1. Guideline Update for the
Management of Intravascular
Catheter-Related Infections
Sarah Nelson, Pharm.D.
Critical Care Pharmacy Resident
October 21 & 22, 2009

2. Objectives
 Identify common microorganisms associated with
intravascular catheter-related infections
 Analyze treatment options for infections associated
with short-term catheters
 Analyze treatment regimens for infections associated
with long-term and dialysis catheters
 Recognize appropriate utilization of antibiotic lock
therapy
 Summarize pathogen-specific treatment
recommendations for select microorganisms

3. Background

4. Epidemiology
 300 million catheters are used in the United
States each year
 Functions of intravascular catheters include
 Administration of fluids and medications
 Administration of blood products
 Administration of total parenteral nutrition
 Monitor hemodynamic status
 Provide hemodialysis
Mermel LA, Allon M, Bouza E, et a. Clinical practice guidelines for the diagnosis and management
of intravascular catheter-related infection: 2009 update by the IDSA. Clin Infect Disease. 2009;49:1-45

5. Epidemiology
 Nosocomial CRBSI > Community-acquired CRBSI
 21.6 cases of CRBSI per 1,000 hospital admissions
 Estimated case fatality rate of 20.6%
 ICU LOS increases by 9 to 11 days
Edgeworth, J. J Hosp Infect. 2009;10:1-8
Al-Rawajfah OM, Stetzer F, Hweitt JB. Infect Control Hosp Epidemiol. 2009;30:000
Ramritu P, Halton K, Collignon P, et al. An J Infect Control. 2008;36:104-17

6. Types of Intravascular Devices
Type Function
Peripheral venous catheter Short-term intravascular administration
Peripheral arterial catheter Monitor hemodynamics & blood gas
Short-term central venous
catheter (CVC)
Short-term intravascular administration
Pulmonary artery catheter Advanced hemodynamic monitoring
Peripherally inserted central
catheter (PICC)
Short-term intravascular administration
(alternative to a CVC)
Long-term CVC Long-term tunneled vascular access
Totally implantable device Long-term subcutaneous port/reservoir
with needle access
Mermel LA, Allon M, Bouza E, et al. Clin Infect Disease. 2009;49:1-45

7. Central Venous Catheters
http://microbix.com

8. Risk Factors for CRBSIs
 Type of intravascular device
 Intended use for catheter
 Insertion site
 Experience & education of installer
 Duration of catheter placement
 Characteristics of catheterized patient
 Utilization of preventative strategies
Mermel LA, Allon M, Bouza E, et a. Clinical practice guidelines for the diagnosis and management
of intravascular catheter-related infection: 2009 update by the IDSA. Clin Infect Disease. 2009;49:1-45

9. Diagnosis of CRBSI
 Catheter tip culture + blood culture
 Sonification of catheter
 Simultaneous quantitative blood cultures
 Differential time to positivity (DTP)
Edgeworth, J. Intravascular catheter infections. J Hosp Infect. 2009;10:1-8

10. Common Pathogens
 Percutaneous Catheters
 Coagulase-negative
staphlococci (CNS)
 Staphlococcus aureus
 Candida species
 Enteric gram-negative
bacilli
 Surgically Implanted &
Peripheral Catheters
 CNS
 Enteric gram-negative
bacilli
 Staphlococcus aureus
 Pseudomonas aeurginosa
Mermel LA, Allon M, Bouza E, et a. Clinical practice guidelines for the diagnosis and management
of intravascular catheter-related infection: 2009 update by the IDSA. Clin Infect Disease. 2009;49:1-45

11. Lorente et al
 Design: prospective cohort
 Patient population: Medical/Surgical ICU pts
with either a CVC or arterial catheter
 Outcome: assess proportion of CRBSI due to
gram – rods and yeast according to catheter
site
Lorente L, Jimenez A, Santana M et al. Microorganisms responsible for intravascular catheter
related bloodstream infection according to catheter site. Crit Care Med. 2007;35:2424-27

12. Lorente et al.
Lorente L, Jimenez A, Santana M et al. Microorganisms responsible for intravascular catheter
related bloodstream infection according to catheter site. Crit Care Med. 2007;35:2424-27
Femoral site n=36 Other site n=52
Gm + bacteria 16 47
CNS 8 29
MRSA 2 7
E. faecalis 4 2
Other 2 9
Gram – bacteria 14 4
E. coli 10 1
P. aeurginosa 1 2
Candida albicans 6 1

13. Antibiotic Selection

14. Empiric Antibiotic Selection
 Are antibiotics indicated?
 Signs/symptoms of infection
 Patient characteristics
 Where is the catheter located?
 Can/should the catheter be removed?

