Effectiveness of preemptive barrier

precautions in controlling nosocomial

colonization and infection by methicillin-
resistant Staphylococcus aureus in a burn
unit
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yes platform+medline author author

Nas
ia Safdar, MD, MSa, John Marx, MPHb, Nicholas A. Meyer, MDc, Dennis G. Maki, MDab

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Background
We report the effectiveness of preemptive enhanced barrier precautions in containing a
methicillin-resistant Staphylococcus aureus (MRSA) outbreak in a university hospital burn
unit and further controlling endemic nosocomial MRSA infection in the unit during the
succeeding 27 months.
Methods
During a 6-month period, 12 patients in a 7-bed burn unit were found to be colonized (7) or
infected (5) by MRSA. An epidemiologic study was undertaken.
Results
Seven of the 10 strains of MRSA from patients that were available for DNA typing were
clonally identical. Early in the outbreak, a health care worker was found to be a concordant
nasal carrier and was successfully decolonized with nasal mupirocin. However, despite
stringent compliance with isolation of MRSA-positive patients (targeted precautions), new
cases of MRSA colonization or infection continued to occur. The outbreak was rapidly
terminated after implementing preemptive barrier precautions with all patients in the unit: a
new, clean gown and gloves for any physical contact with the patient or their environment.
Although 25% of all nosocomial S aureus isolates in our hospital are resistant to methicillin,
the incidence of endemic MRSA colonization and infection in the burn unit has remained
very low since implementing barrier precautions unit wide (baseline rate, 2.2 [95% CI: 1.0-
4.2] cases per 1000 patient-days; outbreak rate, 7.2 [95% CI: 4.4-11.0] cases per 1000
patient-days; post-outbreak termination endemic rate, 1.1 (95% CI: 0.4-2.3) cases per 1000
patient-days). The rate ratio comparing the outbreak and the baseline period was 3.20 (95%
CI: 1.40-7.95, P = .002); the rate ratio comparing the postoutbreak period with the baseline
period was 0.48 (95% CI: 0.14-1.53, P = .10), and it has not been necessary to screen
personnel for MRSA carriage to prevent nosocomial MRSA infections in this highly
vulnerable population.
Conclusion
Preemptive barrier precautions were highly effective in controlling the outbreak and, most
notably, have also been highly effective in maintaining a very low incidence of nosocomial
MRSA infection endemically in the succeeding 27 months of follow-up. Use of clean gloves,
with or without a gown, bears consideration for all high-risk hospitalized patients to prevent
cross transmission of all multiresistant nosocomial pathogens.
Madison, Wisconsin

Catheter-Associated Bloodstream Infections

in the NICU: Getting to Zero
Sabra Curry, NNP-BC, MSN, APN; Michele Honeycutt, RN, BSN, CIC; Gail Goins, RNC;
Craig Gilliam, BSMT, CIC
Authors and Disclosures
Posted: 06/15/2009; Neonatal Network. 2009;28(3):151-155. © 2009 Neonatal Network

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• Abstract and Introduction

• Quality Improvement Initiative Methods
• Line Insertion/Dressing Change Procedure
• Line Maintenance
• Staff Education/Motivation
• Results
• Conclusion
• References

