Intensive and Critical Care Nursing 43 (2017) 12–22

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Intensive and Critical Care Nursing

journal homepage: www.elsevier.com/iccn

Original article

Prevention of central venous line associated bloodstream infections in

adult intensive care units: A systematic review
Diana Carolina Velasquez Reyes a,∗ , Melissa Bloomer b , Julia Morphet a
a
Monash University, School of Nursing and Midwifery Peninsula campus, McMahons Road, Frankston VIC, 3199, Australia
b
Deakin University, School of Nursing and Midwifery, PO Box 20000, Geelong, VIC, AUS 3217, Australia

a r t i c l e i n f o a b s t r a c t

Article history: Background: In adult Intensive Care Units, the complexity of patient treatment requirements make the
Received 27 February 2017 use of central venous lines essential. Despite the potential benefits central venous lines can have for
Received in revised form 3 May 2017 patients, there is a high risk of bloodstream infection associated with these catheters.
Accepted 23 May 2017
Aim: Identify and critique the best available evidence regarding interventions to prevent central venous
line associated bloodstream infections in adult intensive care unit patients other than anti-microbial
Keywords:
catheters.
Blood stream infection prevention
Methods: A systematic review of studies published from January 2007 to February 2016 was undertaken.
Catheter
Catheterisation
A systematic search of seven databases was carried out: MEDLINE; CINAHL Plus; EMBASE; PubMed;
Central line associated blood stream Cochrane Library; Scopus and Google Scholar. Studies were critically appraised by three independent
infection reviewers prior to inclusion.
Central venous line Results: Nineteen studies were included. A range of interventions were found to be used for the preven-
Infection prevention-control tion or reduction of central venous line associated bloodstream infections. These interventions included
Intensive care dressings, closed infusion systems, aseptic skin preparation, central venous line bundles, quality improve-
Systematic review ment initiatives, education, an extra staff in the Intensive Care Unit and the participation in the ‘On the
CUSP: Stop Blood Stream Infections’ national programme.
Conclusions: Central venous line associated bloodstream infections can be reduced by a range of inter-
ventions including closed infusion systems, aseptic technique during insertion and management of the
central venous line, early removal of central venous lines and appropriate site selection.
© 2017 Elsevier Ltd. All rights reserved.

Implications for clinical practice

• Interventions other than high cost devices such as antimicrobial-coated catheters offer an alternative or complementary solution
to central venous line associated bloodstream infections in adult Intensive Care Units.
• The findings in this study show that low cost interventions such as education, surveillance, checklists, reporting and central
venous line bundles and aseptic management of these devices have positive outcomes in reducing central venous line associated
bloodstream infections rates.

Introduction volume intravenous fluids, parenteral nutrition, cardiovascular

Patients admitted to Intensive Care Units (ICUs) require spe-
cialised management of life threatening conditions. The complexity
of the treatment and the procedures that patients in ICU may
require, make central venous lines essential (College of Intensive
Care Medicine of Australia and New Zealand [CICM], 2011). High
∗ Corresponding author.
E-mail address: dianacvere@hotmail.com (D.C. Velasquez Reyes).
measurements, medication administration and blood infusions all
require the use of central venous lines (Walder et al., 2002; World
Health Organization, 2014). Despite their potential benefits, the risk
of central venous line associated bloodstream infections (CLABSI)
is high (Siempos et al., 2009). A CLABSI is a laboratory-confirmed
bloodstream infection (BSI) in a patient who had a central venous
line within the 48 hours prior to development of the BSI, not related
to an infection at another site (Centre of Control and Disease
Prevention, 2014; Fagan et al., 2013; Kallen et al., 2010; O’Grady
et al., 2011, 2002).