15. Catheter Removal
 Short-term CVC
 Not necessary unless: pt is severely ill, no other
sources of fever identified, pt has secondary
infections
 Long-term CVC/Port
 Not necessary unless complicated infection is
apparent (tunnel infection, port abscess,
secondary infections present)
Mermel LA, Allon M, Bouza E, et a. Clinical practice guidelines for the diagnosis and management
of intravascular catheter-related infection: 2009 update by the IDSA. Clin Infect Disease. 2009;49:1-45
Rijnders BJ, Peetermans WE, Verwaest C et al. Watchful waiting vs. immediate catheter removal in ICU patients with
suspected CRI: a randomized trial. Inten Care Med. 2004;30:1073-80

16. Empiric Antibiotic Therapy
 Gram + pathogen:
 Vancomycin is recommended
 Daptomycin if MRSA MIC consistently > 2 mcg/mL
 Gram – pathogen:
 Not always necessary
 Choice based off antibiogram and severity of
illness
 Single agent vs. double coverage of P. aeurginosa
 Double coverage should be used if pt is neutropenic, severely ill
with sepsis, or colonized with P. aeurginosa
Mermel LA, Allon M, Bouza E, et a. Clinical practice guidelines for the diagnosis and management
of intravascular catheter-related infection: 2009 update by the IDSA. Clin Infect Disease. 2009;49:1-45

17. Empiric Antifungals
 Not necessary unless patient is septic AND
has any of the following:
 TPN
 Prolonged use of broad-spectrum antibiotics
 Malignancy
 Transplant recipient
 Femoral catheter in place
 Multi-site Candida colonizaton
Mermel LA, Allon M, Bouza E, et a. Clinical practice guidelines for the diagnosis and management
of intravascular catheter-related infection: 2009 update by the IDSA. Clin Infect Disease. 2009;49:1-45

18. Tailored Antibiotic Therapy
 Detailed summary of preferred antibiotics
listed in guidelines
 Local antibiogram helps dictate tailored
therapy
 Duration of therapy dictated by site of
infection and pathogen isolated
 Day 1 of treatment is the first day on which a
negative blood culture is obtained
Mermel LA, Allon M, Bouza E, et a. Clinical practice guidelines for the diagnosis and management
of intravascular catheter-related infection: 2009 update by the IDSA. Clin Infect Disease. 2009;49:1-45

19. Guideline Algorithms

20. Patient with a short term CVC or arterial
line with acute febrile illness
Mild or moderately ill (no
hypotension or organ failure)
Seriously ill (hypotension,
hypoperfusion, s/sx organ dysfunction)
Consider
antimicrobial
therapy
Blood cultures (2
sets, 1 peripheral)
If no other
source of fever,
remove CVC or
AC and culture
tip, replace or
exchange CVC
Blood cultures (2
sets, 1 peripheral),
remove CVC or AC
and culture tip,
replace or
exchange CVC
Initiate
appropriate
antimicrobial
therapy
Blood culture (-) &
catheter not cultured
Blood culture (-) &
catheter culture (-)
Blood culture (-) &
catheter culture ≥15 CFU
Blood culture (+) &
catheter culture ≥15 CFU
Continued fever & no
other source found,
remove & culture
CVC or AC
Look for other
source of infection
See figure 2For S. aureus, treat for 5-7 days. For
all other microbes, monitor for s/sx
infection and send repeat blood
cultures appropriately

21. Short-term CVC or AC-related bloodstream infection
Complicated Uncomplicated (infection and fever
resolved within 72 hours, no
hardware, evidence of endocarditis or
suppurative thrombophlebitis, & if S.
aureus, no active malignancy or
immunosuppression)
Suppurative
thrombophlebit
is, endocarditis,
osteomyelitis,
etc
S. aureus Enterococcus Gram - bacilli Candida spCNS
Remove
catheter &
treat 4-6
weeks, 6-8
weeks for
osteomyleitis
Remove
catheter
and treat
with
systemic
Abx for 5-7
days
If catheter
is retained,
add ALT for
10-14 days
Remove
catheter
and treat
with
systemic
Abx for ≥
14 days
Remove
catheter
and treat
with
systemic
Abx for 7-
14 days
Remove
catheter
and treat
with
systemic
Abx for 7-
14 days
Remove
catheter
and treat
with
systemic
Abx for ≥
14 days
after 1st
negative
culture

