Infected Long-term Intravascular Access Devices in Adults

Publication: 01/04/2009  --
Last review: 15/06/2018  
Next review: 15/06/2021  
Clinical Guideline
CURRENT 
ID: 1680 
Approved By: Improving Antimicrobial Prescribing Group 
Copyright© Leeds Teaching Hospitals NHS Trust 2018  

 

This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Guideline for Management of Infected Long-term Intravascular Access Devices in Adults

Please also refer to the Vascular Access Device Selection Guide Description: http://nww.lhp.leedsth.nhs.uk/images/word2.gif

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Summary
Infected Long-term Intravascular Access Devices in Adults

Intravascular catheter-related infections affecting long-term vascular access devices include exit site, “tunnel” infections and bloodstream infection, 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

  • CRBSI: Paired peripheral and through-line blood cultures [same volume, same time] should be sent from all lumens of the potentially infected line [Blood culture sampling guideline].
    • Intravascular catheter tips should only be sent for culture to confirm a clinical suspicion of a catheter related infection (CRI), not as a matter of routine.
  • Exit site infection: pus sample (preferred) or exit site swab for microbiology.

Treatment

Exit site infections without systemic signs of infection or positive Blood Cultures can be treated with oral antimicrobials.
When treating CRBSI with the intravascular catheter in situ, antimicrobials must be infused via / come into contact with all potentially infected lumens.  Oral antimicrobials alone don’t have a place in this setting.
Once an infected catheter has been removed, if a patient has made a good clinical recovery antimicrobials can be switched to an oral alternative if clinically appropriate.

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Background

Some intravascular access devices have been developed for “long-term” use (arbitrarily defined as >30 days use1).  These devices are used for a variety of clinical indications such as prolonged course of intravenous treatment [e.g. with chemotherapeutic agents or antimicrobials]; regular haemodialysis; and home parenteral nutrition.   Examples of long-term catheters in use in LTHT include Broviac, Hickman, Groshong, Tesio, Portacath, and peripherally inserted central catheters [PICC lines].  A variety of methods for reducing the risk of infection have been incorporated into the design of these devices.  Some are totally implanted and the port is accessed via percutaneous puncture; some have a “cuff” distal to the insertion site, which becomes fibrosed and anchors the catheter in situ; “tunnelled” devices have a portion of catheter that is under the skin before the entry point into the vein.

Infection is the major complication associated with long-term intravascular catheters and can have serious consequences such as metastatic infection [e.g. osteomyelitis, endocarditis] and death.  Catheter related infections [CRI] associated with intravascular catheters can be divided clinically into local [exit site and tunnel infections] and bloodstream infections, but these entities may coexist.  The incidence of catheter related bloodstream infections [CRBSI] ranges widely between institutions and patient groups.

Infection of long-term vascular access devices begins with colonisation of either the external surface or lumen of the catheter, the latter being more common in long-term device infection.  Micro-organisms can gain access to the lumen of a catheter via a contaminated hub or infusate.  The external surface of a catheter may become colonised as a result of contamination during insertion, via exit site colonisation or secondary to a bacteraemia from a distant source2.  It is axiomatic that a catheter must be colonised before invasion of tissues or bloodstream can occur. The longer a catheter remains in place, the more likely it is to become colonised3.

  • The most common cause of CRI are Coagulase-negative staphylococci, particularly Staphylococcus epidermidis; with Staphylococcus aureus, Candida species and enterococci are also commonly implicated4.
  • Other biofilm forming Gram-negative organisms such as Pseudomonas aeruginosa and Stenotrophomonas maltophilia can also colonise catheters and subsequently cause infection.  Enterobacteriaceae [such as Escherichia coli, Citrobacter, Enterobacter and Serratia species] are frequently encountered and may be more commonly associated with a femoral insertion site. 
  • Alpha-haemolytic streptococci have emerged as a cause of CRI, particularly in patients with haematological malignancy.

This guideline should be used in conjunction with the LTHT guideline: Central Venous Catheters in Adults and Children - Guideline for the Insertion, Management, Replacement and Removal of. The use of catheters designed and marketed to carry a lower risk of CRI is an issue that needs to be resolved after an evaluation of the evidence and of the particular risks in various clinical areas.  This guideline does not assess such prophylactic measures.  The guideline is based on generic principles and should therefore be applicable across different specialties and clinical areas throughout LTHT.  Specifically this guideline is applicable to renal patients and oncology patients - including those with haematological malignancy.  Guidance relating to patients receiving parenteral nutrition is included, acknowledging the specific needs of this group.  It also should be used in conjunction with other LTHT antimicrobial prescribing policies, including those relating to the management of “neutropenic sepsis”.

All intravascular catheters should be suitable for the intended purpose and the use limited to that intended purpose in the interests of minimising CRI. The requirement for a catheter to remain in place should be kept under close review.

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Clinical Diagnosis

Clinical diagnosis of CRBSI is notoriously unreliable4 and CRBSI must be considered in any patient with an intravascular catheter and systemic signs of infection, or bacteraemia or fungaemia without an alternative explanation

Early work in patients receiving parenteral nutrition determined that only 15% of intravascular catheters, which were removed because of suspected infection, and the tip cultured, were actually shown to be the cause of CRBSI5. Simple investigations can now establish a diagnosis of CRBSI affecting the lumen(s) of a catheter with a high degree of confidence, without removing the catheter.  This enables more objective decisions regarding attempted catheter salvage or removal.  Clearly, unnecessary removal of a long-term intravascular catheter can be dangerous, inconvenient and costly.

History.