http://dx.doi.org/10.1016/j.iccn.2017.05.006
0964-3397/© 2017 Elsevier Ltd. All rights reserved.
 D.C. Velasquez Reyes et al. / Intensive and Critical Care Nursing 43 (2017) 12–22
A 2010 study conducted in the United States of America (USA)
identified that about 41,000 patients developed CLABSI (Centre
for Disease Control and Prevention, 2011; Virginia Department of
Health, 2013). Around 18,000 of those affected were ICU patients,
and one in four may die (Centre for Disease Control and Prevention,
2011; Virginia Department of Health, 2013). CLABSI is also asso-
ciated with increased cost in patient care (Walder et al., 2002),
estimated at USD$33,000 (Stevens et al., 2014).
Consequently, there is increased interest in ways to reduce
and prevent CLABSI (Dumont and Nesselrodt, 2012; O’Grady et al.,
2011). In 2008, a systematic review was undertaken evaluating
strategies other than antimicrobial-coated catheters to reduce risk
of CLABSI in the ICU (Ramritu et al., 2008b). In 2011, the Centre
for Disease Control and prevention published updated guidelines
for the prevention of intravascular catheter associated infections
(O’Grady et al., 2011, 2002). Despite these guidelines, and advances
in understanding related to infection patterns, pathogen agents,
different pathogenesis, epidemiology and new diagnosis and pre-
vention techniques in the last decade (Kim et al., 2011), no update
of this systematic review has been undertaken.
The aim of this systematic review was to identify all existing
interventions to prevent and/or reduce CLABSI in adults in ICU,
other than antimicrobial-coated catheters. Literature published
from 2007 was included, as that is when the previous systematic
review was undertaken (Ramritu et al., 2008b).
Methods
This systematic review followed the Cochrane Effective Practice
and Organisation of Care Review Group (EPOC) recommenda-
tions to assess quality in systematic reviews (Chandler et al.,
2013). Randomised controlled trials and observational studies
which investigated interventions for the prevention or reduction of
CLABSI in adult ICU patients were included. The quality of evidence
for each included study was determined based on the Grades of Rec-
ommendations, Assessment, Development and Evaluating (GRADE)
Working Group (Schünemann et al., 2011). Only studies with a high
or moderate quality rating were included.
Inclusion criteria
• Studies conducted in ICUs with adult patient populations were
included.
• All interventions which sought to prevent and/or reduce CLABSI
including the CDC recommended interventions (Centre for
Disease Control and Prevention, 2011; Centre of Control and
Disease Prevention, 2014; O’Grady et al., 2011, 2002) and the
Institute of Healthcare Improvement (IHI) compilation of bundle
of interventions designated to work together to reduce CLABSI
were included.
Outcome measures
The following outcome measures were examined following the
suggestions given by the Cochrane EPOC Review Group (Chandler
et al., 2013).
Primary outcomes
• Central venous line associated bloodstream infection rates (per
1000 central venous line days)
• Identification and incidence rate of pathogen agents identified
in the colonised central venous lines detected (laboratory test
report data)
• Mortality and comorbidity rates related to CLABSI.
13
• Increased length of hospitalisation (measured in days) caused by
the presence of CLABSI.
Secondary outcomes
• Measurement of the time (measured in days) from central venous
line insertion to removal.
• Length of stay in ICU, measured from the day of admission to ICU
to the day of discharge from ICU.
Exclusion criteria
• Studies published in languages other than English.
• Non-academic studies, conference abstracts, oral presentation or
not original research.
• Characteristics of participants not reported, no baseline data,
studies with no clear description of the intervention applied.
• Studies with unclear aim, methodology, or data collection, or
those with missing data were excluded.
• Studies conducted wholly or in part with paediatric populations
where the results were not reported separately.
• Studies where ICUs were included together with another ward
(e.g. emergency department, coronary care units) where the
results were not reported separately.
• Studies where antimicrobial-coated catheters were used were
excluded from this review because several systematic reviews
have recently been published on this topic (Antonelli et al., 2012;
Liu et al., 2014; Raad, 2012; Ramritu et al., 2008a).
Search strategy
MEDLINE; CINAHL Plus; EMBASE; PubMed; Cochrane Library,
Google Scholar and Scopus databases were searched using the
following keywords (or abbreviations) and MeSH search terms;
‘catheteri*ation-central venous’, infection*, prevention*, blood-
stream*.
Data collection
The Cochrane Collaboration RevMan software (The Cochrane
Collaboration, 2014) was used for data entry and management.
The data were extracted following The Cochrane’s manual check-
list (Higgins and Green, 2011). One researcher screened the titles
and abstracts of each study. The three researchers then analysed
the full-text of 87 studies meeting the inclusion criteria for full text
assessment.
Assessment of methodological quality
Three researchers assessed the quality of each study, to deter-
mine inclusion, using the Meta-Analysis of Statistics Assessment
and Review Instrument (MAStARI) tool (Joanna Briggs Institute,
2014).
Assessment of risk of bias in included studies
The Cochrane Risk and Bias Assessment (RoBANS) tool and
guideline were applied to each of the included studies (Higgins
et al., 2011).
Data synthesis
Outcome measures and statistical analysis, such as relative risk
(RR), probability (p), Pearson Correlation Coefficient, Confidence
Interval (CI) and the statistical power of the mean were analysed.
14 D.C. Velasquez Reyes et al. / Intensive and Critical Care Nursing 43 (2017) 12–22

1,500 studies idenfied

825 through database search & 675 through Google Scholar search

1,500 studies screened by tle/abstract

1,413 studies excluded:

651 duplicates

371 non central line catheters

221 non adult ICU seng

150 non-academic research studies

17 not English language

3 not published aer 2006

87 full text studies assessed for eligibility

68 studies excluded aer full text crical appraisal:

3 Full text wrien in a language other than English

16 not in ICU seng, not central line catheters

14 Oral presentaons/ conference/posters studies

13 Paral or full use of anmicrobial coated catheters

3 Characteriscs of parcipants not reported, no baseline data
1 No clear descripon or correlaon of the intervenon
5 Poor methodology measurement of the intervenon related with the aim of
study. No confounder discussed
5 Missing data, lack of central line associated bloodstream infecons rate
reported
1 Different bundles applied during intervenon but not reported or considered in
the outcomes measurements, no confounders considered
1 Different types and brands of caps were used during intervenon.
Characteriscs of parcipants not reported
5 Weak methodology, surveys and self-reported data, correlaon between
intervenon and outcome not clear, missing data characteriscs of parcipants not
reported.
1 Various intervenons were applied during study, no clear indicaon which
intervenon reduced the CLABSI rate

19 studies included in the systemac review

Fig. 1. PRISMA flow diagram.

