Review article

Korean J Pediatr 2019;62(3):79-84 Korean J Pediatr 2019;62(3):79-84

https://doi.org/10.3345/kjp.2018.07003
pISSN 1738-1061• eISSN 2092-7258
Korean J Pediatr

Central line-associated bloodstream infections

in neonates
Hye Jung Cho, MD, Hye-Kyung Cho, MD, PhD
Department of Pediatrics, Gil Medical Center, Gachon University College of Medicine, Incheon, Korea

Newborn infants, including premature infants, are high-risk patients susceptible to various micro­ Corresponding author: Hye-Kyung Cho, MD, PhD
organisms. Catheter-related bloodstream infections are the most common type of nosocomial infections Department of Pediatrics, Gil Medical Center,
Gachon University College of Medicine, 21, Nam-
in this population. Regular education and training of medical staffs are most important as a preventive dongdae-ro 774 beongil, Namdong-gu, Incheon
strategy for central line-associated bloodstream infections (CLABSIs). Bundle approaches and the use of 21565, Korea
checklists during the insertion and maintenance of central catheters are effective measures to reduce the Tel: +82-32-458-2652
incidence of CLABSIs. Chlorhexidine, commonly used as a skin disinfectant before catheter insertion and Fax: +82-32-460-2362
E-mail: hkcho@gilhospital.com
dressing replacement, is not approved for infants <2 months of age, but is usually used in many neonatal https://orcid.org/0000-0003-0990-1350
intensive care units due to the lack of alternatives. Chlorhexidine-impregnated dressing and bathing,
recommended for adults, cannot be applied to newborns. Appropriate replacement intervals for dressing Received: 2 September, 2018
and administration sets are similar to those recommended for adults. Umbilical catheters should not be Revised: 6 December, 2018
Accepted: 19 December, 2018
used longer than 5 days for the umbilical arterial catheter and 14 days for the umbilical venous catheter.
It is most important to regularly educate, train and give feedback to the medical staffs about the various
preventive measures required at each stage from before insertion to removal of the catheter. Continuous
efforts are needed to develop effective and safe infection control strategies for neonates and young
infants.

Key words: Central venous catheter, Intensive care units, Bacteremia, Newborn infant

Introduction
Healthcare-associated infections (HAIs) in the neonatal intensive care unit (NICU) result in
significant morbidity and late mortality among hospitalized newborns. Almost 25% of very
low birth weight (VLBW, <1,500-g birthweight) infants experience more than one episode of
nosocomial infection, which is a major threat to the infants. The risk factors for HAIs in the
NICU include prematurity, low birthweight, invasive procedures, indwelling vascular catheters,
endotracheal tubes, ventricular shunts, parenteral nutrition with lipid emulsions, alterations
in the skin and mucous membrane barriers, broad-spectrum antibiotics, and prolonged
hospitalization.1)
Bloodstream infections (BSIs) are the most common type of HAI occurring in the NICU.
Late-onset sepsis occurring after 3 days of birth occurs in 20%–36% of VLBW babies.1) Most
cases of late-onset sepsis are caused by central venous catheters (CVCs). Premature infants
who experience catheter-related infections have a high mortality rate, poor growth and neuro­
Copyright © 2019 by The Korean Pediatric Society
developmental outcomes, as well as prolonged hospital stay, leading to increased medical costs.
2) This is an open-access article distributed under the
Therefore, more efforts are needed to reduce the incidence of CVC-related infections among
terms of the Creative Commons Attribution Non-
NICU patients, and to enhance their survival and prognosis. Commercial License (http://creativecommons.org/
licenses/by-nc/4.0/) which permits unrestricted non-
Here, we will focus on the basic concepts of catheter-related BSIs in NICUs and briefly review commercial use, distribution, and reproduction in any
strategies for preventing them. medium, provided the original work is properly cited.

https://doi.org/10.3345/kjp.2018.07003 79
Cho HJ and Cho HK • Central line-associated bloodstream infections in neonates