22. Long-term CVC or port-related bacteremia or fungemia
UncomplicatedComplicated
Tunnel
infection/
port
abscess
Suppurative
thrombophlebitis,
endocarditis,
osteomyelitis
S. aureus Enterococcus Gram - bacilli Candida spCNS
Remove
CVC/P
and treat
with
systemic
Abx for 7-
10 days
Remove
CVC/P and
treat with
systemic Abx
for 4-6 weeks,
6-8 weeks for
osteomyelitis
Retain
CVC/P and
treat with
systemic
Abx + ALT
for 10-14
days
Remove
CVC/P and
treat with
systemic Abx
for 4-6 weeks
Retain
CVC/P and
treat with
systemic
Abx + ALT
for 7-14
days
Remove
catheter
and treat
with
systemic
Abx for ≥
14 days
after 1st
negative
culture
Remove and
treat with
systemic
Abx 7-14
days
OR
Retain and
treat with
systemic +
ALT for 10-
14 days
Remove CVC/P if there is clinical deterioration,
persisting bacteremia or signs of complicated infection

23. Tunneled HD catheter with suspected CRBSI
Empiric Abx + ALT
Negative blood cultures Persistent bacteremia/fungemia
and fever
Resolution of bacteremia/fungemia and
fever in 2-3 days
Stop Antibiotics CNS Gram - bacilli S. aureus C. albicans Remove CVC
and administer
antibiotics
Antibiotic tx for 10-
14 days, retain CVC
and continue ALT OR
replace CVC
Remove CVC &
treat with
systemic Abx for
3 weeks if TEE-
Replace catheter
and treat with
systemic Abx for ≥
14 days after 1st
negative culture
Systemic Abx
4-6 weeks and
look for signs
of complicated
infection
Persistent bacteremia/fungemia
and fever
Remove CVC
and administer
antibiotics
Systemic Abx
4-6 weeks and
look for signs
of complicated
infection

24. Guideline Changes

25. Changes to the 2009 Guidelines
 Short-term CVC
 Addition of arterial line infection
 Alteration of treatment duration
 Inclusion of antibiotic lock therapy
 Inclusion of specific therapy for Enterococcus sp.
 Long-term CVC
 Distinguishes hemodialysis catheter infection vs. long-
term CVC and port infection
 Alteration of treatment duration
 Inclusion of antibiotic lock therapy
 Inclusion of specific therapy for Enterococcus sp.
Mermel LA, Allon M, Bouza E, et a. Clinical practice guidelines for the diagnosis and management
of intravascular catheter-related infection: 2009 update by the IDSA. Clin Infect Disease. 2009;49:1-45

26. Coagulase-negative staphylococcus
 Most common contaminant AND cause of
CRBSI
 Benign clinical course
 Rarely leads to sepsis
 Little evidence to drive treatment
recommendations
 Remove catheter & DO NOT treat
 Treat systemically and/or ABL
Mermel LA, Allon M, Bouza E, et a. Clinical practice guidelines for the diagnosis and management
of intravascular catheter-related infection: 2009 update by the IDSA. Clin Infect Disease. 2009;49:1-45

27. S. aureus
 Important to determine uncomplicated from
complicated infection to determine treatment
duration
 Infective endocarditis commonly associated with S.
aureus bacteremia
 TEE should be completed 5-7 days after onset of bacteremia
 Risk factors associated with complicated S. aureus
bacteremia:
 + blood cultures >72 hours after initiation of Abx
 Community-acquired infection
 Skin changes consistent with septic emboli
Mermel LA, Allon M, Bouza E, et a. Clinical practice guidelines for the diagnosis and management
of intravascular catheter-related infection: 2009 update by the IDSA. Clin Infect Disease. 2009;49:1-45