When the data was homogenous, a Forest Plot was created to illus-
trate the strength of the effect of the intervention. Due to the
heterogeneity of the interventions and their reported results, meta-
synthesis was undertaken of the qualitative research studies.
Results
Search results
From the database searches, a total of 1500 studies were iden-
tified (Fig. 1).
Risk of bias in included studies
All the included randomised controlled studies had a low risk
of bias (Kwakman et al., 2012; Marsteller et al., 2012; Mimoz et al.,
2007; Pedrolo et al., 2014; Speroff et al., 2011; Timsit et al., 2012;
Timsit et al., 2009; Yousefshahi et al., 2013) due to their random
sequence generation, blinding of outcome assessment and inter-
vention exposure measurement. Eleven studies had unclear risk
of bias, because the interventions could not be blinded (e.g., the
nature of the interventions, or methodology of reporting. However,
the studies were include as the confounders/bias were considered
in the reporting of results (Bonello et al., 2008; Cherifi et al., 2013;
Jeong et al., 2013; Maki et al., 2011; Marsteller et al., 2014; McLaws
and Burrell, 2012; Parikh et al., 2012; Rangel-Frausto et al., 2010;
Scheithauer et al., 2014; Tang et al., 2014; Vilins et al., 2009). None
of the studies included in this review reported a high risk of bias.
After the full text quality appraisal was independently under-
taken by the three researchers, and following the risk of bias
assessment, 19 studies were included in this systematic review
(Fig. 1).
 D.C. Velasquez Reyes et al. / Intensive and Critical Care Nursing 43 (2017) 12–22
Interventions of included studies
The studies examined a variety of interventions, including edu-
cation based interventions (Bonello, Fletcher, 2008; Cherifi, Gerard,
2013; Scheithauer et al., 2014; Speroff et al., 2011; Tang et al.,
2014), skill-mix based interventions (Bonello et al., 2008; Cherifi
et al., 2013; Marsteller et al., 2014; Marsteller et al. 2012; Parikh
et al., 2012, Scheithauer et al., 2014), equipment based interven-
tions (Maki et al., 2011; Rangel-Frausto et al., 2010; Vilins et al.,
2009), various dressings (Pedrolo et al., 2014; Scheithauer et al.,
2014, Timsit et al., 2012; Timsit et al., 2009) and aseptic based
interventions (Bonello et al., 2008; Jeong et al., 2013; Kwakman,
Muller, 2012; McLaws and Burrell, 2012; Mimoz, Villeminey, 2007;
Rangel-Frausto et al., 2010; Speroff et al., 2011; Yousefshahi et al.,
2013). Several studies evaluated the use of the different central
venous line insertion bundles including the Institute for Health-
care Improvement (IHI) bundle (Bonello et al., 2008; Cherifi et al.,
2013; Jeong et al., 2013; McLaws and Burrell, 2012; Parikh et al.,
2012; Pedrolo et al., 2012). Many of these studies combined the IHI
bundle with other interventions, including education (web semi-
nars, monthly educational sessions, auditing and feedback based
infection programs) (Yousefshahi et al., 2013), face to face meet-
ings, teleconferences and/or online in-services (Bonello et al., 2008;
Speroff et al., 2011; Tang et al., 2014), teamwork strategies and
standardised data collection tools (Bonello et al., 2008; Jeong et al.,
2013), surveillance interventions (Jeong et al., 2013; Scheithauer
et al., 2014; Tang et al., 2014) and other care bundles (e.g. the ven-
tilator associated pneumonia bundle) (Bonello et al., 2008; Speroff
et al., 2011).
Dressings
Five studies examined the effect of various central venous line
insertion site dressings on CLABSI rates (Kwakman et al.„ 2012;
Pedrolo et al., 2014; Scheithauer et al., 2014; Timsit et al., 2012;
Timsit et al., 2009). Four studies compared chlorhexidine impreg-
nated dressings with other dressings including medical honey
dressing (Kwakman et al., 2012), standard dressing (Scheithauer
et al., 2014; Timsit et al., 2009), sterile gauze and micropore tape
(Pedrolo et al., 2014), transparent Tegaderm 3 M dressing (Timsit
et al., 2012), Tegaderm Transparent Film Dressing 3 M (Timsit et al.,
2012) and highly adhesive Tegaderm HP Transparent Film Dressing
3 M (Timsit et al., 2012).
There was no significant difference in CLABSI and skin colonisa-
tion rates when chlorhexidine dressings were compared with other
dressings (Table 1). However, one study found that Chlorhexidine
dressings lowered the number of Gram-positive bacterial infections
(Scheithauer et al., 2014). In one study comparing chlorhexidine
dressings with standard dressings, dressings in both cohorts were
changed at either three or seven days. The authors reported that
CLABSI was less common with chlorhexidine dressings (Table 1).
The authors also reported a catheter colonisation of 142 out of
1657catheters (7.8%) in the three day dressing change group (10.4
per 1000 catheter-days) and 168 of 1828 catheters (8.6%) in the
seven day dressing change group (11.0 per 1000 catheter-days), a
mean absolute difference of 0.8% (95% CI, −1.78% to 2.15%) (HR,
0.99; 95% CI, 0.77–1.28) (Timsit et al., 2009). The remaining four
studies reported changing the dressings every seven days unless
dressing edges detached, dressing integrity was compromised or
discharge accumulated in the catheter opening (leaking or soiled
dressings) (Kwakman et al., 2012; Pedrolo et al., 2014; Scheithauer
et al., 2014; Timsit et al., 2012). In addition to the dressings, these
studies also used other interventions to reduce CLABSI including
maximal sterile barriers (Timsit et al., 2012; Timsit et al., 2009),
care bundles (Pedrolo et al.„ 2014; Timsit et al., 2012; Timsit et al.,
2009), and antiseptic skin preparation prior the insertion of the cen-
15
Fig. 2. Comparing open vs. closed infusion containers studies.
tral venous line (Kwakman et al., 2012; Pedrolo et al., 2014; Timsit
et al., 2012; Timsit et al., 2009) (Table 1).
Open vs. closed infusion containers
Three studies compared open and closed infusion containers
(Maki et al.„ 2011; Rangel-Frausto et al.„ 2010; Vilins et al., 2009).
(Table 2, Fig. 2) Open infusion containers were defined as com-
mercially available glass bottles, burettes and semi-rigid plastic
containers that must admit air (air filter or needle) to empty, requir-
ing external venting (Maki et al., 2011; Rangel-Frausto et al., 2010;
Vilins et al., 2009). Closed infusion containers were defined as
fully collapsible plastic containers that did not require any exter-
nal venting to empty, with self-sealing injection ports (Viaflex
or Viaflo) (Maki et al., 2011; Rangel-Frausto et al., 2010). Meta-
analysis indicated that closed infusion container systems reduced
CLABSI (Fig. 2). In each of these three studies, a standard central
venous line management protocol was in place, including hand
hygiene with alcohol based hand rub, and a care protocol docu-
menting and evaluating the gauze dressing condition.
Aseptic skin preparation
Chlorhexidine skin antiseptic was used as skin preparation prior
to central venous line insertion in ten studies (Bonello et al.„ 2008;
Cherifi et al.„ 2013; Jeong et al., 2013; Kwakman et al., 2012;
McLaws and Burrell, 2012; Mimoz et al.„ 2007; Rangel-Frausto
et al., 2010; Speroff et al., 2011; Timsit et al., 2012; Yousefshahi
et al., 2013). However, only two studies examined the effective-
ness of the antiseptic applied at the central venous line insertion
site in the reduction of central venous line pathogen colonization
(Mimoz et al., 2007; Yousefshahi et al., 2013). One study com-
pared topical Chlorhexidine with an antiseptic agent composed
of hydrogen peroxide (H2 O2 ) and silver (Sanosil 2%) (Yousefshahi
et al., 2013). The antiseptic agent composed of hydrogen per-
oxide (H2 O2 ) and silver produced a lower number of positive
central venous line tip cultures than the Chlorhexidine, however,
there was no significant difference between the two (Yousefshahi
et al., 2013) (Tables 3 and 4). Skin antisepsis with 0.1% octeni-
dine dihydrochloride and 2% 2-phenoxyethanol (octenisept) was
applied in one study in combination with Chlorhexidine dressings
(Scheithauer et al., 2014). Alcohol povidone-iodine was also com-
pared against Chlorhexidine in four studies (Mimoz et al., 2007;
Timsit et al., 2012; Timsit et al.„ 2009; Yousefshahi et al., 2013) and
only one study reported a higher prevention of CLABSI when using
Chlorhexidine as skin antiseptic compared to alcohol povidone-
iodine (Mimoz et al., 2007). One study compared a Chlorhexidine
bath one day prior to central venous line insertion, with Povidone-
Iodine scrub immediately preceding central venous line insertion,
with no reduction in CLABSI rates (Yousefshahi et al., 2013) (Table
3).
16 D.C. Velasquez Reyes et al. / Intensive and Critical Care Nursing 43 (2017) 12–22

