whose cath-
eters had been filled with amikacin. The rate of recurrences after
treatment with vancomycin was 21.88% and that after treatment
with teicoplanin was 57.14% (p < 0.001 in chi-squared test). The rate
of infections with the same microbial species, in the absence of
systemic antibiotic treatment, was 75% in patients managed with
catheter replacement and 19.44% in patients managed with
antibiotic-ethanol lock therapy (p < 0.0001 vs. patients receiving
systemic antibiotic treatment). Much fewer infections were
observed in patients who received empirical treatment consisting
of 2 or 3 antibiotics irrespective of the management of the catheter-
related infection compared to patients who received just one sys-
temic antibiotic (p < 001). The analysis (Multivariate Logistic
Regression) of the relationships of factors that could potentially
affect the recurrence of infection with the same microbial species
showed that the absence of systemic antibiotic treatment was the
only factor that was significantly associated with the recurrence of
infection with the same microbial species in patients managed by
catheter replacement (b ¼ 0.36; p < 0.0001) (Fig. 2). Recurrence of
CRBSI with the same microbial species after an episode managed
with antibiotic-ethanol lock therapy was, on the other hand,
associated with the person servicing the parenteral nutrition
catheter (b ¼ 0.32; p < 0.0001) (Fig. 3).
No differences were observed when the cumulative survival of
patients from the first CRBSI episode according to the management
approach employed (Fig. 4).
Comparison of late results of treatment with catheter replace-
ment and ethanol/antibiotic lock shows both methods as equally
efficient. Early CRBSI recurrence (until 60 days) were observed in 2
(1%) treated by catheter replacement and 4 (4%) treated by ethanol/
antibiotic lock (chi-square test p ¼ 0.13) and until 120 days
respectively in 5 (2.2%) and 7 (7%), treated (chi-square test
p ¼ 0.66).

Table 1
Demographic data of antibiotic-ethanol and catheter removal groups (n ¼ 181).

Treatment

Antibiotic-ethanol lock Catheter removal

Gender Male 23 75
Female 25 58
Age ± SD 54.8 ± 15 55.1 ± 18
Catheter care Independent 28 (58.3%) 66 (49.7%)
Caregiver 20 (41.7%) 67 (50.3%)
Fig. 1. Likelihood of using the catheter without recurrence of infection with the same
Place of residence Urban 30 (62.5%) 98 (73.7%)
microbial species according to the treatment approach (p ¼ 0.00169 [NS] in
Rural 18 (37.5%) 35 (26.3%)
CoxeMantel test).

ski et al. / Clinical Nutrition 34 (2015) 918e922
M. Ławin
Fig. 2. Effect of various factors on the development of recurrent CRBSI with the same
microbial species after treatment with catheter removal.
4. Discussion
When evaluating the effectiveness of treatment of catheter-
related infections, one should not only take into account the im-
mediate outcomes (control of the acute infection and eradication of
the source of infection) but also patient survival after treatment,
duration of fault-free use of the catheter and the rate of infection
recurrences.
If the goal of the treatment is to preserve a permanent catheter,
then antibiotic lock therapy or ethanol lock therapy becomes the
only option. The body of experience gained so far and the resulting
current recommendations confirm the justifiability of antibiotic
lock therapy for the treatment of catheter-related infections
without the need to remove the catheter in patients requiring long-
term venous access [5,13,14]. Rannem et al. successfully managed
some of the infections solely with antibiotics administered through
the catheter and Buchman et al., in patients treated between 1986
and 1989, managed to preserve 87% catheters using this method
Fig. 3. Effect of various factors on the development of recurrent CRBSI with the same
microbial species after antibiotic-ethanol lock therapy.
921
Fig. 4. Patient survival likelihood according to the treatment approach employed
during the first episode of CRBSI (p ¼ 0.48663[NS] in CoxeMantel test).
[15,16]. More recent studies, however, showed a greater efficacy of
antibiotic lock therapy compared to antibiotic infusion through the
catheter [17,18] and a longer survival of the dialysis catheter after
lock therapy versus catheter replacement (154 and 71 days,
respectively) [19].
A number of factors contributing to infection recurrence after
antibiotic lock therapy have been identified. It is believed that the
principal factor that interferes with successful eradication of mi-
croorganisms colonising the catheter and contributing to re-
currences of infections with these microorganisms is the biofilm
and its resistance to antibiotics [6,7]. Studies were therefore con-
ducted to investigate the use of substances along with the antibiotic
that would destroy the biofilm or facilitate penetration of antibi-
otics into the biofilm: N-acetylcysteine, macrolide antibiotics
(especially erythromycin) and ethanol [20e22]. The properties of
ethanol, such as good penetration into the biofilm, no risk of se-
lection of resistant strains, low cost, low risk of recurrences and low
risk of emergence of resistance, make it an ideal agent to eradicate
microorganisms from catheters [23]. Experimental studies show,
however, that the older the biofilm is and the shorter the exposure
time, the less effective ethanol is [24].
These two methods were combined into one, antibiotic-ethanol
lock therapy, on the premise that after four days of exposure
ethanol would destroy the biofilm, which would facilitate pene-
tration of the antibiotic and eradication of the remaining micro-
organisms from the inner surface of the catheter. The low number
of recurrences and the long follow-up period confirm that this
premise was correct. The comparison of the remote outcomes in
the group of patients managed with catheter replacement with the
outcomes in the group of patients managed with antibiotic lock
therapy showed that both methods are generally equally effective.
Survival of patients after antibiotic-ethanol lock therapy
compared to survival of patients managed with catheter replace-
ment, after excluding cancer patients from the analysis, were
similar. The median duration HPN from the first episode of CRBSI
was 1193 days (IQR: 631e1524) in patients managed with antibiotic
and ethanol lock therapy and 1026 days (IQR: 566e1580) in pa-
tients managed with catheter replacement.
Our study has several limitations. The first is that taurolidine use
for prevention was not a possible alternative since the study was
started in 2005, when taurolidine lock was not a true alternative for
prevention of CRBIs. Second, the groups were not randomly chosen
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ski et al. / Clinical Nutrition 34 (2015) 918e922
M. Ławin
but according to a protocol making the value of our study weaker.
However, the large number of patients followed for a long time is
giving a strong signal of the equal value of the 2 strategies.
5. Conclusions
We conclude that the use of antibiotic-ethanol lock therapy in
the management of CRBSI is equally effective as catheter replace-
ment, after exclusion of absolute indications of catheter removal.
No complications associated with catheter filling with ethanol were
observed. The duration of catheter use and survival after treatment
of a CRBSI episode and patient survival did not differ relative to the
approach employed. Recurrences of CRBSIs with the same micro-
bial species over a period of up to 120 days after the completion of
treatment were observed in 7% of patients managed with
antibiotic-ethanol lock therapy and 2.2% of patients managed with
catheter replacement. Development of recurrences of CRBSIs was
associated with the absence of systemic antibiotic treatment.
Statement of authorship
MŁ is responsible for planned the article and manuscript
preparation. ŁG performed statistical analysis KM, IF collections
and analysed data, PS reviewed the data and revised the manu-
script. All authors read and approved the final manuscript.
Conflict of interest statement
Each author declared no conflict of financial or personal in-
terests in this study.
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