Definition of catheter-related BSIs Etiology of CLABSI in NICUs

There are 2 major definitions of BSIs associated with CVCs: cathe­ In the NICU population, the etiological organism of CLABSI is
ter-related bloodstream infection (CRBSI) and central line-associated similar to that among adults, but the proportion of gram-negative
bloodstream infection (CLABSI) (Table 1).3) SI refers to the presence organisms such as Klebsiella pneumoniae, E. coli, and Enterobacter
of bacteremia originating from the intravenous (IV) catheter and is cloacae is relatively high. This is due to increased bacterial trans­
more of a clinical definition. To diagnose this, a specific laboratory location from the gastrointestinal tract, especially in babies recei­ving
test is required to confirm that the source of the BSI is a catheter. long-term parenteral nutrition, which is associated with impaired
CLABSI, on the other hand, refers to a primary BSI that has not been bowel wall function and primary mucosal pathology, gastroin­
associated with infection at other sites in a patient who had a central testinal surgery or lack of enteral nutrition.7) While gram-positive
line within 48 hours of symptom onset. Culturing the catheter tip or bacteria including CoNS and Staphylococcus aureus are more im­
peripheral blood is not a criterion for CLABSI. The CLABSI definition portant in developed countries, gram-negative bacteria are found
is more practical than the CRBSI definition for surveillance. However, more often in developing countries.7-9) In Korea, the proportion of
it may overestimate the true rate of CVC-related infections. gram-positive bacteria has been reported to be higher.10)

Need for the definition of BSI specifically adapted Pathogenesis of CLABSI

for neonates There are several potential pathways and sources causing CLABSI
According to the National Healthcare Safety Network in the (Fig. 1).11) First, the catheter insertion site can serve as a port of entry
United States, CLABSI in children ≤1 year of age is defined as pri­
mary BSI with symptoms of fever (>38°C), hypothermia (<36°C),
apnea, or bradycardia. BSIs caused by a recognized pathogen
(e.g., Escherichia coli) isolated from ≥1 blood culture or common
skin commensal (e.g., coagulase-negative staphylococci [CoNS])
cultured from ≥2 blood cultures drawn on separate occasions are
included.4) However, these definitions for children aged ≤1 year are
not suitable in some aspects for neonates due to differences in the
symptoms of infection. Body temperature seldom exceeds 38.0°C,
artificially adjusted by lowering the incubator temperature, but
hypothermia, hyperthermia and temperature instability can occur.
Other definitions often include temperature instability, tachycardia,
prolonged recapillarization, metabolic acidosis, and newly de­
veloped hyperglycemia.5) Some attempts have been made to in­clude Fig. 1. Potential pathways and sources leading to central line-associated
other diagnostic methods such as antigen testing or to include both bloodstream infections. HCW, health care worker. Reprinted from
‘laboratory confirmed’ BSIs and clinical BSIs.6) Crnich et al. Clin Infect Dis 2002;34:1232-42, with permission of Oxford
University Press.11)

Table 1. Two definitions of central venous catheter-related bloodstream infections

Bloodstream infection Definitions
Catheter-related bloodstream infection Clinical signs of sepsis and positive peripheral blood culture in the absence of an obvious source other than CVC
with one of the following:
Positive semiquantitative (>15 CFU) or quantitative (>103 CFU) culture from a part of the catheter with the same
organisms isolated peripherally
Simultaneous quantitative blood cultures with a ratio of ≥3:1 (CVC vs. peripheral)
Time difference of ≤2 hours leading to culture positive between CVC and peripheral cultures
Central line-associated bloodstream infection Primary bloodstream infection in a patient who had a central line within the 48 hours period before development
of infection
Infection must not be related to an alternative cause
CVC, central venous catheter; CFU, colony forming unit.
Adapted from Bell T, et al. Infect Dis Clin North Am 2017;31:551-9, with permission of Elsevier.3)