Table 1
Examination of studies comparing dressings.

Author & year Group ICUs in Patients in CLABSI n (%) Positive Culture CLABSI/1000 RR (95% CI) p
sample sample Swab n (%) catheter days

Kwakman et al. (2012) Control 1 106 – 36 (34) – NR 0.98

Revami (honey) and gauze 1 129 – 44 (34) –
Pedrolo et al. (2014) Chlorhexidine dressing 2 43 6 – – NR 0.52
(13.95)
Gauze and Micropore 2 42 5 – –
(11.9)

Author & year Group ICUs in Central line CLABSI n (%) Positive Culture CLABSI/1000 RR (95% CI) p
sample days Swab n (%) catheter days

Scheithauer et al. (2015) Chlorhexidine dressing 2 7282 11 – 1.5/1000 (0.75–2.70) <0.001

Standard dressing 2 4938 29 – 5.87/1000 (0.93–8.43)

Author & year Group ICUs in Catheters in CRBSI (n) Positive Culture CRBSI/1000 RR (95% CI) p
sample sample Swab n (%) catheter days

Timsit et al. (2012) Chlorhexidine dressing 12 2108 9 75 0.5 1.284 0.45

(0.67–2.45)
Adhesive dressing 12 998 10 97 1.3
Standard dressing 12 1067 12 89 1.3
Timsit et al. (2009) Chlorhexidine dressing 7 1825 – – 1.3 0.24 0.05
(0.09–0.65)
Standard dressing 7 1953 – – 0.4

Note: ICU = Intensive Care Unit; NR = not reported; CLABSI = Central line associated blood stream infection; CRBSI = Catheter related blood stream infection; RR = Risk Ratio.

Table 2
Comparing open vs. closed infusion containers studies.

Author & Year Group No. ICUs in No. of patients in Rate of CLABSI per Rate of CLABSI per RR p
sample sample 1000 central 1000 central (95%CI)
line-days line-days
(infections/days) (%)

Maki et al. (2011) Open 15 2237 153/15,189 10.2 0.33 <0.001

Closed 15 2136 45/13,456 3.3 (0.24–0.46)
Rangel-Frausto et al. (2010) Open 4 548 59/3661 16.1 0.20 <0.001
Closed 4 548 13/4055 3.2 (0.11–0.36)
Vilins et al. (2009) Open 3 483 28/4297 6.5 0.49 0.03
Closed 3 642 13/4041 3.2 (0.26–0.95)

Table 3
Examination of studies comparing antiseptics.

Author & Year Group ICUs in Patients in CRBSI Catheter Tip CRBSI/1000 RR (95%CI) P
sample sample Positive Culture n catheter days (%)
(%)

Yousefshai et al. Chlorhexidine 3 113 – 29 – 1.05 0.75

(2013)
(21.3) (0.76–1.45)
Sanosil 2% 3 136 – 26 –
(23.0)
Mimoz et al. (2007) Chlorhexidine 1 242 4 28 1.7 2.01 0.002–0.009
(11.6) (1.24–3.24)
Alcohol based-Povidone-iodine 1 239 10 53 4.2 1.87
(22.2) (1.18–2.96)

Note: CRBSI = Catheter Related Bloodstream Infection, ICU = Intensive Care Unit, RR = Risk Ratio.

