Clinical Nutrition ESPEN 50 (2022) 155e161

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Clinical Nutrition ESPEN

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Original article

Catheter-related bloodstream infection management in patients

receiving home parenteral nutrition: An observational cohort study
Michelle Gompelman a, b, *, Erna Causevic a, Chantal P. Bleeker-Rovers b,
Geert J.A. Wanten a
a
Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands
b
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Centre, Nijmegen, the Netherlands

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

Article history: Background and aims: Patients with intestinal failure receiving home parenteral nutrition (HPN) are
Received 16 August 2021 susceptible to central-line associated bloodstream infections (CLABSIs), with crucial roles for adequate
Received in revised form (empiric) antimicrobial therapy and effective catheter management strategies. Our aim was to link recent
22 May 2022
epidemiologic CLABSI data with clinical outcomes and to identify risk factors for therapeutic failure to
Accepted 3 June 2022
decide on the safest and most accurate CLABSI management in patients receiving HPN.
Methods: A retrospective observational cohort study was conducted. All data on CLABSIs (period 2010
Keywords:
e2020) in adult patients receiving HPN were retrieved. The efficacy of attempted catheter salvage and
Catheter-related bloodstream infections
Long-term venous catheters
empiric antimicrobial treatment (b-lactam antibiotics) in our center, with a low prevalence of
Home parenteral nutrition methicillin-resistant staphylococci, was investigated. Multivariate cox-regression analysis was performed
Central venous catheter salvage to identify risk factors for recurrent CLABSI.
Antibiotic therapy Results: 389 CLABSIs occurred in 149 patients. The overall infection rate was 0.64 per 1000 central
venous catheter (CVC) days. Most CLABSIs were caused by Coagulase-negative staphylococci (37%).
Attempted CVC salvage was successful in 70% of the cases. Empiric antimicrobial therapy was found to be
adequate in only 47% of cases, mainly because of insufficient Coagulase-negative staphylococci coverage.
According to the Cox model, patients with a replaced CVC had a 50% lower risk of a new CLABSI than
patients with a retained (salvaged) CVC during follow-up (HR 0.50; 95% CI 0.35e0.72, P < 0.001).
Conclusions: CVC salvage can be achieved in most CLABSI cases but seems associated with a shorter
CLABSI-free survival. Importantly, based on our findings, a glycopeptide containing antibiotic treatment
regimen will increase the likelihood of adequate empiric coverage.
© 2022 The Author(s). Published by Elsevier Ltd on behalf of European Society for Clinical Nutrition and
Metabolism. This is an open access article under the CC BY license (http://creativecommons.org/licenses/
by/4.0/).

1. Introduction thrombophlebitis, septic emboli, and endocarditis [3e7]. The

Patients who require long-term (and often lifelong) vascular
access, such as a central venous catheter to administer home
parenteral nutrition (HPN), are at considerable risk for developing
catheter-related complications, such as central line-associated
bloodstream infections (CLABSIs) [1,2].
CLABSIs are life-threatening and not infrequently complicated
by septic shock or metastatic infectious foci, such as septic
* Corresponding author. Intestinal Failure Unit, Department of Gastroenterology
and Hepatology, Radboud University Medical Center, Geert Grooteplein Zuid 10,
6500HB, Nijmegen, the Netherlands.
E-mail address: michelle.gompelman@radboudumc.nl (M. Gompelman).
cornerstone of CLABSI preventive strategies in patients on HPN is
strict adherence to hygiene measures that concern catheter
handling [8]. Also, the use of anti-septic catheter locking solutions,
like taurolidine, is a valuable CLABSI prevention measure [9].
Although the development of successful CLABSI preventive
strategies is key, there will always remain a risk for acquiring a
CLABSI, and therefore further improvement of available CLABSI
management strategies is required. So far, these strategies
comprise, amongst others, accurate diagnostics, appropriate
empiric and tailored antimicrobial therapy, and deciding on when
to attempt central venous catheter (CVC) salvage. Although the
strength of current CLABSI management recommendations for
patients with HPN support are judged as strong, the level of evi-
dence varies between moderate and very low [10]. Optimal and

