Medicines Q&As
Q&A 379.1
Which antibiotics should be used to treat colonized central venous
catheters and how should they be administered?
Prepared by UK Medicines Information (UKMi) pharmacists for NHS healthcare professionals
Date prepared: 26th August 2011
Background
Catheter related blood stream infections (CRBSI) are relatively common infections with an incidence
reported to be around 1-10/1000 patient days [1]. CRBSIs independently increase both hospital cost
and length of stay [2-3]. CRBSIs occur most commonly from migration of pathogens from skin flora or
from contamination of the catheter hub [4-5], but can also occur from seeding from a secondary site
infection or from injection of a contaminated infusate [5-6]. Catheter-related infections can present as
exit site reactions, cellulitis along the subcutaneous tract, septicaemia or a combination of the above
[7-8] however true CRBSIs involve systemic infection and evidence implicating the catheter as its
source [9].
Central venous catheters are commonly used in patients who may already have impaired immune
function, such as those undergoing chemotherapy, haemodialysis patients and those in ITU [5,10].
These patients are therefore are at a higher risk of acquiring infections. Prompt and effective
treatment is needed to minimise further complications and deterioration of the patient [8].
CRBSIs often require catheter removal for effective treatment, however in some patients, who have a
continued need for an intravenous catheter, and in whom there are limited options for future lines,
catheter salvage may be attempted [3,5]. CRBSIs can be particularly complicated to treat if the
catheter is not removed as bacterial biofilms can develop in the catheter which can be resistant to the
penetration of antibacterials, and need much higher concentrations of antibiotics than those given
systemically [11]. Therefore, in patients where catheter salvage is attempted, effective treatment
protocols are needed to increase the chance of catheter salvage whilst reducing morbidity and
mortality.
Answer
Where a CRBSI is highly suspected the general principles of treating CRBSIs empirically are the
same as those used for treating infections of unknown origin but with particular attention to the likely
pathogens involved in CRBSI [2,7]. Local policies should be followed where available. The decision
to salvage the catheter is a complex one and should be made on an individual basis taking into
account factors such as the clinical condition of the patient, the continuing need for the central line,
the pathogen(s) involved and the response to treatment [5,8]. If the catheter is no longer required it
should always be removed [12]. The information provided here is aimed at assisting the selection of
an appropriate antibiotic to treat a CRBSI and is not intended to guide the decision as to whether or
not to remove the catheter. Where attempts at catheter salvage are unsuccessful i.e. the blood
cultures remain positive 72 hours after the initiation of appropriate antimicrobial therapy, fever does
not resolve, or the patient deteriorates, the catheter should be removed [2,5]. Where catheter salvage
is attempted it is recommended that both systemic antibiotics and antibiotic line locks are used
concurrently [2,5]
Pathogens
The most common pathogens implicated in CRBSI are:



Coagulase-negative staphylococci (in particular S.epidermis)
Staphylococcus aureus
Candida
From the NHS Evidence website www.evidence.nhs.uk
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Medicines Q&As
 Enterococci
 Gram negative bacilli
[ 2, 5, 12-14]
Although a variety of other bacteria have been implicated and combinations of pathogens have been
found. Coagulase-negative staphylococci are frequently cited as the most common pathogens which
cause CRBSI [2,5,7,8,10,11] although specific populations can have different prevalence of infection
[8]. Most of these pathogens are methicillin resistant [2] and teicoplanin resistance is also observed
with coagulase-negative staphylococci [15]; this should be taken into account when considering
empirical treatment [2].
In 2009 the Infectious Diseases Society of America (IDSA) updated their guidelines for the diagnosis
and management of CRBSI [2]. They have produced evidence based guidelines which are endorsed
by the European Society of Clinical Microbiology and Infectious Diseases and are used as a basis for
the EPIC-2 guidelines for prevention of hospital acquired infections in the NHS [9]. Information on the
antibiotic of choice, including suggested dosages are given according to pathogen and there is also
guidance on choice of empirical therapy and antibiotic lock [2].
Systemic Treatment
Systemic antibiotics are generally given whether or not the catheter is removed [2,7]. The duration of
antibiotic treatment depends on the pathogen involved, whether the patient experiences infective
complications such as endocarditis or osteomyelitis and whether the line remains in situ [2,8].