Central venous line bundles
Seven studies used central venous line bundles as an interven-
tion (Bonello et al., 2008; Cherifi et al., 2013; Jeong et al., 2013;
McLaws and Burrell, 2012; Parikh et al., 2012; Pedrolo et al., 2014;
Scheithauer et al., 2014; Speroff et al., 2011; Tang et al., 2014; Timsit
et al., 2012). A key focus of central venous line bundles is early
removal of central venous lines (Table 5). The heterogeneity of the
reported data restricted meta-analysis, therefore meta-synthesis
was conducted. Three studies implemented the central venous
line bundle outlined by the IHI (Bonello et al., 2008; Jeong et al.,
2013; Tang et al., 2014). This bundle has been examined in differ-
ent studies, and results indicated a positive reduction in CLABSI
rates (Al-Tawfiq et al., 2012; Blot et al., 2014; Sacks et al., 2014)
(Table 6). Three studies used alternative bundles together with
multiple interventions to reduce CLABSI, with all reporting a reduc-
tion in infection rates (Cherifi et al., 2013; McLaws and Burrell,
2012; Yousefshahi et al., 2013) (Table 6). As a key component of the
central venous line bundle, the early removal of central venous line
was examined as an effective practice to reduce CLABSI (McLaws
and Burrell, 2012). This study estimated probabilities for CLABSI at
different dwell times to identify the dwell time that was closest
to being infection free, less than1 in 100 chance of infection, they
reported the safest dwell time was the lowest cumulative probabil-
ity of CLABSI, 1 in 100 chance, for a cumulative catheter dwell time
of seven days giving an adjusted CLABSI rate of 1.8/1000 line days
(McLaws and Burrell, 2012). This is consistent with other studies
 D.C. Velasquez Reyes et al. / Intensive and Critical Care Nursing 43 (2017) 12–22 17

Table 4
Aseptic skin preparation used in each study.

Bonello et al. (2008) Not specified

®
Cheriffi et al. (2013) Skin antisepsis was performed with 0.5% chlorhexidine in 70% alcohol (Cedium , QUALIPHAR) or with 5% alcoholic
®
povidone-iodine (Iso-Betadine solution hydroalcoolique, MEDA Pharma).
Jeon et al. (2013) Skin antisepsis was performed with Chlorhexidine (2% chlorhexidine in 70% of one of the following: isopropyl alcohol,
alcohol, povidone-iodine, or a mixture of alcohol and povidoneiodine).
Kwakman et al. (2012) Skin antisepsis was performed with 0.5% chlorhexidine in 70% alcohol.
Mcklaws et al. (2012) Skin antisepsis was performed with 2% alcoholic chlorhexidine.
Mimoz et al. (2007) Skin antisepsis was 5% povidone-iodine in 70% ethanol (Betadine Alcoolique; Viatris Pharmaceuticals, Meı́rignac,
France) or a combination of 0.25% chlorhexidine gluconate, 0.025% benzalkonium chloride, and 4% benzylic alcohol
(Biseptine; Bayer HealthCare, Gaillard,France).
Rangel et al. (2010) Not specified.
Speroff et al. (2011) Not specified use of chlorhexidine skin antisepsis.
Timsit et al. (2012) Skin preparation was with alcoholic povidone-iodine (PVI) or alcoholic chlorhexidine solution in accordance to
standard procedure in each ICU. First, the insertion site was scrubbed with a detergent (4% aqueous PVI solution,
Betadine Scrub; Viatris Pharmaceuticals, Merignac,France) or 4% chlorhexidine solution (Hibiscrub; Molnlycke Health
Care, Wasquehal, France); rinsed with sterile water; and dried with sterile gauze. An alcohol-based antiseptic solution
(5% PVI in 70% ethanol [Betadine Alcoholic Solution; Viatris Pharmaceuticals] or 0.5% chlorhexidine, 67% ethanol
[Molnlycke Health Care]; or 0.25% chlorhexidine, 0.025% benzalkonium chloride, 4% benzyl alcohol [Biseptine Bayer
Healthcare, Gaillard, France]) was then applied for at least 1 min.
Yosefshahi et al. (2013) Skin preparation was bath with Chlorhexidine 2%. and 10% Povidone-Iodine.

