Central Line

Associated
Bloodstream Infections
Anthony J. Baldea, Jr., MD, and
Christine S. Cocanour, MD, FACS, FCCM

INTRODUCTION
Central venous catheters (CVCs) are indispensible to the care of
surgical patients. Fluid and blood product administration, hemodynamic monitoring, and dispensation of high-tonicity solutions such
as antibiotics, vasopressors, and total parenteral nutrition are
common indications for the approximately 7 million CVCs placed
annually in the United States alone. One potential drawback associated with CVCs is that these indwelling devices provide a route for
microorganisms to gain access to a patients bloodstream. Bacteremia
from colonization and subsequent infection from CVCs is termed
catheter-related bloodstream infection (CRBSI). This diagnosis is
problematic because whether the bloodstream infection (BSI) is from
the central line or from another source can be difficult to establish;
therefore, simpler definitions are used for surveillance. Central line
associated bloodstream infection (CLABSI) is the term used by the
Centers for Disease Controls (CDCs) National Healthcare Safety
Network and is defined as a BSI in a patient who had a central line
within 48 hours before the development of the BSI and in whom no
other source of infection is found. CLABSI is the most prevalent
nosocomial infection, with an estimated 41,000 infections occurring
in U.S. hospitals each year.
CLABSI is a significant burden on our healthcare system; it is
associated with increased intensive care unit (ICU) and hospital
length of stay (LOS) and higher mortality. A significant associated
economic burden also exists, as each CLABSI is estimated to add an
attributable cost of $5734 to $36,441 to the patients hospitalization.
Beginning October 1, 2008, the Center for Medicare and Medicaid
Services (CMS) considers CLABSI to be a never event and refuses
to pay for any associated additional healthcare costs. This has led to
a heightened national focus on decreasing CLABSI, with significant
progress being made. From 2001 to 2009, the incidence rate of
CLABSI in ICU cases dropped 58%. With the continued emphasis
on eliminating the adverse clinical sequelae and decreasing the financial burden that accrues from the development of nosocomial infections, the importance of understanding how to prevent, properly
diagnose, and adequately treat CLABSI becomes paramount to surgical practice. This chapter focuses on the prevention and clinical management of CLABSI in short-term, nontunneled CVCs.

PREVENTION
Sixty-five percent to 70% of CLABSI cases are estimated to be preventable with the application of current evidence-based strategies.
Many institutions have implemented central line insertion and
maintenance bundles in an attempt to decrease CLABSI rates. The
implementation of these catheter-care bundles has led to promising
results, with a more than 50% reduction in CLABSI rates. These
evidence-based bundles focus on basic concepts: maintenance of
sterile conditions during insertion of CVCs, recommendations for
site of insertion and catheter selection, optimization of postinsertion
catheter care, appropriate catheter surveillance, and comprehensive

education of the entire healthcare team. The following prevention

guidelines are specifically of interest to the surgeon. For a complete
set of recommendations, please see the CDCs 2011 Guidelines for
the Prevention of Intravascular Catheter-Related Infections.

Hand Hygiene
Perhaps the most overlooked method of preventing CLABSI is also
the simplest: hand washing with conventional soap and water or with
alcohol-based foams or gels before the procedure. Despite the
repeated emphasis in the literature and constant reminders from
hospital administration, physicians consistently show poor compliance with basic hand hygiene, with an estimated 32% rate of appropriate hand-washing technique and frequency among physicians.

Skin Preparation
Minimization of CVC contamination at the time of catheter placement is critical. A key component of this process is skin preparation.
Multiple studies have shown that the preferred agent for skin antisepsis is a greater than 0.5% chlorhexidine preparation with alcohol,
which has an approximate 50% reduction in CLABSI rates when
compared with the use of alcohol-based povidone-iodine solutions.
The site should be scrubbed and allowed to dry for at least 30 seconds
or according to the manufacturers recommendation before proceeding with venipuncture.

Full Barrier Precautions

The placement of a CVC should entail the same sterile precautions
that are followed in the operating room. The use of full barrier precautions (consisting of a mask, cap, sterile gloves, sterile gown, and
a sterile full body drape) lowers CLABSI rates dramatically. The cost
effectiveness of this strategy has been proven because the costs associated with purchasing these barrier supplies are more than offset by
the savings accrued from CLABSI prevention.