Table 1: Guidelines for the systemic treatment of catheter infections by pathogen [2,5,7,16]
Infection
S aureus (Methicillinsensitive)
S aureus (Methicillinresistant)
Coagulase-negative
staphylococci
Catheter removal
generally recommended
Yes – failure to remove
catheter leads to
significant morbidity
Yes – failure to remove
catheter leads to
significant morbidity
No
Enterococci
No
Candida albicans
Yes
Recommended Antibiotics
Length of treatment
Penicillinase-resistant
penicillin
At least 14 days a
Glycopeptide, linezolidb (if
glycopeptide resistance),
daptomycin
Penicillinase-resistant
penicillin
Glycopeptide c if methicillin
resistance
Aminopenicillin ±
aminoglycoside
Or glycopeptide ±
aminoglycoside if ampicillin
resistance
Azole, echinocandin or
amphotericin –b lipid based
formulation
At least 14 days a
5-7 days after
defervescenced
If line retained treat
for 10-14 days
5-14 days after
defervescence
Treat for 14 days
following first
negative blood
culture a
Others
Dependent on pathogen
As per sensitivity
Dependent on
pathogen
aConsider treatment for 4-6 weeks in patients at risk of endocarditis.or with persistent bacteremia or
fungemia 72 hours after initiation of appropriate antimicrobials, or removal of the catheter [2,5]. In
patients with confirmed endocarditis or osteomyelitis consider up to 8 week’s antimicrobial therapy [2].
bLinezolid should not be used for empirical therapy [2]
c Vancomycin is preferred if there is local teicoplanin resistance [16]
d defervescence – return to normal temperature
From the NHS Evidence website www.evidence.nhs.uk
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Medicines Q&As
Initial antibiotic therapy will be empirical and based on the severity of the patient’s condition, the likely
pathogens involved and the local resistance patterns [5,8]. Broad spectrum Gram positive cover
should be provided due to the high incidence of CRBSIs due to Gram positive organisms. Cover for
Gram-negative bacteria and fungal infections may also be added dependent on the patient’s clinical
condition and their infection and antimicrobial history [5,8,13].
Vancomycin is frequently cited as the antibiotic of choice for empirical treatment [8,10]; however
consideration should be given to the prevalence of vancomycin resistance in the institution [2,8].
There is a question over the liberal use of vancomycin as this may lead to further vancomycin
resistance developing [13]. The clinical success rate is reduced if the minimum inhibitory
concentration for vancomycin in treating MRSA is greater than 2mg/L [2].
Empirical treatment should be altered based on culture results as soon as these are available [7,8].
Antibiotic Line Lock
Bacteria involved in CRBSI can form biofilms within the catheter lumen which may be resistant to
treatment with the concentrations of antibiotics achieved when given systemically [2,11]. If the
bacteria in the biofilm are not eradicated then they can continue to produce systemic infections until
the line is removed. Prompt treatment is necessary as the longer the biofilm is present, the more
resistant the microorganisms within it become to antimicrobial therapy [6] Antibiotic line-locks allow
much higher concentrations of antibiotics to be applied directly to the catheter without associated
systemic effects [11,17]. Although there is still some debate on the effectiveness of line locks,
combining antibiotic line locks with systemic antibiotic treatment has been effectively used to treat
CRBSI resulting in eradication of the infection, and increased infection free survival, whilst the
catheter remains in situ [3,17].
The technique involves filling the catheter lumen with an antibiotic at concentrations of 100-1000
times greater than those needed to kill the organisms involved [2,11] and leaving it in situ for
approximately 6-24 hours [2,3,6,11,18] or up to 48 hours in between dialysis sessions in intermittent
haemodialysis [2]. For CRBSIs they are used alongside systemic antibiotics but they have been used
alone in cases where there it is thought that the infection is limited to the catheter itself [2,3].
The majority of evidence for their use in line locks involves non-comparative studies or uncontrolled
trials, where suitability of the patient for treatment with line lock or catheter removal was decided by
the clinician treating the patient [17]. Therefore the comparison of success rates made between those
treated with line-locks and those patients who had their catheters removed may be influenced by
selection bias and a lack of statistical power due to the small numbers of patients involved [17].
There is insufficient evidence to recommend the use of one antibiotic over another. As with the wide
use of systemic vancomycin in treating CRBSIs there has also been concern over the generalized use
of vancomycin in line locks and the development of antimicrobial resistance [17-18]. It has also been
reported that vancomycin only has limited effectiveness against bacteria embedded in a biofilm [10,
19].
Heparin is often recommended to be used with antibiotics in line-locks to help antibiotics penetrate
into the biofilm [2-3,11]. There is guidance available on the use of heparin line locks to maintain
patency of catheters between dialysis sessions following concerns that heparin in the line lock can
leach out into the systemic circulation and exert a therapeutic effect [20-21] . NICE guidelines
recommend that preferably, sodium chloride 0.9% injection is used to flush and lock catheter lumens;
however heparin locks can be used when recommended by the manufacturer [22]. Information
coming from in vitro stability studies of heparin and antibiotic line lock solutions shows that increasing
concentrations of antibiotic need higher concentrations of heparin to maintain solubility and prevent
precipitation [20]. The IDSA guidelines recommend using 50-100units of heparin per lock [2].
