Part 1: Definitions, Epidemiology & Pathogenesis

1. Definitions

1.1 Central Line (Central Venous Catheter)

A central line is defined as an intravascular catheter that terminates at or close to the heart or in one of the great vessels and is used for infusion, blood withdrawal, or hemodynamic monitoring. For the purpose of surveillance, the great vessels include the superior vena cava, inferior vena cava, brachiocephalic veins, internal jugular veins, subclavian veins, external iliac veins, common iliac veins, femoral veins, and — in neonates — the umbilical artery and umbilical vein.¹²

Devices that qualify as central lines include:

Device Type	Examples
Nontunneled central venous catheters	Acute-care multilumen catheters inserted at the subclavian, internal jugular, or femoral sites
Tunneled central venous catheters	Hickman, Broviac, Groshong catheters
Implanted ports	Subcutaneous reservoirs with attached catheters (when needle-accessed)
Peripherally inserted central catheters (PICCs)	Catheters inserted via peripheral veins whose tip resides in the SVC/IVC
Hemodialysis catheters	Tunneled and nontunneled catheters used for renal replacement therapy
Pulmonary artery catheters	Swan-Ganz catheters used for hemodynamic monitoring
Umbilical catheters	Umbilical artery and umbilical venous catheters in neonates
Introducer sheaths	When used as a vascular access device (unless removed within the same calendar day as insertion)

Notably excluded from the central line definition: arterial catheters (including intra-aortic balloon pump devices), peripheral intravenous catheters, and midline catheters.¹

1.2 CLABSI — Central Line-Associated Bloodstream Infection

CLABSI is a surveillance definition used by the national healthcare safety reporting system and is not intended to represent a clinical diagnosis of catheter-related infection. CLABSI is defined as a laboratory-confirmed bloodstream infection (LCBI) in a patient who had a central line in place for more than two calendar days on the date the bloodstream infection was identified — specifically, the central line must have been in place on the date of the event or the day before. If a central line was in place for more than two calendar days and then removed, the CLABSI surveillance window extends through the day after the central line was removed.¹²

A laboratory-confirmed bloodstream infection requires at least one of the following criteria to be met:

LCBI Criterion 1: A recognized pathogen (i.e., an organism not on the common commensal list) is identified from one or more blood cultures, AND the organism identified in blood is not related to an infection at another site.

LCBI Criterion 2: The patient has at least one of the following signs or symptoms — fever (>38.0 C), chills, or hypotension — AND the same common commensal organism (e.g., coagulase-negative staphylococci, viridans group streptococci, Corynebacterium spp., Bacillus spp., Propionibacterium spp., Aerococcus spp., Micrococcus spp.) is identified from two or more blood cultures drawn on separate occasions within two days of each other, AND the organism is not related to an infection at another site.¹²

Key points for CLABSI surveillance:

CLABSI is an association, not causation — the presence of a central line is temporally associated with the bloodstream infection, but the central line is not necessarily the proven source
There is no minimum dwell time for the catheter; however, the central line must be in place for >2 calendar days
The event must not be secondary to another identified source of infection (e.g., urinary tract infection, pneumonia, surgical site infection, or intra-abdominal abscess)
The date of the event is the date the first positive blood culture was collected¹

CRBSI is a clinical definition requiring specific microbiologic evidence that the catheter is the source of the bloodstream infection. Unlike CLABSI, CRBSI demands rigorous laboratory confirmation and is used for clinical decision-making and research — not for routine surveillance. The clinical and laboratory criteria for CRBSI include:³⁴

Criterion	Method	Threshold
Catheter tip culture (semi-quantitative)	Maki roll-plate technique	≥15 colony-forming units (CFU) from a 5-cm catheter tip segment
Catheter tip culture (quantitative)	Sonication or vortexing	≥10^3 CFU from the catheter segment
Paired quantitative blood cultures	Simultaneous cultures from catheter and peripheral vein	Colony count ratio from catheter ≥3:1 compared with peripheral
Differential time to positivity (DTP)	Simultaneous blood cultures drawn from catheter lumen and peripheral vein, incubated in continuous monitoring system	Catheter-drawn culture turns positive ≥2 hours before the peripheral culture

CRBSI is confirmed when the same organism is isolated from both the catheter (by one of the above methods) and from a peripheral blood culture, with no other apparent source of infection.³⁴