  • Rigors, chills or fever after use of the line is highly suggestive (their absence does NOT rule out CRBSI). 
  • Other symptoms of CRBSI are those of bloodstream infection from any source and include general malaise, anorexia, vomiting.
  • Patients with a tunnel infection usually complain of pain along the tract. 
  • Those with exit site infection may complain of pain and or a discharge from the exit site.

Examination.

  • Exit site infections manifest with either inflammation at the exit site [>1cm] and/or a purulent exudate, systemic signs of infection may be present.  [Evidence level D]
    • Exit site infections can affect all types of vascular access device except those with totally implanted ports.
  • Tunnel infections present with inflammation and/or tenderness along the subcutaneous portion of the catheter, systemic signs of infection may be present. [Evidence level C]
  • CRBSI may coexist with exit site or tunnel infections, which can be accompanied by an isolated fever, other signs of systemic infection, sepsis or septic shock, using current definitions6

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Investigation
  • Exit site infection affecting any type of vascular access device is a clinical diagnosis.
    • A pus sample (preferable) or exit site swab can be sent for culture to determine the pathogen. [Evidence level C]
  • Paired peripheral and through-line blood cultures [same volume, same time] should be sent from all potentially infected lumens when CRBSI is suspected. (See Standard Operating Procedure for Blood Culture Sampling in Adults ) [Evidence level B].
    • Differential time to positivity [DTP] is a blood culture-based method for diagnosing luminal colonisation or CRBSI7
    • 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 CRBSI7,8
      • 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%7,8

The principle is that in the presence of intra-luminal microbial colonisation / infection, blood sampled through that lumen will have a higher bacterial load than blood collected via another site. This means that the luminal blood sample will generate a positive signal identifiably quicker on a continuously monitored blood culture incubation system.  If a known volume of blood is collected via the lumen of an intravascular catheter and the same volume of blood is then drawn from a peripheral vein, the time taken for each aerobic blood culture set to become positive can be used to determine whether the sampled catheter is the likely source of infection. .

  • Acridine orange leukocyte cytospin, quantitative blood cultures and endoluminal brush techniques are sensitive and specific methods of in situ diagnosis of intravascular catheter colonisation but are labour intensive, expensive and are therefore not routinely available in Leeds.

  • Intravascular catheter tips should be sent for culture if the catheter is being removed for suspected infection. Don’t send if the catheter has been removed for another reason. Evidence level C.
  • Semi-quantitative catheter tip culture [often called the “Maki roll”] is a simple and inexpensive method for retrospectively diagnosing colonisation of the external surface of an intravascular catheter.  It lacks sensitivity because only the external surface is cultured [missing luminal colonisation] and lacks specificity because the surface of the catheter may become contaminated with organisms colonising the exit site. 
    Positive Intravascular catheter tips in the absence of positive blood cultures or systemic signs of infection are rarely clinically significant.  In this situation, observation and repeat blood cultures as clinically indicated are recommended. Evidence level D.

There is no evidence that surveillance blood cultures of intravascular catheters are of benefit and this service is not therefore offered by the microbiology department.

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Treatment

General principles
Factors affecting the management of CRI affecting a long term intravascular catheter include:

  • Severity of illness
  • Underlying disease[s]
  • Availability of alternative vascular access sites
  • The pathogen[s] involved and the location of the infection 9,10

The options for treatment for CRI are:

  1. Removal of the intravascular catheter +/- antimicrobial therapy.
  2. Antimicrobial therapy without removing the catheter [attempted catheter salvage].

It is preferable that decisions are based on objective microbiological results, as removal and reinsertion of cuffed, tunnelled lines is not straightforward.  Empirical decisions based on clinical suspicion alone should be avoided wherever possible.

The possibility of a contemporaneous primary source of infection distant from the intravascular catheter should be considered, particularly in Staphylococcus aureus CRI and when fever or bacteraemia persist >72 hours after catheter removal11,12. [Evidence level B].

Isolated exit site infection
When there is a diagnosis of exit site infection without clinical evidence of bloodstream infection (blood cultures should still be taken) oral antimicrobial therapy may be indicated. When infection is severe/extensive or blood cultures are also positive, intravenous therapy and catheter removal are required.

Catheter Related Blood Stream Infection (CRBSI)
CRBSI is a microbiological diagnosis.  Given the poor predictive value of clinical diagnosis of CRBSI and the risks of changing intravascular catheters, individual management of suspected bloodstream infection should be based on a risk assessment. This decision needs to take into consideration that tests to assist in the in situ diagnosis of CRBSI [i.e. without removing the catheter] are currently culture-based and take at least 24 hours to give a result [see above].

Appropriate antimicrobial therapy is usually effective for treatment of CRBSI, but is less effective at eliminating microbial colonisation of an intravascular catheter. The microbial biofilm is relatively resistant to antimicrobial agents and organisms may persist after an apparently good clinical response to antimicrobials, only to relapse at a later date.