Consideration should be given to the strength of heparin solution used in antibiotic line-locks as high
concentrations of heparin may lead to a therapeutic anticoagulant effect. The use of heparin in line
locks is a local decision and where its use is advised it should be prescribed, staff administering it
should be fully trained and a policy on its use available [21].
From the NHS Evidence website www.evidence.nhs.uk
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Medicines Q&As
Theoretically there could also be a potential for the antibiotic in the line to leach out into the systemic
circulation, however although the concentration of antibiotic in the line lock is high, the total amount
given in the line lock is generally only a small fraction of the total dose given. Therefore even if the
total dose leached into the systemic circulation this should not be clinically important in adults [6].
Antimicrobial line locks containing taurolidine and citrate are in use in the UK [15, 23]. Taurolidine
has been shown to have broad-spectrum antimicrobial activity [6] and citrate is used as an
anticoagulant, but may also enhance antimicrobial activity [6, 10]. The FDA advises against using
citrate concentrations which exceed 4% as higher concentrations have been shown to impair cardiac
function [6]. At present the majority of evidence for taurolidine and citrate line-locks is in prevention of
CRBSI rather than treatment [6, 10]. Further research into the use of taurolidine-citrate line locks for
the treatment of CRBSIs is warranted.
Ethanol has been suggested as suitable for use as an antimicrobial in antibiotic lock therapy however
as there is insufficient evidence at this time, its use cannot be recommended [2, 24].
There are reviews on the evidence of the use of antibiotic lock therapy to treat CRBSIs [3,11,17] and
on the stability and in vitro efficacy of antibiotic lock solutions [20].
Summary
CRBSIs are common infections occurring in patients with long-term central venous catheters.
Patients can have their catheter removed or can be treated whilst the catheter remains in situ
(catheter salvage). The choice of initial antibiotic is empiric and based on the likely pathogens
involved and local patterns of resistance. Where the patient is treated with the catheter in situ,
antibiotic line lock is generally added to systemic treatment to help sterilise the catheter. Duration of
treatment depends on whether the catheter is removed, the pathogens involved and whether the
patient develops any complications.
Limitations
The aim of this document is to provide guidance on the appropriate treatment of catheter related
infections. The decision to attempt catheter salvation is complex and based on multiple factors. This
Q&A does not attempt to guide decisions on whether catheter salvation should be attempted. The
use of antibiotic line locks and other treatments to prevent CRBSI is not covered here.
Disclaimer
 Medicines Q&As are intended for healthcare professionals and reflect UK practice.
 Each Q&A relates only to the clinical scenario described.
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 The authors of Medicines Q&As are not responsible for the content of external websites and
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must use your judgement to determine the accuracy and relevance of the information they
contain.
 See www.ukmi.nhs.uk/activities/medicinesQAs/default.asp for full disclaimer.
References
1. The Renal Association. Vascular Access for Haemodialysis. Guideline. Issue date: 2011
Accessed online via http://www.renal.org on 25/07/2011
2. Mermel LA, Allon M, Bouza E, et al, Clinical practice guidelines for the diagnosis and
management of catheter-related infection: 2009 update by the Infectious Diseases Society of
America. Clin Infect Dis. 2009; 49(1): 1-45
3. Bestul MB, VandenBussche HL. Antibiotic lock technique: review of the literature.
Pharmacotherapy. 2005; 25(2) 211-27
4. Snaterse M, Ruger W, Scholte op Reimer WJM, Lucas C. Antibiotic-based catheter lock
solutions for prevention of catheter-related bloodstream infection: a systematic review of
randomised control trials. J Hosp Infect. 2010; 75: 1-11
From the NHS Evidence website www.evidence.nhs.uk
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Medicines Q&As
5. Leonidou L, Gogos CA. Catheter-related bloodstream infections: catheter management
according to pathogen. Intl J Antimicrob Agents. 2010; 36S: S26 –S32
6. Bagnall-Reeb H. Evidence for the use of the antibiotic lock technique. J Infusion Nursing.
2004; 27(2): 118-22
7. Wolf HH, Leithauser M, Maschmeyer G, et al. Central venous catheter-related infections in
hematology and oncology. Ann Hematol. 2008; 87: 863-76
8. Sabatier C, Ferrer R, Valles J. Treatment strategies for central venous catheter infections.
Expert Opin Pharmacother. 2009; 10(14): 2231-43
9. Pratt RJ, Pellowe CM, Wilson JA, et al. Epic2: National evidence based guidelines for
preventing healthcare-associated infections in NHS hospitals in England. J Hosp Infect.