https://doi.org/10.1016/j.clnesp.2022.06.003
2405-4577/© 2022 The Author(s). Published by Elsevier Ltd on behalf of European Society for Clinical Nutrition and Metabolism. This is an open access article under the CC BY
license (http://creativecommons.org/licenses/by/4.0/).
M. Gompelman, E. Causevic, C.P. Bleeker-Rovers et al.
well-defined CLABSI management strategies will lead to a higher
chance of catheter survival. Besides, recurrent CLABSIs in patients
on HPN with subsequent CVC removals may lead to a permanent
loss of venous access in the long term [11]. Even so, inadequate use
of empiric broad-spectrum antimicrobial therapy may result in a
rise in antimicrobial resistance and increased mortality [12,13].
There is an obvious need for studies that focus on CLABSI
epidemiology and management outcomes in patients with HPN
support. To the best of our knowledge, studies that give a complete
overview of both clinical outcomes per pathogen type as an analysis
of risk factors for both acquiring a CLABSI and for CVC salvage
failure are scarce [14e16]. Our primary objective, therefore, was to
link recent epidemiologic CLABSI data with clinical outcomes and
to identify risk factors for therapeutic failure to decide on the safest
and most accurate CLABSI management in patients receiving HPN.
2. Materials and methods
A retrospective observational study was conducted between
2010 and 2020 at a tertiary referral centre for chronic intestinal
failure (CIF) patients in the Netherlands (Radboudumc, Nijmegen).
The study population comprised adult patients with CIF who
received home parenteral nutrition (HPN). Exclusion criteria were
age <18 years and HPN duration of less than 90 days. Patient data
and information about hospital admissions and routine checks
were collected from a prospectively maintained electronic database
(Castor EDC). This software provides data management compliant
with Good Clinical Practice (GCP), current privacy laws (AVG/Gen-
eral Data Protection Regulation), and security standards (ISO27001
and NEN7510). Ethical approval was waived by the local ethics
committee (Reference number 2020e6119).
2.1. Definitions
CLABSI was defined according to the criteria of the Centers for
Disease Control and Prevention (CDC) [17]. Sepsis was diagnosed in
a patient when the Quick SOFA (qSOFA) score was
2 [18].
A CLABSI was defined as cured in case of clinical and biochem-
ical resolution at 7e14 days after the termination of CLABSI treat-
ment. A relapse infection implied a re-infection within 30 days with
the same causative pathogen and an identical antibiogram. A
recurrent infection manifested within 30e100 days from the first
CLABSI and was caused by the same causative pathogen with an
identical antibiogram [14,19e23].
CVC salvage was defined as retention of the venous access
during a CLABSI. It was considered successful when the catheter
was retained for at least 60 days after initiation of CLABSI treatment
and no relapse or recurrence occurred.
2.2. CLABSI and CVC management
When HPN is initiated at our center, patients and/or their care-
givers are trained in aseptic handling and catheter management by
specialized nurses [24]. Patients receive 2% taurolidine (Taurosept,
Geistlich Pharma AG Wolhusen, Switzerland) as standard CVC lock
solution for infection prevention. Our current standardised antimi-
crobial treatment approach of a suspected CLABSI with hemody-
namic stability (qSOFA < 2) implies the use of a b-lactam (mostly
flucloxacillin or ceftriaxone) as empiric antimicrobial therapy. In the
case of hemodynamic instability (qSOFA
2), an aminoglycoside
(gentamicin) is started next to the b-lactam antibiotic. The reason for
b-lactam antibiotics as the first choice for CLABSI management is the
low methicillin-resistant Staphylococcus aureus (MRSA) prevalence
in the Netherlands and the adopted associations between MRSA
156
Clinical Nutrition ESPEN 50 (2022) 155e161
isolation and glycopeptide (e.g. vancomycin and teicoplanin) expo-
sure [25]. Therefore, glycopeptides are preferably preserved for
second-line therapy. However, in case coagulase-negative staphylo-
cocci (CoNS) are cultured, antibiotic treatment is switched into a
glycopeptide containing regimen directly.
In general, CVC salvage is attempted in a non-complicated
infection that is not caused by Candida species or Staphylococcus
aureus. In the period before 2013, CVC salvage was occasionally
attempted in non-complicated S. aureus infections. A CLABSI is
considered complicated when persistent fever (
72 h), positive
follow-up blood cultures (
48 h), septic shock, (septic) thrombo-
phlebitis, endocarditis, and/or other metastatic infectious foci are
present.
2.3. Statistical analysis
Descriptive statistics were applied for continuous and categor-
ical data. Unpaired student’s t-tests were used to compare normally
distributed, continuous variables; otherwise, non-parametric tests
(ManneWhitney U or KruskaleWallis test) were used. Results are
presented as means with standard deviations. Chi-square and
Fisher’s exact tests were applied for categorical data, presented as
numbers with percentages. Two-tailed P < 0.05 was considered
statistically significant. A Kaplan Meier curve was produced to
display the CLABSI-free survival (%) of salvaged and non-salvaged
CVCs. Time was calculated as time in days between the date of
the first positive blood culture until a new CLABSI. Data were
censored upon discontinuation of HPN, death, removal of the CVC,
or at the end of the follow-up period. A log-rank test was applied to
explore CLABSI-free survival differences between salvaged and
non-salvaged CVCs. A multivariate Cox logistic regression model
was built to adjust for potential confounders influencing CLABSI-
free survival, such as type of catheter and pathogen category. Var-
iables entered in the multivariate analysis were those with at least
90% non-missing observations and a univariate p-value of <0.1. For
categorical variables the p-value of the overall test was used. Sta-
tistical analysis was performed with SPSS Statistics version 25 and
Graphpad Prism version 5.
3. Results
3.1. CLABSI rate
In the period between 2010 and 2020, data of 398 patients were
retrieved from the (C)IF registry database. One hundred forty-nine
patients experienced one or more CLABSI(s) (Fig. 1). The overall
CLABSI rate was 0.64 per 1000 catheter days. In 2014, the infection
rate was the highest, with 0.83 per 1000 catheter days
(Supplemental Fig. S1). The infection rate was the lowest in venous
port systems (0.16 per 1000 catheter days) and the highest in
peripherally inserted central catheters (PICCs) (1.32 per 1000
catheter days) (Supplemental Fig. S2).
3.2. Patient demographics and CVC characteristics
Patients who experienced
1 CLABSI(s) were compared with
those without a CLABSI during the follow-up period. Table 1 sum-
marises the patient demographics, and CVC characteristics studied.
Patients with
1 CLABSI(s) were on average older, used more often
chronic opioids, and had more frequently intestinal dysmotility as
the underlying disease. Also, CLABSI’s occurred more frequently in
multiple lumen catheters, femoral inserted CVCs, and when the
HPN administration frequency was higher.
M. Gompelman, E. Causevic, C.P. Bleeker-Rovers et al. Clinical Nutrition ESPEN 50 (2022) 155e161

