Central Line Associated Blood Stream Infections (CLABSI)


Article Author:
Yazan Haddadin


Article Editor:
Hariharan Regunath


Editors In Chief:
Kranthi Sitammagari
Mayank Singhal


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes


Updated:
1/20/2019 8:12:50 AM

Introduction

A central line-associated bloodstream infection (CLABSI) is defined as a laboratory-confirmed bloodstream infection not related to an infection at another site that develops within 48 hours of a central line placement. Of all the healthcare-associated infections, CLABSIs are the most costly, accounting for approximately $46,000 per case. Most cases are preventable with proper aseptic techniques, surveillance, and management strategies.[1][2]

Etiology

Based on the National Healthcare Safety Network (NHSN) data from January 2006 to October 2007 the order of selected pathogens associated with causing CLABSI are as follows. Gram-positive organisms (coagulase-negative staphylococci, 34.1%; enterococci, 16%; and Staphylococcus aureus, 9.9%) are the most common, followed by gram negatives (Klebsiella, 5.8%; Enterobacter, 3.9%; Pseudomonas, 3.1%; E.coli, 2.7%; Acinetobacter, 2.2%), Candida species (11.8%), and others (10.5%).[3][4]

Epidemiology

CLABSIs lead to prolonged hospital stays and increase health care costs and mortality. An estimated 250,000 bloodstream infections occur annually, and most are related to the presence of intravascular devices. In the United States, the CLABSI rate in intensive care units (ICU) is estimated to be 0.8 per 1000 central line days. International Nosocomial Infection Control Consortium (INICC) surveillance data from January 2010 through December 2015 (703 intensive care units in 50 countries) reported a CLABSI rate of 4.1 per 1000 central line days. Many central lines are found outside the ICUs. In one study, 55% of ICU patients and 24% of non-ICU patients had central lines. However, as more patients are located outside of the ICU, 70% of hospitalized patients with central venous catheters were outside the ICU. CLABSI rates outside ICUs are assumed to be similar to those within ICUs.[5]

Pathophysiology

Central lines are of two types: (1) tunneled catheters are implanted surgically (by creating a subcutaneous track before entering vein) into the internal jugular, subclavian, or femoral vein for long-term (weeks to months) indications such as chemotherapy or hemodialysis and (2) non-tunneled catheters, the most commonly used central venous catheters, that are percutaneously inserted and account for most CLABSIs. Within 7 to 10 days of central venous catheter placement, bacteria on the skin surface migrate along the external surface of the catheter from the skin exit site towards the intravascular space. The absence of tunnel (a 10 subcutaneous portion of the catheter contains a cuff that causes a fibrotic reaction around the catheter, creating a barrier to bacterial migration) places non-tunneled catheters at higher risk for CLABSIs. CLABSIs that occur beyond 10 days are usually caused by contamination of the hub (intraluminal) typically from a health care provider's contaminated hands but rarely from a host and often due to a breach of standard aseptic precautions to access hub. Less common mechanisms include hematogenous seeding of bacteria from another source or from a contaminated infusate.

Host factors that increase the risk of CLABSI are chronic illnesses (hemodialysis, malignancy, gastrointestinal tract disorders, pulmonary hypertension), immune compromised states (bone marrow transplant, end-stage renal disease, diabetes mellitus), malnutrition, total parenteral nutrition (TPN), extremes of age, loss of skin integrity (burns), prolonged hospitalization before line insertion, catheter type, catheter location (femoral line has the highest, followed by internal jugular, then subclavian), conditions of insertion (emergent versus elective, use of full barrier precautions versus limited), catheter site care, and skill of the catheter inserter. Pseudomonas is commonly seen in association with neutropenia, severe illness, or known prior colonization. Candida is associated with the following risk factors: femoral catheterization, TPN, prolonged administration of broad-spectrum antibiotics, hematologic malignancy, or solid organ or hematopoietic stem cell transplantation. Certain bacteria such as staphylococci, Pseudomonas and Candida produce extracellular polysaccharide [slime (biofilm)] which favor increased virulence, adherence to catheter surface and resistance to antimicrobial therapy.[6]