80 https://doi.org/10.3345/kjp.2018.07003
 Korean J Pediatr 2019;62(3):79-84

for organisms. In this case, endogenous skin flora of the patient and policies for catheter-related infection prevention. This involves en­
extrinsic organisms from the hands of healthcare workers or even couraging them to practice what they already know by regularly
from contaminated disinfectants are potential sources. Sec­ond, reminding, rather than giving them new principles.14) It is also
during catheter hub operation it can be contaminated with orga­ necessary to regularly assess how well all staffs involved in the
nisms from the patient's skin flora or healthcare workers’ hands. insertion and maintenance of IV catheters are aware of the guide­
Third, fluids or drugs can be contaminated during the preparation lines and how well they are practicing them. In addition, an effec­
process or the manufacturing process of the company. Finally, there tive way to prevent CLABSI is by allowing only skilled medical
may be a secondary infection that causes catheter infection due personnel to manage insertion and maintenance of peripheral and
to hematogenous dissemination of infection in other parts of the central intravascular catheters, for example, designated nurse peri­
body.11) pherally inserted central catheter (PICC) teams (i.e., specially trained
One of the major steps in the process of catheter infection is the nurses who are responsible for PICC insertions at a hospi­tal).15) It
formation of biofilms extraluminally and intraluminally. Biofilm is should also be ensured that appropriate patient-to-nurse ratios are
composed of bacteria embedded within an extracellular polysac­ maintained within the NICU, as elevated patient-to-nurse ratios are
charide matrix on the catheter surface.12) These biofilms develop associated with increased CLABSI incidence.16)
within 24 hours of catheter insertion by organisms on the skin and
are mainly formed on the external surface of the catheter. Over 2. Selection of the PICC site
time, a biofilm is formed on the inner surface of the catheter, which There is no preferred location of the upper or lower limb as a PICC
occurs mainly in the process of connecting and disconnecting the location.15,17,18) Further research is needed on this issue. For long-
catheter hub. This usually occurs in long-term catheters that remain term surgically implanted central lines, the subclavian or femoral
in situ for more than 10 days. Bacteria embedded in biofilms are less vein is preferred to the internal jugular vein due to the high risk of
susceptible to the effects of antibiotics due to their low metabolic CLABSI.19,20)
rate. The minimum inhibitory concentrations for microorganisms in
a biofilm are known to be up to 1,000 fold higher than planktonic 3. Intervention bundle for CVC insertion and maintenance
organisms.13) In addition, biofilms are highly impenetrable to anti­ To prevent CLABSI, an intervention bundle is recommended
biotics. Therefore, it is difficult to eradicate the infection without re­ for insertion and maintenance of CVC (Table 2).21) When using an
moving the infected device. intervention bundle, it is better to use a checklist to encourage com­
pliance with medical staff training and recommendations. In a Uni­
ted States study, the incidence of CLABSI was reduced by about 40%
Prevention strategies for CLABSI in the NICU after the administration of a bundle compared to before. In ad­dition,
there was a difference in the incidence of CLABSIs depending on
1. Education, training, and staffing the utilization rate of the checklist, which suggested that using the
It is very important to educate medical staff regularly and re­ checklist as well as the bundle could prevent more cases of CLABSI.8)
peatedly about the indications for IV catheter use, the appropriate
practices during catheter insertion and maintenance, and other

Table 2. Suggestive elements of the bundles for insertion and maintenance of central catheters to prevent catheter-related infection (elements of the
bundle can be adjusted according to the environment of each neonatal intensive care unit)
Insertion bundle Maintenance bundle
Establish a central catheter kit or cart with all the items required for the Perform hand hygiene with an alcohol-based product or disinfectant containing soap
procedure before or after accessing the catheter, or before or after changing the dressing.
Perform hand hygiene with an alcohol-based product or disinfectant- Daily access the catheter insertion sites to identify signs of infection and dressing
containing soap before and after palpating insertion sites and before integrity
and after inserting the central catheter
Use maximal barrier precautions (sterile gown, sterile gloves, surgical At least, if the dressing is damp, soiled or loosened, change the dressing aseptically
mask, hat, and large sterile drape) and disinfect the skin around the insertion site with a suitable disinfectant (e.g., 2%
chlorhexidine, 70% alcohol).
Disinfect the skin with a proper antiseptic (e.g., 2% chlorhexidine, 70% Develop and use standardized intravenous tubing setup and changes
alcohol) before catheter insertion
Use either a sterile transparent semipermeable dressing or sterile gauze Maintain aseptic technique and scrub the hub using appropriate disinfectant when
to cover the insertion site replacing intravenous tubing and when accessing the catheter
Daily review catheter necessity to immediately eliminate when it is no longer essential
Adapted from Schulman J, et al. J Perinatol 2009;29:591-9, with permission of Springer Nature Publishing AG.21)