1.4 Distinguishing CLABSI from CRBSI

Feature	CLABSI	CRBSI
Purpose	Surveillance and benchmarking	Clinical diagnosis and treatment decisions
Specificity	Lower (association-based)	Higher (causation-based)
Requires catheter tip culture	No	Yes (or paired quantitative cultures / DTP)
Requires peripheral blood culture	Not necessarily (can meet criteria with catheter-drawn cultures alone for some criteria)	Yes (paired comparison required)
Used for national reporting	Yes	No
Overestimates true catheter-source infection	Yes (by approximately 20–30%)	No
Practical use	Quality improvement, public reporting, benchmarking	Individual patient management

1.5 Mucosal Barrier Injury Laboratory-Confirmed Bloodstream Infection (MBI-LCBI)

Mucosal barrier injury CLABSI is a specific subtype of CLABSI that occurs in patients with evidence of mucosal barrier breakdown — most commonly due to recent allogeneic hematopoietic stem cell transplant, absolute neutrophil count ≤500 cells/mm^3, or grade 3–4 gastrointestinal graft-versus-host disease — and in whom the bloodstream infection is caused by an enteric organism (e.g., Enterococcus spp., viridans group streptococci, Candida spp., Bacteroides spp., Clostridium spp., or Enterobacterales). MBI-LCBI events are separately categorized because they likely result from translocation across damaged gastrointestinal or oral mucosa rather than from the catheter itself. This distinction was introduced to reduce penalization of oncology and transplant units for infections that may not be catheter-preventable.¹²

2. Epidemiology

2.1 Incidence and Rates by ICU Type

CLABSI rates are reported as the number of infections per 1,000 central line-days, which allows valid comparisons across units with different patient volumes and central line utilization rates. Rates vary substantially by ICU type, patient population, and geographic region.

CLABSI Rates by ICU Type (United States, National Healthcare Safety Network Pooled Mean Data):¹⁵⁶

ICU Type	Historical Rate (2001) per 1,000 CL-Days	Recent Rate (2020–2022) per 1,000 CL-Days	Approximate Reduction
Medical ICU	5.0	0.8–1.1	~78–84%
Surgical ICU	4.6	0.7–1.0	~78–85%
Medical/Surgical ICU	4.0	0.8–1.0	~75–80%
Coronary care unit	3.5	0.5–0.8	~77–86%
Pediatric ICU	6.6	0.7–1.0	~85–89%
Neonatal ICU (≤750 g birthweight)	11.3	1.5–2.5	~78–87%
Neonatal ICU (751–1000 g)	6.4	1.0–1.5	~77–84%
Neonatal ICU (1001–1500 g)	4.0	0.5–1.0	~75–88%
Neonatal ICU (>2500 g)	2.9	0.3–0.6	~79–90%
Burn ICU	7.0	1.5–2.5	~64–79%
Trauma ICU	5.5	0.8–1.2	~78–85%
Long-term acute care	3.6	1.0–1.5	~58–72%

Note: Rates fluctuated during 2020–2021 due to the COVID-19 pandemic, with many facilities reporting temporary CLABSI increases of 25–50% attributed to staffing shortages, PPE demands, prone positioning complexity, and high central line utilization.⁶

2.2 Attributable Mortality

Each episode of CLABSI carries attributable mortality estimated at 12–25%, depending on the study methodology, patient population, and causative organism. Meta-analytic data suggest:³⁷

Overall attributable mortality: 12–25%
Crude ICU mortality in patients with CLABSI: 25–35% (compared with 15–20% in matched patients without CLABSI)
Attributable mortality by organism:
- Candida spp.: 25–40%
- Staphylococcus aureus: 20–30%
- Pseudomonas aeruginosa: 20–35%
- Coagulase-negative staphylococci: 5–10%
- Enterococcus spp. (including VRE): 15–25%

2.3 Cost and Length of Stay

The economic burden of CLABSI is substantial:³⁷⁸

Parameter	Estimate
Attributable excess length of stay	10–20 additional hospital days per episode
Attributable cost per episode	$30,000–$45,000 (2020 USD)
Annual U.S. cost burden (estimated)	$1.8–$2.7 billion
CMS nonpayment policy	CLABSI classified as a “reasonably preventable” hospital-acquired condition; additional hospital costs for CLABSI episodes are not reimbursed under the Deficit Reduction Act (2008 onward)