Table 5 to face, learning sessions at least (three per month), education in

Institution of Healthcare Improvement IHI central venous line bundles.
Central venous line bundles strategies compiled by the IHI
Hand hygiene
Maximal sterile barrier precautions during insertion
Chlorhexidine skin antisepsis
Daily assessment of central vascular catheter necessity
Prompt removal of central venous lines
Avoidance of femoral site
examining the effect of a central venous line bundle on CLABSI with
similar positive results (Furuya et al., 2011; , Loveday et al., 2014).
Combining multiple interventions with central venous line
bundles
A variety of initiatives that could be combined with central
venous line bundles (Table 5) primarily focussed on staff educa-
tion, surveillance, development of tools and teamwork practices.
The combination of any of these interventions with bundles were
found to reduce CLABSI (Bonello et al., 2008; Cherifi et al., 2013;
McLaws and Burrell, 2012; Tang et al., 2014).
Quality improvement initiatives
These initiatives included compliance checklists (Bonello et al.,
2008; Jeong et al., 2013; McLaws and Burrell, 2012; Tang et al.,
2014), surveillance (Cherifi et al., 2013; Tang et al., 2014), feed-
back (Jeong et al., 2013), hand hygiene education programs (Jeong
et al., 2013; Speroff et al., 2011), visual promotion of central venous
line care campaigns (Jeong et al., 2013; Speroff et al., 2011), cre-
ation of collaborative teams (Jeong et al., 2013; Speroff et al.,
2011), tools, guidelines or protocols (McLaws and Burrell, 2012;
Speroff et al., 2011). The virtual collaborative intervention included
monthly educational conference calls, web seminars, individual
online coaching and email report access related to central venous
line management (Speroff et al., 2011). These different combina-
tions of interventions resulted in a significant reduction in CLABSI
rates (Bonello et al., 2008; Cherifi et al., 2013; McLaws and Burrell,
2012; Tang et al., 2014) (Table 6).
Education
In four studies the IHI bundle was combined with educational
programs delivered in the ICU (Cherifi et al., 2013; Jeong et al., 2013;
Speroff et al., 2011; Tang et al., 2014). It included interdisciplinary
improvement team implementing organisational changes related
to the central venous line bundle, they introduced sharing goals and
methods by collaborative charter, monthly conferences calls face
‘Plan to Do, Study Act (PDSA) methodology, bed side checklists edu-
cation and interdisciplinary interactive team rounds. Only two of
these studies demonstrated a significant reduction in CLABSI rates
(Cherifi et al., 2013, Tang et al., 2014) (Table 6).
Increasing ICU medical staffing
One study examined the effect of staffing skill mix on infection
rates, by comparing infection rates before and after the introduction
of an extra intensivist in the ICU (Parikh et al., 2012), demonstrating
an intensivist as a cost effective and beneficial strategy in reducing
CLABSI rates (Parikh et al., 2012) (Table 7). Not only were more lives
saved when there was an extra intensivist in the ICU, but the cost
of the intensivist was cheaper than the expenses associated with a
higher CLABSI rate (Barnett et al., 2010; Parikh et al., 2012; Stevens
et al., 2014).
Participating in on the CUSP
Two studies examined the outcomes arising from participation
in On the CUSP, a national program in the USA, and its impact in
reducing CLABSI (Marsteller et al., 2014; Marsteller et al., 2012).
Both studies reported significant reductions in CLABSI after apply-
ing the intervention. The first study additional of the On the CUSP
national program examined the positive outcome of mandatory
reporting and CLABSI reduction. After comparing CLABSI rates from
hospitals where a mandatory reporting public reports of central
venous line associated infections rates was in place (Table 8).
Discussion
From the nineteen studies included in this review, fifteen
reported a positive impact in the reduction of CLABSI (Bonello
et al., 2008; Cherifi et al., 2013; Maki et al., 2011; Marstelleret al.,
2014, Marsteller et al., 2012; McLaws and Burrell, 2012; Mimoz
et al., 2007; Parikh et al., 2012; Rangel-Frausto et al., 2010;
Tang et al., 2014; Timsit et al., 2012; Timsit et al., 2009; Vilins
et al., 2009; Yousefshahi et al., 2013). Open infusion containers,
chlorhexidine dressings, aseptic interventions for central venous
line maintenance including central venous line bundles, manda-
tory reporting, communication and continuing education based
interventions were effective in reducing CLABSI rates. In addition,
checklists, facilitating feedback, regular rounds and supervision
and extra intensivist in the ICU were also successful interventions.
Chlorhexidine skin preparation prior to central venous line inser-
tion was not shown to significantly reduce the rate of CLABSI. (Jeong
18 D.C. Velasquez Reyes et al. / Intensive and Critical Care Nursing 43 (2017) 12–22

Table 6
Examination of studies comparing central line bundles.

Author & year Group ICUs in Patients in CLABSI n (%) CLABSI/1000 RR (95% CI) p
sample sample catheter days

Jeong et al. (2013) Baseline 4 79 4.7 6/1290 0.39 0.76

Intervention 4 309 1.8 7/3899 (0.11–1.39)
McLaws et al. (2012) First 12 months 37 4166 3.8 27/7176 (2.5–5.5) 0.002
Last 6 months 37 NR 1.6 26/16,100 (1.0–2.4)
Tang et al. (2014) Baseline 5 NR 1.6 17/10,325 NR 0.03
Intervention 5 481 0.6 6/9388

Author & year Group ICUs in Patients in Mean CLABSI n Mean of RR (95% CI) p
sample sample (%) CLABSI/1000 days

Bonello et al. (2008) First 3 months 12 NR 0.52 5.2/1000 NR NR

Last 3 months 12 NR 0.27 2.7/1000
Cherifi et al. (2013) Before intervention 5 1354 4.00 24/1000 0.49 0.212
(0.24–0.98)
During intervention 5 1571 1.81 12/1000
After intervention 5 1439 2.73 16/1000 1.37 0.413
(0.65–2.89)

Author & year Group Hospitals in Hospitals in Tool Hospitals in Virtual Median Median RR (95% CI) p
sample kit group collaborative group CLABSI/1000 CLABSI/1000
catheter days in catheter days in
Tool kit group Virtual
collaborative group

Speroff et al. (2011) Baseline 59 29 30 2.42 1.84 NR NR

(0.65–6.80) (0.00–3.83)
3 months 59 29 30 2.47 2.24
(1.48–5.35) (0.54–4.69)
6 months 59 29 30 2.54 2.28
(0.00–4.98) (0.00–3.73)
9 months 59 29 30 1.23 1.75
(0.00–3.93) (0.00–3.74)
12 months 59 29 30 1.17 1.18
(0.00–3.61) (0.00–2.71)
15 months 59 29 30 1.77 2.04
(0.00–3.30) (0.00–4.91)
18 months 59 29 30 1.16 2.76
(0.00–5.46) (0.00–4.67)

Note: ICU = intensive care unit; NR = not reported; CRBSI = Catheter related blood stream infection.

Table 7
Examination of a study increasing ICU medical staffing.

Author & Year Group No. of ICUs in No. patients in No. CLABSI per Rate of CLABSI RR (95%CI) p
sample sample 1000 central line per 1000 central
days line days (%)
(infection/days)

Parikh et al. (2012) First year before intervention 1 1113 13/1531 8.5 8.32 0.0006
(1.91–36.28)
Last year after intervention 1 1068 2/1185 1.7

Note:CI = confidence interval, CLABSI = Central line bloodstream infection, ICU = Intensive Care Unit, RR = Risk Ratio.