28. S. aureus
 Wilcox et al
 Design: randomized, double-blind, non-inferiority
 Intervention:
 Vancomyin (weight-based dosing)
 Linezolid 600 mg every 12 hours
 Endpoint: Microbiological and clinical cure
 Outcome:
 Microbiological cure:
 86% for vancomycin vs. 81% for linezolid
 Clinical cure:
 76% for vancomcyin vs. 79% for linezolid
Wilcox MH, Tack KJ, Bouza E et al. Complicated skin and skin-structure infections and catheter-related bloodstream
infections: non-inferiority of linezolid in a phase 3 study. Clin Infect Dis. 2009;48:203-12

29. Enterococcus sp.
 New addition to the guidelines
 Account for 10% of all nosocomial
bloodstream infections
 60% of E. faecalis was resistant to vancomycin
 No good data to support
 Role of combination therapy
 Duration of treatment
Jones Rn, Marshall SA, Pfaller MA et al. Nosocomial enterococcal blood stream infections in the SCOPE program.
Diagn Microbiol Infect Dis. 2004;39:309-17

30. Gram - bacilli
 Rate of gram – bacilli associated CRBSI is
decreasing
 Resistance to gram – bacilli increasing
 Role of double antibiotic coverage for CRBSI
Wilcox MH, Tack KJ, Bouza E et al. Complicated skin and skin-structure infections and catheter-related bloodstream
infections: non-inferiority of linezolid in a phase 3 study. Clin Infect Dis. 2009;48:203-12

31. Gram - bacilli
 Safdar N et al.
 Design: meta-analysis
 Outcome: mortality in monotherapy vs.
combination therapy in gram – bacteremia
 Results:
 Combination therapy for P. aeurginosa demonstrated
a significant mortality benefit (OR 0.5, 95% CI 0.3-0.79)
 Mortality not reduced with utilization of combination
therapy for other gram - bacilli
Safdar N, Handelsman J, Maki D. Does combination antimicrobial therapy reduce mortality in gram-negative bacteremia?
Lancet Infect Dis. 2004;4:519-27

32. Antibiotic Lock Therapy

33. Antibiotic Lock Therapy (ALT)
 Attempt to salvage current intravascular
catheter
 Small amount of antibiotic is retained in the
catheter lumen to eradicate colonized
microorganisms
 Used in combination with systemic antibiotics
for 7-14 days
Segara-Newnham M, Martin-Cooper EM. Antibiotic Lock Technique: a review of the literature.
Annals of Pharmacotherapy. 2005;39:311-8

34. Advantages of ALT
 Negligible risk of adverse effects
 Increased local concentration of antibiotic
 Ease of administration
 Ability to administer in an outpatient setting
 Decreases need for catheter replacement
 Cost-saving measure
Segara-Newnham M, Martin-Cooper EM. Antibiotic Lock Technique: a review of the literature.
Annals of Pharmacotherapy. 2005;39:311-8

35. Types of ALT
 Antibiotics
 Cefazolin, 5mg/mL
 Vancomycin, 5mg/mL
 Ampicillin, 10 mg/mL
 Ceftazidime, 0.5 mg/mL
 Ciprofloxacin, 0.2 mg/mL
 Gentamicin, 1 mg/mL
 Ethanol 70%
Mermel LA, Allon M, Bouza E, et a. Clinical practice guidelines for the diagnosis and management
of intravascular catheter-related infection: 2009 update by the IDSA. Clin Infect Disease. 2009;49:1-45

36. Fernandez-Hidalgo et al.
 Design: retrospective/prospective
 Intervention
 Gram + organism: vancomycin 2 mg/mL
 Gram - organism: ciprofloxacin 2mg/mL OR amikacin 2
mg/mL
 Treatment duration: 10-14 days
 Outcomes
 Cure: negative cultures at 1 month
 Treatment failure: positive cultures or presence of fever
>72 hours after start of ALT or expansion of infection
 Relapse: new episode of infection with same
microorganism within 30 days of treatment completion
Fernandez-Hidalgo N, Almirante B, Calleja R, et al. Antibiotic lock therapy for long-term intravascular catheter-related
bacteremia: results of an open, non-comparative study. J Antimicro Chemotherapy. 2006:57:1172-80

37. Fernandez-Hidalgo et al.
Organism No. of isolates
Gram + organisms 80
CNS 56
S. aureus 20
E. faecalis 2
other 3
Gram – organisms 26
E. coli 11
P. aeurginosa 5
other 10
Polymicrobial infection 8
Fernandez-Hidalgo N, Almirante B, Calleja R, et al. Antibiotic lock therapy for long-term intravascular catheter-related
bacteremia: results of an open, non-comparative study. J Antimicro Chemotherapy. 2006:57:1172-80

