Guidelines for the management of paediatric line-related sepsis

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Objectives

This document aims to provide assistance with clinical management of probable or confirmed paediatric line-related sepsis in GG&C, including diagnosis, decisions regarding line salvage if necessary, and use of antimicrobial agents.  The prevention of line related infections, and the use of line locks to prevent line infections, is outwith the scope of this guideline. 

From the perspective of managing infections as well as to conserve valuable antibiotics and prevent resistance from developing, it is always ideal to remove infected lines or other prosthetic material. Line salvage therapy should only be considered when it is thought to be in the best interests of the patient and the benefits associated with this are thought to outweigh the risks.  For example, in patients with multiple previous lines, limited ongoing options for vascular access, or a significant bleeding risk, one might have a lower threshold for considering line salvage. In all cases, the best decisions regarding line removal or salvage are made in the context of the wider multi-disciplinary team which should include a member of the vascular access team. These discussions may be informed by up to date imaging to assess available options for subsequent replacement of central venous access. Risks of line salvage therapy include ongoing or worsening sepsis due to continuing indwelling source of infection, and failure of salvage therapy or recurrence of infection.

It is always good practice to ensure individualised management plans tailored to each patient’s unique needs and circumstances. These guidelines are purely to facilitate this process and are not a substitute for senior clinical review and discussion with an infection specialist where appropriate.  Local departmental guidelines may already be in use to facilitate management of line related infections; these should be referred to and if in any doubt the most appropriate course of action should be discussed with an infection specialist.

This document does not provide a comprehensive account of the pathophysiology, potential sources or metastatic complications associated with individual organisms. Organisms not covered in this document, or line sepsis with mixed organisms, should also be discussed with an infection specialist.

“Infection specialist” refers to a specialist in clinical microbiology or infectious diseases.

General approach to line infections

It is recognised that each patient and situation is unique. The following initial actions are recommended in patients with possible or probable line related sepsis:

  1. Urgent senior clinical review
  2. Blood cultures (preferably pre-antibiotic)
    • Paired line and peripheral blood cultures taken with clear labelling of the request forms
    • All lumens of multilumen lines should be sampled separately
    • If peripheral cultures are not obtainable, consideration should be given to arterial cultures
  3. Review for other sources of infection – may require further investigations/imaging etc. Even with an underlying primary source of infection, the line may be secondarily infected.
  4. Consultation of previous microbiology results – previous resistant or unusual infections may mean that empirical antimicrobials recommended in this guideline or in the therapeutics formulary are inappropriate and alternative regimes may be required. For haemato-oncology and other patients at high-risk of recurrent line infections there may be a condition specific guideline or an existing individualised line infection antibiotic plan which should be followed.
  5. If in any doubt, early senior clinical review and discussion with an infection specialist should occur
  6. It is generally against best infection specialist advice to salvage an infected line. However, an early decision regarding salvage, along with institution of lock and systemic antibiotic therapy (through the line to be salvaged) should be made. Where a lock cannot be used, systemic antibiotics should be administered through the line.
  7. In a patient in whom line sepsis is suspected, and in whom there is a strong reason why line salvage is being considered, line locks and systemic antibiotics down the line should be used. In addition, due to the risk of metastatic septic complications and physiological instability, an early discussion with critical care services is warranted based on level of concern and the species of pathogen isolated. If continued use of the line results in ongoing signs of sepsis then the line should be removed.
  8. In well patients, single positive cultures with Coagulase Negative Staphylococci might not be significant and these should be repeated prior to initiation of specific therapy.
  9. Repeat line and peripheral cultures with tailoring of treatment (lock and systemic) to microbiology results are essential if line salvage is attempted. Discuss any antibiotic resistant organisms with an infection specialist. The line should ideally be removed if blood cultures remain positive at 72 hours post initiation of salvage therapy.
  10. Line removal forms the mainstay of optimal management of these infections. When line sepsis is likely, line tips should be sent for culture and the results chased. If lines are removed but line sepsis is not likely, there is no clinical need to send line tips for culture.  In problem situations or when problem organisms are cultured, renewed efforts should be made to remove the line. Certain situations may also prompt a search for other deep sources or metastatic complications (see tables 1 & 2 in section Problem situations and organisms below).
  11. When line retention and salvage has been attempted using systemic and lock therapy for the recommended durations, line and peripheral cultures should be obtained 48 hours after stopping all antimicrobial therapy
Line rest

Line rest and rechallenge a few days later may allow more bacteria to grow within the line and risk severe septic showers on rechallenge. This might reduce the efficacy of salvage therapy. Removal of an infected line is always ideal when managing line infections, but if this is not possible then a decision to salvage should be made early and salvage therapy that includes line locks, instituted as soon as practicable, guided by senior clinical input. Line removal is indicated in patients who are severely unwell, haemodynamically unstable, or with signs of insertion site infection, severe exit site infection or tunnel infection. If line removal is still not possible then discuss the case urgently with senior clinicians, intensive care and infection specialists.