et al., 2013; Kwakman et al., 2012; Pedrolo et al., 2014; Speroff et al.,
2011).
Important findings from this study should be considered in ICUs
looking to reduce CLABSI rates. Choice of dressing is important.
Chlorhexidine dressings were used in each study comparing dress-
ing’s types, and are shown to have positive outcomes in decreasing
skin flora which decreases CLABSI incidence.
This study found that Chlorhexidine skin preparation was
equally effective as alcohol-based povidone iodine for preventing
CLABSI in most cases as other studies have shown (Adams and
Wilson, 2012; Bashir et al., 2012), but that there was no differ-
ence between Chlorhexidine and the antiseptic agent composed of
hydrogen peroxide (H2 O2 ) and silver (Yousefshahi et al., 2013). Reg-
ular/daily bathing with Chlorhexidine had no effect on CLABSI rates
(Noto et al., 2015; Seyman et al., 2014), although there was reduced
blood culture contamination (Popovich et al., 2010). One reason for
this finding may be the conclusion that dressing changes should
be minimised to reduce CLABSI rates (O’Grady et al., 2011; Rupp
et al., 2013). Only two studies reported side effect dermatitis when
applying chlorhexidine dressings (Timsit et al., 2012; Timsit et al.,
2009), no other data was collected regarding this important con-
sideration. Further analysis of skin side effects are recommended
in future studies.
Early removal of central venous lines is recommended, ideally
before day eight (Exline et al., 2013; Mangum et al., 2013; Weeks
et al., 2014). Early removal of central venous lines is one of the key
features of central venous line bundles, and several studies included
in this systematic review reported reduced CLABSI rates associated
with bundle use (Bonello et al., 2008, McLaws and Burrell, 2012;
Tang et al., 2014). Another important feature of the central venous
line bundles found to be reported was the aseptic skin preparation
methods prior the insertion of central venous line. Hence central
venous line bundles should be promoted across ICUs.
 D.C. Velasquez Reyes et al. / Intensive and Critical Care Nursing 43 (2017) 12–22 19

Table 8
Examination studies analysing participation in On the CUSP: Stop BSI National Program and mandatory reporting.

Author, year & period No. of ICU in sample Mean rate of CLABSI per 1000 RR according to study quarters
central line days according to
study quarters

Control group Inter group Control group Inter group Control group Inter.group
n n M M RR RR

Marsteller et al. (2012)

Baseline 22 23 2.71 4.48 1.00 1.00
1st Q NR 1.12 NR 0.25
2nd Q NR 1.83 NR 0.41
3rd Q 2.16 1.33 0.79 0.30
4th Q 0.56 0.96 0.21 0.21
5th Q 0.52 0.88 0.19 0.20
6th Q 0.83 0.85 0.31 0.19

No. of ICUs in sample Mean Rate of CLABSI per 1000 central line days

n Group PR policy<1 year Group PR policy<1 year Group VR policy Group NR Policy
M M M M

Marsteller et al. (2014) 1046

Baseline 2.49 1.85 2.20 1.90
1stQ 2.33 1.52 1.89 1.65
2ndQ 2.00 1.22 1.46 1.32
3rdQ 1.61 1.29 1.83 0.96
4thQ 1.49 1.24 1.38 0.96
5thQ 0.90 1.21 1.91 1.11
6thQ NR 1.16 1.11 1.15

Note: BSI = Bloodstream infection, CI = Confidence interval, CLABSI = Central line associated bloodstream infection, ICU = Intensive Care Unit, Inter = Intervention, NR = not
reported status, PR < 1 year = Public reporting had begun for one year or less, PR > 1 year = Public reporting had begun for more than one year, Q = Quarter RR = Risk Ratio,
VR = Voluntary reporting.

In addition, central venous line bundles in combination with Conclusion

quality improvement or educational interventions further reduces
CLABSI rates (Cherifi et al., 2013; Ramritu et al., 2008b; Tang et al.,
2014). Quality improvement interventions have previously been
shown to reduce CLABSI rates (Blot et al., 2014), and are an inex-
pensive way to improve patient outcomes in ICU.
Despite favourable outcomes with closed infusion systems
(Maki et al., 2011, Rangel-Frausto et al., 2010, Vilins et al., 2009),
open infusion systems continue to be used in some developing
countries such as Argentina, Brazil, Colombia and Mexico (Garrett
et al., 2002; Macías et al., 1999; Maki et al., 2011; Rangel-Frausto
et al., 2010; Rosenthal and Maki, 2004). Further research should be
conducted to analyse and address the factors impeding the change
towards closed infusion container systems in developing countries.
Only one study included in this review examined the impact
of an additional intensivist, demonstrating a reduction on CLABSI
rates (Parikh et al., 2012). There are however several other studies
examining a variety of healthcare associated infections in different
populations, which have similarly reported that additional staffing
is effective at reducing healthcare associated infections and health-
care costs (Chordas, 2004; Peters and Locke Nagele, 2010; Spaeth
et al., 2003; Terry, 2002).
Finally, the mandatory reporting of CLABSI rates was associated
with reduced CLABSI rates. This finding is consistent with other
literature (Marsteller et al., 2014), which reported the incidence
of methicillin resistant staphylococcus aureus (MRSA) is similarly
reduced by mandatory reporting (Biswal et al., 2015; Edge et al.,
2007; Pearson et al., 2009; Sheps and Birnbaum, 2012).
This systematic review identified several interventions able to
reduce or prevent CLABSI. Aseptic technique, which includes the
application of skin antiseptic pre-central venous line insertion,
and aseptic central venous line maintenance is essential. Closed
infusion systems should be used at all times. Central venous line
bundles, which promote appropriate insertion site selection, asep-
tic central venous line management and early removal; as well
as increased intensivist staffing were both found to contribute
to reduction and prevention of CLABSI and Quality improvement
initiatives aimed at education and safety practices should be under-
taken. Finally mandatory reporting CLABSI is imperative to the
prevention or reduction of CLABSI in adult ICUs.
Funding
The authors have no sources of funding to declare.
Ethical statement
Ethical statement not applicable the authors undertook a sys-
tematic review, no ethical statements to declare.
Conflict of interest
The authors have no conflict of interest to declare.

