SIDP – Antimicrobial Stewardship Certificate Program

Intravascular Catheter-Related Blood Stream Infections

SIDP
The Society of Infectious Diseases Pharmacists

Intravascular Catheter‐Related
Bl d St
Blood Stream IInfections
f ti
Antimicrobial Stewardship Certificate Program

James R. Beardsley, PharmD, BCPS

Assistant Director of Pharmacy
Wake Forest Baptist
Medical Center

Objectives
• Design an appropriate empiric treatment regimen
for a patient with a suspected catheter
catheter‐related
related
blood stream infection (CRBSI) based on patient‐
specific risk factors.
• Develop a definitive treatment plan for CRBSIs
caused by various common pathogens.
• Determine when catheter removal is an essential
element of the treatment plan for treating a
specific CRBSI.

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SIDP – Antimicrobial Stewardship Certificate Program
Intravascular Catheter-Related Blood Stream Infections

Outline
• Epidemiology
• Background definitions
• Microbiology
• Diagnosis
• Treatment
• Prevention

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Abbreviations
CRBSI – Catheter‐related blood stream infection
CVC – Central Venous Catheter
Cx – culture; BCX – blood culture
ABX – antibiotic
Dx – diagnosis
Tx – treatment
LOS – length of stay
Cfu – colony forming units
GN – gram negative
MRSA – methicillin‐resistant Staphylococcus aureus
C&S ‐ culture and susceptibility
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Intravascular Catheter-Related Blood Stream Infections

Epidemiology
• Estimated 250,000‐500,000 CRBSIs/yr in
USA
• 0.5 – 5.6 CRBSIs per 1000 catheter days
• Impact of CRBSIs
– Increased LOS
– Increased days of mechanical ventilation
– Increased healthcare costs (up to $35
$35,000
000 per
episode)
– Increased mortality (in most studies)
Safdar N, et al. Ann Intern Med 2005;142:451-466; Edwards JR, et al. Am J Infect
Control 2008;36:609-26; Blot SI, et al. ICD 2005;41:1591-8;
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Siempos II, et al. Crit Care Med 2009;37:2283-2289

Types of Intravascular Devices

• Peripheral venous catheter – Usually inserted into the
veins of forearm or hand: most commonly used short‐term
IV device
• Peripheral arterial catheter – for short‐term use;
commonly used to monitor hemodynamic status &
determine ABGs; risk of BSI may approach that of CVCs
• Midline catheter – Peripheral catheter inserted via
antecubital fossa into proximal basilic or cephalic veins,
but does not enter central veins; lower rate of infection
than CVCs
• Short‐term CVC – Most commonly used CVC; accounts for
majority of all CRBSIs
• Pulmonary artery catheter – Inserted through teflon
inducer; usually in place for average of 3 days
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Mermel LA, et al. CID 2009;49:1-45

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Intravascular Catheter-Related Blood Stream Infections

Types of Intravascular Devices (cont.)

• Pressure‐monitoring system – Used in conjunction with
arterial catheter
• Peripherally inserted central catheter – Inserted via
peripheral vein into superior vena cava; risk of infection
similar to CVCs
• Long‐term CVC – Surgically implanted CVC (eg, Hickman,
Broviac, Groshong) with tunneled portion exiting skin and
a dacron cuff just inside exit site; used to provide vascular
access to pts requiring prolonged chemotherapy,
chemotherapy home‐
home
infusion therapy, or hemodialysis
• Totally implantable device – A subcutaneous port or
reservoir with self‐sealing septum is tunneled beneath the
skin & accessed by a needle through intact skin; low rate of
infection SIDP

Definitions of IV CRBSIs
Infection Definition
Catheter Significant growth of 1 microorganism in a
colonization quantitative or semiquantitative culture of the
catheter tip, subcutaneous catheter segment, or
catheter
h hub
h b
Phlebitis Induration or erythema, warmth, and pain or
tenderness along the tract of a catheterized or
recently catheterized vein
Exit site infection
Microbiological Exudate at catheter exit site yields a microorganism
with or without concomitant bloodstream infection
Clinical Erythema, induration, and/or tenderness within 2 cm
of the catheter exit site; may be associated with
other signs and symptoms of infection, such as fever
or purulent drainage emerging from the exit site,
with or without concomitant bloodstream infection
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Adapted from Table 3, CID 2009;49:1-45

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Intravascular Catheter-Related Blood Stream Infections

Definitions of IV CRBSIs (cont.)