History and Physical

Clinical manifestations vary depending on the severity of illness. Fever and chills are the most common manifestations but may be masked if the patient is immunocompromised or at extremes of an age where atypical presentations of sepsis occur (altered mental status, hypotension, lethargy, fatigue). Exit site examination to look for signs of inflammation of tunneled catheters with inspection and palpation of the subcutaneous track is important. Patients may report pain, swelling, or discharge from the exit site and redness surrounding the exit site or along the subcutaneous track when exit site or tunnel infections are present. For long-term catheters, difficulty in drawing blood or poor flow are considered risk factors and manifestations of CLABSI. 

Evaluation

In addition to the clinical exam, lab investigations are important for diagnosis and management. Blood culture is the most important step towards diagnosis in addition to complete blood count, serum electrolytes, and renal and liver function tests, which are necessary to assess for severity and/or co-morbidities. In suspected cases, paired blood cultures (one each from the central line and peripheral vein) must be drawn and labeled accordingly before sending to the lab. In the case of poor peripheral access or when unable to obtain peripheral sample, then two or more samples must be drawn from different lumens of a multi-lumen central line. The following definitions help in arriving at diagnosis:

Catheter-related bloodstream infection (CRBSI) - Infectious Diseases Society of America (IDSA) definition: Catheter-related bloodstream infection (CRBSI) is the preferred term used by IDSA. The definite diagnosis of CRBSI requires one of the following: Isolation of the same pathogen from a quantitative blood culture drawn through the central line and from a peripheral vein with the single bacterial colony count at least threefold higher in the sample from central line as compared to that obtained from peripheral vein (or) same organism recovered from percutaneous blood culture and from quantitative (>15 colony-forming units) culture of the catheter tip (or) a shorter time to positive culture (>2 hours earlier) in the central line sample than the peripheral sample (differential time to positivity [ DTP ])[7]

CLABSI - Centers for Disease Control and Prevention (CDC) definition: CLABSI is a surveillance definition used by the CDC and defined as recovery of a pathogen from a blood culture (a single blood culture for organism not commonly present on the skin, and two or more blood cultures for organism commonly present on the skin) in a patient who had central line at the time of infection or within 48 hours before development of infection. The infection cannot be related to any other infection the patient might have and must not have been present or incubating when the patient was admitted to the facility.[4]

In the case of tunneled catheters, the accepted definitions for exit site and tunnel infections are as follows:

Exit site infection: Signs of inflammation confined to an area (typically < 2 cm) surrounding the catheter exit site and the presence of exudate that proves to be culture positive.

Tunnel infection: Inflammation extending beyond 2 cm from exit site (along with the track or cephalad towards the vein entry site or extending beyond the cuff), typically associated with pain and tenderness along the subcutaneous track and culture-positive exudate at the exit site that may not be seen unless expressed by palpation. 

Treatment / Management

When CLABSI is suspected, empiric therapy should be based on the most likely organism, host factors, and the overall clinical picture. While awaiting cultures, empiric treatment should be instituted promptly. In general, a reasonable coverage for common gram-positive and gram-negative organisms will be necessary. The local prevalence and antimicrobial susceptibility patterns in institutional antibiograms should be taken into account. The following are some considerations.