https://doi.org/10.3345/kjp.2018.07003 81
Cho HJ and Cho HK • Central line-associated bloodstream infections in neonates

4. Skin antiseptics in infants and neonates for pediatric patients <18 years old and nonpremature neonates due
Before inserting a peripheral venous catheter, it is recommended to the lack of sufficient evidence in this age group.14,28,29)
to disinfect the skin using 70% alcohol, tincture of iodine or alco­
holic chlorhexidine gluconate (CHG) solution. Before inserting the 8. Umbilical catheters
CVC or peripheral arterial catheter and changing the dressing, it Umbilical arterial (UA) or umbilical venous (UV) catheter is com­
is necessary to disinfect the skin with >0.5% CHG with alcohol, monly used in the management of sick neonates, but they can lead
tincture of iodine, iodophor, or 70% alcohol.14) There is a lack of to serious complications including infection. To prevent catheter-
studies comparing CHG formulations with alcohol or povidone- related infection, before inserting an umbilical catheter, it is recom­
iodine with alcohol preparations. The disinfectant must be dried mended to disinfect the insertion site with antiseptics (tincture of
before inserting the catheter. iodine is contraindicated, but other iodine agents [e.g., povidone
No recommendation is made about the preferred antiseptic for iodine] may be used). Topical antibiotics at the site of insertion are
catheter insertion and exit site care.22) The use of CHG is not ap­ also contraindicated in the umbilical catheter. It is recommended
proved in infants <2 months of age due to reports of serious contact that low-doses of heparin (0.25–1.0 U/mL) be added to the fluid
dermatitis as well as concerns about systemic absorption and possi­ injected into the UA catheter to maintain its patency. If UA and UV
ble toxic effects. Nevertheless, many centers currently use it. In a catheters are no longer needed, they should be removed as soon as
survey on the use of CHG in NICUs in the US, more than half re­ possible. An umbilical catheter can be replaced if it malfunctions
ported having used CHG. Of these, 51% experienced adverse skin and there is no other indication for removal. The total period of
reactions, most of which occurred in VLBW infants. No respondents catheter use should not exceed 5 days for UA catheter, or 14 days for
experienced neurologic toxicities in this study. UV catheter. When CRBSIs occur or signs of vascular insufficiency
Due to the risk of thyroid dysfunction associated with the use of or thrombosis are seen, UA or UV catheters should be removed and
iodine agents, it has not been widely used in NICUs.23-26) never be replaced.14)

