• Summary
  Click here to print a Quick Reference Guide
• Background
• Clinical Diagnosis
• Investigation
• Treatment
• Non-Antimicrobial Treatment
• Empirical Antimicrobial Treatment
• Duration of Treatment
• Treatment Failure

Definition

Catheter related bloodstream infection (CRBSI) are defined as:

• Infant > 72 hours old
• The presence of a central venous catheter
• Isolation of recognised pathogens from blood culture or catheter tip that are not related to infection at another site
  
  OR
  
  
• Bacteraemia occurring within 48 hours of a central line removal with clinical signs of sepsis and no other apparent source of infection with or without positive culture through the catheter

Investigations

• Full blood count (FBC) with white cell differential
• C reactive protein (CRP)
• Peripheral blood culture (labelled peripheral)
• Central line blood culture (all lumens and clearly labelled with the site)

Treatment
Non-Antimicrobial

• Resuscitate as indicated
• Discuss with consultant if considering line removal

Antimicrobial

• Commence empirical Teicoplanin and Gentamicin. If baby is already on Teicoplanin and Gentamicin for late onset sepsis and is not improving/ deteriorating, consider escalating to Meropenem   and Vancomycin via implicated CVC. An approval code will be needed from Microbiology for use of meropenem - if out of hours, do not delay dose to obtain code. Commence meropenem and discuss with Microbiology retrospectively at the first opportunity in working hours.
• Amend antimicrobial therapy with microbiology results.

See full guideline for organism-specific recommendations and duration of therapy.

Duration of treatment
See full guideline

Switch to oral agent(s)
Not recommended

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Central venous catheters (CVC) are required for a variety of uses during management of babies on the neonatal units such as parenteral nutrition and administration of medication. CVC used within the neonatal unit are percutaneous intravascular catheters (e.g. Nutriline, Premicath) and tunnelled surgical lines (e.g. Broviac).

CRBSI’s are a leading cause of healthcare-associated infections. CRBSI’s are usually associated with several risk factors, including prolonged catheter placement, low birth weight, and prematurity. CRBSI’s contribute to increased morbidity and mortality, prolonged hospital admission, and the need for additional therapies. CRBSI associated with intravascular catheters can be divided clinically into local (exit site) and bloodstream infections, but these entities may coexist.

CRBSI’s can occur by four distinct pathways, including external and internal catheter surface colonisation pathways, intrinsic contamination, and hematogenous seeding. External surface pathway infection may start with the colonisation of the skin insertion site by micro-organisms of the skin flora, whereas, internal surface pathway infection occurs by colonisation of the hub and intraluminal surface of the catheter. Contamination of the fluids or drugs intravenously administered (known as "intrinsic contamination") constitutes another process responsible for infection and hematogenous seeding of the catheter during a bloodstream infection of any origin represents a third pathway (Lee, 2011). The longer a catheter remains in place, the more likely it is to become colonized (Sandoe et al., 2003).

CRBSI’s most frequently result from pathogens such as:

• Gram-positive cocci - including Staphylococcus aureus and Coagulase-Negative Staphylococci

And sometimes:

• Gram-negative organisms
• Yeasts/Candida

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Infection is suspected/diagnosed on clinical assessment.

CRBSI’s can present with or without signs of exit site or tunnel infection, therefore, exudate and erythema may or may not be associated with an CRBSI.

An infant developing CRBSI may present with:

• Tachypnoea or significant increase in oxygen or respiratory support
• Clinically significant increase in apnoea’s and bradycardia’s
• Hypotension
• Hypo or hyperglycaemia
• Lethargy, irritability or poor handling
• Poor perfusion (capillary refill time significantly prolonged)
• Temperature instability
• Ileus or feed intolerance
• Decreased urine output
• Metabolic acidosis

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• A peripheral AND CVC blood culture should be sent. At least 1ml of blood should be obtained from ALL lumens of the central catheter maintaining aseptic technique. Positivity of the blood culture increases with the blood volume sent. All specimens should be clearly labelled either peripheral or central.
• Full blood count (FBC) with white cell differential
• C reactive protein (CRP)
• Exit site infection affecting any type of vascular access device is a clinical diagnosis. The pathogen responsible can be determined by sending ideally a pus sample or (second best) an exit site swab to the microbiology laboratory for culture
• Intravascular catheter tips should only be sent for culture to confirm a clinical suspicion of a catheter related infection, not as a matter of routine

Differential time to positivity (DTP) is a blood culture-based method for diagnosing luminal colonisation or CRBSI. The DTP is the difference in time taken to show a positive result for the same organism in both the central and peripheral venous samples (i.e. a paired set). A DTP >2 hours in favour of central blood cultures has a sensitivity of 72-94%, and specificity of 91-95% for CRBSI (Blot et al, 1999; Catton et al, 2005). DTP >2 hours will fail to detect some CRBSI, but a positive result has a high probability of being CRBSI.

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The definitive treatment for infection arising from a CVC is removal of the CVC and thus the source of infection. However, CVC are frequently precious assets and should be removed if the risk of leaving the catheter in situ outweighs the risk of removal and when other venous access is available. Removal of a line should always be discussed with the consultant.

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• Resuscitation/supportive treatment as indicated
• Investigate as above
• If the line remains in situ repeat blood cultures 48 hours after stopping antibiotics
• Should the line have to be removed there should ideally be a central line free interval of 48 hours.

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• Commence empirical Teicoplanin and Gentamicin. If baby is already on Teicoplanin and Gentamicin for late onset sepsis and is not improving/deteriorating, consider escalating to Meropenem   and Vancomycin via implicated CVC. An approval code will be needed from Microbiology for use of meropenem - if out of hours, do not delay dose to obtain code. Commence meropenem and discuss with Microbiology retrospectively at the first opportunity in working hours.
• Amend antimicrobial therapy with microbiology results.
• Remove CVC after 48 hours if there is deterioration despite apparently appropriate antimicrobial therapy. Always discuss with consultant before removing line
• Give the antibiotics through the line
• Rationalise the antibiotics once sensitivities are known. Stop Gentamicin if only Gram-positive bacteria are cultured which are the most likely pathogens in neonatal CRBSI .

Please refer to E-Meds protocol for specific dosing and therapeutic dose monitoring

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Treatment Duration¹

Table 1. Length of treatment of central venous catheter related sepsis.

1. In all cases the recommended duration of treatment assumes complete resolution of clinical and laboratory signs of infection. In other situations, specific microbiological advice should be sought.
2. The specified duration starts from the date of the last positive blood culture or line removal, whichever is later

When to Remove the Line

Central venous catheters are frequently precious assets and should be removed only:

• after discussion with a with a consultant and
• when other venous access is available.

Where recommended, the line should be removed unless the risk of removal is considered greater than the risk of not.

Line removal is strongly recommended in the following situations:

• Bacteraemia, sepsis or local complications that become life threatening
• Infection with micro-organisms known to be difficult to eradicate (e.g. Staphylococcus aureus, Bacillus spp., Mycobacteria, and Fungi)
• Relapse of infection after antibiotics have been discontinued.
• After 48 hours of antibiotic treatment if there is deterioration in the clinical condition.

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Please contact Microbiology if the patient is not responding to the recommended antimicrobial regimens.

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