  1. Parenteral vancomycin, if methicillin resistance in staphylococci (MRSA) is prevalent, otherwise a parenteral anti-staphylococcal penicillin or cephalosporin such as nafcillin or cefazolin would suffice. If MRSA isolates are exhibiting a minimum inhibitory concentration of > 2 mg/mL for vancomycin or in the case of vancomycin-resistant enterococci (VRE), daptomycin is the drug of choice. 
  2. Antibiotics active against gram-negative bacilli should be preferably based upon local susceptibility patterns; usual choices include a beta-lactam/lactamase inhibitor combination, cefepime, and carbapenem with or without an aminoglycoside. Agents against Pseudomonas aeruginosa are required in the setting of neutropenia, severe illness, or known prior colonization;
  3. Echinocandins (micafungin, caspofungin, anidulafungin) are preferred agents for suspected candidemia if azole resistance is suspected (prior azole use or prevalent nonalbicans candida such as C.glabrata or C.krusei). Otherwise, intravenous fluconazole would suffice. Antifungal therapy must be considered in the setting of femoral catheterization, TPN, prolonged administration of broad-spectrum antibiotics, hematologic malignancy, or solid organ or bone marrow transplant recipients.

Once antimicrobial susceptibility results are available, de-escalation to specific and appropriate therapy is recommended. If blood cultures have no growth, the need for further empiric antibiotic therapy should be reassessed. If unexplained fever or sepsis persists in a patient with a short-term central venous or arterial catheter and paired peripheral venipuncture and catheter blood cultures have failed to identify CLABSI, the catheter should be removed and its tip sent for culture. 

All non-tunneled catheters causing CLABSI should be removed promptly, sometimes even before it is proven with the above criteria when clinical suspicion is high. Only for long-term catheters, salvage (systemic therapy coupled with antimicrobial lock [heparin + high concentration of antimicrobial agent that is selected based on susceptibility results]) can be attempted in few limited instances such as:

  1. Uncomplicated CLABSI caused by organisms other than Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus spp, Micrococcus species, Propionibacteria, fungi, or mycobacteria.
  2. Restricted to patients with limited vascular access or those who need central access for survival.

In the case of hemodialysis catheters, pure exit site infections can be treated with short-course topical or systemic antimicrobials. All tunnel infections will require catheter removal due to high risk of CLABSI. Additional indications for removal in CLABSI from hemodialysis access include:

  1. Persistent symptoms > 36 hours or severe sepsis, hemodynamic instability(shock) and metastatic infection.
  2. Blood cultures that remain positive > 72 hours of appropriate antimicrobial therapy.
  3. Difficult to clear organisms (S. aureus, Pseudomonas or fungi).
  4. Recurrence of uncomplicated CLABSI (any non-virulent organism) when salvaged for difficult access. 

Duration of therapy: For uncomplicated bloodstream infection (i.e., no associated suppurative thrombosis, endocarditis, or metastatic infection) that arises in the absence of factors that increase the risk of hematogenous spread of infection (e.g., no intravascular hardware, immunosuppression) and resolves within 72 hours of catheter removal, intravenous antimicrobial therapy is recommended for the following durations based on the organism isolated:

  1. S. aureus - 14 days in the absence of endocarditis
  2. Coagulase-negative staphylococci - 7 days
  3. Enterococci and gram-negative bacilli - 10 to 14 days
  4. Candida - 14 days in the absence of retinitis

Pearls and Other Issues

Prevention Guidelines During Insertion

Recent data reveal no difference in the infection rate based on the insertion catheter site. The following are some key components of a prevention program, abstracted from an extensive list provided by the CDC and IDSA.[8][9][6]

  1. Hand hygiene by washing hands with soap and water or with alcohol-based gels or foams. Gloves do not obviate the need for hand hygiene. 
  2. Strict aseptic technique by using maximal sterile barrier precautions, including a full-body drape when inserting central venous catheters.
  3. Use of 2% chlorhexidine skin preparations for disinfecting/ cleaning skin before insertion.
  4. Ultrasound guidance by an experienced provider for placement to circumvent mechanical complications and reduce the number of attempts. 
  5. Avoid the femoral vein as a choice for central line placement, and prefer the subclavian vein when possible for non-tunneled catheters.
  6. Promptly remove any central line that is no longer required.
  7. Replace central lines placed during an emergency (asepsis not assured) as soon as possible or at least within 48 hours. 
  8. Use a checklist.

