Central Venous Catheter Infections: Definitions Definitive

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ENDOTOXIN DRIP

• Mathew A Cherian

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I have no disclosures
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Estimated annual number of central
lineassociated blood stream infections
(CLABSIs), by health-care setting and year
United States, 2001, 2008, and 2009
MMWR / March 4, 2011 / Vol. 60 / No. 8
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• Catheter associated blood stream infections are
  associated with a mortality of 12 to 25.
• Each central line associated blood stream
  infection costs the system 16550/-.

MMWR / March 4, 2011 / Vol. 60 / No. 8
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Bacterial Biofilm Formation

• Once bacteria reach a threshold density they
  sense quorum through quorum sensing pathways.
• These pathways allow bacteria to sense their own
  density.
• Different molecules used by different bacteria to
  sense quorum
• Gram negativesAcyl Homoserine lactones( the acyl
  chain varies from species to species).

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Mechanism of Quorum sensing in gram
negative bacteria
Mechanism of Quorum sensing in gram
positive bacteria
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Quorum-sensing molecules regulating various
functions in Gram negative bacteria
Phil. Trans. R. Soc. B 2007 362, 1119-1134
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ONCE BACTERIA REACH QUORUM THIS ACTIVATES

• Virulence
• Swarming and motility
• BIOFILM FORMATION
• Secondary metabolite producton
• Conjugation
• GROWTH INHIBITION
• PRODUCTION OF EXOTOXINS

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• Several human-pathogenic bacteria are known to
  produce Acyl homoserine Lactone dependent
  biofilms including Pseudomonas aeruginosa,
  Burkholderia cepacia, Serratia marescens.
• Biofilms are aggregates of microorganisms that
  adhere to a solid surface in a matrix composed
  of extracellular biopolymers.

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BIOFILM FORMATION
Scanning electron micrograph
Phase contrast
CLINICAL MICROBIOLOGY REVIEWS, Apr. 2002, p.
167193
SCIENCE VOL. 280 10 APRIL 1998
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Biofilm polymers
Nat. Prod. Rep., 2010, 27, 343369
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Once bacteria are protected in the biofilm a
1000X concentration of antibiotics is required to
be effective
CLINICAL MICROBIOLOGY REVIEWS, Apr. 2002, p.
167193
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CVC infectionsClassification
v
Extraluminal colonization
Endoluminal colonization
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Entrance/Insertion Site
Exit Site
Tunnel
Sites of extraluminal central venous catheter
infections
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Central Venous Catheter InfectionsDefinitions

• Catheter Colonizationbacterial growth without
  inflammation.
• Catheter Infectionbacterial growth with a host
  response(inflammation, local or systemic).
• Colonization need not be treated under most
  circumstances but does put the patient at a
  higher risk of developing a line infection.

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Central Venous Catheter Infections Definitions

• Definitive diagnosis of a catheter related blood
  stream infection requires
• 1.Atleast one positive PERIPHERAL BLOOD CULTURE
• 2.Either a positive blood culture of the same
  organism drawn from the suspected line the or if
  the catheter was removed a positive
  semiquantitative/ quantitative culture of gt15 cfu
  from a 5 cm catheter tip segment or gt102 cfu by
  sonification.

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• For a defiitve diagnosis if the diagnosis is
  based on blood cultures, quantitative blood
  cultures showing a 3 fold excess of cfu in the
  blood culture drawn from the central catheter,
  over that drawn from the periphery OR a
  differential time to positivity of gt2 hours
  between the 2 blood cultures(catheter before
  peripheral).

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• If a simultaneous catheter and peripheral blood
  draw cannot be done two blood culture should be
  drawn from two separate lumens and a 3 fold
  difference in quantitative culture between the
  two indicates a probable catheter infection.

Pediatr Infect Dis J. 2005 May24(5)445-9.
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Definition of SIRS

• Any two or more of the following
• Temperature gt38.5C or lt35.0C
• Heart rate of gt90 beats/min
• Respiratory rate of gt20 breaths/min or PaCO2 of
  lt32 mm Hg
• WBC count of gt12,000 cells/mL, lt4000 cells/mL, or
  gt10 percent immature (band) forms
• SepsisSIRSinfection

Septic shock. Lancet 2005 36563
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Severe sepsisSepsis Syndrome one of the
following

• Areas of mottled skin
• Capillary refilling requires three seconds or
  longer
• Urine output lt0.5 mL/kg/hr for at least one hour,
  or renal replacement therapy
• Lactate gt2 mmol/L
• Acute lung injury or acute respiratory distress
  syndrome (ARDS) RESPIRATORY FAILURE WITH
  INFILTRATES IS NOT ALWAYS PNEUMONIA AND MAY BE
  ARDS/ALI FROM EXTRAPULMONARY INFECTION INCLUDING
  LINE INFECTIONS
• Cardiac dysfunction, as defined by
  echocardiography or direct measurement of the
  cardiac index
• Abnormal electroencephalographic (EEG) findings
• Abrupt change in mental status
• Platelet count lt100,000 platelets/mL
• Disseminated intravascular coagulation