Fig. 1. Flowchart of data collection. Abbreviations: IF: intestinal failure; CLABSI: central line-associated bloodstream infection; HPN: home parenteral nutrition.

Table 1
Baseline characteristics of the study population.

(a) Patient demographics

Total HPN patients without CLABSIs HPN patients with CLABSIs P-valuea
N ¼ 398 N ¼ 249 (%) N ¼ 149 (%)

Age at start inclusion, mean years (SD) 52.5 (15.6) 54.6 (15.2) 49.1 (16.0) 0.001b
Gender
Female 271 (68) 169 (68) 102 (68) 0.90
Indication HPN 0.28
Short bowel syndrome 168 (42) 108 (43) 60 (40)
Intestinal fistula 26 (7) 19 (8) 7 (5)
Intestinal dysmotility 145 (36) 81 (33) 64 (43) 0.04
Mechanical obstruction 15 (4) 10 (4) 5 (3)
Extensive small bowel mucosal disease 19 (5) 12 (5) 7 (5)
Other 26 (7) 19 (8) 6 (4)
Underlying disease short bowel syndrome 0.38
Mesenteric ischemia 43 (26) 23 (21) 20 (33)
Crohn’s disease 50 (30) 33 (31) 17 (28)
Radiation enteritis 8 (5) 5 (5) 3 (5)
Surgical complications 27 (16) 17 (16) 10 (17)
Intestinal volvulus 6 (4) 5 (5) 1 (2)
Familial polyposis 2 (1) 2 (2) 0
Abdominal trauma 1 (1) 0 1 (2)
Other 31 (19) 23 (21) 8 (13)
Underlying disease intestinal dysmotility 0.30
Primary/idiopathic 70 (49) 36 (44) 34 (53)
Secondary 75 (52) 45 (56) 30 (47)
Median HPN duration in months (IQR) 41 (15e84) 34 (11e77) 48 (25e92) 0.004c
Taurolidine intolerance 26 (7) 14 (6) 12 (8) 0.35
Chronic opioid use 134 (34) 71 (30) 63 (43) 0.01
Immunocompromised 71 (18) 49 (20) 22 (15) 0.22