  • Removal of intravascular catheter.
  • Removal of the intravascular catheter is the most reliable means of eliminating infection, usually in combination with antimicrobial therapy. [Evidence level B].
  • The decision to remove an intravascular catheter as a matter of urgency is a clinical one, dependent upon the severity of the infection and the likelihood of CRI.  A senior member of the clinical team should be involved in any decisions regarding removal, often in conjunction with advice from Microbiology [Evidence level D].
  • Where intravascular access is still required, new catheters should be re-sited away from areas of inflamed skin. [Evidence level C].
  • If possible, the insertion of a replacement long-term vascular access device should be deferred until the previous infection has been successfully treated or at least controlled with appropriate antimicrobial therapy.
    • No microbial growth from blood cultures taken 72 hours after removal of the infected catheter provides microbiological evidence of this. [Evidence level C].
    • If time permits, such blood cultures should be post completion of the course of systemic antimicrobial therapy. [Evidence level C].
  • For patients dependent on parenteral nutrition this is unlikely to be possible: please refer to appendix 1 for specific guidance.
  • Catheters should ideally be removed in the following situations10,13: [Evidence level C]
    • Bacteraemia, sepsis or local complications [e.g. signs of tunnel or exit site infections] persisting >72h after commencing therapy. Micro-organisms known to be difficult to eradicate [e.g. S. aureus,  Bacillus spp., mycobacteria, and fungi].
    • Presence of metastatic complications [e.g. infective endocarditis, infected pulmonary embolism].
    • Relapse of infection after antibiotics have been discontinued.
  • Catheter removal alone may be sufficient for intravascular catheters colonised by low-grade pathogens, such as coagulase-negative staphylococci9,10 [Evidence level B]. $
    • Exceptions to this recommendation, where patients should receive appropriate antimicrobial therapy until the catheter is removed, are: [Evidence level D].
      • Patients with any intravascular prosthetic material [e.g. pacing system, prosthetic heart valves]
      • Previous endocarditis
      • Structural cardiac lesion known to predispose to endocarditis
      • Dacron/PTFE vascular grafts within 6 months of implantation
      • Immunosuppressed

2. Intravascular catheter salvage

Certain patient populations will present considerable problems with line change [e.g. a Tesio line in a haemodialysis patient with difficult vascular access, the haemato-oncology patient with access problems and a severe coagulopathy, patients dependant on parenteral nutrition long-term.] It may be appropriate to attempt salvage of an infected cuffed or tunnelled intravascular catheter because infection and catheter colonisation can sometimes be eradicated with antimicrobial therapy alone14, 15, 16. It should be noted that some reported success rates with systemic antimicrobial therapy alone are relatively low; 22-37%13. See also section on antimicrobial therapy.

  • A catheter salvage technique should be considered when the risk of replacing the catheter is high (e.g. coagulopathy)
  • Alternative vascular access sites are limited/not available
  • Ideally there should be:
    • No evidence of metastatic complications
    • A microbial cause known to be amenable to medical therapy
    • A haemodynamically stable patient
    • A rapid clinical response to antimicrobial therapy and negative blood cultures after 72 hours of therapy
  • Intravenous antimicrobials need to be administered via all potentially infected lumens.  This can be done by alternating use of lumens for antimicrobial infusions or by splitting each dose and giving half via each lumen. [Evidence level C].
  • If catheter salvage is attempted, then repeat luminal blood cultures should be taken after cessation of antimicrobial therapy to assess microbiological clearance. Evidence level C.
  • In patients with an Infected Long-term Intravascular Access Devices which is present for administration of Parental Nutrition (PN) specific treatment guidance is given in Appendix 1.

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Empirical Antimicrobial Treatment

1. Systemic antimicrobial therapy

  • Empirical antimicrobial therapy for CRI should be initiated when it is considered inappropriate to wait for the results of microbiological tests. 
  • For example, if a patient has sepsis or septic shock or an obvious diagnosis e.g. exit site infection and microbiology samples have been taken. Evidence level C. Empiric therapy should only be initiated after attempting to obtain paired “through-line” and peripheral blood cultures. Evidence level C
  • Empiric therapy should be modified when the causative organism is known i.e. to directed or targeted therapy. Evidence level C
  • In patients with an Infected Long-term Intravascular Access Devices which is present for administration of Parental Nutrition (PN) specific treatment guidance is given in Appendix 1.

Empiric antimicrobial therapy.

  • Clinical exit site infection with no systemic symptoms of infection:  oral Flucloxacillin Description: electronic Medicines Compendium information on Flucloxacillin 500mg 6 hourly (known meticillin-susceptible Staphylococcus aureus from exit site) or oral Doxycycline Description: electronic Medicines Compendium information on Doxycycline 200mg daily (MRSA risk factors)
  • Severe/extensive exit site/tunnel infection or systemic symptoms suggesting bloodstream infection.
  • Empirical therapy should normally include Teicoplanin electronic Medicines Compendium information on Teicoplanin , due to the high prevalence of meticillin-resistance in staphylococci
  • The prevalence of Gram-negative bacteria causing CRI is variable but no clinical features can reliably rule-out this possibility and the empirical regimen should include Gram negative cover in the severely ill patient [sepsis / septic shock].
  • If the recommended regimen is considered inappropriate because of the risk of adverse effects, the case should be discussed with the on-call or unit-specific microbiologist.

Recommended regimen:

Teicoplanin electronic Medicines Compendium information on Teicoplanin IV (see dosing guideline)
+/-
Ceftazidime 1g 8-hourly IV (for <65s) or piperacillin/tazobactam Description: electronic Medicines Compendium information on Piperacillin/tazobactam 4.5g 8-12 hourly IV (for >65s) in patients with sepsis or septic shock.
 
Intermittent haemodialysis patients:

If a patient receives intermittent haemodialysis and would be receiving all/part of their treatment as an outpatient or has a Tesio line, then Vancomycin electronic Medicines Compendium information on Vancomycin can be substituted instead of Teicoplanin electronic Medicines Compendium information on Teicoplanin to aid with dosing on dialysis days. Please discuss with the renal team if this would be appropriate.

