Guideline Update For The Management Of Intravenous Catheter Related Infections

Guideline Update for the Management of Intravascular Catheter-Related Infections

Sarah Nelson, Pharm.D.Critical Care Pharmacy Resident

October 21 & 22, 2009

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

Background

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

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 daysEdgeworth, J. J Hosp Infect. 2009;10:1-8Al-Rawajfah OM, Stetzer F, Hweitt JB. Infect Control Hosp Epidemiol. 2009;30:000Ramritu P, Halton K, Collignon P, et al. An J Infect Control. 2008;36:104-17

Types of Intravascular DevicesType FunctionPeripheral 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

Central Venous Catheters

http://microbix.com

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


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

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


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

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 47CNS 8 29MRSA 2 7E. faecalis 4 2Other 2 9Gram – bacteria 14 4E. coli 10 1P. aeurginosa 1 2Candida albicans 6 1

Antibiotic Selection

Empiric Antibiotic Selection Are antibiotics indicated?

Signs/symptoms of infection Patient characteristics

Where is the catheter located?

Can/should the catheter be removed?

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;49:1-45Rijnders 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

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


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


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


Guideline Algorithms

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

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 thrombophlebi

tis, 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


with systemic Abx for ≥ 14 days


with systemic

Abx for 7-14 days


with systemic

Abx for 7-14 days


with systemic Abx for ≥ 14 days after 1st negative culture

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


with systemic Abx for ≥ 14 days after 1st negative culture

Remove and treat with systemic Abx 7-14

daysOR

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

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

Guideline Changes

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.


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


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


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 bloodstreaminfections: non-inferiority of linezolid in a phase 3 study. Clin Infect Dis. 2009;48:203-12

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

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 bloodstreaminfections: non-inferiority of linezolid in a phase 3 study. Clin Infect Dis. 2009;48:203-12

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

Antibiotic Lock Therapy

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

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

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%


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 completionFernandez-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

Fernandez-Hidalgo et al.Organism No. of isolatesGram + organisms 80CNS 56S. aureus 20E. faecalis 2other 3Gram – organisms 26E. coli 11P. aeurginosa 5other 10Polymicrobial 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

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 daysFernandez-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

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 bacteremiaFortun 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

Fortun et al.

Organism ALT + systemic therapy

N=19

Systemic therapy onlyN=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

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

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

Prevention of CRBSI

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 cathetersEdgeworth, J. Intravascular catheter infections. J Hosp Infect. 2009;10:1-8

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 effectivenessof antimicrobial-coated catheters in intensive care units. An J Infect Control. 2008;36:104-17

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

Questions?

Guideline Update For The Management Of Intravenous Catheter Related Infections

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