Guidelines for the management of suspected central venous catheter infection for infants (excluding neonates on the Neonatal Intensive Care Unit (NICU)) and children

• Summary
• Aims
• Background
• Clinical Diagnosis
• Severity Assessment
• Investigation
• Non-antimicrobial treatment
• Empirical antimicrobial treatment
• Directed antimicrobial treatment (when microbiology results are known)
• Oral switch
• Duration of therapy
• Treatment failure

Summary

Intravascular catheter-related infections affecting long-term vascular access devices include exit site, “tunnel” infections and bloodstream infections; these are collectively known as Catheter Related Blood Stream Infections (CRBSI).

History & Examination

• Clinical diagnoses of line infections are unreliable
• CRBSI usually presents with a fever or other signs of a systemic inflammatory response.
  • Rigors, chills or fever after line use is highly suggestive
  • Other symptoms of CRBSI are those of bloodstream infection from any source and include general malaise, anorexia, vomiting
• Sepsis or septic shock may be present. 
• There may be no signs of exit site or tunnel infection.
• Exit site infections present with either erythema at the exit site [>1cm] and/or a purulent exudate.  There may be pain at the site.
• Tunnel infections present with inflammation and/or tenderness along the subcutaneous portion of tunnelled catheters.

Investigations required

• Paired peripheral and central Blood Cultures should be sent from all potentially infected lumens when CRBSI is suspected - take same volume, generally up to 3mL
• FBC, CRP
• U&E’s, LFT, calcium, magnesium & phosphate
• Urine for culture and sensitivity
• Exit site infection: pus sample (preferred) or exit site swab for microbiology.

Non-Antimicrobial Management

• CVC removal
• Administer plasma expanders if required (10ml/kg of 0.9% Sodium Chloride over 30 minutes).
• Administer antipyretic (i.e. Paracetamol) when temperature 38°C or above.

Empirical (initial) antimicrobial treatment

• First line antibiotics are Vancomycin (if allergic use Teicoplanin ) and Ceftazidime (if allergic use Aztreonam ) via the CVC . See table 1 detailing administration and monitoring of antibiotic therapy. Prescribe on eMEDS using Protocol-Paediatrics-General-Line care- Paediatric Central venous catheter (CVC) infection in children with PN- FIRST LINE (Use ALLERGY if patient allergic to Vancomycin or Ceftazidime)
• Start antibiotics after blood cultures taken and within 60 minutes if patient is at moderate or high risk of sepsis. See Considering Sepsis in Paediatrics (leedsth.nhs.uk)   
• For oncology patients follow Neutropenic Sepsis/Febrile Neutropenia guidelines
• If CVC salvage is planned give the appropriate IV antibiotics for 10-14 days as directed by microbiology.
• If the infected CVC is removed 5-14 days treatment is recommended depending on the pathogen and clinical response, as directed by microbiology.

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Aims

• To improve the diagnosis and management of suspected CVC infections in infants and children

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Background

The central venous catheter (CVC) is essential for the management of children requiring long term treatment with intravenous therapies. Catheter types in use are peripherally inserted central catheters (PICC), tunnelled surgical lines (e.g., Broviac/Hickman) and implanted venous access devices (e.g., Port-a-Cath).

There are often a limited number of sites for CVC placement; therefore, treatment of the infection without removal of the CVC is often necessary. When the infection is life threatening or there is a confirmed fungal infection or when conservative management of a bacterial catheter related blood stream infections (CRBSI) has failed (i.e., if the same organism is grown again, post-treatment) the CVC should be removed. The Microbiologist and Paediatric Consultant /Surgeon and medical staff must discuss the nature of the organism, the clinical condition and venous access limitations of the patient to ensure that line removal is warranted.

Infection is the major complication associated with long-term CVCs and can have serious consequences such as bloodstream infection, metastatic infection (osteomyelitis, endocarditis) and death.
CRBSI can be divided clinically into local (exit site) and bloodstream infections, but these entities may coexist.

CRBSI begins with colonisation of the:

• internal lumen of the CVC - micro-organisms can gain access to the lumen of a catheter via a contaminated hub or infusate. This is more common in long-term CVC.
• external surface of a CVC - may become colonized as a result of contamination during insertion, via exit site colonisation or secondary to a bacteraemia from a distant source (Elliott et al., 1997).