2.4 Secular Trends

The most dramatic period of CLABSI reduction occurred between 2006 and 2013, coinciding with widespread adoption of evidence-based insertion bundles and statewide collaborative improvement programs. The landmark statewide collaborative initiative in Michigan demonstrated a 66% reduction in median ICU CLABSI rates (from 2.7 to 0 per 1,000 catheter-days at 18 months) with sustained results through 36 months of follow-up.⁴ Nationally, CLABSI rates declined by approximately 50% between 2008 and 2013, and by an additional 14% between 2015 and 2019.⁵⁶

The COVID-19 pandemic reversed some of these gains: national data demonstrated a significant increase in CLABSI in 2020 (approximately 24% increase in the standardized infection ratio) and 2021 (approximately 21% increase), attributed to pandemic-related disruptions in infection prevention practices, staffing challenges, and the critically ill patient population associated with severe COVID-19. Recovery toward pre-pandemic baselines has been ongoing.⁶

Understanding the pathogenesis of catheter colonization and infection is essential for rational prevention strategy design. Central venous catheters can become colonized — and subsequently cause bloodstream infection — through four principal mechanisms.³⁹

3.1 Extraluminal Colonization (Skin Migration)

This is the most common mechanism for short-term catheters (<10–14 days). Skin organisms at the insertion site migrate along the external surface of the catheter through the subcutaneous tract to colonize the intravascular catheter tip. The extraluminal pathway predominates during the first 1–2 weeks after insertion, before a fibrin sheath fully develops around the catheter.

Key organisms: Staphylococcus epidermidis, Staphylococcus aureus, and other skin flora

Prevention targets: Skin antisepsis at insertion, maximal sterile barriers, chlorhexidine-impregnated dressings, antimicrobial-impregnated catheters (outer surface coating)

3.2 Intraluminal Colonization (Hub Contamination)

This is the most common mechanism for long-term catheters (>10–14 days). Organisms are introduced into the catheter lumen through contamination of the catheter hub, needleless connector, or injection/infusion ports during manipulation (medication administration, blood draws, tubing changes). Once inside the lumen, organisms form biofilm on the internal catheter surface and can cause sustained bloodstream infection.

Key organisms: Coagulase-negative staphylococci, gram-negative bacilli, Candida spp.

Prevention targets: Hub antisepsis (“scrub the hub”), aseptic technique during access, needleless connector disinfection caps, minimizing line manipulations, antimicrobial lock therapy

3.3 Infusate Contamination

Rarely, intravenous fluids or admixtures become contaminated during preparation or administration, leading to catheter-related bloodstream infection. This mechanism accounts for a small proportion of catheter-related infections but can cause outbreaks.

Key organisms: Gram-negative water organisms (Serratia marcescens, Burkholderia cepacia complex, Ralstonia spp., Enterobacter spp.)

Prevention targets: Aseptic admixture preparation, proper storage of compounded medications, timely administration set changes for lipid-containing solutions, surveillance for infection clusters

3.4 Hematogenous Seeding

Organisms from a remote site of infection (e.g., urinary tract infection, intra-abdominal abscess, surgical site infection) seed the catheter via the bloodstream and adhere to the fibrin sheath or biofilm on the catheter surface. This mechanism is the least common route of catheter colonization.

Key organisms: Variable, depending on primary infection source

Prevention targets: Source control of remote infections, prompt catheter removal when catheter colonization is suspected in the setting of documented remote-source bacteremia

3.5 Biofilm Formation

Regardless of the initial colonization route, biofilm formation is a central feature of catheter-related infection pathogenesis. Within hours of catheter insertion, host proteins (fibronectin, fibrinogen, collagen) deposit on the catheter surface, creating a conditioning film that facilitates microbial adhesion. Once adhered, organisms produce an extracellular polymeric matrix (biofilm) that:³⁹

Protects organisms from host immune defenses (phagocytosis, complement)
Confers resistance to systemic antibiotics (biofilm MICs are typically 100–1,000 times higher than planktonic MICs)
Allows periodic shedding of planktonic organisms into the bloodstream, causing intermittent or sustained bacteremia/fungemia
Makes catheter-related infections refractory to antibiotic therapy alone, often requiring catheter removal for definitive cure

4. Microbiology

The microbiology of CLABSI has evolved over recent decades with changes in empiric antibiotic use, increased use of antimicrobial-impregnated catheters, and the expanding population of immunocompromised patients.¹³¹⁰

4.1 Distribution of Causative Organisms

Organism	Approximate Proportion of CLABSI
Coagulase-negative staphylococci	25–35%
Staphylococcus aureus (MSSA + MRSA)	15–20%
Enterococcus spp. (including VRE)	10–15%
Candida spp.	8–12%
Klebsiella spp.	5–8%
Enterobacter spp.	4–6%
Pseudomonas aeruginosa	3–5%
Escherichia coli	3–5%
Acinetobacter spp.	2–4%
Serratia marcescens	1–3%
Other gram-negative bacilli	3–5%