5. In-line filters 9. Systemic prophylactic antimicrobials

There are 2 main IV filters according to pore size; the 0.22-μ filter In a meta-analysis on the use of prophylactic systemic antibiotics
is used for aqueous solutions, and the 1.2-μ filter is recommended in neonates with CVCs, its use was not effective in reducing overall
for larger molecule solutions such as lipids. The 0.22-μ filter has mortality. In addition, there is a lack of evidence on long-term neu­
also been reported to remove air, microorganisms and particulate rodevelopmental outcome and the use of antibiotics has con­cerns
matter. However, in-line filters are not recommended for use only to about the selection of resistant organisms.30)
prevent CLABSI. A meta-analysis of in-line filter effects on mortality
and morbidity in neonates reported no difference in death, proven 10. Antimicrobial locks
septicemia, or suspected septicemia during admission.27) There have been reports that using antibiotic lock solutions
have been effective in lowering CRBSIs in neonates. There are data
6. Catheter dressing regimens from each study on newborns in which fusidic acid, vancomycin,
Gauze dressing and transparent-semipermeable dressing are both or amikacin was used. However, its use did not effectively lower
available. If the patient is sweating or the site is bleeding or oozing, mortality and there were insufficient data on long-term effects on
gauze dressing should be used until this is resolved. antimicrobial resistance. Therefore, prophylactic antimicrobial lock
Topical antibiotics should not be used on the insertion site because solution can be considered in patients with long-term catheters
they have the potential to promote fungal infection and antibiotic who have a history of multiple CRBSI despite optimal maximal ad­
resistance. Regarding gauze dressings used on short-term CVC sites, herence to aseptic technique.31)
it is recommended to change them every 2 days. It is recommended
that transparent dressing used on short-term CVC sites be changed 11. Chlorhexidine bathing
every 7 days, except when infants are more likely to lose their In adults, daily skin cleansing with 2% chlorhexidine is recom­
catheter while replacing dressings.14) mended to prevent CRBSIs,14) but data on the efficacy and safety
of chlorhexidine bathing in neonates and infants are very limited.
7. Chlorhexidine-impregnated dressings Recently, there have been some reports that chlorhexidine bathing
Chlorhexidine-impregnated dressings are not recommended for has reduced the incidence of CLABSI, but there is a lack of evidence
the protection of the site of short-term, nontunneled CVCs for pre­ in neonates and premature infants.32)
mature neonates due to the risk of serious adverse skin reactions. No
recommendation is made about the use of chlorhexidine-impreg­ 12. Administration of IV fat emulsions
nated dressings to protect the site of short-term, nontunneled CVCs Since lipids are essential for growth and development, infants