38. Fernandez-Hidalgo et al.
 Treatment success occurred in 93 cases (82%)
 Gram + infection cure rate: 78%
 Gram - infection cure rate: 92%
 By treatment day 7, all cultures were negative
 Unsuccessful outcomes occurred in 21 cases
 Treatment failure: 13 cases
 Relapses: 7 cases
 Death: 1 case
 Mean catheter salvage duration: 163 days
Fernandez-Hidalgo N, Almirante B, Calleja R, et al. Antibiotic lock therapy for long-term intravascular catheter-related
bacteremia: results of an open, non-comparative study. J Antimicro Chemotherapy. 2006:57:1172-80

39. Fortun et al.
 Design: prospective, randomized
 Intervention
 Systemic therapy alone
 Systemic therapy + ALT
 Gram + organism: vancomycin 2 mg/mL
 Gram - organism: ciprofloxacin 2mg/mL OR gentamicin 2 mg/mL
 Treatment duration: 14 days
 Outcomes
 Cure: negative cultures 2-5 days after completion of
treatment and no colonization present
 Treatment failure: catheter removal, persistence of
colonization, relapse of bacteremia
Fortun J, Grill F, Martin-Davis, P. et al. Treatment of long-term intravascular catheter-related bacteremia with
antibiotic lock therapy. J Antimricob Chemotherapy. 2006;58:816-821

40. Fortun et al.
Organism ALT + systemic
therapy
N=19
Systemic therapy only
N=29
CNS 14 19
S. aureus 3 4
Gram -
bacteria
2 6
Fortun J, Grill F, Martin-Davis, P. et al. Treatment of long-term intravascular catheter-related bacteremia with
antibiotic lock therapy. J Antimricob Chemotherapy. 2006;58:816-821

41. Fortun et al.
Fortun J, Grill F, Martin-Davis, P. et al. Treatment of long-term intravascular catheter-related bacteremia with
antibiotic lock therapy. J Antimricob Chemotherapy. 2006;58:816-821

42. Ethanol Locks
 Antiseptic agent, bactericidal
 Active against gram + and gram – organisms
and fungi
 Non-toxic in doses administered
 Advantageous in patients with multi-drug
resistant pathogens
 May be best option for PREVENTION of CRBSI
and catheter colonization
Broom J, Woods M, Allworth A. Ethanol lock therapy to treat tunnelled central venous catheter associated blood
stream infections: results from a prospective trial. Scandinavian Journal of Infect Disesase. 2008;40:399-406

43. Prevention of CRBSI

44. Preventative Strategies
 Hand hygiene
 Sterile precautions during insertion
 Skin antisepsis (chlorhexidine, iodine)
 Daily inspection and documentation of exit site
 Avoidance of femoral site utilization
 Removal of device as soon as it is no longer
required
 Utilization of antimicrobial impregnated catheters
Edgeworth, J. Intravascular catheter infections. J Hosp Infect. 2009;10:1-8

45. Antimicrobial Impregnated CVCs
 Coating of catheters with antimicrobial compounds
External coating with chlorhexidine and silver sulfadiazine
(CH-SS)
 Silver, platinum, or carbon coating
 Antimicrobial coatings
 minocycline + rifampin (MR)
 vancomycin
 cefazolin
 Only externally coated CH-SS and MR coated
catheters reduced the risk of CRBSI as compared to
uncoated catheters
Ramritu P, Halton K, Collignon P, et al. A systematic review comparing the relative effectiveness
of antimicrobial-coated catheters in intensive care units. An J Infect Control. 2008;36:104-17

46. Take Home Points
 CRBSI are common and can happen with a variety of
intravascular devices
 CNS is the predominant pathogen causing CRBSI
 Pt characteristics may predispose them to other pathogens
 Catheter removal is not always necessary
 ‘Watch and wait’ method or antibiotic lock therapy may help avoid
catheter replacement
 Antibiotic lock therapy plays a larger role in current guidelines
 Guidelines demonstrate proper treatment for short-term,
long-term, tunneled, and port infections
 Prevention of CRBSI should not be forgotten

47. Questions?