Choice of Insertion Site

The subclavian, the internal jugular, and the femoral veins are the
primary sites of CVC placement. In choice of a site, the benefits of
use of that site must be weighed against the risk of infectious complications and the risk for mechanical complications such as pneumothorax, subclavian artery puncture, subclavian vein laceration,
subclavian vein stenosis, hemothorax, thrombosis, air embolism, and
catheter misplacement. CLABSI rates are lowest for short-term, nontunneled CVCs, when the chosen insertion site is the subclavian vein.
Because the density of skin flora is a major risk factor for CRBSI, the
femoral vein should be avoided in adults as it has a high colonization
rate when compared with the internal jugular or subclavian vein. In
addition, catheters placed in the femoral vein are associated with a
higher risk of deep venous thrombosis.
The use of ultrasound scan guidance for the placement of
CVCs is now recommended; its use substantially decreases mechanical complications and the number of attempts required for
cannulation.

Catheter Selection
The choice of CVC has several potentially important implications
on CLABSI rates. In general, one should select the CVC with the
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Central LineAssociated Bloodstream Infections

minimal number of lumens essential for patient management

because infection rates increase with an increased number of catheter
lumens. A chlorhexidine/silver sulfadiazine or minocycline/rifampinimpregnated catheter is recommended whenever the catheter is
expected to be in place for more than 5 days; both have been shown
to decrease CLABSI rates.

Catheter Care
Sterile gauze or a sterile, transparent, semipermeable dressing can be
used to cover the CVC site to minimize colonization. If the dressing
becomes damp, loosened, or soiled, it should be changed. Routine
dressing changes for short-term CVCs should be performed every 2
days for gauze dressings or at least every 7 days for transparent dressings. The use of a chlorhexidine-impregnated sponge placed at the
skin insertion site can further decrease the risk for CRBSI.
Topical and systemic antibiotics should not be used for the sole
purpose of CLABSI prophylaxis because the former is associated with
fungal overgrowth and both are associated with promoting antimicrobial resistance.
Daily skin cleansing with 2% chlorhexidine rather than bathing
with soap and water significantly decreases CLABSI rates.

Daily Assessment of Central Venous

Catheter Necessity
Because the risk of CLABSI rises the longer that the catheter is in
place, CVCs that are no longer essential to patient care should be
removed as soon as possible. To accomplish this goal, daily assessment of the necessity of the CVC should be made by the surgical
team. Catheter tip cultures do not need to be routinely obtained on
removal.

Replacement of Central Venous Catheters

The routine replacement of CVCs that are functioning and have no
local or systemic signs of infection is not necessary. Although this
practice has been advocated to decrease CLABSI rates in the very
high-risk population of adult burn patients, the same results have
not been replicated in other critically ill patients; in fact, routine
replacement increases CLABSI rates.
Catheter insertion over a guidewire should only be performed in
replacement of a malfunctioning catheter, in exchange of a pulmonary artery catheter for a CVC, or in someone with difficult access
in which the risk of complications from a new puncture is greater
than the risk of infection. This technique is associated with a significantly lower rate of mechanical complications. Guidewire exchange
should not be performed in those patients with CRBSI because the
source of infection is often colonization of the insertion tract.

DIAGNOSIS AND TREATMENT

The most sensitive clinical finding of CRBSI is fever; this, however,
has very poor specificity. Purulence and inflammation around the
catheter insertion site is more specific but has poor sensitivity. A
definitive diagnosis of CRBSI requires that peripheral blood cultures
grow the same organism as that grown from a catheter tip or from
quantitative catheter and peripherally obtained cultures of differential time to positivity criteria. Given the lack of reliable clinical indicators, a high index of suspicion of CRBSI in the proper clinical
scenario is mandatory to initiate the workup, confirm the diagnosis,
and implement an appropriate treatment strategy.

Diagnostic Workup
The suspicion of CRBSI should prompt the collection of peripheral
blood cultures before antimicrobial therapy is started. If sufficient
suspicion exists that the CVC is the source of infection, it should be
removed and the distal 5cm of the catheter tip sent for culture. The
preferred method of microbiologic analysis of short-term CVCs is
the roll plate technique with semiquantitative culture. Growth of
greater than 15 colony-forming units (CFUs) from this segment of
catheter is indicative of catheter colonization. A CRBSI is present
when the same organism grows from both the peripheral blood and
the catheter tip. Clinical improvement within 24 hours of catheter
removal suggests that the catheter was the source of infection, but
without positive cultures, it is not proven.
When it is unclear whether the CVC is the source of infection,
and its removal is not desirable, quantitative blood cultures should
be obtained, one from a peripheral vein and one from the CVC.
CRBSI is diagnosed if the bacterial count from the catheter-drawn
blood is threefold greater than that from the peripheral blood. If the
laboratory has the ability to perform differential time to positivity
(DTP), a CRBSI is defined when the growth of microbes from the
CVC-drawn blood occurs at least 2 hours before the growth of
microbes from the peripherally drawn blood. The suspicion of
CLABSI should be heightened in a patient with no other obvious
source of infection and multiple positive blood cultures.
The organisms that most commonly cause CLABSI are: Staphylococcus aureus, coagulase-negative Staphylococcus species, Candida
species, and enteric gram-negative bacilli. The presence of
common skin flora on only one blood culture typically represents a
contaminated specimen and does not necessarily mandate immediate treatment.