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Directed Antimicrobial Treatment (when microbiology results are known)

Directed therapy
For treatment recommendations for uncomplicated* CRBSI for specific pathogens please see

  • Table 2 for Gram-positive pathogens,
  • Table 3 for Gram-negative pathogens
  • Table 4 for fungal pathogens.
  • Table 5 for antimicrobial lock options where salvage is to be attempted
  • Where pathogens are not included in the tables, discussion with Microbiology is recommended

Other options may also be recommended by Microbiology depending on antimicrobial susceptibility pattern / clinical circumstances

* uncomplicated CRI is when the only source of infection is the catheter, with no clinical evidence of metastatic infection or concurrent deep-seated infection

Oral agents for non-severe exit site infection should be determined by susceptibilities or discussion with microbiology.

2. Intravascular catheter salvage

“Antibiotic lock therapy” has been used, either alone or in conjunction with systemic antimicrobials, for treatment of CRBSI when attempting to salvage an intravascular catheter.13,17,18,19,20,21,22,23,24,25

This approach involves instilling a high concentration of an appropriate antimicrobial into the catheter lumen and leaving the solution in the lumen for a variable period of time.  The rationale is to expose organisms that are adherent to the catheter lumen to a sustained high concentration of antimicrobial.  Some in vitro data support this theory.26,27

Many of the published studies present uncontrolled observation data.  Only one of these was a randomised, placebo controlled trial and this failed to demonstrate a statistically significant benefit for antimicrobial lock treatment, although there was a trend towards improved outcomes in the cohort that received it [33% failure rate in the line lock group vs. 57% at day 180]24. Of the earlier open trials, a pooled response rate of 83% of catheter salvage without relapse has been reported; and therapy including an antibiotic lock component was significantly more likely to result in catheter salvage than systemic antimicrobials alone.10

  • The likelihood of success varies with the causative pathogen, with success being less likely if S. aureus, Pseudomonas aeruginosa, or Candida species is involved.10 The minimum dwell time for an antimicrobial lock is usually 8 hours.10,24 [Evidence level B]
  • Use of such a lock may not always be feasible if the line is in frequent use for other requirements.
    •  If the line has two or more lumens, then consideration should be given to rotating the antimicrobial lock between lumens on a daily basis.
  • The maximum dwell time would normally be seven days prior to changing the lock.
    [Evidence level D]
  • The choice of particular antimicrobial agent to be used depends on the causative organism[s]. Suitable agents include vancomycin Description: electronic Medicines Compendium information on Vancomycingentamicin and taurolidine 28, 29, 30, 31, 32, 33, 34.
    • Taurolidine, a very broad spectrum antimicrobial agent, is an active component of the intravenous catheter lock solution, Taurolock TM. This solution has been developed primarily, and is licensed as a medical device, for prophylaxis against catheter related bloodstream infections and is safe and well-tolerated 35, 36.
    • Taurolidine has cidal activity against Gram-negative and Gram-positive bacteria, as well as fungi and mycobacteria 29, 34, 37.
  • There is currently relatively little published experience using this compound in the treatment of CRBSI however it has been found to have a successful salvage rate of > 80% when used locally 30, 32
  • 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 electronic Medicines Compendium information on 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 10mg/ml) 28.
  • Please see table 5 for more details on line lock agents and their durations of use.
  • 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.10 [Evidence level C].
  • If the patient has been receiving prophylactic line locks, then an alternative agent should be used for salvage therapy

  • For patients who are not already established on regular appropriate antibiotics, it is advised that the line lock be administered immediately AFTER a dose of IV antibiotics given via a peripheral cannula.
    Rationale: It has been observed that some patients suffer from a ‘septic shower’ following administration of line locks, as bacteria present within the lumen end up forced into their circulation. This has been noted in PN patients with gram negative bacteria in their lines, although the clinical deterioration could occur with other high-virulence pathogens. .

When not to use “line locks”:

  • Antimicrobial lock therapy is NOT recommended for exit site infections or tunnel infections when luminal Blood Cultures are negative. [Evidence level D].
  • Catheter salvage should not be attempted in confirmed catheter infections caused by S. aureus or Candida species except in exceptional circumstances [e.g. long term venous access required and no other site available] and in discussion with Microbiology. [Evidence level D]

Antimicrobial allergy
contact microbiology for advice.

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Duration of Treatment

See table

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Switch to oral agent(s)

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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Treatment Failure
Please contact microbiology if the patient is not responding to the recommended antimicrobial regimens.

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Provenance

Record: 1680
Objective:
  • To provide evidence-based recommendations for appropriate investigation of suspected infection of long-term intravascular access devices in adults
  • To make recommendations regarding removal of infected intravascular catheters.
  • To provide evidence-based recommendations for appropriate empirical or directed antimicrobial therapy of intravascular catheter-related infection in adults.
  • To recommend appropriate dose, route of administration and duration of antimicrobial agents.
  • To advise in the event of antimicrobial allergy.
  • To standardise the approach to management of intravascular catheter-related infection affecting long-term intravascular access devices in adults.
  • To document the principles underlying management of infected long-term intravascular access devices.
Clinical condition:

Infected long-term intravascular access devices

Target patient group:
Target professional group(s): Secondary Care Doctors
Secondary Care Nurses
Pharmacists
Adapted from:

Evidence base

Evidence base

  1. Pratt, R. J., Pellowe, C., Loveday, H. P. & other authors (2001). The epic project: developing national evidence-based guidelines for preventing healthcare associated infections. Phase I: Guidelines for preventing hospital-acquired infections. Department of Health (England). Journal of Hospital Infection 47 Suppl, S3-82.
  2. Elliott, T. S., Moss, H. A., Tebbs, S. E., Wilson, I. C., Bonser, R. S., Graham, T. R., Burke, L. P. & Faroqui, M. H. (1997). Novel approach to investigate a source of microbial contamination of central venous catheters. Eur J Clin Microbiol Infect Dis 16, 210-213.
  3. Sandoe, J. A., Kumar, B., Stoddart, B., Milton, R., Dave, J., Nair, U. R. & Wilcox, M. H. (2003). Effect of extended perioperative antibiotic prophylaxis on intravascular catheter colonization and infection in cardiothoracic surgery patients. J Antimicrob Chemother 52, 877-879.
  4. Pearson, M. L. (1996). Hospital Infection Control Practices Advisory Committee. Guidelines for Prevention of Intravascular-device-related Infections. Infect Control Hosp Epidemiol 17, 438-473.
  5. Ryan, J. A., Jr., Abel, R. M., Abbott, W. M., Hopkins, C. C., Chesney, T. M., Colley, R., Phillips, K. & Fischer, J. E. (1974). Catheter complications in total parenteral nutrition. A prospective study of 200 consecutive patients. N Engl J Med 290, 757-761.
  6. Singer, M., Deutschman, C. S., Seymour, C. W., Shankar-Hari, M., Annane D., Bauer M, et al. 2016. The Third International Consensus definitions for sepsis and septic shock. J Am Med Assoc. 315, 801-810.. .
  7. Blot, F., Nitenberg, G., Chachaty, E., Raynard, B., Germann, N., Antoun, S., Laplanche, A., Brun-Buisson, C. & Tancrede, C. (1999). Diagnosis of catheter-related bacteraemia: a prospective comparison of the time to positivity of hub-blood versus peripheral-blood cultures. Lancet 354, 1071-1077.
  8. Catton, J. A., Dobbins, B. M., Kite, P. & other authors (2005). In situ diagnosis of intravascular catheter-related bloodstream infection: a comparison of quantitative culture, differential time to positivity, and endoluminal brushing. Critical Care Medicine 33, 787-791.
  9. Bouza, E., Burillo, A. & Munoz, P. (2002). Catheter-related infections: diagnosis and intravascular treatment. Clin Microbiol Infect 8, 265-274.
  10. Mermel, L. A., Farr, B. M., Sherertz, R. J., Raad, II, O'Grady, N., Harris, J. S. & Craven, D. E. (2001). Guidelines for the management of intravascular catheter-related infections. Infection Control and Hospital Epidemiology 22, 222-242.
  11. Raad, II & Sabbagh, M. F. (1992). Optimal duration of therapy for catheter-related Staphylococcus aureus bacteremia: a study of 55 cases and review. Clin Infect Dis 14, 75-82.
  12. Raad, I., Narro, J., Khan, A., Tarrand, J., Vartivarian, S. & Bodey, G. P. (1992b). Serious complications of vascular catheter-related Staphylococcus aureus bacteremia in cancer patients. Eur J Clin Microbiol Infect Dis 11, 675-682.
  13. Krishnasami, Z., Carlton, D., Bimbo, L., Taylor, M. E., Balkovetz, D. F., Barker, J. & Allon, M. (2002). Management of hemodialysis catheter-related bacteremia with an adjunctive antibiotic lock solution. Kidney international 61, 1136-1142.
  14. Capdevila, J. A., Segarra, A., Planes, A. M., Ramirez-Arellano, M., Pahissa, A., Piera, L. & Martinez-Vazquez, J. M. (1993). Successful treatment of haemodialysis catheter-related sepsis without catheter removal. Nephrol Dial Transplant 8, 231-234.
  15. Raad, I., Davis, S., Khan, A., Tarrand, J., Elting, L. & Bodey, G. P. (1992a). Impact of central venous catheter removal on the recurrence of catheter- related coagulase-negative staphylococcal bacteremia. Infection Control and Hospital Epidemiology 13, 215-221.
  16. Sandoe, J. A., Witherden, I. R., Au-Yeung, H. K., Kite, P., Kerr, K. G. & Wilcox, M. H. (2002). Enterococcal intravascular catheter-related bloodstream infection: management and outcome of 61 consecutive cases. Journal of Antimicrobial Agents and Chemotherapy 50, 577-582.
  17. Arnow, P. M. & Kushner, R. (1991). Malassezia furfur catheter infection cured with antibiotic lock therapy. Am J Med 90, 128-130.
  18. Benoit, J. L., Carandang, G., Sitrin, M. & Arnow, P. M. (1995). Intraluminal antibiotic treatment of central venous catheter infections in patients receiving parenteral nutrition at home. Clin Infect Dis 21, 1286-1288.
  19. Bregenzer, T. & Widmer, A. F. (1996). Bloodstream infection from a Port-A-Cath: successful treatment with the antibiotic lock technique. Infect Control Hosp Epidemiol 17, 772.
  20. Dannenberg, C., Bierbach, U., Rothe, A., Beer, J. & Korholz, D. (2003). Ethanol-lock technique in the treatment of bloodstream infections in pediatric oncology patients with broviac catheter. J Pediatr Hematol Oncol 25, 616-621.
  21. Johnson, D. C., Johnson, F. L. & Goldman, S. (1994). Preliminary results treating persistent central venous catheter infections with the antibiotic lock technique in pediatric patients. Pediatr Infect Dis J 13, 930-931.
  22. Krzywda, E. A., Andris, D. A., Edmiston, C. E., Jr. & Quebbeman, E. J. (1995). Treatment of Hickman catheter sepsis using antibiotic lock technique. Infect Control Hosp Epidemiol 16, 596-598.
  23. Messing, B., Peitra-Cohen, S., Debure, A., Beliah, M. & Bernier, J. J. (1988). Antibiotic-lock technique: a new approach to optimal therapy for catheter-related sepsis in home-parenteral nutrition patients. Jpen 12, 185-189.
  24. Rijnders, B. J., Van Wijngaerden, E., Vandecasteele, S. J., Stas, M. & Peetermans, W. E. (2005). Treatment of long-term intravascular catheter-related bacteraemia with antibiotic lock: randomized, placebo-controlled trial. J Antimicrob Chemother 55, 90-94.
  25. Ruiz-Valverde, M. P., Barbera, J. R., Segarra, A., Capdevila, J. A., Evangelista, A. & Piera, L. (1997). Successful treatment of catheter-related sepsis and extraluminal catheter thrombosis with vancomycin and fraxiparin without catheter removal. Nephron 75, 354-355.
  26. Andris, D. A., Krzywda, E. A., Edmiston, C. E., Krepel, C. J. & Gohr, C. M. (1998). Elimination of intraluminal colonization by antibiotic lock in silicone vascular catheters. Nutrition (Burbank, Los Angeles County, Calif 14, 427-432.
  27. Bestul, M. B. & Vandenbussche, H. L. (2005). Antibiotic lock technique: review of the literature. Pharmacotherapy 25, 211-227.
  28. Berrington, A. & Gould, F. K. (2001). Use of antibiotic locks to treat colonized central venous catheters. J Antimicrob Chemother 48, 597-603.
  29. Collyns, T. A., Young, A., Weis, C., Robinson, G., Hufton, M., Roberts, S. & Chester, J. (2007).First report world-wide of clinical use of taurolidine - 4% citrate catheter lock solution to tackle an intravascular catheter colonised with a mycobacteria; with a very successful outcome. Abstract K-1738. In 47th Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, USA.
  30. Collyns, T. A. & Wilson, H.L (2015). Efficacy of taurolidine-4% citrate solution in salvaging infected long-term intravascular catheters in haematology patients, p1214. In European Conference of Clinical Microbiology and Infectious Diseases. Copenhagen, Denmark.
  31. Fortun, J., Grill, F., Martin-Davila, P., Blazquez, J., Tato, M., Sanchez-Corral, J., Garcia-San Miguel, L. & Moreno, S. (2006). Treatment of long-term intravascular catheter-related bacteraemia with antibiotic-lock therapy. J Antimicrob Chemother 58, 816-821.
  32. Koldehoff, M. & Zakrzewski, J. L. (2004). Taurolidine is effective in the treatment of central venous catheter-related bloodstream infections in cancer patients. Int J Antimicrob Agents 24, 491-495.
  33. Sanchez-Munoz, A., Aguado, J. M., Lopez-Martin, A., Lopez-Medrano, F., Lumbreras, C., Rodriguez, F. J., Colomer, R. & Cortes-Funes, H. (2005). Usefulness of antibiotic-lock technique in management of oncology patients with uncomplicated bacteremia related to tunneled catheters. Eur J Clin Microbiol Infect Dis 24, 291-293.
  34. Torres-Viera, C., Thauvin-Eliopoulos, C., Souli, M., DeGirolami, P., Farris, M. G., Wennersten, C. B., Sofia, R. D. & Eliopoulos, G. M. (2000). Activities of taurolidine in vitro and in experimental enterococcal endocarditis. Antimicrobial Agents and Chemotherapy 44, 1720-1724.
  35. Allon, M. (2003). Prophylaxis against dialysis catheter-related bacteremia with a novel antimicrobial lock solution. Clin Infect Dis 36, 1539-1544.
  36. Jurewitsch, B., & Jeejeebhoy, K. N. (2005) Taurolidine lock: the key to prevention of recurrent catheter-related bloodstream infections. Clin Nutr, 24, 462-5.
  37. Shah CB, Mittelman MW, Costerton JW, Parenteau S, Pelak M, et al. (2002) Antimicrobial activity of a novel catheter lock solution. Antimicrob Agents Chemother 46: 1674–1679