Infection Definition
Tunnel infection Tenderness,, erythema,
y , and/or
/ induration >2 cm from
the catheter exit site, along the subcutaneous tract of a
tunneled catheter (e.g., Hickman or Broviac catheter),
with or without concomitant bloodstream infection
Pocket infection Infected fluid in the subcutaneous pocket of a totally
implanted intravascular device; often associated with
tenderness, erythema, and/or induration over the
pocket; spontaneous rupture and drainage, or necrosis
of the overlying skin, with or without concomitant
bloodstream infection
Bloodstream Concordant growth of a microorganism from infusate
infection ‐ and cultures of percutaneously obtained blood cultures
Infusate related with no other identifiable source of infection
Adapted from Table 3, CID 2009;49:1-45 SIDP

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Definitions of IV CRBSIs (cont.)
Infection Definition
Blood‐ Bacteremia or fungemia in a patient who has an intravascular device and >1
stream positive blood culture result obtained from the peripheral vein, clinical
infection ‐ manifestations of infection (e.g., fever, chills, and/or hypotension), and no
apparent
pp source for bloodstream infection ((with the exception
p of the
Catheter
catheter).
related
One of the following should be present: a positive result of semiquantitative
(>15 cfu per catheter segment) or quantitative (>102 cfu per catheter
segment) catheter culture, whereby the same organism (species) is isolated
from a catheter segment and a peripheral blood culture; simultaneous
quantitative cultures of blood with a ratio of >3:1 cfu/mL of blood (catheter
vs. peripheral blood); differential time to positivity (growth in a culture of
blood obtained through a catheter hub is detected by an automated blood
culture system at least 2 h earlier than a culture of simultaneously drawn
peripheral blood of equal volume).

Note that this definition differs from the definition of central line–associated
bloodstream infection used for infection‐control surveillance activities.
Adapted from Table 3, CID 2009;49:1-45 SIDP

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Common Pathogens
• Coag‐negative staphylococci (CONS)
• S. aureus
• Candida species
• Enteric gram‐negative bacilli
• P. aeruginosa
• Enterococcus species

Mermel LA, et al. CID 2009;49:1-45

Wisplinghoff H, et al. CID 2004;39:309-17 SIDP

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Pathogenesis
• Organisms from skin  migrate along
external surface of catheter  colonization
of tip  blood
– Most common for short term catheters

• Lumen of hub contaminated  migrate

d
down internal
i t th t  blood
l llumen off catheter bl d
– Most common for long‐term & implantable
catheters

Raad I. Arch Intern Med 2002;162:871-878 SIDP

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Key Issues in Management of CRBSIs

• For suspected infection
– Proper
P diagnostic
di ti workup
k
– Choice of empiric therapy
– Catheter removal required?
• After diagnostic data available
– Antibiotic choice for definitive treatment
– Length of therapy
– Catheter removal required?
– What follow‐up is needed?

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Diagnosis and Treatment

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Catheter Cultures
• Catheter tip (not sub‐Q segment) should be Cx’d
by:
– Semiquantitative (roll plate) technique
OR
– Quantitative (luminal flushing or sonication) method
• Roll plate technique is preferred for catheters
indwelling < 14 days, since colonization is
usually along outside of catheter
• Only catheters removed for suspected CRBSIs
should be cultured
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Blood Cultures
• Obtain BCX prior to initiating ABX therapy
• Paired blood samples from catheter and
peripheral vein are recommended
• If peripheral vein unavailable, draw blood
from different catheter lumens

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Definitive Diagnosis of CRBSI

• Same organism grows from percutaneous
BCX & from cath tip Cx
OR
• Same organism grows from BCXs drawn
from peripheral vein and from catheter hub
AND
Hub‐drawn BCX has colony count > 3 fold
higher or DTP of >2 hours less than
peripheral BCX
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Results Suggestive of CRBSI

• 2 quantitative BCXs obtained through 2
catheter
h lumens
l iin which
hi h one Cx
C has
h > 3‐
3
fold greater colony count than the other
• Applicable if BCX cannot be obtained via
peripheral vein

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General Approach to Diagnosis

Patient with a short‐term central venous catheter
(CVC) or arterial catheter (AC) & an acute febrile
episode

Mild or moderately ill (no Seriously ill (BP, perfusion, signs &
hypotension or organ failure) symptoms of organ failure)

If no source of fever
fever, BCX (2 sets; 1
2 sets of remove CVC & AC, peripheral).
Consider Initiate
culture tip & insert at Remove CVC &
Anti‐ Blood anti‐
new site or exchange AC, CX tip, &
microbial cultures (1 microbial
over guidewire or cx insert at new
therapy peripheral) therapy
insertion site plus site or exchange
hubs where available over guidewire