2007; 655: S1-S64
10. Raad I, Hanna H, Maki D. Intravascular catheter-related infections: advances in diagnosis,
prevention and management. Lancet infect Dis. 2007; 7: 645-57
11. Segarra-Newnham M, Martin-Cooper EM. Antibiotic lock technique. A review of the literature.
Ann Pharmacother. 2005; 39: 311-17
12. Flynn PM. Diagnosis and management of central venous catheter-related bloodstream
infections in pediatric patients. Pediatr Infect Dis J. 2009; 28: 1016-7
13. Katneni R, Hedayati SS. Central venous catheter-related bacteremia in chronic
haemodialysis patients: epidemiology and evidence-based management. Nature Clinical
Practice Nephrology. 2007; 3(5): 256-66
14. O’Grady NP, Chertow DS. Managing bloodstream infections in patients who have short-term
central venous catheters. Cleve Clin J Med. 2011; 78(1): 10-17
15. Personal communication, Consultant microbiologists. University Hospitals Bristol NHS
Foundation Trust. 26/08/2011
16. Personal communication, Antimicrobial pharmacist. University Hospitals Bristol NHS
Foundation Trust, 30/08/2011
17. Korbila IP, Bliziotis IA, Lawrence KR, Falagas ME. Antibiotic-lock therapy for long-term
catheter-related bacteremia: a review of the current evidence. Expert Rev Anti-Infect Ther.
2007; 5(4): 639-52
18. Fortun J, Grill F, Martin-Davila P, et al. Treatment of long-term intravascular catheter-related
bacteraemia with antibiotic-lock therapy. J Antimicrobial Chemo. 2006; 58: 816-21
19. Troidle L, Finkelstein FO. Catheter-related bacteremia in hemodialysis patients: the role of the
central venous catheter in prevention and therapy. Int J Artif Organs. 2008; 31(9): 827-33
20. Droste JC, Jeraj HA, Macdonald A, Farrington K. Stability and in vitro efficacy of antibioticheparin lock solutions potentially useful for treatment of central venous catheter-related
sepsis. J Antimicrobial Chemo. 2003; 51: 849-55
21. The Renal Association. Haemodialysis: Anticoagulation and catheter lock solutions.
Guideline. Issue date: December 2009. Accessed online via http://www.renal.org on
25/07/2011
22. NICE National Institute for Health and Clinical Excellence. Infection Control NICE Clinical
Guideline CG2. Issue date: 2003. Accessed online via www.nice.org.uk on 25/07/2011
23. TauroPharm GmbH. Product Information – TauroLock. Acessed online via
http://www.kimal.co.uk/access-taurolock.htm on 26/08/2011
24. DRUGDEX Drug Consult: Antibiotic lock therapy for catheter related infection. Accessed via
www.thomsonhc.com on 25/07/2011
Quality Assurance
Prepared by
Nicola Greenhalgh, South West Medicines Information, University Hospitals Bristol NHS Foundation
Trust
Date Prepared
26th August 2011
From the NHS Evidence website www.evidence.nhs.uk
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Medicines Q&As
Checked by
Julia Kuczynska, South West Medicines Information, University Hospitals Bristol NHS Foundation
Trust
Date of check
31st August 2011
Search strategy
Embase: *CENTRAL VENOUS CATHETERS AND *INFECTION/dt AND *CATHETER INFECTION
[limit to Human and English Language]
CATHETER INFECTION AND ANTIBIOTIC THERAPY [Limit to: (Publication Types Review) and
English language]
Medline: BACTEREMIA AND ANTI-BACTERIAL AGENTS AND CATHETERIZATION, CENTRAL
VENOUS
*CATHETERIZATION, CENTRAL VENOUS and *INFECTION
In-house database/ resources
National Institute for Health and Clinical Excellence http://www.nice.org.uk/
The Renal Association: http://www.renal.org/home.aspx
British Society for Antimicrobial Chemotherapy http://www.bsac.org.uk/
National Electronic Library for Medicines http://www.nelm.nhs.uk/en/
Consultant microbiologists. University Hospitals Bristol NHS Foundation Trust.
Specialist anti-infective pharmacist. University Hospitals Bristol NHS Foundation Trust
From the NHS Evidence website www.evidence.nhs.uk
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