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Abstract and Introduction

Abstract
The neonatal population is at a particularly high risk for catheter-associated bloodstream
infections (CABSI). Chlorhexidine for skin antisepsis is well documented to effectively
decrease the incidence of bloodstream infections associated with central venous catheters in
other populations. The project described in this article demonstrates that chlorhexidine for
central venous catheter insertion and line maintenance in the neonatal population safely and
effectively reduces CABSI.
Introduction
Reducing catheter-associated adverse events by 50 percent was identified as the top health
care safety priority for the Centers for Disease Control in 2005.[1] Neonates, especially those
of low and very low birth weight, are at particularly high risk for infection due to their
compromised immune status. Central venous catheters (CVCs) are often necessary to
administer intravenous fluids and medications, but their insertion and use are not without
risk. The most common complication is bloodstream infection, which occurs at rates of 3.1–
6.4 per 1,000 CVC days in NICUs according to the National Healthcare Safety Network
(NHSN).[2]
Procedures to minimize the occurrence of catheter-associated bloodstream infections
(CABSIs) are an important issue. The Institute for Healthcare Improvement (IHI), a nonprofit
organization that focuses on health care improvement, as part of the national Protecting 5
Million Lives from Harm campaign, identified a bundle of best practice measures to aid in
the reduction of CABSI.[3] Bundling groups of best practices, as in this case with central lines,
has been shown to result in better outcomes than implementing them individually. The
components of the bundle include the use of maximum sterile barrier precautions for line
insertion, optimal hand hygiene practices, daily assessment of the need for a CVC, and the
use of chlorhexidine gluconate (CHG) for skin antisepsis.
The most common mechanism of a CABSI is migration of the infectious organism from the
insertion site of the catheter and colonization at its distal end. Organisms that typically cause
CABSI are coagulase negative staphylococci, Staphylococcus aureus, and
Enterobacteriaceae.[4] The most common organism related to CABSI in our NICU during
2007 was coagulase negative staphylococci, specifically S. epidermidis, accounting for 38
percent of all CABSIs.
Our NICU at Arkansas Children’s Hospital is an 85-bed Level IV regional referral center that
averages 800 admissions per year. The average daily census in 2003 was 54, which has
increased to 80 in 2008. All admissions to the unit are transported to the facility because
obstetric services are not available in-house. Infants are managed by a team of neonatologists,
neonatal nurse practitioners (NNPs), neonatal fellows, and pediatric residents. The primary
CVCs that are used include peripherally inserted central catheters (PICCs) and Broviac
catheters. The PICCs are 26 gauge and 28 gauge L-Caths (Becton-Dickinson, Sandy,Utah)
that are inserted by the NNPs. Broviac catheters are used primarily for patients with
gastrointestinal surgical diagnoses who will require long-term hyperalimentation therapy.
These are tunneled catheters that are placed by the general surgery team in the operating
room. In 2007, 388 PICCs were placed, 26 patients were admitted with PICCs from referring
hospitals, and 56 Broviacs were inserted ( Table 1 ).
The literature supports the use of CHG for skin antisepsis.[5] However, its use in the neonatal
population has received limited attention. At our institution, the pediatric intensive care unit
(PICU) implemented the IHI best practices bundle for the prevention of CABSI ( Table 2 ).
Between 1997 and 2005, annual CABSI rates decreased from 9.7 to 3 per 1,000 catheter
days.[6]

Section
1 of

Quality Improvement Initiative Methods

This quality improvement project (internal review board exempt) extended part of the IHI
bundle to the neonatal population by introducing CHG (alcohol-based) as a skin antisepsis
and a CHG impregnated patch (Biopatch, Johnson & Johnson Gateway, Piscataway, New
Jersey) around the catheter insertion site to provide an additional antimicrobial barrier.
Beginning in 2003, a series of best practice measures was implemented in the NICU,
including the optimal use of hand hygiene and the use of maximum sterile barrier precautions
during line insertion ( Table 3 ). In 2004, a dedicated CVC team of NNPs and expert bedside
nurses was appointed to be responsible for the insertion of PICCs and proactive management
of all CVCs. Proactive management included weekly data collection of insertion date, birth
weight, parenteral infusion/medications, dressing site evaluation, line complications, line
necessity, and the date when the line is discontinued. As part of the team, the Infection
Control Department collects the denominator data and identifies bloodstream infections
according to the NHSN definitions. Infection rates are calculated based on this information
with the following formula:
Line Insertion/Dressing Change Procedure
The implementation of CHG for skin antisepsis began in March 2006. Initially, because of
concerns related to the integrity of premature skin, CHG was used for skin antisepsis for the
insertion of PICCs and dressing changes in all CVCs, including PICCs and Broviacs for
infants weighing more than 2,000 g or who were greater than two weeks of age.
The Biopatch was placed on all patients with Broviac catheters. Broviac dressings are
changed weekly in coordination with the Biopatch changes. A randomized trial of the
Biopatch concluded, "The patch provides protection against catheter tip colonization.
Suppressing catheter site colonization with local antisepsis is an effective means of reducing
the risk of CABSI" (p. 1432).[7] The CVC team elected not to place the Biopatch on infants
with PICC lines for two reasons:
1. PICC lines are not trimmed. Therefore, the line is curled on the skin, making it difficult to
allow the Biopatch to be in direct contact with the skin.
2. Dressing changes occur every two weeks unless the integrity of the dressing has been
compromised. According to the manufacturer recommendations, the Biopatch has to be
changed every 7 days, requiring more frequent dressing changes and subsequently, a greater
risk for dislodgement. The average PICC line duration has been approximately 21 days.
To provide better continuity of care for CVCs, the dedicated CVC team was expanded in
August 2006. Two NNPs taught and trained the additional NNPs regarding the use of CHG
for PICC placement. These two NNPs also performed the majority of the dressing changes
for the Broviac catheters. Also added to the team was a staff registered nurse who served as
data collector for CVCs. In addition, this nurse was the staff educator and also served as a
primary resource for PICC dressing changes. After six months, no adverse skin conditions
were associated with CHG use in the PICC population (weighing more than 2,000 g or
greater than two weeks of age). In the Broviac population, 2 of 56 patients developed minor
skin irritation with the use of the CHG patch. Because of the rarity of adverse skin conditions,
the process was expanded to the population of infants weighing more than 1,000 g or who
were greater than two weeks of age. This extension began in September 2006. As of August
2008, there have been no adverse skin conditions noted in this patient population from using
CHG for skin antisepsis for line placement and dressing changes.
Two infants with Broviac catheters who required long-term care tolerated the use of CHG for
six months, then developed skin irritation around the insertion site. The decision was made to
stop the use of CHG and the Biopatch. One of these infants was able to keep the line in place
for 361 days without a CABSI. Toward the end of this infant's hospitalization, the team used
the Algidex Ag patch (DeRoyal, Powell, Tennessee) as part of his CVC care regimen. This is
a sterile patch that is coated with an ionic silver alginate that provides a broad-spectrum
antimicrobial barrier.
Beginning in September 2007, we expanded the use of CHG for skin antisepsis for
procedures including bladder taps, insertion of peripheral intravenous catheters, and
peripheral arterial lines. We do not use it for umbilical line insertion, ventricular taps, and
lumbar punctures because of the manufacturer recommendations. No adverse skin reactions
were noted with this extended use of CHG.