A CVC must be colonized before invasion of tissues or bloodstream can occur. The longer a catheter remains in place, the more likely it is to become colonised (Sandoe et al., 2003).
The most common causative organisms of significance are:

• Gram negative bacilli
• Staphylococcus aureus
• Enterococcus species
• Coagulase negative Staphylococcus
• Candida species

Definition

1. Exit site infection - purulent exudate or erythema surrounding the exit site
2. CVC related bloodstream infection (CRBSI), meaning
   • A positive blood culture taken through the CVC
   • A positive peripheral blood culture taken before CVC removal
   • Differential time to positivity [DTP]
   • The same microorganism isolated from both sites.

However, in many cases the only information will be a positive blood culture in a sick patient with a CVC and no other focus for infection

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Clinical Diagnosis

Assess the child's general clinical condition

1. An infant or child developing CRBSI may present with

• Temperature above 38°C
• Tachycardia
• Tachypnoea and / or grunting respiration
• A fall in blood pressure
• Peripheral shut down, may feel cold and clammy
• Irritability and lethargy
• Enteral feed intolerance e.g., increased diarrhoea/stoma output and/or vomiting
• Apnoeic episodes
• Unstable blood sugars (particularly in neonates)
• Take note of parent’s concerns – they know their child best; be worried if they are worried.
• Wobbliness after line access

2. Exit site infection is diagnosed on clinical grounds (exudate and erythema) and may or may not be associated with CRBSI.

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Severity Assessment

Catheters should ideally be removed in the following situations: [Evidence level C]

•Bacteraemia, sepsis or local complications that become life threatening. Micro-organisms known to be difficult to eradicate [e.g. S. aureus, Bacillus spp., mycobacteria, and fungi].

•Relapse of infection after antibiotics have been discontinued.

Salvaging the CVC is recommended in preference to removing the CVC in consultation with the children’s medical team and microbiology in patients that lack of venous access can become life limiting.

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Investigation

• Paired peripheral and central Blood Cultures should be sent from all potentially infected lumens when CRBSI is suspected - take same volume, generally up to 3mL
• 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. A negative central blood culture at >100 hours incubation had a negative predictive value of 100%
• FBC, CRP
• U&E’s, LFT, calcium, magnesium & phosphate
• Urine for culture and sensitivity
• Exit site infection: pus sample (preferred) or exit site swab for microbiology.

[Evidence level D]

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Non-antimicrobial treatment

• CVC removal - The definitive treatment for CVC infection is removal of the CVC and thus the source of infection, usually in combination with antimicrobial therapy. [Evidence level B].
• Administer plasma expanders if required (10ml/kg of 0.9% Sodium Chloride over 30 minutes).
• Administer antipyretic (i.e., Paracetamol when temperature 38°C or above.

[Evidence level D]

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Empirical antimicrobial treatment

Recommendation: Start antibiotics after blood cultures taken and within 60 minutes if patient is at moderate or high risk of sepsis. See Considering Sepsis in Paediatrics (leedsth.nhs.uk)

Recommendation: First line (empirical) intravenous (IV) antibiotics are Vancomycin (if allergic use Teicoplanin ) and Ceftazidime (if allergic use Aztreonam ) via the CVC . See table 1 detailing administration and monitoring of antibiotic therapy.
[Evidence level D]

For oncology patients follow Neutropenic Sepsis/Febrile Neutropenia guidelines

Recommendation: If attempting to salvage a CVC administer systemic antimicrobials via the infected line.
[Evidence level B]

Recommendation: For multi-lumen CVCs, alternate lumens for administration of antimicrobials every 24 hours.

Recommendation: Review the antibiotic treatment when culture sensitivities are obtained

Recommendation: If CVC salvage is being attempted, antimicrobial line locks should be used together with systemic antimicrobials, where possible. If the patient was receiving line locks for prophylaxis, then a different line lock agent should be chosen. Discuss with Microbiology.
[Evidence level B/D]

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Directed antimicrobial treatment (when microbiology results are known)

Recommendation: If only Gram positive bacteria are cultured, Ceftazidime /Aztreonam can be stopped and gram positive therapy modified according to susceptibilities.