(b) CVC characteristics

Total CVCs in HPN patients CVCs in HPN patients P-valued

N ¼ 1519 without CLABSIs with CLABSIs
N ¼ 650 (%) N ¼ 869 (%)

Central venous access

Type
Tunneled 928 (61) 380 (59) 548 (63) 0.19
Non-tunneled 106 (7) 39 (6) 67 (8) 0.24
PICC 107 (7) 52 (8) 55 (6) 0.17
PAC 273 (18) 137 (21) 136 (16) 0.003
Shunt 98 (7) 33 (5) 65 (7) 0.08
Site of insertion
V. Jugularis 730 (62) 331 (68) 399 (58) 0.001
V. Subclavia 268 (23) 121 (25) 147 (22) 0.19
V. Femoralis 142 (12) 26 (5) 115 (17) <0.001
Type of lumen
Multiple lumens 115 (12) 35 (9) 80 (14) <0.001
Type of infusion
Fluids and/or electrolytes 161 (12) 84 (14) 77 (10) 0.02
Nutrition 1194 (88) 507 (86) 687 (90) 0.001
Frequency of infusions per week
2 60 (4.5) 31 (5.3) 29 (3.8) 0.18
3-5 207 (14) 134 (23) 73 (10) <0.001

6 1081 (80) 418 (72) 663 (87) <0.001

Abbreviations: CLABSI: central line-associated bloodstream infection; CVC: central venous catheter; HPN: home parenteral nutrition; IQR: Interquartile range; SD: standard
deviation; PICC: peripherally inserted central catheter, PAC: Port-A-Cath.
a
Chi-square test was performed unless stated otherwise.
b
Independent student’s T-test.
c
Mann-Whitney U test. Missing data in all variables were <5%.
d
Chi-square test was performed. Missing data in all variables were <10%. In case missings were >5%, sensitivity analysis was performed: no changes in outcomes were seen.