n our effort to further reduce CABSI starting in September 2007, the focus expanded to line
maintenance. Rizzo has reported, "Contamination of catheter hubs by medical personnel is
the most common source of infection for long term catheters. This occurs by introducing the
organisms when the catheter is manipulated; these pathogens then migrate intraluminally
with the potential of reaching the distal tip in the bloodstream" (p. 217).[1] CHG (3.15
percent) prep pads are used to clean the tubing connection sites and access ports for tubing
changes, medication administration, and blood sampling on all CVCs, peripheral intravenous
lines, arterial lines, and umbilical lines. All connections are scrubbed for 30 seconds with
CHG and allowed to dry prior to accessing the port or line.

Staff Education/Motivation
An important aspect of implementing any change is to actively involve the people
participating in this change. Ongoing education and participation of the bedside staff was a
priority throughout this project. In addition to formal staff education, informal discussion and
information sharing took place on a regular basis. Approximately 18 months into the project,
several inservices were held to review the progress achieved. To motivate the staff, a goal
was set to reach 100 days between catheter infections. This was accomplished in November
2007, with 117 days between Broviac CABSIs. The CABSI occured in a patient with a
vascular tumor who was receiving chemotherapy treatment through the Broviac catheter on a
weekly basis. This milestone was celebrated with an ice cream sundae party. At that time, the
staff completed a questionnaire that contained eight questions about the implementation of
the project in the NICU, the goal being to stimulate their interest and increase ownership in
the project. A drawing for several gift cards took place to show appreciation for their
continued commitment to this project.

he biggest impact on CABSI was in the patient population who required the use of Broviac
catheters. In 2005, there was a total of 20 Broviac CABSIs, for a rate of 9.3 infections per
1,000 catheter days. After beginning the use of CHG for skin antisepsis and line maintenance
and use of the CHG-impregnated patch, the number of infections decreased over the next two
years to 7 infections during 2007, for a rate of 3.3 infections per 1,000 catheter days (Figure
1). The number of Broviac line days remained steady over this three-year time frame.
Figur
e 1.

(Enlarge
Image)

[ CLOSE WINDOW ]
Figure 1.
PICC usage increased from 5,151 line days in 2005 to 8,148 line days in 2007. Despite the
increase in line days, the incidence of CABSI in this patient population fell from 21
infections during 2006 to 14 infections during 2007. The infection rate over these three years
decreased from 3.1 infections per 1,000 catheter days in 2005 to 1.7 infections per 1,000
catheter days during 2007 (Figure 2). In July 2008, another milestone was reached with 114
days since the last CABSI in the PICC population, surpassing the 63-day record from 2007.
Figur
e 2.