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Adapted from fig 1 CID 2009;49:1-45

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Empiric Therapy: Gram‐Positives

• Need to cover MR staphylococcus in
everyone
• Vancomycin usually drug of choice
• Consider daptomycin if most local MRSA
isolates have vancomycin MICs >2mcg/mL
• Linezolid
Li lid nott recommended
d d for
f empiric
i i
therapy

CID 2009;48:209-12
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Empiric Therapy: Gram‐Negatives

• Gram negative coverage for pts with risk factors
– Critically ill
– Sepsis
– Neutropenic
– Femoral catheter
– Known focus of gram negative rod infection
• Specific agent should be based on local
susceptibility data and severity of illness
• Combination (2 GN drugs) recommended if
critically ill & recent colonization or infection with
MDR gram negative pathogen(s) – can de‐escalate
to one drug when C&S results available
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Empiric Therapy: Candida

• Empiric therapy for Candida needed:
– Infections involving femoral catheters
– Septic patients with
• TPN
• Prolonged use of broad spectrum ABX
• Hematologic malignancy
• Bone marrow or solid organ transplantation
• Candida colonization at multiple sites
• Use echinocandin (or fluconazole in select
pts)
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Response to Culture Data

Blood CXs (+) &
Blood CXs (‐) & Blood CXs (‐) & Blood CXs (‐) & CVC & AC  15
CFU by roll‐plate
CVC & AC not CVC & AC CVC & AC
or  102 by
cultured cultures (‐)  15 CFU methods
sonication

If continued For S. aureus: treat 5‐

fever & no other 7 days, monitor See definitive
source found,
found Look for another closely for signs of t t
treatment t
remove & source of infection, repeat BCX recommendations
culture CVC & infection accordingly. If due to
other microbes:
AC monitor for signs of
infection, repeat BCX
accordingly

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Adapted from fig 1 CID 2009;49:1-45

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Complicated Infections
• Complicated infections are those associated
with
– Suppurative thrombophlebitis
– Endocarditis
– Osteomyelitis
– Possible metastatic seeding
• Remove catheter
h
• Tx w/ systemic ABX for 4‐6 wks (6‐8 wks for
osteomyelitis in adults)
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Treatment for Uncomplicated Short‐

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Term CVC or AC‐Related BSIs Based on

Pathogen
Gram‐
Coag‐negative
g g
S aureus
S. E t
Enterococcus negative
ti C did spp.
Candida
staphylococci
bacilli

‐Remove Remove
Remove Remove
catheter & treat Remove catheter &
catheter & catheter &
with systemic catheter & treat with
treat with treat with
ABX for 5‐7 treat with antifungal
g
systemic
i systemic
days systemic ABX therapy for
ABX for ABX for 7‐14
‐If catheter is for 7‐14 days 14 days after
14 days days
retained, treat 1st negative
with systemic blood CX
ABX + ABX lock
therapy for 10‐
14 days Adapted from fig 2, CID 2009;49:1-45 SIDP

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Treatment for Uncomplicated Long‐Term CVC
or Port‐Related BSIs Based on Pathogen
Coagulase‐
Gram (‐) Candida
negative S. aureus Enterococcus
bacilli spp.
staph.

May retain Remove May retain Remove

CVC/P & use Remove CVC/P &
infected CVC/P & use CVC/P &
systemic ABX Tx for 7‐14 days.
catheter & systemic ABX for For CVC/P salvage: Tx with
+ ABX lock for 7‐14 days + ABX
then Tx with use systemic and antifungal
10‐14 days. lock therapy for
Remove ABX for 4‐6 ABX lock Tx for 10‐ therapy
7‐14 days. 14 days. If no for 14 days
CVC/P if there weeks unless Remove CVC/P if
is clinical patient meets response, remove after 1st
there is clinical CVC/P r/o
CVC/P,
d t i ti
deterioration criteria for deterioration or negative
or persisting endocarditis or blood CX
shorter persisting or suppurative
or relapsing relapsing
duration of thrombo‐phlebitis,
bacteremia, bacteremia,
work up for therapy (see & if not present,
work up for
complicated recom‐ Tx with ABX for 10‐
complicated 14 days
infection & Tx mendation 80 infection & Tx
accordingly in guidelines) accordingly SIDP
Adapted from fig 3, CID 2009;49:1-45