Catheter Removal
A dilemma arises when a patient with a CVC has clinical signs of
infection but whether the CVC is the cause is not clear. The decision
to remove the catheter is made based on the clinical status of the
patient and the appearance of the catheter insertion site. If a patient
with a CVC has development of severe hemodynamic decompensation or signs of end organ failure in the setting of no other identified
source of infection, the most prudent strategy is to obtain blood
cultures, remove the CVC, culture the catheter tip, and start empiric
antibiotics. In patients with severe immunocompromise, the catheter
should likewise be removed if a CRBSI is suspected. If the insertion
site has purulent drainage or is severely inflamed, the catheter should
be removed. If the patient does not have the aforementioned clinical
signs and also has no identified source of infection, the catheter may
be left in place while awaiting the results of the blood cultures as
described previously. In a study by Rijnders and colleagues in 2004,
this watchful waiting strategy led to a 62% reduction in unnecessary catheter removal, without any significant changes in hospital
length of stay or mortality.

Empiric Antimicrobial Selection

In the setting of a patient with a septic or neutropenic condition with
suspected CRBSI, prompt initiation of appropriate empiric antimicrobials and removal of the CVC are essential to improving outcomes. In most healthcare settings, vancomycin is the preferred
empiric antibiotic because of the high incidence of methicillinresistant S. aureus (MRSA). In institutions that have a high percentage of MRSA isolates with a vancomycin minimum inhibitory
concentration (MIC) value of more than 2g/mL or when the use
of vancomycin is contraindicated, an alternative antibiotic, such as
daptomycin, should be selected. Empiric antibiotic coverage for
multidrug-resistant gram-negative bacilli (such as Pseudomonas

S UR G I C AL C RITIC AL C ARE

aeruginosa) should be added for patients with profound neutropenia,

severely ill patients with sepsis, patients with femoral CVCs, and
patients known to have colonization with these pathogens. To
increase the likelihood of appropriate empiric antimicrobial therapy,
the broad-spectrum antibiotic of choice in this setting should be
selected based on the institutions unit-specific antibiogram and the
susceptibility patterns of the organisms colonizing each individual
patient. In addition, empiric therapy for suspected CRBSI from candidemia should be added if the patient has any of the following risk
factors: prolonged use of broad-spectrum antibiotics, use of total
parenteral nutrition, history of solid-organ or bone marrow transplant, presence of a femoral CVC, or use of total parenteral nutrition.
To minimize the development of multidrug-resistant organisms, the
cornerstone of treatment is to initiate broad-spectrum empiric antimicrobial coverage and promptly deescalate this therapy as soon as
culture speciation and susceptibilities are known.

Therapy of Specific Pathogens

The diagnostic workup and management of a patient with a CRBSI
depends on which specific pathogen is identified. The recommended duration of antimicrobial therapy varies depending on the
pathogen, patient factors, and any associated complications from the
bacteremia.
Coagulase-Negative Staphylococcus Species
Coagulase-negative Staphylococcus species commonly colonize the
skin and represent the most common cause of CRBSI. Because the
ubiquitous skin colonization with Staphylococcus species leads to
high rates of contaminated blood cultures, whether a positive blood
culture indicates a true CRBSI or contamination is difficult to tell. A
high proportion of positive blood cultures drawn from multiple sites
is indicative of a true coagulase-negative staphylococci CRBSI. Treatment for patients with an uncomplicated coagulase-negative staphylococci CRBSI consists of catheter removal and antibiotics given for
5 to 7 days. Vancomycin is the preferred antibiotic because most
coagulase-negative staphylococci are methicillin resistant. Alternatively, in patients without intravascular or orthopedic hardware, the
catheter is removed and the patient is observed without antibiotics.
Additional blood cultures are obtained after catheter removal to
confirm that bacteremia has resolved.
The presence of persistent bacteremia despite CVC removal
should prompt further diagnostic investigation for other sources
(such as endocarditis and septic thrombophlebitis). In the setting in
which it is deemed clinically mandatory to keep the CVC in place
and the patient has a suspected coagulase-negative Staphylococcus
CLABSI, antibiotic catheter lock therapy is an option. This approach
involves instillation of an antibiotic-heparin solution into the catheter lumen without removal of the CVC. This method, in conjunction with a longer course (10 to 14 days) of systemic antibiotic
therapy, clears approximately 80% of coagulase-negative Staphylococcus infections without removal of the CVC. Failure of this approach
to appropriately resolve the bacteremia should lead to CVC removal.
Staphylococcus Aureus
S. aureus bacteremia has a 25% to 30% risk of hematogenous complications, including infective endocarditis and other deep tissue
infections. Failure to remove the CVC in the setting of S. aureus
bacteremia and suspected CLABSI leads to delayed response to
therapy, a higher relapse rate, and increased risk of complications.
The treatment of uncomplicated S. aureus CRBSI is to remove the
CVC and treat with systemic targeted antibiotic therapy for a course
of at least 14 days. The strongest predictor of development of a complication from S. aureus CLABSI is failure of the bacteremia or fevers
to resolve within 72 hours of instituting these measures. In this