(Enlarge
Image)

[ CLOSE WINDOW ]
Figure 2.
The cost to treat 1 CABSI is estimated to range between $34,508 and $56,000 for an average
cost of $45,000.[5] The average number of CABSIs from 2003 to 2007 was 29 per year, for an
estimated cost of $1.3 million to treat these infections. The largest reduction in CABSI in this
unit occurred after line maintenance with CHG was implemented. For the first seven months
in 2008, only 2 CABSIs have occurred, 1 in an oncology patient with leukemia being treated
with chemotherapy who developed yeast sepsis and the other in a 34-week gestational age
infant who grew Staphylococcus warneri from the PICC. The trend for 2008 will drop
CABSI incidence to 1 per quarter and save an average of $1.1 million annually. The cost of
an alcohol prep pad is 4 cents, and a CHG prep pad costs 12 cents.
The success of this five-year project can be attributed to using a multidisciplinary, stepwise
approach (see Table 3 ) similar to the one used in the PICU.[6] This stepwise approach was
taken to reduce the CABSI rate in a very fragile population who require frequent and long-
term use of central lines.
Success was not immediate, as evidenced by the CABSI rate in PICCs during the second
quarter of 2006. Maintaining focus and commitment of the bedside staff was a challenge;
however, with perseverance and dedication, substantial reduction in CABSI was achieved.
The overall CABSI rate for both Broviacs and PICCs combined for 2007 was 2.1 infections
per 1,000 catheter days, down from 4.9 infections per 1,000 catheter days in 2005 even as
total line days increased 40 percent, from 7,312 to 10,241.
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neonatal intensive care unit • PI, povidone-iodine • uz
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PPE, personal protective equipment ef
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Journal home > Archive > Original Articles > Full text

Original Article
Journal of Perinatology (2004) 24, 446–453. doi:10.1038/sj.jp.7211125 Published online 6
May 2004

Prevention and Treatment of Nosocomial Sepsis in the NICU

Disclosures: None.
Reese Clark MD1,2, Richard Powers MD3, Robert White MD4, Barry Bloom MD5,
Pablo Sanchez MD6 and Daniel K Benjamin Jr MD, MPH, PhD2
1
1. Pediatrix Medical Group, Inc., (R.C.), Sunrise, FL, USA
2
2. Duke University Medical Center, (R.C., D.K.B.), Durham, NC, USA
3
3. Children's Mercy Hospital, (R.P.), Oakland, CA, USA
4
4. Memorial Hospital of South Bend, (R.W.), South Bend, ID, USA
5
5. Wesley Medical Center, (B.B.), Wichita, KS, USA
 6
6. University of Texas Southwestern Medical Center, (P.S), Dallas, TX, USA
Correspondence: Reese H. Clark, MD, Pediatrix Medical Group, Inc., 1301 Concord Terrace,
Sunrise, FL 33323-2825, USA
Top of page

Abstract
Nosocomial sepsis is a serious problem for neonates who are admitted for intensive care. It is
associated with an increase in mortality, morbidity, and prolonged length of hospital stay.
Thus, both the human and fiscal costs of these infections are high. Although the rate of
nosocomial sepsis increases with the degree of both prematurity and low birth weight, no
specific lab test has been shown to be very useful in improving our ability to predict who has
a "real" blood-stream infection and, therefore, who needs to be treated with a full course of
antibiotics. As a result, antibiotic use is double the rate of "proven" sepsis and we are
facilitating the growth of resistant organisms in the neonatal intensive care unit. The purpose
of this article is to describe simple changes in process, which when implemented, can reduce
nosocomial infection rates in neonates and improve outcomes.
Top of page