Evidence levels:
A. Meta-analyses, randomised controlled trials/systematic reviews of RCTs
B. Robust experimental or observational studies
C. Expert consensus.
D. LTHT consensus.

Approved By

Improving Antimicrobial Prescribing Group

Document history

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Related information

Appendix 1. Issues specific to long term central vascular access devices (CVAD) used for parenteral nutrition (PN).

Parental Nutrition catheter salvage advice

Definitive management is catheter removal, but for many patients with difficult access / lifelong requirements, their CVAD is a life line.  Because of this, catheter salvage should be attempted if safe.  The decision to remove the catheter should be based on:

  • Clinical condition of the patient
  • The likelihood the CVAD is the source of the infection
  • The organism grown
  • The number of potential alternatives for venous access9.

If possible, the decision to remove a dedicated PN feeding catheter must be discussed with the PN team.

Salvage should NOT usually be attempted in the following situations:

  • Significant shock not responding to treatment
  • Bacteraemia persisting after 72 hours of appropriate treatment
  • Microorganisms known to be difficult to eradicate e.g. S. aureus, Mycobacterium spp, Pseudomonas species, Stenotrophomonas maltophilia and fungi
  • Presence of metastatic complications e.g. endocarditis or infected pulmonary embolism
  • Relapse of a CRBSI caused by the same bacteria after an appropriate course of antibiotics has been completed
  • Blocked CVADs or those that are not possible to bleed where there is a high clinical suspicion that the CVAD is the source of infection
  • Exit site infection in patients with a PICC and infections that involve the cuff in patients with a tunnelled catheter

During catheter salvage

  • The CVAD should NOT be used for PN or delivery of any medications other than the appropriate antibiotics being used to treat the infection
  • Alternative access should be sought.  Particularly with patients dependent on PN, it is important that they are not left without fluids.  A cannula for short term fluids is appropriate whilst blood cultures are awaited.
  • If the patient is asymptomatic after a minimum of 72 hours of appropriate catheter salvage therapy, a midline catheter can be inserted. PN may be administered through this until the long term CVAD can be re-used.
  • If the patient demonstrates a good response to catheter salvage therapy (apyrexial by day 5 of therapy and no evidence of on-going infection), treatment should continue for a total of 10 days. The catheter may be used for the administration of intravenous therapies without the need for repeat blood cultures.
  • If a patient spikes a temperature ≥38oC after re-starting infusions via the long term CVAD, stop infusions and repeat paired cultures.