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3.3. Clinical characteristics of CLABSIs
Most CLABSIs were monobacterial (78%). Coagulase-negative
staphylococci were the most common causative pathogens (37%),
followed by Gram-negative bacteria (19%), with Klebsiella spp. being
the most prevalent (9%). Candida spp. were cultured in 6% of the
CLABSIs (Supplemental Fig. S3). 61% (n ¼ 112) of the cultured CoNs
were methicillin resistant. Two CLABSIs were caused by extended
spectrum beta lactamase (ESBL) producing Gram negative bacteria.
One CLABSI was caused by MRSA.
Clinical presentation with hemodynamic instability (qSOFA
2)
at admission occurred in 52 (14%) of the CLABSI cases (Table 2). The
median duration of hospital admission was 11 days (IQR 6e19).
Sixty-four patients (17%) had a complicated course of infection (e.g.,
endocarditis, infected thrombophlebitis, other metastatic infection
foci. 18F-FDG PET/CT scanning was performed in 91 patients (23%):
metastatic infectious foci were found in 48% of these. Most patients
were directly hospitalised at our affiliation (76%, N ¼ 297), while 91
patients were initially admitted and/or treated in other hospitals (1
missing). There were no differences in clinical outcomes between
these patients.
3.4. Comparison of CLABSI outcomes between different causative
pathogen categories
CLABSIs caused by Staphylococcus aureus presented more
frequently with metastatic infection, especially in the lungs
(P < 0.001) compared to the other pathogens (Table 2). Septic
thrombophlebitis was most frequently seen in S. aureus and yeast
infections (P ¼ 0.006). CLABSIs caused by Gram-negative bacteria or
with polymicrobial origin presented with a higher qSOFA score
2
(P ¼ 0.003), while 94% of the CLABSIs caused by CoNs presented
with a qSOFA score of 1 (not displayed). Relapse infections were
most frequently seen in CLABSIs with CoNS and Gram-negative
bacteria (Resp. 13% and 11%, P ¼ 0.003). Patients with yeast CLAB-
SIs developed more new infections <1 month (P ¼ 0.04) and had
the longest length of hospital stay (median 20 days; IQR 15e31,
P < 0.001). Patients with CLABSIs caused by other Gram positives
than S. aureus and CoNS (n ¼ 16, not displayed in the table) died
more frequently during the hospital admission (18% vs 0.5%
p < 0.001).
3.5. Antimicrobial therapy
Empiric antimicrobial therapy was used in 76% (290/389) of the
CLABSIs, of which a cephalosporin (mostly ceftriaxone) was
administrated most frequently (47%), followed by flucloxacillin
(37%). Additional Gram-negative coverage in case of hemodynamic
instability was started in 15% of the cases. Excluding patients
treated in other hospitals, empiric therapy was administrated in
only 38% (90/239) of the cases according to protocol. The choice of
empiric treatment based on former culture results was mainly the
reason for protocol deviation (Supplemental Table S1). Based on the
causative pathogen’s antibiogram, empiric therapy was considered

Table 2
Comparison of clinical characteristics between CLABSI causative pathogens.

Total S. aureus CoNS Gram-negative Polymicrobial Yeast P-valueb

bacteria

N ¼ 389 N ¼ 65 N ¼ 144 N ¼ 74 N ¼ 61 N ¼ 25

Hospital admission duration, median days (IQR) 11 (6e19) 15 (10e23)ab 9 (5e16)aef 8 (5e15)bcd 13 (7e21)dfg 20 (15e31)ceg <0.001c
Admission on ICU (%) 51 (13) 7 (11) 18 (13) 13 (18) 10 (16) 3 (12) 0.55
Duration, median days (IQR) 3 (1e6) 2 (1e18) 5 (2e8) 2 (1e5) 2 (1e3)a 5 (3e5)a 0.02c
Sepsis (qSOFA score
2) (%) 52 (14) 8 (12) 10 (7)ac 16 (20)ab 15 (21)cd 1 (5)bd 0.003
Complications (%) 64 (17) 23 (35)abe 12 (8)acd 9 (12)b 12 (20)de 7 (28)c <0.001
Septic shock 16 (4) 2 (3) 2 (1) 6 (8) 4 (7) 1 (4) 0.88
Septic thrombophlebitis 19 (5) 7 (11)a 3 (2)ab 4 (5) 1 (2)c 4 (16)bc 0.006
Endocarditis 3 (1) 1 (2) 1 (1) 0 (0) 0 (0) 1 (4) 0.40
Metastatic infection 36 (9) 18 (28)abe 5 (4)ad 2 (3)bc 8 (13)cde 3 (12) <0.001
Lung 28 (7) 15 (23)abd 3 (2)ac 2 (3)b 5 (8)d 3 (12)c <0.001
Outcome (%)
< 1 month
Cured 289 (75) 48 (74)a 111 (77)b 60 (81)c 46 (75)d 13 (52)abcd 0.006
Relapse infection 29 (8) 0ab 19 (13)ad 8 (11)bc 1 (2)cd 1 (4) 0.003
New infection 27 (7) 1 (2)ab 9 (6) 3 (4) 8 (13)a 4 (16)b 0.04
In-hospital death 6 (2) 0 1 (1) 1 (1) 0 1 (4) 0.003d
Related to CRBSI 1 (0) 0 0 0 0 1 (4) 0.05d
3 months
Cured 298 (78) 52 (81) 115 (79) 59 (80) 43 (69) 20 (83.3) 0.49
Recurrence (1e3 months) 17 (5) 4 (6) 9 (6) 1 (1) 2 (3) 0 0.44
New infection 56 (15) 6 (9) 16 (11) 14 (19) 13 (21) 4 (17) 0.23
Death (0e3 months) 11 (3) 2 (3) 5 (3) 0a 4 (7)a 0 0.04
6 months
Cured 288 (78) 49 (79) 108 (77) 59 (80) 44 (76) 17 (71) 0.92
New infection 75 (20.2) 13 (21.0) 28 (20.0) 13 (17.6) 14 (24.1) 6 (25) 0.78
12 months
Death (0e12 months) 37 (10) 3 (6) 14 (10) 6 (8) 6 (10) 4 (16) 0.17
CVC salvage attempted (%)a 136 (35) 7 (11)abe 66 (46)ad 35 (47)bc 18 (30)cde N/a <0.001
Successful CVC salvage 95 (70) 3 (43) 48 (73) 25 (71) 13 (72) N/a 0.51