INTRODUCTION
Effective strategies to prevent nosocomial sepsis must include continuous monitoring and
surveillance of infection rates and distribution of pathogens; strategic nursery design and
staffing; emphasis on staff accountability for incidence of nosocomial infections; programs to
increase emphasis on hand-washing compliance; cautious insertion and handling of central
venous catheters; minimizing central venous catheter duration; and prudent use of
antimicrobial agents. Educational programs and feedback to NICU personnel improve
compliance with infection control programs.1
Hand Hygiene
The simplest strategy for decreasing nosocomial sepsis and the most difficult with which to
achieve compliance is good hand hygiene.2, 3, 4, 5, 6 The rationale for hand washing is to reduce
transient and resident microflora.7, 8, 9, 10, 11, 12, 13, 14 Several hand-washing products have been
studied. The residual effect of chlorhexidine gluconate and Triclosan® appear to provide an
advantage over other disinfectants.13, 15, 16, 17 Waterless alcohol products are equally effective
in initial antisepsis and improve compliance.18, 19, 20 Ensuring that hand-washing techniques13,
17
(duration of wash, type of soap) are appropriate is important. In addition, locating hand-
washing opportunities close to the site of care improves compliance and reduces the risk of
crosscontamination. Several controlled trials of hand washing demonstrate that it is effective
at reducing nosocomial infections.8, 21, 22, 23, 24, 25
Compliance with hand washing can be improved by reducing barriers19, 20, 21, 26, 27, 28, 29 and
actively promoting compliance.17, 18, 19, 20, 30 Defining specific policies, which eliminate hand-
related artificial fingernails and hand jewelry that spread infection, can help reduce infection
rates. Several studies have shown that Pseudomonas outbreaks have been associated with
long and artificial nails.31, 32 Artificial nails are also more often colonized with pathogenic
organisms than natural nails.33, 34
Use of Human-milk Feedings
In a prospective controlled trial, neonates fed breast milk were less likely to become septic
compared to formula-fed neonates.35 Hylander et al.36 showed that human-milk feedings
reduced the odds of sepsis/meningitis compared to preterm milk feedings (OR=0.43; 95% CI:
0.23 to 0.81). The efficacy of breast milk also appears to be dose dependent and neonates for
whom breast milk is the primary source of nutrition have fewer episodes of infection than
when breast milk is only a small part of the daily nutrition.37
Intravenous Immunoglobulin
Meta-analysis of clinical trials in low-birth-weight neonates shows that prophylactic
intravenous immunoglobulin administration resulted in a significant reduction in sepsis
(clinical signs and symptoms of sepsis and positive blood culture for bacteria or fungi
decreased by 3%) and the occurrence of serious infection (clinical signs and symptoms in
conjunction with positive cultures from blood, cerebrospinal fluid, urine was decreased by
4%).38 However, the use of intravenous immunoglobulin is not associated with improvement
in other important outcomes (necrotizing enterocolitis, intraventricular hemorrhage, or length
of hospital stay); therefore, most authors do not recommend routine use of intravenous
immunoglobulin to prevent nosocomial sepsis.38, 39, 40
NICU Design
Several design factors may reduce the incidence of nosocomial sepsis. Overcrowding,
inadequate design of sinks and soap containers, inconvenient placement of supplies, improper
maintenance of surface-covering materials (e.g., carpet), and poorly designed air
flow/isolation facilities can also increase the occurrence of neonatal sepsis. Elements of a
well-designed NICU, with respect to reduction of nosocomial infection, include: 120 to
180 ft2 per bed space, sinks within 20 ft of each bed, and having all commonly used
equipment easily accessible at each bedside. Each NICU needs at least one isolation room
with enough space for two commonly infected babies and an area for hand washing,
gowning, and storage of clean and soiled materials located directly outside or immediately
inside the entry door to the room.41 It is important to remember that good designs are of little
value without good policies, and bad designs can largely be rescued with good policies.
Reducing Intravascular Line-Related Infections
Line and line-connection contamination

Catheter-related sepsis has been shown to result from entry of microbes extraluminally via
the skin at the insertion site and through the catheter hub after colonization of the hub during
repeated manipulations.42, 43 Sepsis appearing within a short time period after catheter
insertion is usually from skin contamination, while hub colonization results in bloodstream
infection occurring after the first week of line duration. The same microorganism is often
isolated from both the patient's skin and the catheter hub. This suggests that the health-care
provider's hands may transfer skin flora to the inner surface of the catheter hub during hub
manipulation and replacement of the infusion set and emphasizes the importance of good
hand hygiene.44, 45, 46, 47
The design of line setups can influence the risk of infection and reducing the number of ports,
decreasing the use of three-way stopcocks, and limiting the number of catheter lumens may
decrease the occurrence of line sepsis.46, 47 Strategies that reduce the likelihood of line sepsis
include: minimizing blood sampling by batching laboratory specimen draws;48 prepping of
hubs with disinfectants;44, 49 use of an alternative hub design with an antiseptic chamber;50, 51, 52
and use of better hub connectors with needleless systems.
Line insertion
How the line is placed is equally important. Choosing a good site will reduce the number of
percutaneous sticks required for successful placement of the line and decrease the likelihood
of line contamination during the process. The skin should be carefully prepped before line
placement. Available prep solutions include alcohol, povidone-iodine, and chlorhexidine
gluconate. Garland et al.53 compared the efficacy of 0.5% chlorhexidine gluconate in 70%
isopropyl alcohol to povidone-iodine in a nonrandomized prospective study in neonates.
Chlorhexidine gluconate antisepsis was associated with decreased peripheral intravenous
catheter colonization. In a prospective randomized trial of povidone-iodine, alcohol, and
chlorhexidine gluconate in a surgical intensive care unit, chlorhexidine gluconate was
associated with the lowest incidences of local catheter-related infection and bacteremia.54 The
new guidelines from the US Department of Health and Human Services Centers for Disease
Control suggest that 2% chlorhexidine gluconate-containing solutions are the agent of first
choice in skin antisepsis for line insertion.42, 43
While placing a central venous catheter, the use of gown and gloves are both important. The
concept of maximal barrier precautions stipulates the use of sterile cap, mask, gown, gloves,
and drape. The rationale for this procedure is the reduction of contamination during the
insertion process of the indwelling catheter. The benefits of this procedure have been
demonstrated in prospective randomized trials in adult critical care patients.55, 56
Reducing the time the central line catheter is in place