Line tips

Line tips should only be sent to microbiology for culture when there is a clinical suspicion of line sepsis. When these are sent, the results should be chased up by the responsible clinical team.

There is evidence that the following organisms, when cultured from a line tip but not blood cultures, MAY warrant clinical review, further investigations, consideration of a period of intravenous antimicrobial treatment, due to the association with deep sources or metastatic septic complications:

  • Staphylococcus aureus or lugdunensis (typically 5-7 days IV treatment post line-removal)
  • Candida species or other fungi/yeasts
  • Gram-negative organisms

If in doubt, discuss with an infection specialist.

Lock therapy

Paediatric patients weighing less than 3kg should be discussed with the paediatric infectious diseases team prior to using locks.

Antimicrobial line locks deliver a high concentration of antimicrobial agent direct to the lumen of the line and remain in situ for a period of time before being aspirated and replaced. Line locks should be replaced at least every 24 hours.  The line lock should be removed before infusion of the next dose of systemic antibiotic down the line, or, where applicable, other intravenous solution, or medication.

Line locks are an adjunct and not a replacement for systemic antimicrobials and are used as a final attempt at line salvage. For suspected bacterial line related infection, the initial choice of lock therapy suggested is taurolock. Lock therapy can then be guided by culture results and antimicrobial sensitivities. When using antibiotic locks, the choice of lock should ideally be a different class of antimicrobial from the agent used systemically. A number of different antibiotics can be used as a lock. Antibiotic locks not mentioned in this guideline may be considered under the guidance of microbiology and pharmacy based on the organism and antibiotic sensitivities.

For fungal/candidal infection and Staphylococcus aureus/lugdunensis infection, line removal is strongly recommended. Line salvage with antibacterial or antifungal locks should not be attempted unless in exceptional circumstances and should be discussed with an infection specialist first.

There may be instances where it is not possible to use antibiotic lock therapy, or locks cannot be instilled or changed with regularity, and these cases should be discussed with an infection specialist.

Lastly, the volume of lock instilled will vary according to the length and type of line: this cannot be defined in a protocol and must be individualised for the patient.

See Quick Reference Guideline section below for suggested antibiotic lock formulations and clinical management flowchart.

Blocked lines

Urokinase administration may be required if a line cannot be aspirated or is considered to be blocked.  Further information on troubleshooting and general line-related care can be found at the vascular access device practice website on Staffnet [NOTE: you must be connected to the NHSGGC network to view]:

 

Replacing lines

If a line has been removed due to line sepsis and another line is required, this should ideally be placed in a different location. Guidewire exchange in insertion site infections is not appropriate as it can lead to bacteraemia and septic emboli.

Ideally, clearance of bacteraemia should be documented prior to replacing a line. This usually means a minimum of 48 hours of negative cultures.

Duration of antibiotic therapy post line-removal

This should be discussed with an infection specialist and may vary according to the organism and clinical circumstances. In patients with suspected deep foci of infection, such as endocarditis, septic thrombophlebitis, bony infection, or another deep or potentially infected nidus of infection or prosthesis, a more prolonged course of antibiotics may be required on discussion with the infection specialist

As a general guide:

  • Staphylococcus aureus or candida species:  Assuming the line has been removed, these organisms require at least 14 days of IV antimicrobial therapy from the date of the first negative blood culture at or after line removal, provided no deep sources or metastatic complications present
  • Gram negative bacilli and enterococci: 7-14 days post line removal
  • Coagulase-negative staphylococci: 5- 7 days post line removal depending on other comorbid factors, but may not require treatment at all
Line Sepsis and Antibiotic Lock Guidance for On Call Pharmacists and Clinicians – Quick Reference Guideline
  • In order to avoid errors in preparation, it is suggested that a commercially pre-prepared preparation such as taurolock be used out of hours if required, and antibiotic locks be prepared during working hours after choice of antibiotic lock is agreed by an infection specialist.
  • Maximum dwell time should be 24 hours.
  • The concentration of lock suggested in different guidelines varies.
  • If heparinised solutions are required to lock the line, consult with pharmacy prior to initiating antimicrobial lock therapy.
  • The risk of accidentally flushing an antibiotic lock will depend on the volume and concentration flushed, and patient factors. If antimicrobial locks are accidentally flushed into a patient, get a senior clinical review and discuss with pharmacy.