82 https://doi.org/10.3345/kjp.2018.07003
 Korean J Pediatr 2019;62(3):79-84

and children require a higher proportion of dietary fat than adults.33) of pediatrics. 20th ed. ed. Philadelphia (PA): Elsevier Saunders, 2016:
However, IV fat emulsion (IVFE) has several safety issues especially 909-25.
2. Goudie A, Dynan L, Brady PW, Rettiganti M. Attributable cost and
when used in neonates and young infants. Because manufacturers length of stay for central line-associated bloodstream infections.
do not produce small-volume products, using them in the original Pediatrics 2014;133:e1525-32.
container with an infusion pump can cause fatal complications due 3. Bell T, O'Grady NP. Prevention of central line-associated bloodstream
to problems with the pump itself or mishandling. On the other hand, infections. Infect Dis Clin North Am 2017;31:551-9.
4. Centers for Disease Control and Prevention. National Healthcare
to infuse IVFE using a syringe pump, it needs to be repackaged Safety Network (NHSN) Patient Safety Component Manual 2017
into a syringe, during which microbial contamination may occur. [Internet]. Atlanta (GA): Centers for Disease Control and Prevention;
Moreover, because IVFE has high growth potential for bacteria 2017 [cited 2018 Sep 1]. Available from: https://www.cdc.gov/nhsn/
and fungi, its risk of microbial contamination is high.34) There is no pdfs/validation/2017/pcsmanual_2017.pdf.
5. Nationales Referenzzentrum für Surveillance von nosokomialen
preferred infusion method.
Infektionen. NEO-KISS Protocol, Nosocomial infection surveillance
There is a debate about proper IVFE hang time. While the Ameri­ for preterm infants with birthweight <1500g [Internet]. Berlin (Ger­
can Association of Pediatrics recommends that a daily dose of many): Nationales Referenzzentrum für Surveillance von nosoko­
IVFE should be infused during 18–24 hours due to infants’ low-fat mialen Infektionen; 2010 [cited 2018 Aug 16]. Available from: http://
www.nrz-hygiene.de/fileadmin/nrz/module/neo/NEO-KISSProtocol_
tolerance,33) the Centers for Disease Control and Prevention recom­
english_240210.pdf.
mend it should be infused within 12 hours. However, it is acceptable 6. van der Zwet WC, Kaiser AM, van Elburg RM, Berkhof J, Fetter WP,
to administer its daily dose for up to 24 hours if it is unavoidable.14) Parlevliet GA, et al. Nosocomial infections in a Dutch neonatal inten­
sive care unit: surveillance study with definitions for infection speci­
fically adapted for neonates. J Hosp Infect 2005;61:300-11.
13. Replacement of administration sets 7. Mobley RE, Bizzarro MJ. Central line-associated bloodstream infec­
If not used to infuse blood, blood products, or IVFE, administra­ tions in the NICU: Successes and controversies in the quest for zero.
tion sets that are continuously used, including secondary sets and Semin Perinatol 2017;41:166-74.
add-on devices, should be replaced no more frequently than at 8. Schulman J, Stricof R, Stevens TP, Horgan M, Gase K, Holzman IR, et
al. Statewide NICU central-line-associated bloodstream infection rates
96-hour intervals, but at least every 7 days. No recommendation
decline after bundles and checklists. Pediatrics 2011;127:436-44.
is made regarding the frequency for replacing intermittently used 9. Couto RC, Carvalho EA, Pedrosa TM, Pedroso ER, Neto MC, Biscione
administration sets. The tubing set used to administer blood, blood FM. A 10-year prospective surveillance of nosocomial infections in
products, or IVFEs should be replaced within 24 hours of initiating neonatal intensive care units. Am J Infect Control 2007;35:183-9.
10. Chun P, Kong SG, Byun SY, Park SE, Lee HD. Analysis of neonatal
the infusion.14)
sepsis in one neonatal intensive care unit for 6 years. Korean J Pediatr
2010;53;495-502.
11. Crnich CJ, Maki DG. The promise of novel technology for the preven­
tion of intravascular device-related bloodstream infection. I. Patho­
Conclusions genesis and short-term devices. Clin Infect Dis 2002;34:1232-42.
12. Raad I, Costerton W, Sabharwal U, Sacilowski M, Anaissie E, Bodey
Prevention of CLABSI is essential to improve the outcomes and GP. Ultrastructural analysis of indwelling vascular catheters: a
prognoses of NICU patients. It is most important to regularly edu­ quantitative relationship between luminal colonization and duration
cate, train and give feedback to medical staffs about the various of placement. J Infect Dis 1993;168:400-7.
preventive measures required at each stage from before insertion to 13. Aslam S. Effect of antibacterials on biofilms. Am J Infect Control
2008;36:S175.e9-11.
removal of the catheter. In order to improve the quality of infection 14. Centers for Disease Control and Prevention. Guidelines for the preven­
control, continuous efforts are needed to develop effective and safe tion of intravascular catheter-related infections, 2011 [Internet].
infection control strategies for neonates and young infants. Atlanta (GA): Centers for Disease Control and Prevention; 2017 [cited
2018 Aug 16]. Available from: https://www.cdc.gov/infectioncontrol/
guidelines/bsi/.
15. Krein SL, Kuhn L, Ratz D, Chopra V.Use of designated nurse PICC
Conflicts of interest teams and CLABSI prevention practices among U.S. Hospitals: a
wurvey-based study. J Patient Saf 2015.
No potential conflict of interest relevant to this article was re­ 16. Tucker J; UK Neonatal Staffing Study Group. Patient volume, staffing,
and workload in relation to risk-adjusted outcomes in a random
ported. 
stratified sample of UK neonatal intensive care units: a prospective
evaluation. Lancet 2002;359:99-107.
17. Panagiotounakou P, Antonogeorgos G, Gounari E, Papadakis S,
Labadaridis J, Gounaris AK. Peripherally inserted central venous
References catheters: frequency of complications in premature newborn depends
on the insertion site. J Perinatol 2014;34:461-3.
1. Stoll BJ, Shane AL. Infections of the neonatal infant. In: Kliegman
18. Wrightson DD. Peripherally inserted central catheter complications in
RM, Stanton BF, St Geme III JW, Schor NF, editors. Nelson textbook
neonates with upper versus lower extremity insertion sites. Adv

https://doi.org/10.3345/kjp.2018.07003 83
Cho HJ and Cho HK • Central line-associated bloodstream infections in neonates