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scenario, endocarditis should be suspected, and a transesophageal

echocardiogram should be performed. Other diagnoses that should
likewise be entertained are suppurative thrombophlebitis and osteomyelitis. In the situation of complicated S. aureus CLABSI, the duration of antibiotic therapy should be expanded to 4 to 6 weeks.
Gram-Negative Bacilli and Other Bacterial Species
Although the usual sources of gram-negative bacillary bacteremia are
noncatheter sources (i.e., urinary tract infection, intraabdominal
infection, pneumonia), the rate of gram-negative bacillus-related
CLABSI appears to be increasing, representing a prevalence rate of
up to 40% of all CLABSI in some series. This trend is thought to
result from increased rates of solid organ transplants, improved care
of chronically ill patients with immunocompromise, and changes in
antibiotic utilization patterns. Catheter retention correlates with
increased rates of treatment failure and risk of recurrent bacteremia,
and CVC removal leads to a 1% risk of relapse. Thus, the current
Infectious Disease Society of America (IDSA) recommendation in
the setting of a gram-negative bacillus-related CLABSI is to remove
the CVC and treat with systemic antibiotics for at least 7 days.
The treatment recommendations are similar for Enterococcus
CLABSI, with ampicillin as the antibiotic of choice. Vancomycin
may be used for Enterococcus species resistant to ampicillin, with an
agent like daptomycin reserved for vancomycin-resistant Enterococcus species. For less-virulent bacterial species that are difficult to
eradicate (i.e., Bacillus, Propionibacteria, Corynebacterium, Micrococcus species), the general recommendation (after contamination is
ruled out with multiple positive blood cultures) is to likewise
remove the CVC and treat with targeted systemic antibiotics for at
least 7 days.
Candida Species
For patients with CLABSI and candidemia, prompt CVC removal has
consistently been shown to decrease CLABSI-related mortality. The
choice of antifungal agent depends on the species of Candida. Fluconazole is the agent of choice for most Candida species. It is preferred over amphotericin B because of an enhanced safety profile and
equivalent treatment rates. In institutions with increased prevalence
of fluconazole-resistant Candidal species, such as Candida glabrata
and Candida krusei, the most efficacious and safest antifungal agent
is an echinocandin (i.e., caspofungin). The current IDSA-approved
treatment recommendation of uncomplicated catheter-related candidemia is to remove the CVC and initiate systemic antifungal
therapy for at least 14 days after the first negative blood culture. In
the setting of complicated candidemia, such as association with
endocarditis or septic thrombophlebitis, the duration of antifungal
treatment is extended to 4 to 6 weeks.

SUMMARY
Central venous catheters are commonly used instruments for
complex, critically ill surgical patients. To minimize the negative
sequelae associated with central lineassociated bloodstream infections, strict adherence of all healthcare workers to simple, preventative measures is essential as is daily assessment of catheter necessity.
A high index of suspicion regarding the identification of a central
lineassociated bloodstream infection is paramount because the
signs and symptoms are generally nonspecific. Diagnosis is confirmed with the same organism harvested from multiple blood cultures and the catheter tip culture. The cornerstone of treatment of
central lineassociated bloodstream infection is timely diagnosis,
catheter removal, prompt initiation of appropriate antimicrobial
therapy, and deescalation of therapy once the susceptibility pattern
of the offending organism is known.

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