Vancomycin (5mg/mL) and sodium chloride 0.9% antibiotic lock:

Method for preparation and administration

  1. Reconstitute 500mg vial of Vancomycin with 10mL water for injection (to give concentration of 50mg/mL) – draw up 1mL (50mg).
  2. Add 1mL (50mg) of Vancomycin to 9mL of sodium chloride 0.9% to give a final concentration of 5mg/mL Vancomycin and a total volume of 10mL.
  3. Instil the required volume for size and type of central venous access device
  4. **Make sure that the line is not flushed during this time by labelling appropriately**Repeat the preceding steps as appropriate for each lumen.
  5. Aspirate the solution from the line prior to using the line or changing the lock
  6. Document in patient’s medical notes & get senior clinical review if unable to aspirate.

Gentamicin (5mg/mL) and sodium chloride 0.9% antibiotic lock:

Method of preparation and administration

  1. Use Gentamicin 20mg/2ml injection, withdraw 2ml.
  2. Add 2 mL of 0.9% Sodium Chloride to give a final concentration of Gentamicin 5mg/1mL and a total volume of 4 mL.
  3. Instil the required volume for size and type of central venous access device
  4. **Make sure that the line is not flushed during this time by labelling appropriately** Repeat the preceding steps as appropriate for each lumen.
  5. Aspirate the solution from each lumen prior to using the line or changing the lock
  6. Document in patient’s medical notes & get senior clinical review if unable to aspirate.

Ciprofloxacin (2mg/mL):

Method for preparation and administration

  1. Use Ciprofloxacin infusion bag (concentration of 2mg/mL)
  2. Instil the required volume for size and type of central venous access device
  3. Make sure that the line is not flushed during this time by labelling appropriately** Repeat the preceding steps as appropriate for each lumen.
  4. Withdraw the volume added to each lumen prior to using the line or changing the lock
  5. Document in patient’s medical notes & get senior clinical review if unable to aspirate.

Taurolock

Instructions for use can be found at: https://www.taurolock.com/en/download/instructions-use

However, always check the actual instructions supplied with the product on the ward.

Prescription of locks and labelling of lumens:

Line locks should be prescribed on the Kardex as illustrated below.

When salvaging a line, it is ideal to reserve the line purely for antimicrobial therapy (locks and systemic antibiotics) for the duration of salvage treatment. Peripheral access should be cited for any other IV therapies. 

For multilumen lines where peripheral access is not available and the patient requires IV therapy of any description in addition to IV antibiotics, it may be necessary to lock different lumens on rotation.

For single lumen lines where peripheral access is not available, the lumen must be locked with antibiotic solution when not in use. Prior to using the line, the lock should be removed and discarded, and the line flushed. After using the line, fresh lock should be instilled until the next use, or 24 hours, whichever is first.

Lumens that are locked should be clearly labelled.

Flowchart

Problem situations and organisms

Line removal is strongly recommended in specific problem situations or in infections with problem organisms (Tables 1 and 2).  If line removal is not deemed possible or is deemed unsafe, discuss with an infection specialist for individualised advice as a prolonged course of targeted antibiotic therapy along with specific line locks may be required. Unstable patients should be discussed early with an intensive care specialist.

Table 1: Problem Situations where line removal strongly recommended

Severe sepsis

Haemodynamic instability

Infectious Endocarditis or evidence of metastatic complications

Erythema or exudate due to suppurative thrombophlebitis

Persistent bacteraemia after 72 hours of antimicrobial therapy to which an organism is susceptible

Evidence of tunnel infection

Evidence of insertion site infection or severe exit site infection

Table 2: Problem organisms

Highly virulent organisms:

  • Fungi
  • Staphylococcus aureus or lugdunensis
  • Pseudomonas aeruginosa

Organisms that may be less virulent but can be difficult to eradicate:

  • Mycobacterium species
  • Bacillus species
  • Propionibacterium/Cutibacterium species
  • Micrococcus species

Environmental and multidrug resistant organisms:

  • Multidrug resistant Gram-negative organisms
  • Pseudomonas species
  • Stenotrophomonas species
  • Chryseomonas species
  • Chryseobacterium species
  • Acinetobacter species
  • Elizabethkingia species
  • Cupriavidus species
  • Vancomycin or linezolid resistant Enterococci and other resistant Gram-positive organisms
References
Editorial Information

Last reviewed: 01 February 2021

Next review: 28 February 2023

Author(s): Dr Ash Deshpande, Consultant Microbiologist, QEUH; Dr Louisa Pollock, Consultant Paediatrician, RHC

Approved By: Antibiotic Users Committee

Reviewer Name(s): Mr T Bradnock & Dr G Bell