Recommendation: If only Gram negative bacteria are cultured, Vancomycin/Teicoplanin  can be stopped and gram negative therapy modified according to susceptibilities.

For oncology patients follow Neutropenic Sepsis/Febrile Neutropenia guidelines http://nww.lhp.leedsth.nhs.uk/common/guidelines/detail.aspx?ID=4006

Recommendation: If cultures are negative consider alternative diagnoses because negative cultures have a high negative predictive value.
[Evidence level C]

Prophylactic use of Antimicrobial line locks

Antimicrobial lock therapy should be considered for confirmed luminal catheter infections caused by the Gram positive organisms coagulase negative staphylococci, enterococci, streptococci, and coryneforms.

The agent that should normally be used is taurolidine (Taurolock TM).

If Taurolock TM contra-indicated, an alternative is Vancomycin (concentration 5mg/mL).

Antimicrobial lock therapy should also be considered for confirmed luminal catheter infections [i.e., differential time to positivity of 2 hours or more in paired peripheral and through-line blood cultures] caused by “coliforms” [Enterobacteriaceae].

Suitable agents would include taurolidine or Gentamicin. [Evidence Level D]

Normally taurolidine (Taurolock TM) should be considered as first line lock therapy for “coliforms” (Enterobacteriaceae) and other Gram-negative bacilli.

If Taurolock TM contra-indicated, an alternative is Gentamicin (concentration 2mg/mL)

Salvage of long-term catheters confirmed to be infected with organisms other than those listed above should also only be attempted after discussion with Microbiology. [Evidence level D].

Although the duration of antimicrobial lock therapy has varied among different studies; it most often is two weeks. [Evidence level C].

If an antimicrobial lock is being used, then depending on the clinical scenario and microbiological results, it may be in addition to, or instead of, systemic therapy. [Evidence level C].

If the patient has been receiving prophylactic line locks, then an alternative agent should be used for salvage therapy

Recommendation: Prophylaxis with antimicrobial line locks should be used in children with recurrent CRBSI (2 episodes in a 6 month period), as a lack of venous access becomes life limiting.
[Evidence level D]

Recommendation: If a patient has 2 bacterial CRBSIs in a 6 month period, initial prophylaxis should be Taurolock™,
[Evidence level D]

Guidelines for use of Taurolock in infants and children

• Recommendation: Taurolock™ should be commenced when a course of antimicrobial treatment is completed and the clinical decision for prophylactic line lock has been made. Patients should remain on Taurolock™ until treatment is no longer required and the CVC is removed, or they require a change of prophylactic agent. [Evidence level D]
• 1-2mL* of Taurolock™ should be instilled into the line slowly (max 1mL per 5 seconds) to lock the line whilst not in use.
• Taurolock™ may cause mild hypocalcaemic symptoms if instillation is not done slowly as directed.
• Taurolock™ should be aspirated prior to accessing the CVC.

* See Appendix for ‘Prime, flush and line lock volume table’

See appendix - TaurolockTM use in PN dependent patients

See table of antimicrobials below for details of the presentation and administration of line locks and refer to the Department of Microbiology Protected (restricted) antimicrobial Prescribing Guidelines: - Taurolidine - based catheter lock solutions (TauroLock™) for further information.

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Oral switch

Exit site infections without systemic signs of infection of positive blood cultures can be treated with oral antimicrobials.

When treating suspected or microbiologically confirmed CRBSI with the intravascular catheter in situ, antimicrobials must be infused via all potentially infected lumens. Oral antimicrobials only have a place in this setting if clinically and microbiologically appropriate in conjunction with antimicrobial lock[s], or if the infection has been confirmed to be solely extra-luminal.

Once an infected catheter has been removed, if a patient has made a good clinical recovery IV antimicrobials can be switched to an oral alternative if clinically appropriate.  [Caution should be exercised in this respect for Staphylococcus aureus bloodstream infection which has a high propensity to seed distant sites and relapse - longer courses of intravenous therapy are usually recommended]

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Duration of therapy

Recommendation: If CVC salvage is planned give the appropriate IV antibiotic/s for 10-14 days.
[Evidence level B]

Recommendation: If the infected CVC is removed 5-14 days treatment is recommended depending on the pathogen and clinical response, as directed by microbiology.
[Evidence level B]

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Treatment failure

See CVC removal and Discuss with Microbiology

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