The best method for reducing the risk of line infections is to reduce the duration of time that
the central catheter is used.42, 43 Several studies show a direct correlation between the use and
duration of deep lines and the incidence of sepsis in neonates.1, 57, 58, 59 In the largest of the
studies, Chathas et al60 showed a critical time of 21 days, after which the risk for sepsis
became significant. Most very-low-birth-weight infants will be close to full enteral calories
by 21 days of age; thus, removing the central lines by 21 days is feasible. Introduction of
early feedings with breast milk, consistent advancing of feeding volumes, and deciding to
remove the deep lines in some infants before full enteral calories are introduced are important
proactive strategies that can be used to reduce the risk of line sepsis.61, 62
Vancomycin prophylaxis for central lines

In meta-analysis, prophylactic use of vancomycin reduced blood-stream infection rates. In all

five randomized-controlled trials reviewed, a decrease in the incidence of overall sepsis
events and coagulase-negative Staphylococci sepsis events was reported. The authors
conclude, however, that the clinical benefits are minimal and do not justify routine use of
vancomycin prophylaxis.63 In addition, the risk of developing vancomycin resistance could
not be conclusively disproved,63 and remains a concern with all strategies of prophylaxis with
antimicrobial agents. Vancomycin-resistant enterococci are emerging as a serious problem,
especially in immune-compromised patients and those admitted for intensive care.64, 65
Surface-coated central catheters

In adults, use of heparin-bonded central venous catheters reduced the nosocomial infection
rate by 88%.66 Other materials that reduce bacterial adherence and the risk of colonization,
when bonded to central venous catheters, include salicylic acid,43 silver,67, 68 and the
glycopeptide, teicoplanin.69 Antiseptic bonding may also decrease the incidence of blood-
stream infection. Agents used include cefazolin,70 iodine,71, 72 minocycline-rifampin73 and
chlorhexidine-silver-sulfadiazine.74 Of note, none of these studies has involved neonates.43, 73,
74, 75, 76, 77
Until clinical studies documenting the efficacy, safety, and absence of emergence of
antibiotic resistance in neonates are carried out, routine clinical use of catheters with
antiseptic coatings is not warranted in the NICU.43
Removing the line when there is a positive culture

The outcome for patients whose central catheter is not removed after identification of
pathogenic bacteria is worse than it is for those patients whose catheters are removed
promptly.78, 79 One positive blood culture for Staphylococcus aureus or a Gram-negative rod
warrants immediate central line removal in a neonate.78 In neonates who have just one
positive central line culture for coagulase-negative Staphylococci, clinicians may attempt
medical management without central catheter removal, but documentation of subsequent
negative blood cultures is crucial.78, 79, 80, 81 In neonates who have four consecutive positive
cultures or 4 or more days of positive cultures for coagulase-negative Staphylococci, the
likelihood of successfully clearing the line is low78, 80 and, in some studies, there is evidence
that the risk of end organ damage and poor outcome is high.78
Managing Process
Bloom et al.82 evaluated the performance of 52 NICUs on acquired infection, identified
higher and lower centers, contrasted their processes, and isolated meaningful differences.
Eight high and eight low centers were observed using the observation guide written from this
rigorous evaluation process. The network average was 3.4 episodes/1000 patient days. The
average of the high centers was 10.4 episodes/1000 patient days and the average of the low
centers was 0.5 episodes/1000 patient days. In all, 15 meaningful differences were isolated.
For example, "low" infection rate centers used two people or a closed endotracheal suction
system and Tenderfoot® auto lancets for lab sampling; washed hands prior to each patient
interaction; and had the intent to limit days for intravenous, central venous, and umbilical
lines. In contrast, "high" infection rate centers used an open system for endotracheal
suctioning, hand-held lancets, and gloves as a substitute for hand washing, and had no focus
on a time limit for I.V.s, central or umbilical lines. These data suggest that simple process
changes can reduce the occurrence of nosocomial sepsis.
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STRATEGIES THAT DO NOT APPEAR TO DECREASE NOSOCOMIAL