Prevention Guidelines During Maintenance

  1. Disinfect the catheter hubs, injection ports, and connections before accessing the line.
  2. Replace administration sets other than sets used for lipids or blood products every 96 hours.
  3. Assess the need for the central line daily.

Enhancing Healthcare Team Outcomes

Central line-associated bloodstream infection (CLABSI) is a very common problem in the intensive care unit. These infections are associated with over 28,000 deaths each year and cost over $2 billion. Only through best practices, protocols, checklists, and establishing a culture of patient safety in healthcare institutions can one reduce CLABSI to zero.[10] One of the major reasons why central lines are removed is because of an infection or suspicion of an infection. This type of clinical practice not only leads to longer admission but repeat procedures and an increased rate of complications from central lines.

The major problem with central lines is that there are many types of lines, some which are directly inserted, others which are tunneled, and others which are inserted into the forearm and passed into the large veins of the heart. In many hospitals, central lines are inserted by many specialists including anesthesiologists, surgeons, emergency room physicians, radiologists, and critical care physicians.[11] In addition, the use of a central line is not limited to any one nurse but all nurses. This heterogeneity has resulted in varied outcomes, but in almost every study, infections continue to be a common problem.

Evidence-Based Medicine

Over the years, many guidelines have been established; some hospitals have a policy that for long-term access, the line can only be inserted by a dedicated team that consists of the surgeon, nurses, and a pharmacist who will monitor the patient. In addition, when administering TPN, one port is dedicated to nutrition only. Plus, in some units, only nurses with training in central lines are allowed to infuse medications and other solutions. Evidence-based guidelines show that by adhering to protocols, one can reduce the rate of CLABSI. However, to ensure compliance, audits of doctors who insert the central lines and nurses who monitor the lines for infections is vital.[6] (Level III)


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Central Line Associated Blood Stream Infections (CLABSI) - References

References

Hallam C,Jackson T,Rajgopal A,Russell B, Establishing catheter-related bloodstream infection surveillance to drive improvement. Journal of infection prevention. 2018 Jul     [PubMed]
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Atilla A,Doğanay Z,Kefeli Çelik H,Demirağ MD,S Kiliç S, Central line-associated blood stream infections: characteristics and risk factors for mortality over a 5.5-year period. Turkish journal of medical sciences. 2017 Apr 18     [PubMed]
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Ziegler MJ,Pellegrini DC,Safdar N, Attributable mortality of central line associated bloodstream infection: systematic review and meta-analysis. Infection. 2015 Feb     [PubMed]
Bell T,O'Grady NP, Prevention of Central Line-Associated Bloodstream Infections. Infectious disease clinics of North America. 2017 Sep     [PubMed]
Lissauer ME,Leekha S,Preas MA,Thom KA,Johnson SB, Risk factors for central line-associated bloodstream infections in the era of best practice. The journal of trauma and acute care surgery. 2012 May     [PubMed]
Lee KH,Cho NH,Jeong SJ,Kim MN,Han SH,Song YG, Effect of Central Line Bundle Compliance on Central Line-Associated Bloodstream Infections. Yonsei medical journal. 2018 May     [PubMed]
Norris LB,Kablaoui F,Brilhart MK,Bookstaver PB, Systematic review of antimicrobial lock therapy for prevention of central-line-associated bloodstream infections in adult and pediatric cancer patients. International journal of antimicrobial agents. 2017 Sep     [PubMed]
Sagana R,Hyzy RC, Achieving zero central line-associated bloodstream infection rates in your intensive care unit. Critical care clinics. 2013 Jan     [PubMed]
Takashima M,Schults J,Mihala G,Corley A,Ullman A, Complication and Failures of Central Vascular Access Device in Adult Critical Care Settings. Critical care medicine. 2018 Aug 7     [PubMed]

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