Septic shock. Lancet 2005 36563
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Cost of Removing line (alternate
access, Procedural complications)
How sick is the patient
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Microbiology of central line associated blood
stream infection

• Coagulase-negative staphylococci 31 percent
• Staphylococcus aureus 20 percent
• Enterococci 9 percent
• Candida species 9 percent
• Escherichia coli 6 percent
• Klebsiella species 5 percent
• Pseudomonas species 4 percent
• Enterobacter species 4 percent
• Serratia species 2 percent
• Acinetobacter baumannii 1 percent

Clin Infect Dis. 200439(3)309
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Extraluminal infections

• Extra-luminal infections may occur in the
  presence or absence of accompanying bacteremia or
  systemic symptoms.
• Any drainage/exudate at the exit site should
  be swabbed for culture and gram stain if present.

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Extraluminal infections
Erythematous CVC site
Systemic symptoms
Swab site and send blood cultures from
periphery and CVC
Bacteremic or severe sepsis
Non bacteremic, no severe sepsis
Remove line
Bacteremicminimum 14 days systemic therapy and
more depending on organism
Try systemic antimicrobials , modify according to
swab results, remove line if worsenng or lack of
response at 72 hrs
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Extraluminal infections
Eryhtematous CVC site
Swab the site for culture and gram stain and send
blood cultures(fungal and mycobacterial if
immunocompromised)
Tunnel erythema without alternative explanation
Exit site erythema, no purulent drainage, no
systemic symptoms,non bacteremic
Drainage and purulence/systemic symptoms, but no
severe sepsis no bacteremia
Remove the line
Try topical antimicrobials-mupirocin /lotrimin
depending on swab
Try Systemic antimicrobials, modify by swab
results
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Exchange of a catheter over the wire and
antibiotic lock therapy are not options for
extraluminal infections.
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Intraluminal Infections
Patient with short term central venous
catheter/arterial catheter and systemic symptoms
Send blood cultures from PERIPHERAL VEIN and from
catheter
Severe sepsis
No severe sepsis
Consider empiric antimicrobials
Initiate empiric antibiotic therapy
No other source of fever identified
Remove CVC/AC and send tip for culture and
sensitivity
Remove short term CVC or AC/exchange on guidewire
All cultures negativediscontinue ABx, look for
other source
Catheter c/s ve but blood c/s vetreat if S
aureus for 5 to 7 days, if other organisms
reasonable to discontinue therapy if symptoms
have resolved
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Both short term Central venous catheter/Arterial
catheter and blood cultures
positive
Supurative thrombophlebitis/endocarditis/
osteomyelitis/fever or bacteremia persist at 72
hrs
Uncomplicated bacteremia which resolves and
clinically improves by 72 hrs
Remove catheter and administer 4-6 weeks of
systemic antibiotics
Enterococcus/ Gram-ve bacilli not Pseudomonas
Coag-ve Staph(rpted ultures)
Staph aureus
Candida species
Remove catheter and treat for 5 to 7 days OR
retain catheter and treat with lock therapy and
systemic therapy for 10-14 days
Remove CVC/AC and treat for minimum of 4 weeks
unless specific criteria are met for shorter Rx
Remove catheter and treat with systemic Abx for
14 days after ve culture
Remove catheter and treat with systemic Abx for
7-14 days
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• If the short term CVC is retained due to lack of
  alternative access, risk of removing the line due
  to coagulopathy, either antibiotic lock therapy
  for the same duration as systemic antibiotics OR
  guidewire exchange should be performed at a
  minimum.
• If the catheter is retained consider follow up
  blood cultures after the completion of systemic
  therapy.

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Intraluminal Infections
Patient with long term(tunneled) central venous
catheter and systemic symptoms
Send blood cultures from PERIPHERAL VEIN and from
catheter
Severe sepsis
No severe sepsis
Consider empiric antimicrobials
Initiate empiric antibiotic therapy
No other source of fever identified
Remove CVC/AC and send tip for culture and
sensitivity
All cultures negativediscontinue ABx if symptoms
resolved, look for other source
Catheter c/s ve but blood c/s vetreat if S
aureus for 5 to 7 days, if other organisms
reasonable to discontinue therapy if symptoms
have resolved
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Both long term CVC and blood cultures positive
Supurative thrombophlebitis/endocarditis/
osteomyelitis/fever or bacteremia persists at 72
hrs after starting appropriate ABx
Uncomplicated bacteremia which resolves and
clinically improves by 72 hrs
Remove catheter and administer 4-6 weeks of
systemic antibiotics
Enterococcus/ Gram-ve bacilli/ Not Pseudomonas
Staph aureus
Coag-ve Staph
Candida species
Retain catheter and treat with lock therapy and
systemic therapy for 10-14 days
Remove catheter and treat for minimum of 4 weeks
unless specific criteria are met for shorter Rx
Remove catheter and treat with systemic Abx for
14 days after ve culture
Retain catheter and treat with lock therapy and
systemic therapy for 7-14 days
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• If the catheter is retained consider follow up
  blood cultures after the completion oof systemic
  therapy.