INFECTION
While changes in process can reduce the frequency of nosocomial infection, a number of
different approaches and processes have been studied and were not found to influence the
occurrence of nosocomial infections. Ventilator circuit changes more often than one time per
week were not associated with a decrease in pneumonia or sepsis.83 Changing the frequency
of tracheal suctioning from every 4 hours to every 8 hours did not change pneumonia or
blood-stream infection rate.84 In addition, the use of closed tracheal suctioning had no effect
on the incidence of nosocomial pneumonia, when compared with the open-suction method in
intensive care unit patients, and actually increased the incidence of tracheal colonization
versus open circuit.85 A study in neonates also showed no benefit with regard to a reduction in
infections.84 Gowning before entering the NICU has no effect on reducing nosocomial
infection.86, 87, 88 Infusion of fresh-frozen plasma increased immunoglobulin G levels, but did
not improve bacterial opsonification or decrease infection rates.89, 90, 91 Maintaining skin
integrity is important, but overuse of emollients can increase the risk of infection.92, 93, 94, 95
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TREATMENT DECISIONS FOR BLOOD-STREAM INFECTIONS

Who to Treat
Determining whom to treat and for how long are difficult clinical decisions and there is no
consensus on how to establish as to who has life-threatening sepsis. While some authors
report that inflammatory markers (interleukin-6,96, 97, 98 interleukin-8;99, 100, 101, 102, 103, 104, 105, 106
and C-reactive protein96, 107, 108, 109, 110, 111, 112) change with acquired infection in the premature
infant, only two articles have suggested a laboratory methodology that could be used to
decrease antibiotic exposure on the basis of specific criteria.104, 105
Antibiotic Choice
A specific antibiotic choice must be driven by hospital-specific guidelines based on the major
causes of nosocomial sepsis and organism susceptibility patterns in that specific hospital.
However, it is equally important to recognize that our choice of antimicrobial agents
influences the types of neonatal sepsis and their antibiotic resistance patterns. De Man et al.113
investigated whether the emergence of resistant strains could be halted by modifying
empirical antibiotic regimens. The authors assigned two similar NICUs to different empirical
antibiotic regimens. In one NICU, penicillin G and tobramycin were used for early-onset
septicemia; flucloxacillin and tobramycin were used for late-onset septicemia; and no broad-
spectrum beta-lactam antibiotics, such as amoxicillin and cefotaxime, were used. In the other
NICU, intravenous amoxicillin with cefotaxime was the empirical therapy. The relative risk
for colonization with strains resistant to the empirical therapy was 18 times higher for the
amoxicillin–cefotaxime regimen compared with the penicillin–tobramycin regimen (95% CI
5.6 to 58.0, p<0.01). The authors concluded that a regimen avoiding amoxicillin and
cefotaxime reduces the resistance problem.113
A second common problem in the NICU is the overuse of vancomycin.114, 115 Stoll et al.,115
studying very low birth-weight neonates (401 to 1500 g), found that 56% of 6215 infants
received at least one course of antibiotics started after day 3 of birth and 44% were treated
with a course of vancomycin. Vancomycin use was inversely related to birth weight (401 to
500 g, 78%; 501 to 750 g, 75%; 751 to 1000 g, 60%; 1001 to 1250 g, 36%; 1251 to 1500 g,
18%). Interestingly, 30% of patients without culture-proven infection also received this
drug.115
The question that remains to be answered is whether it is safe NOT to prescribe vancomycin
at the time of the initial workup. Karlowicz et al.116 showed that coagulase-negative
Staphylococcus is rarely fulminant and the mortality rate among neonates with coagulase-
negative Staphylococci is no different from uninfected neonates.115 It may be reasonable to
consider treating stable neonates with oxacillin or nafcillin instead of vancomycin for the 24
to 48 hours that it takes to identify a positive culture for coagulase-negative Staphylococci,
but this approach should be subjected to prospective study before being utilized.116
An equally important issue is what antibiotics should be chosen to cover for the Gram-
negative organisms — amikacin, tobramycin, or cephalosporin. Overuse of cephalosporins
has been associated with the emergence of resistant organisms113 and higher rates of fungal
infections.117 The current recommendation is to use an aminoglycoside in combination with
oxacillin or nafcillin as Gram-positive coverage for neonates with suspected and not-yet-
proven sepsis.
Duration of Treatment
Improved culture media and new technology integrated into blood culture systems have
shortened the incubation time required to detect positive culture results. Investigators have
shown a 97% to 100% yield at 48 hours for positivity of blood cultures.118, 119, 120, 121, 122, 123, 124,
125
These data suggest that in the absence of clinical signs of sepsis, which suggest that the
blood culture is falsely negative, antibiotics can be stopped after 48 hours of treatment, if the
blood culture is negative.
The best way to reduce the overuse of antibiotics in the NICU is to establish protocols that
lead to the appropriate stopping of antibiotics in neonates whose cultures are negative and
who have no evidence of sepsis after a 48-hour course of therapy.
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NOSOCOMIAL CANDIDA SEPSIS