Neonatal Care 2013;13:198-204. tion in preterm infants: a randomised trial. Arch Dis Child Fetal Neo­
19. Vegunta RK, Loethen P, Wallace LJ, Albert VL, Pearl RH. Differences natal Ed 2018;103:F101-6.
in the outcome of surgically placed long-term central venous cathe­ 27. Foster JP, Richards R, Showell MG, Jones LJ. Intravenous in-line
ters in neonates: neck vs groin placement. J Pediatr Surg 2005;40:47- filters for preventing morbidity and mortality in neonates. Cochrane
51. Database Syst Rev 2015;(8):CD005248.
20. Breschan C, Platzer M, Jost R, Schaumberger F, Stettner H, Likar R. 28. Levy I, Katz J, Solter E, Samra Z, Vidne B, Birk E, et al. Chlorhexidine-
Comparison of catheter-related infection and tip colonization impregnated dressing for prevention of colonization of central venous
between internal jugular and subclavian central venous catheters in catheters in infants and children: a randomized controlled study.
surgical neonates. Anesthesiology 2007;107:946-53. Pediatr Infect Dis J 2005;24:676-9.
21. Schulman J, Stricof RL, Stevens TP, Holzman IR, Shields EP, Angert 29. Garland JS, Alex CP, Mueller CD, Otten D, Shivpuri C, Harris MC, et
RM, et al. Development of a statewide collaborative to decrease NICU al. A randomized trial comparing povidone-iodine to a chlorhexidine
central line-associated bloodstream infections. J Perinatol 2009;29: gluconate-impregnated dressing for prevention of central venous
591-9. catheter infections in neonates. Pediatrics 2001;107:1431-6.
22. Lai NM, Taylor JE, Tan K, Choo YM, Ahmad Kamar A, Muhamad NA. 30. Jardine LA, Inglis GD, Davies MW. Prophylactic systemic antibiotics
Antimicrobial dressings for the prevention of catheter-related infec­ to reduce morbidity and mortality in neonates with central venous
tions in newborn infants with central venous catheters. Cochrane catheters. Cochrane Database Syst Rev 2008;(1):CD006179.
Database Syst Rev 2016;3:CD011082. 31. Taylor JE, Tan K, Lai NM, McDonald SJ. Antibiotic lock for the pre­
23. Williams FL, Watson J, Day C, Soe A, Somisetty SK, Jackson L, et al. vention of catheter-related infection in neonates. Cochrane Data­base
Thyroid dysfunction in preterm neonates exposed to iodine. J Perinat Syst Rev 2015;(6):CD010336.
Med 2017;45:135-43. 32. Quach C, Milstone AM, Perpête C, Bonenfant M, Moore DL, Perreault
24. Smerdely P, Lim A, Boyages SC, Waite K, Wu D, Roberts V, et al. T. Chlorhexidine bathing in a tertiary care neonatal intensive care
Topi­cal iodine-containing antiseptics and neonatal hypothyroidism in unit: impact on central line-associated bloodstream infections. Infect
very-low-birthweight infants. Lancet 1989;2:661-4. Control Hosp Epidemiol 2014;35:158-63.
25. Linder N, Davidovitch N, Reichman B, Kuint J, Lubin D, Meyerovitch 33. Kleinman RE. Pediatric nutrition handbook. 6th ed. Elk Grove (IL):
J, et al. Topical iodine-containing antiseptics and subclinical hypo­ American Academy of Pediatrics, 2009:529.
thyroidism in preterm infants. J Pediatr 1997;131:434-9. 34. Crill CM, Hak EB, Robinson LA, Helms RA. Evaluation of microbial
26. Kieran EA, O'Sullivan A, Miletin J, Twomey AR, Knowles SJ, contamination associated with different preparation methods for neo­
O'Donnell CPF. 2% chlorhexidine-70% isopropyl alcohol versus 10% natal intravenous fat emulsion infusion. Am J Health Syst Pharm
povidone-iodine for insertion site cleaning before central line inser­ 2010;67:914-8.

84 https://doi.org/10.3345/kjp.2018.07003