Following CVAD removal:

  • Always site the new catheter away from inflamed skin
  • A new long term catheter should not be inserted until the bacteraemia has ended.  It is difficult to define specific criteria on which to make this assessment but consideration should be given to the success of source control i.e. catheter removal, drainage of any abscess, and clinical improvement e.g. resolution of cellulitis and improvement in inflammatory markers.

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Table 1. Empirical antimicrobial treatment of catheter-related infection in long-term catheters in adults.

Pathogen

Treatment with intravascular catheter removal

Attempted intravascular catheter salvage

Antimicrobial Agent

Dose**/route

Duration

Antimicrobial Agent[s]

Dose/route

Duration

Exit site infection
- no known pathogen (empirical)
- no systemic symptoms/signs
- no MRSA risk factors  

Flucloxacillin Description: electronic Medicines Compendium information on Flucloxacillin

500mg 6h PO

Review at 24 hours

N/A

Suspected catheter-related bloodstream infection (CRBSI)
-no known pathogen (empirical)
sepsis/septic shock 

Teicoplanin electronic Medicines Compendium information on Teicoplanin  
Plus
Ceftazidime Description: electronic Medicines Compendium information on Ceftazidime (<65s) OR
Piperacillin/tazobactam Description: electronic Medicines Compendium information on Piperacillin/tazobactam (>65s)

see dosing guidelines
1g 8h IV

4.5g 8h IV

Review at 24 hours

N/A

Suspected CRBSI
-no known pathogen (empirical)
-no  sepsis/septic shock

Teicoplanin electronic Medicines Compendium information on Teicoplanin

IV - see dosing guidelines

Review at 24 hours

N/A

** All doses assume normal renal function. Please ensure appropriate dose adjustments are made for patients on haemodialysis. These patients will be on Hi flux or haemodiafiltration 

 

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Table 2. Antimicrobial treatment of CRBSI (long-term intravascular catheters) caused by Gram positive pathogens.

Pathogen

Treatment with intravascular catheter removal

Attempted intravascular catheter salvage

Antimicrobial Agent

Dose**/route

Duration

Antimicrobial Agent

Dose**/route

Duration

Staphylococcus aureus
Meticillin-susceptible


Meticillin-resistant

Flucloxacillin Description: electronic Medicines Compendium information on Flucloxacillin

1g 6h IV

14 days

Not recommended

Teicoplanin electronic Medicines Compendium information on Teicoplanin

 
IV - see dosing guidelines

14 days

Not recommended

Coagulase-negative staphylococci

Meticillin-susceptible

 

Meticillin-resistant

Line removal sufficient in most situations$

Flucloxacillin Description: electronic Medicines Compendium information on Flucloxacillin (coupled with or followed by TaurolockTM lock therapy: Systemic antibiotic stopped when systemically better)

1g 6h IV

14 days total

Line removal sufficient in most situations$

Teicoplanin electronic Medicines Compendium information on Teicoplanin (coupled with /followed by TaurolockTM lock therapy: Systemic antibiotic stopped when systemically better)

 IV - see dosing guidelines

14 days total

Coryneforms [diphtheroids]

Line removal sufficient in most situations$

Teicoplanin electronic Medicines Compendium information on Teicoplanin (coupled with /  followed by  Taurolock TM lock therapy: Systemic antibiotic stopped when systemically better)

IV - see dosing guidelines

14 days total

Oral streptococci [penicillin-susceptible]

Benzyl penicillin Description: electronic Medicines Compendium information on Benzyl penicillin

1.2g 6 h IV

2-7days

Systemic penicillin
(coupled with /followed by Taurolock TM lock therapy: Systemic antibiotic stopped when systemically better)

1.2g 6h IV

14 days total

Enterococcus species
Amoxicillin Description: electronic Medicines Compendium information on Amoxicillin-susceptible

Amoxicillin Description: electronic Medicines Compendium information on Amoxicillin  -resistant, Vancomycin Description: electronic Medicines Compendium information on Vancomycin susceptible.

Amoxicillin Description: electronic Medicines Compendium information on Amoxicillin

1g 6h IV

5 days

Amoxicillin Description: electronic Medicines Compendium information on Amoxicillin + Gentamicin*
+/- Taurolock TM line lock

1g 6h IV
“low dose” IV#

14 days

Teicoplanin electronic Medicines Compendium information on Teicoplanin

IV - see dosing guidelines

5 days

Teicoplanin electronic Medicines Compendium information on Teicoplanin + Gentamicin*
+/- Taurolock TM line lock

 IV - See dosing guidelines
“low dose”  IV#

14 days

* provided isolate demonstrates “high-level” susceptibility to Gentamicin ; #, low dose or synergistic dosing requires pre-dose levels <1mg/L and 1 hour post dose levels 3-5mg/L; $, exceptions include endocarditis risk factors and neutropenia; IV, intravenous; po, oral administration.
** All doses assume normal renal function. Please ensure appropriate dose adjustments are made for patients on haemodialysis. These patients will be on Hi flux or haemodiafiltration 

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Table 3. Antimicrobial treatment of CRBSI (long-term intravascular catheters) in adults caused by Gram-negative pathogens.