4.2 Trends and Resistance

MRSA accounts for approximately 50–60% of S. aureus CLABSI in many ICUs, although MRSA bloodstream infection rates have declined nationally with decolonization strategies¹⁰
Vancomycin-resistant enterococci (VRE) represent 25–35% of enterococcal CLABSI, particularly in oncology and transplant populations
Candida CLABSI has increased in proportional share, with a shift toward non-albicans species (C. glabrata, C. parapsilosis, C. auris) that may exhibit antifungal resistance
Multidrug-resistant gram-negative organisms (ESBL-producing Enterobacterales, carbapenem-resistant Enterobacterales [CRE], carbapenem-resistant Acinetobacter baumannii, multidrug-resistant Pseudomonas) are of growing concern, particularly in ICUs with high antibiotic selection pressure¹⁰

5. Risk Factors for CLABSI

Risk Factor	Mechanism / Evidence
Catheter site	Femoral site associated with highest infection risk in adults; subclavian site associated with lowest infection risk (though higher pneumothorax risk)¹³
Catheter type	Nontunneled catheters have higher infection rates than tunneled catheters and implanted ports
Number of lumens	Triple-lumen catheters associated with higher infection risk than single-lumen; use the minimum number of lumens required¹
Catheter dwell time	Risk increases with increasing duration; daily assessment of catheter necessity is critical
Catheter material	Polyvinyl chloride and polyethylene facilitate bacterial adhesion more than silicone or polyurethane
Number of manipulations	Frequent access (medication administration, blood draws, tubing changes) increases hub contamination risk

Risk Factor	Details
Immunosuppression	Neutropenia, corticosteroid therapy, chemotherapy, solid organ transplant, hematopoietic stem cell transplant
Severity of illness	Higher APACHE II/III scores, multiorgan failure
Total parenteral nutrition	Lipid-containing solutions enhance microbial growth; TPN is an independent risk factor for CLABSI
Prolonged ICU stay	Longer duration of ICU care increases cumulative catheter exposure
Burns	Loss of skin barrier integrity, immunosuppression, frequent catheter access
Extremes of age	Neonates (especially very low birth weight) and elderly patients
Prior colonization with resistant organisms	MRSA colonization, VRE colonization, CRE colonization
Existing remote-site infection	Potential for hematogenous seeding of catheter

5.3 Healthcare System and Process Risk Factors

Risk Factor	Details
Nurse-to-patient ratio	Higher patient loads associated with increased CLABSI risk due to reduced time for catheter care and surveillance
Failure to adhere to insertion bundle	Omission of any single bundle element significantly increases infection risk
Inadequate hand hygiene compliance	Baseline hand hygiene rates <50% in many ICUs without active improvement programs
Lack of standardized maintenance practices	Variable hub disinfection, inconsistent dressing changes, absence of daily line necessity review
Float/temporary nursing staff	Less familiarity with unit-specific catheter care protocols
Absence of quality improvement infrastructure	Units without active surveillance, feedback, and bundle compliance monitoring have higher CLABSI rates⁴¹¹

6. Central Line Utilization

Central line utilization ratio — the proportion of patient-days on which a central line is present — is an important metric that complements CLABSI rate monitoring. Reducing unnecessary central line use (by prompt removal of unneeded catheters and by substituting peripheral or midline catheters when appropriate) is a fundamental prevention strategy. The national average central line utilization ratio varies by ICU type:¹⁵

ICU Type	Approximate Central Line Utilization Ratio
Medical ICU	0.45–0.55
Surgical ICU	0.45–0.55
Medical/Surgical ICU	0.35–0.50
Coronary care unit	0.30–0.40
Pediatric ICU	0.35–0.45
Neonatal ICU	0.15–0.30 (varies widely by birthweight category)
Burn ICU	0.55–0.70
Trauma ICU	0.45–0.60

Centers for Disease Control and Prevention, National Healthcare Safety Network. “Bloodstream Infection Event (Central Line-Associated Bloodstream Infection and Non-Central Line Associated Bloodstream Infection).” NHSN Patient Safety Component Manual. 2024. URL: https://www.cdc.gov/nhsn/pdfs/pscmanual/4psc_clabscurrent.pdf ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎
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