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Patients with S aureus central line infection
should have the catheter removed and 4 to 6 weeks
of antimicrobial therapy, but can be considered
for 14 days therapy if

• Non diabetic
• Non immunosuppressed
• Non neutropenic
• Has no prosthetic intravascular device
• No symptoms or signs of metastatic infection
• Has a negative TEE done atleast 5 to 7 days AFTER
  THE ONSET OF BACTEREMIA(to avoid false negatives)
• NO evidence of suppurative thrombophlebitis on
  ultrasound of the affected vein
• Fever and bacteremia resolve within 72 hr after
  initiation of appropriate antibiotic therapy

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• The high risk of infective endocarditis and
  metastatic infection (esp vertebral
  osteomyelitis) dictates the long duration of
  therapy for S aureua bacteremia.
• Studies in which TEEs are performed routinely
  reveal vegetations in 25 of patients. J Am Coll
  Cardiol. 1997 Oct30(4)1072-8
• Risk of vertebral osteomyelitis, which can occur
  upto a year after the bacteremic episode, is 3.
• Arch Intern Med. 2003 Sep 22163(17)2066-72.
  

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In the rare event a catheter is retained
with S aureus bacteremia

• Systemic and antibiotic lock therapy for 4 weeks
  at a minimum.(Nephrol Dial Transplant (2004) 19
  12371244)
• Try to exchange over a guidewire(JPEN J Parenter
  Enteral Nutr. 1988 Nov-Dec12(6)628-32)

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• Administration of IV antibiotics alone is not
  sufficient therapy for CVC infections as the
  majority of patients have recurrence once the
  antibiotic course is completed .
• Am J Kidney Dis. 1999 Dec34(6)1114-24(63.3
  failure rate).
• Ann Intern Med. 1997 Aug 15127(4)275-80(87
  failure for G ve and 50 failure rate for G-ve)

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• Repeat blood cultures should be obtained 48 to 72
  hrs after the initial positive blood culture to
  confirm clearance of bacteremia.
• Duration of antibiotic therapy refers to DAYS
  AFTER FIRST NEGATIVE BLOOD CULTURE, NOT FROM THE
  INITIATION OF ANTIBIOTIC THERAPY.

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Catheters should always be removed if the
following are present

• Staphylococcus aureus bacteremia
• Candidemia
• Pseudomonas bacteremia
• Repeated positive cultures for Propionobacterium,
  Bacillus, Micrococcus
• Any multi drug resistant organism for which few
  options are available in terms of antimicrobials.
• Infective endocarditis
• Septic thrombophlebitis
• Metastatic infection
• Persistently positive fever or blood cultures at
  72 hours after initiation of appropriate Abx
  therapy

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When should a critically ill patient with a
suspected line infection receive anticandideal
therapy empirically

• Femoral catheter
• TPN
• Prolonged use of Abx
• Hematologic malignany
• Stem cell or solid organ transplant
• Colonization with Candida species at multiple
  sites

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• Empiric anti candideal therapy should start
  with an echinocandin unless the patient
• Has had no exposure to azoles in the last 3
  months
• The institutional risk of Candida krusei and
  glabrata is low.

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AREAS OF UNCLEAR EVIDENCE

• If a patient is post chemotherapy, has mucositis,
  do the same rules for catheter removal for
  bacteremia with gut pathogens (enterococci,
  enterobacteriaceae and Candida ) apply.
• What is the management of positive CVC culture
  but ve peripheral cultures in a patient with
  systemic symptoms.
• Sensitivity is low for CVC infection in patients
  who are already on or who have recently received
  ABx ? future role for 16S ribosomal RNA PCR?

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Summary of published studies on effectiveness of
antibiotic-lock therapy for catheter-related
bacteraemia
Journal of Antimicrobial Chemotherapy (2006) 57,
11721180
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Summary of published studies on effectiveness of
antibiotic-lock therapy for catheter-related
bacteraemia
Journal of Antimicrobial Chemotherapy (2006) 57,
11721180
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Antibiotic lock therapySystemic therapy is
ineffective for Staph aureus bacteremia with a
high failure rate(approx 55).

J Antimicrob Chemother. 2006 Jun57(6)1172-80.
Epub 2006 Apr 5
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Preclinical data suggests lock therapy may work
for candideal line infections but it is
clinically not recommended
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Case series and case reports describe small
numbers of patients successfully treated with
Amphoterecin B locksthis is not currently
recommended unless there are unusual cicumstances
preventing catheter removal.
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• A study of antibiotic lock therapy in patients
  with dialysis catheters suggested overall longer
  infection free survival in patients who received
  lock therapy rather than routine catheter
  replacement (154 vs 71 days, P 0.02).
• S aureus clearance rate was still only 40 and
  this study reaffirms that lock therapy should not
  be used for S aureus.

Nephrol Dial Transplant (2004) 19 12371244
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