Pathogen

Treatment with intravascular catheter removal

Attempted intravascular catheter salvage

Antimicrobial Agent

Dose*/route

Duration post line removal

Antimicrobial Agent

Dose*/route

Duration

Enterobacteriaceae e.g. Escherichia coli , Klebsiella spp., Enterobacter spp.

Amoxicillin Description: electronic Medicines Compendium information on Amoxicillin, OR

1g 6h IV

2-7 days

Amoxicillin Description: electronic Medicines Compendium information on Amoxicillin, OR

1g 6h IV

14 days total.

Piperacillin/tazobactam Description: electronic Medicines Compendium information on Piperacillin/tazobactam, OR

4.5g 8h IV

Piperacillin/tazobactam Description: electronic Medicines Compendium information on Piperacillin/tazobactam, OR

4.5g 8h IV

Ceftazidime Description: electronic Medicines Compendium information on Ceftazidime, OR

1g 8h IV

Ceftazidime Description: electronic Medicines Compendium information on Ceftazidime, OR

1g 8h IV

Meropenem Description: electronic Medicines Compendium information on Meropenem, OR

1g 8h IV

Meropenem Description: electronic Medicines Compendium information on Meropenem,

1g 8h IV

Ciprofloxacin Description: electronic Medicines Compendium information on Ciprofloxacin

750mg 12h PO

Coupled with /followed by Taurolock TM lock therapy. 
PO agent on basis of in vitro susceptibility, such as Ciprofloxacin Description: electronic Medicines Compendium information on Ciprofloxacin or Co-trimoxazole Description: electronic Medicines Compendium information on Co-trimoxazole, may be appropriate (in presence of luminal lock/s).

according to susceptibility and patient age (avoid Ceftazidime Description: electronic Medicines Compendium information on Ceftazidime in >65 years)

Pseudomonas aeruginosa

Piperacillin/tazobactam Description: electronic Medicines Compendium information on Piperacillin/tazobactam, OR

4.5g 8h IV

7 days

Not usually recommendedɑ

 

 

Ceftazidime Description: electronic Medicines Compendium information on Ceftazidime, OR

1g 8h IV

Meropenem Description: electronic Medicines Compendium information on Meropenem, OR

1g 8h IV

Ciprofloxacin Description: electronic Medicines Compendium information on Ciprofloxacin

500mg 12h PO

according to susceptibility and patient age (avoid Ceftazidime Description: electronic Medicines Compendium information on Ceftazidime in >65 years) according to susceptibility

Stenotrophomonas maltophilia

Co-trimoxazole Description: electronic Medicines Compendium information on Co-trimoxazole or

1.44g 12hr IV or PO.

7 days if neutropenic. 48 hours if not.

Not usually recommendedɑ

Ceftazidime Description: electronic Medicines Compendium information on Ceftazidime

1g 8h IV

*All doses assume normal renal function; IV, intravenous; PO, oral administration. Please ensure appropriate dose adjustments are made for patients on haemodialysis. These patients will be on Hi flux or haemodiafiltration.
ɑ In discussion with Microbiology, if being attempted.

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Table 4.  Antimicrobial treatment of CRBSI caused by fungi.

Pathogen

Treatment with intravascular catheter removal

Attempted intravascular catheter salvage

Antimicrobial Agent

Dose*/route

Duration post line removal

Antimicrobial Agent

Dose

Duration

Candida spp. fluconazole susceptible

Fluconazole Description: electronic Medicines Compendium information on Fluconazole

400mg daily IV or oral

14 days

Not recommended

Candida spp. fluconazole susceptible – dose dependant

Fluconazole Description: electronic Medicines Compendium information on Fluconazole

800mg daily IV or oral

14 days

Not recommended

Candida spp. fluconazole -resistant

Caspofungin Description: electronic Medicines Compendium information on Caspofungin

70mg loading then 50mg IV daily

14 days

Not recommended

*All doses assume normal renal function; IV, intravenous; po, oral administration. Please ensure appropriate dose adjustments are made for patients on haemodialysis. These patients will be on Hi flux or haemodiafiltration.

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Table 5: Antimicrobial lock options where salvage therapy is indicated.

Agent

Concentration

Minimum dwell time

Maximum dwell time

Taurolidine

Pre-prepared Taurolock TM

8h in every 24h

7 days*

Vancomycin electronic Medicines Compendium information on Vancomycin

5mg/ml

8h in every 24h

7 days

Gentamicin

10mg/ml

8h in every 24h

7 days

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

The volume used should match the volume of the lumen to be locked.

* though can be left in longer if required (but suggest not more than 14 days in treatment setting).  

Where possible, line locks should be used for the longest dwell time possible (up to stated maximum), and alternative access sought if IV treatment(s) required.

For patients who are not already established on regular appropriate antibiotics, it is advised that the line lock be administered immediately AFTER a dose of IV antibiotics given via a peripheral cannula.
Rationale: It has been observed that some patients suffer from a ‘septic shower’ following administration of line locks, as bacteria present within the lumen end up forced into their circulation. This has been noted in PN patients with gram negative bacteria in their lines, although the clinical deterioration could occur with other high-virulence pathogens.

If there are two (or more) lumens and it is not possible to lock off all lumens concurrently, consider alternating the lumen locked with that used for IV access (including systemic antimicrobials where required) on a 24 hourly basis.

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