Diagnosis
The incidence of candidemia is rising steadily, and Candida species are a leading cause of
infectious mortality in the NICU.58, 115, 117, 126, 127, 128, 129 The cumulative incidence of candidemia
in extremely low-birth-weight (<1000 g) infants is 4% to 15%.115, 117, 128 Candida blood-stream
infection is associated with an attributable mortality of 38% and a crude mortality of 30% to
75%.58, 115, 117, 126, 127, 128, 129 Prompt diagnosis and initiation of antifungal therapy are crucial to
survival across patient populations.117
Like other etiologies of neonatal sepsis, the current gold standard for the diagnosis of
neonatal candidiasis is the blood culture. Unfortunately, while the blood culture is sensitive
for bacterial pathogens, it is a poor diagnostic tool for invasive candidiasis. From animal
models, the sensitivity of the blood culture to diagnose catheter-related candidemia and acute,
disseminated, overwhelming candidiasis is approximately 80%, but the sensitivity of blood
culture for transient candidemia is below 50%.130, 131 Data from autopsy studies indicate that
the sensitivity of blood cultures to diagnose chronic disseminated and deep organ candidiasis
is less than 50%.132, 133, 134, 135 Previous analyses of incidence and attributed mortality of
neonatal candidiasis are based on the use of candidemia as equivalent to invasive candidiasis
and may be misleading. Neonatal candidiasis diagnosed by blood-culture techniques
underestimates the burden of disease.132, 133, 134, 136
Prevention
There are two studies evaluating antifungal prophylaxis.128, 129 There have been no trials
examining presumptive therapy or comparing prophylaxis with presumptive therapy. One of
the two trials evaluating prophylaxis did not show substantial benefit.129) Rectal colonization
was decreased, but infection rates were not changed. The other trial showed benefit, but the
control group (N=50) had a very high rate of neonatal candidiasis — 18%. This rate of
systemic candidal infection was higher than reported previously.129 Both of these studies were
single-center studies that enrolled small numbers of neonates (N=100,128 and N=103,129
respectively). A high rate of the primary end point in the control group in a small single-
center study suggests that the degree of estimated effect may be an overestimate.137
In general, prophylaxis exposes far more patients with much greater cumulative doses of
antimicrobial agents than empirical therapy does. Antifungal prophylaxis, in those
populations where it is currently indicated (patients who have received stem-cell
transplantation, for example), reduces, but does not eliminate, invasive fungal infections, and
in those children who receive antifungal prophylaxis, empirical antifungal therapy continues
to show benefit.137
Treatment
The primary modes of treatment are removal of any lines that are the source of infection,
amphotericin, and 5-fluorocytosine in neonates with central nervous system involvement.138
Since the diagnosis of Candida sepsis is difficult to make, some authors suggest empirical
therapy for high-risk neonates.117 End-organ evaluation of the neonate should include a
lumbar puncture, echocardiogram, abdominal ultrasound, and ophthalmologic exam as these
can influence the length of therapy and prognosis.139
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SUMMARY
Nosocomial sepsis is a serious and common problem for neonates who are admitted for
intensive care because it is associated with an increase in mortality, morbidity, and prolonged
length of hospital stay. It is, therefore, critically important to look for simple changes in
processes of care (reducing barriers to hand washing, developing careful protocols for
limiting the duration and contamination of central lines, improving the design of the NICU,
and early feedings), which, when implemented, can help reduce the risk of nosocomial sepsis
and improve outcomes.
Top of page

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