Means, medians and numbers with differing subscripts within rows are significantly different at the p < 0.05 based on post hoc paired comparisons.
Abbreviations: CoNS: coagulase-negative staphylococci; CVC: central venous catheter; ICU: Intensive Care Unit, qSOFA: quick Sepsis Organ Failure Assessment; SD: standard
deviation.
a
5 missings.
b
Chi-square or Fisher exact test (in case of low values) has been applied to compare the pathogens.
c
Kruskal-Wallis test.
d
Statistical difference was caused by a high percentage deaths (3/16) in other Gram-positive spp. category (numbers not displayed).

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adequate in less than half of these cases (47%). Patients receiving
inadequate empiric antibiotics were more frequently still in treat-
ment after one month than patients treated adequately directly
(18% vs 5%, P < 0.01).
Based on blood culture results, tailoring of the antibiotic treat-
ment occurred in 65% of the cases and mostly implied a switch to
teicoplanin (32%). Switch to an oral antibiotic took only place in 26
(7%) of the cases. Treatment duration was, on average, between 10
and 14 days. Acquired antimicrobial resistance was present in 2%,
mostly this concerned a CoNS that became resistant to flucloxacillin
in a relapse infection (5/7).
3.6. CVC salvage
The overall number of attempted CVC salvages was 136/384
(35%) (5 missings excluded), of which 95 were successful (70%).
Reasons to remove the CVC were mainly complicated infection
(28%) and infection due to S. aureus (15%) or Candida spp. (14%)
(Supplemental Table S1). CVC salvage was attempted in nearly half
of the CLABSIs caused by CoNS and Gram-negative bacteria
Fig. 2. Kaplan Meier curve of CLABSI-free survival in salvaged and non-salvaged CVCs.
Log-rank test (P < 0.001). Abbreviations: CVC: central venous catheter. CLABSI: central
line-associated bloodstream infection.
(Table 2). Successful CVC salvage attempt rates did not differ among
the various cultured pathogens (P ¼ 0.51).
3.7. Survival analysis
In Fig. 2, the CLABSI-free survival (%) of salvaged (retained) and
non-salvaged (replaced) CVCs (excluding CLABSIs treated in affili-
ated hospitals) is illustrated in a Kaplan Meier curve: patients with
retained CVCs had a significantly shorter CLABSI-free survival
compared to patients with replaced CVCs (P < 0.001). A multivar-
iate cox regression analysis was performed with CLABSI-free sur-
vival as the endpoint to identify independent risk factors for re-
infection. According to the Cox model, the replaced CVC group
had a 50% lower risk of a new CLABSI than the retained CVC group
during follow-up (HR 0.50; 95% CI 0.35e0.72, P < 0.001 (Table 3).
4. Discussion
This study presents a comprehensive and in-depth analysis of
CLABSI management in a large cohort of CIF patients. For the first
time, an analysis and comparison of clinical characteristics and
outcomes for various causative pathogen categories were per-
formed. The most remarkable finding was the 50% lower risk of a
subsequent CLABSI during follow-up seen in patients of whom the
CVC was not salvaged but removed directly.
This study’s CLABSI rate of 0.64 per 1000 catheter days is in line
with previous studies (range 0.31e1.83) [14e16,26,27]. Important
to add here is that diverging definitions for CLABSIs are used within
studies, which makes comparisons of CLABSI rates rather difficult
[28].
CLABSI rates per year varied; this observation is probably
attributable to the improved data provision from referral centres
over the years (>2013) and to the implementation of both taur-
olidine as catheter lock-solution (>2008) [9], as well as the
implementation of mupirocin nasal ointment to prevent S. aureus
CLABSIs (2012e2014) [29].