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Guide‐Wire Exchange
• Old catheter is removed & new one is placed in
same location over a guide‐wire
• Used when infection is only suspected & one
desires to minimize mechanical complications
or when other potential IV sites are limited
• Removed catheter tip should be cultured if
CRBSI suspected
• If CX of removed catheter tip is positive,
catheter that was exchanged over wire should
be removed & new catheter placed at new site
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Antibiotic Lock Therapy

• Supratherapeutic concentration of ABX
d lli iin catheter
dwelling h llumen
• Used to try to “salvage” catheter (avoid
removal)
• Efficacy depends on pathogen and type of
catheter infection
• Used with systemic ABX (usually for 7‐14
days)
• Dwell times 4 – 48 hours
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Common Lock Solutions

• Gentamicin 3‐5mg/mL +/‐ Citrate
• V
Vancomycini 5mg/mL
5 / L +/‐ / Heparin*
H i *
• Daptomycin 1mg/mL + Heparin*
• Ceftazidime 5mg/mL +/‐ Heparin*
• Ethanol 30% + Citrate
– Ethanol 70% alone in solution

*10 – 100 units for non-dialysis; 1,000 – 5,000 units for

dialysis catheters
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Infections in Hemodialysis Catheters

• Full discussion is beyond the scope of this

course. A ffew key
k caveats:
– Always remove catheter if CRBSI is due to S.
aureus, Pseudomonas species, or Candida
– Empiric therapy should include vancomycin and
also cover GNRs
– If CRBSI is due to methicillin‐susceptible S.
aureus, empiric vancomycin should be changed
to cefazolin

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Additional Pathogen‐Specific
Comments

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Coagulase‐Negative Staphylococcus
• For uncomplicated CRBSI, treat with antibiotics for
5–7 days
y if the catheter is removed , or for 10–14
days, with antibiotic lock therapy, if the catheter is
retained.
• Alternatively, patients with uncomplicated CRBSI
can be observed without antibiotics if they have no
intravascular or orthopedic hardware, the catheter
is removed, and additional blood cultures
(performed on samples collected when the patient is
not receiving antibiotics) are obtained after catheter
withdrawal to confirm the absence of bacteremia.
• CRBSI due to Staphylococcus lugdunensis should be
managed in a manner similar to CRBSI due to S.
aureus.
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Staphylococcus aureus
• Remove catheter (in almost all
circumstances)
• “Short” duration (minimum of 14 days)
allowed for “low risk” pts
• If use short duration, need a TEE 5‐7 days
after onset of bacteremia
• “Standard duration” of Tx is 4‐6 weeks
• For the rare circumstance when long‐term
catheter can’t be removed, use antibiotic
lock + systemic therapy for 4 weeks.
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To Qualify for “Short” Duration Therapy

(minimum 14 days) for S. aureus

• Not a diabetic
• Not immunosuppressed
• No prosthetic intravascular device
• No evidence of suppurative thrombophlebitis,
endocarditis, or other metastatic infection
• Infected catheter is removed
• Fever and bacteremia resolve within 72 h after
initiation of appropriate ABX
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Enterococcus
• Drug of choice
– Ampicillin if ampicillin‐susceptible
– Vancomycin if ampicillin‐resistant (& not VRE)
– Linezolid or daptomycin (based on C&S) if
ampicillin‐resistant VRE
• Need for combination therapy (eg, amp +
gent) for CRBSI not associated with
endocarditis is unresolved

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Candida
• For definite CRBSI due to Candida
– Remove the catheter!
– Give
Gi antifungal
tif l therapy,
th even if ptt improves
i after
ft
catheter removal prior to initiation of antifungal
Tx
• For pts with candidemia, a short‐tern CVC,
and no obvious source of candidemia
– Remove catheter and Cx tip
– If limited venous access, could exchange catheter
over guide‐wire and Cx tip. If tip grows same
species of Candida as BCX, need to remove
catheter
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Raad I, et al. CID 2004;38:1119-1127

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Prevention of CRBSIs
• Recent guidelines from SHEA/IDSA found
in:
Marschall J, et al. Infect Control Hosp
Epidemiol 2008;29:S22‐S30.
• Pharmacists (like all healthcare
professionals) should wash their hands!

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Summary
• CRBSIs are commonly encountered
i f i
infections
• Obtaining appropriate cultures is essential
in making a correct diagnosis
• Specific treatment, including ABX choice,
length of therapy
therapy, and need for catheter
removal, is determined by the specific
pathogen, type of catheter, and patient
condition
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