Limitations
This systematic review included only studies published in
English. There was also a predominant heterogeneity in the inter-
ventions in the included studies. Consideration of the multiple
confounders which could influence the outcomes of the studies
should be taken into account.
Acknowledgement
The researchers have no acknowledgements to make.
• APPENDIX A KEYWORDS AND MeSH SEACRH.
“catheterization”[MeSH Terms] OR catheterization[Text Word]
catheterisation”[MeSH Terms] OR catheterisation[Text Word].
20 D.C. Velasquez Reyes et al. / Intensive and Critical Care Nursing 43 (2017) 12–22

“catheterization, central venous”[MeSH Terms] OR cen- • prevention

tral catheterization[Text Word] “catheterisation, central • control
venous”[MeSH Terms] OR central catheterisation[Text Word] • Catheters, Indwelling
associated[All Fields] AND (“infection”[MeSH Terms] OR infec- • in-dwelling catheters
tion[Text Word]) “infection”[MeSH Terms] OR infections[Text • Catheter-Associated Infection
Word]. • Catheter-Related Infection
“prevention and control”[Subheading] OR prevention[Text • Intensive Care, Surgical
Word]. • Critical care

• Catheter, Central Venous

• Catheters, Central Venous APPENDIX B
• Venous Catheter, Central
• Venous Catheters, Central See Table B1.
• Central Venous Catheter
• Catheter Related Infections
• Infection, Catheter-Related
• Catheter-Associated Infections Appendix C. Supplementary data
• Infections, Catheter-Associated
• preventive therapy Supplementary data associated with this article can be found, in
• preventive measures the online version, at http://dx.doi.org/10.1016/j.iccn.2017.05.006.

Table B1
Excluded studies

Author/year Reason for exclusion

Al-Tawfiq et al. (2013)
Amarasingham et al. (2007)
Barrera et al. (2011)
Barsuk et al. (2014)
Berenholtz et al. (2014)
Cherry et al. (2011)
80
DePalo et al. (2010)
Dilek et al. (2012)
Doherty and Axelrod (2011)
Duane et al. (2009)
DuBose et al. (2008)
Flinchum et al. (2010)
Ghonim et al. (2012)
Hansen et al. (2014)
Hopfner et al. (2012)
Jaggi et al. (2013)
Khalid et al. (2013)
Leblebicioglu et al. (2013)
Lin et al. (2013)
Matocha and Montero (2012)
Matocha and Montero (2012)
McMullan et al. (2013)
Miller et al. (2010)
Ong et al. (2011)
Osorio et al. (2013)
Parada et al. (2013)
Popovich et al. (2010)
Ramirez et al. (2012)
Render et al. (2011)
Rosenthal et al. (2010)
Sacks et al. (2014)
Saldanha et al. (2014)
Seyman et al. (2014)
Stone et al. (2007)
Thom et al. (2014)
Vigorito et al. (2011)
Weeks et al. (2014)
Characteristics of participants not reported, no base line data only comparison with National Healthcare Safety Network data.
No clear description and correlation of the intervention (development of the clinical information technology assessment tool) with
CLABSI rate prevention or reduction.
Poor methodology during intervention using alcohol based hand rub bottles. The amount of alcohol based rub was not quantified. The
replacement of the bottles was done either the bottles were half empty.
Poster, no full text access.
Significant percentage of missing data. No measurement of CLABSI intervention compliance.
Not conducted in ICU setting.
Not conducted in ICU setting.
Use of antibacterial-impregnated catheters.
Poor measurement of outcomes according to aim and interventions of the study. No discussion of confounders.
No access to full text.
Use of antibacterial-impregnated catheters.
Use of antibacterial-impregnated catheters. (ARROWgardBlue PLUS Multilumen CVC, antimicrobial surface coated using Chlorhexidine,
Chlorhexidine acetate and silver sulfadiazine catheters)
No access to full text.
No access to full text.
Use of antibacterial-impregnated catheters.
No access to full text.
Intervention only partially applied. Use of antibacterial-impregnated catheters.
Use of antibacterial-impregnated catheters.
Intervention only partially applied. Use of antibacterial-impregnated catheters.
Poor quality in outcomes measurements, not clear which intervention resulted in the reduction of CLABSI. Self-reported data,
characteristics of participants or confounders not measured or discussed, no confidence intervals provided.
No access to full text.
No access to full text.
Poor quality in the methodology, baseline was extended during study not clear, outcomes measurements not correlated with study aim.
No clear which intervention reduce CLABSI rates.
Poor quality in reporting study outcomes, no confidence interval provided. Use of antibacterial-impregnated catheters.
Use of antibacterial-impregnated catheters. (MultiMed CVC and Intro-Flex) or CVCs impregnated with silver platinum carbon amalgam
and benzalkonium chloride on both surfaces (Vantex antimicrobial catheters)
Study not written in English
No access to full text.
Poor quality in reporting of outcomes. Characteristics of participants not reported. Confidence interval only reported for one outcome.
Different bundles applied during intervention but not reported or considered in the outcomes measurements, no confounders considered.
Poor quality in methodology, different types and brands of caps were used during intervention. Characteristics of participants not
reported.
Poor methodology quality, self-reported data, characteristics of participants not reported.
Use of antibacterial-impregnated catheters.
Use of antibacterial-impregnated catheters. Triple lumen second generation antimicrobial catheter Arrow g + ard Blue Plus antimicrobial
coated catheters were used.
No access to full text.
Poor quality on the methodology, subjective intervention, no characteristics of participants and confounders addressed.
Weak methodology, surveys and self-reported data, correlation between intervention and outcome not clear, characteristics of
participants not reported.
Poor methodology quality various interventions were applied during study, no clear indication which intervention reduced the CLABSI
rate.
Weak methodology self-reported data, demographics measured not relevant to possible confounders of the study.
Weak methodology self-reported data, change of tool during study period. Missing data.
 D.C. Velasquez Reyes et al. / Intensive and Critical Care Nursing 43 (2017) 12–22
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