Table 3
Cox model with endpoint CLABSI-free survival time (n ¼ 294).

Univariate analysis P-value Multivariate analysis P-value

HR (95%-CI) HR (95%-CI)

Retained CVC (Ref.: Replaced CVC)a 0.50 (0.35, 0.72) <0.001 0.50 (0.35, 0.72) <0.001
Patient characteristics
Age (per year) 0.99 (0.98, 1.00) 0.18
Charlson Comorbidity Index (per point) 0.98 (0.89, 1.07) 0.59
Male 1.25 (0.86, 1.81) 0.25
Immunocompromised 0.94 (0.57, 1.55) 0.81
Diabetes 1.08 (0.58, 2.01) 0.81
Motility disorder 1.01 (0.71, 1.43) 0.97
CVC characteristics
Venous access type 0.14
Implanted port (Ref. Non-tunneled CVC) 0.52 (0.24, 1.12) 0.09
Tunneled CVC (Ref. Non-tunneled CVC) 0.87 (0.49, 1.56) 0.64
CVC lock 0.87
Nacl (Ref. Taurolidine) 0.93 (0.55, 1.58) 0.78
Other (Ref. Taurolidine) 0.73 (0.18, 2.80) 0.66
Duration HPN (per month) 1.00 (0.99, 1.00) N/a
HPN administration 5 times/week 0.71 (0.26, 1.92) 0.49
HPN (Ref.: Fluids and/or electrolytes only) 0.79 (0.46, 1.36) 0.40
CLABSI characteristics
Polymicrobial 1.30 (0.82, 2.06) 0.27
CoNS (Ref. other pathogen) 1.29 (0.90, 1.85) 0.16

CLABSIs treated in other hospitals (n ¼ 91) were excluded. Missing data in all variables were <5%.
Abbreviations CVC: central venous catheter, CLABSI: central-line associated bloodstream infection, CoNS: Coagulase-negative staphylococci, HR: Hazard ratio, CI: confidence
interval; Nacl: Natriumchloride; N/a: Not applicable.
a
Proportional hazard assumption was tested graphically by log-minus-log plots and with the time-axis division method by adding an interaction term ‘time’ (750 CVC
days). No significance was seen (p ¼ 0.95).

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M. Gompelman, E. Causevic, C.P. Bleeker-Rovers et al.
We found several differences in patients characteristics between
patients with and without a history of CLABSI(s). These findings are
in agreement with a recent systematic review about infectious
complications in HPN patients performed by Reitzel et al. They also
found that age, multiple lumen CVCs, and a higher infusion fre-
quency were associated with an increased risk for developing
CLABSIs [26].
Relapse of infection was most often observed in infections due
to CoNS and Gram-negative bacteria. Comparison of these data
with other studies is hampered by the fact that different definitions
to delineate relapse were used [6,14,27,30e36].
In our cohort, the use of b-lactam antibiotics as empiric anti-
microbial therapy seems to be suboptimal, and our results suggest
that this choice should be reconsidered for the following reasons:
CoNS were the most common causative pathogens of CLABSIs with
a qSOFA score 1, of which only around 1/3 of the cases were b–
lactam sensitive (mainly intrinsic resistance). Additionally, in five
cases of CoNS infections, the antibiogram of b-lactam switched
from sensitive to resistant in a subsequent CLABSI, suggesting that
certain CoNS may rapidly develop b-lactam resistance. Lastly, CVC
salvage is attempted in almost all CLABSIs caused by CoNS, and any
inadequate delay in treatment is considered as a risk factor for
salvage failure, emphasising the necessity of adequate antibiotic
coverage right from the start [37]. In our opinion, a glycopeptide
such as teicoplanin or vancomycin would be the foremost candidate
as the first choice for empiric antimicrobial therapy in CLABSIs with
hemodynamic stability (qSOFA score 1). Glycopeptides have
excellent CoNS coverage and are appropriate as empiric therapy for
other Gram-positive bacteria, including (methicillin-susceptible
and -resistant) S. aureus as well. CLABSIs with hemodynamic
instability (qSOFA score
2) in our cohort were mostly caused by
Gram-negative bacteria or were polymicrobial in origin. Therefore,
in case of hemodynamic instability, broadening therapy with the
addition of an aminoglycoside or a third-generation cephalosporin
will increase the likelihood of adequate empiric coverage.
CVC salvage was only attempted in 1/3 of the cases, which is
considered as a rather low percentage compared to other studies
[14e16,27]. In recent years, this could be explained by the exclusion
of S. aureus from CVC salvage since 2013, and the relatively high
prevalence of CLABSIs with a complicated course as compared to
previous studies [4e7]. Nevertheless, successful CVC salvage was
achieved in 70%, which is consistent with earlier studies
[5,6,14,33,38]. A potential management strategy to further improve
successful CVC salvage rates at our centre may be the addition of
highly concentrated antimicrobial lock therapy next to systemic
antibiotics. Studies that use this technique show higher successful
CVC salvage rates [27,31,32,35].
Tribler et al. [14] is the only other study that compared CLABSI-
free survival between retained and replaced CVCs. Comparable to
our analysis, including all CLABSIs within the observation period,
they found a significant shorter CLABSI-free survival in patients
with a retained CVC (HR 0.86, 95% CI: 0.74, 0.99; P ¼ 0.03).
Based on the presented findings, modifications to the current
CVC salvage protocols should be considered. For example, patient-
centred decision-making in case CVC salvage is considered as it
appears that CVC salvage is a substantial risk factor for developing a
new CLABSI within a certain amount of time. Furthermore, affili-
ated satellite hospitals should be better informed on CVC salvage
strategies (e.g. attempting CVC salvage in less virulent pathogens
and empiric CoNS coverage), as their number of attempted CVC
salvages was even lower.
Next to its retrospective design, this research has some other
potential limitations that need to be mentioned: although all pa-
tients treated for their CLABSI in other hospitals were included as
well, the study was initiated as a single-centre study. However,
160
Clinical Nutrition ESPEN 50 (2022) 155e161
there are only two centres in the Netherlands where patients on
HPN are treated, so this study is a good representation of the sit-
uation in the Netherlands. Next, our findings and considerations
regarding empiric antibiotic therapy choices may not be fully
generalisable to other regions since differences in antimicrobial
resistance and geographic distribution of bacteria will be present.
Last, we used the CLABSI definition proposed by the CDC [17],
which differs from the more strict CRBSI definition that is used by
the Infectious Diseases Society of America [39]. Some authors argue
that the CLABSI definition could easily lead to an overestimation of
the true central line sepsis incidence [15,40].
5. Conclusion
We identified several potential risk factors for the development
of CLABSIs, most of which bolster results from previous studies. We
also found a decreased CLABSI-free survival in salvaged CVCs. Yet,
successful CVC salvage could still be achieved in most cases.
Importantly, based on our findings, a glycopeptide containing
antibiotic treatment regimen will increase the likelihood of
adequate empiric coverage, also in regions with a low prevalence of
methicillin-resistant staphylococci.
Funding statement
This research did not receive any specific grant from funding
agencies in the public, commercial, or not-for-profit sectors.
Author contribution
Michelle Gompelman: Conceptualization, Methodology, Soft-
ware, Writing-Original draft preparation, Validation. Erna Causevic:
Data curation, Writing-Original draft preparation, Visualization,
Investigation. Geert Wanten: Supervision, Reviewing and Editing:
Chantal Bleeker-Rovers: Supervision, Reviewing and Editing.
Declaration of competing interest
None.
Acknowledgements
We especially thank our statistician Reinier P Akkermans for his
help with the methodological design and statistical analysis. We
also thank all the members of our nutrition team who assisted with
collecting the data.
Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.clnesp.2022.06.003.
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