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Intravenous Catheter Related Infection:Intravenous Catheter Related Infection:Microorganisms and PathogenesisMicroorganisms and Pathogenesis

Prepared by the Daniel Spangler, Principal Scientist, Applied Research, Arrow Internationaland Miroslav Navratil M.D., General Manager SE Europe, Arrow International

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In 1865, Louis PasteurIn 1865, Louis Pasteursuggested that decay wassuggested that decay wascaused by livingcaused by livingorganisms in the air,organisms in the air,which on entering matterwhich on entering mattercaused it to ferment.caused it to ferment.

Sir Joseph ListerSir Joseph Listerrecognized therecognized therelationship betweenrelationship betweenPasteur's research andPasteur's research andhis own. He consideredhis own. He consideredthat microbes ( “invisiblethat microbes ( “invisibleassassins”) in the airassassins”) in the airwere likely causingwere likely causingclinical infections and hadclinical infections and hadto be destroyed beforeto be destroyed beforethey entered the wound.they entered the wound.

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Impact of CVC Related InfectionsImpact of CVC Related Infections

Nosocomial Infections-Hospital acquired, 4th leading cause ofdeath in US(>90,000/yr).

Over 5 million CVCs are inserted annually in the US. It isestimated that 2-12% of CVCs result in sepsis. NationalNosocomial Infections Surveillance (NNIS) data shows that 87%of primary bloodstream infections occurred in patients with acentral line. CVCs contribute to more than 250,000 infectioncases annually in US.

Infection is the most common serious complication associatedwith vascular catheters. Infections are of two types: local andbloodstream.

Catheter related blood stream infection is probably the mostsignificant and life threatening of all medical device relatedinfections. Mortality is estimated at 12%–25%. Estimatedannual deaths 30,000-60,000.

The cost per infection is on average $25,000 per episode.Estimated annual cost of ~$6.25 billion

CDC Guidelines for the Prevention of IntravascularCatheter-Related InfectionsMorbidity and Mortality Weekly ReportRecommendations and Reports August 9, 2002 / Vol. 51 /No. RR-10

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IV Catheter Related Infections are Caused byIV Catheter Related Infections are Caused byBacteria &Bacteria & Yeasts:KnowYeasts:Know the Enemythe Enemy

Gram PositiveGram Positive coccicocci are common to human skin.are common to human skin. CoagulaseCoagulasenegative Staphylococci (negative Staphylococci (S.S. epidermidisepidermidis) are the most common cause) are the most common causeof IV catheter related infection(37%).of IV catheter related infection(37%).

StaphStaph aureusaureus 13%13%

Gram positiveGram positive enterococcienterococci 13%. Enteric bacteria including13%. Enteric bacteria including E.E.faeciumfaecium andand E.E. faecalisfaecalis..

Gram negatives bacilli 14%. Source related to water including waGram negatives bacilli 14%. Source related to water including wastestewater. Many gram negatives are found in the human enteric systewater. Many gram negatives are found in the human enteric systemm((E. coliE. coli).).

YeastsYeasts--8% (8% (CandidaCandida species). C.species). C. albicansalbicans is the 4is the 4thth leading cause ofleading cause ofvascular catheter related infections. CVC Infections withvascular catheter related infections. CVC Infections with CandidaCandidaare associated with the highest mortality rate (26are associated with the highest mortality rate (26--38%).38%).

All other pathogens 15%.All other pathogens 15%.

Reference: CDC Guideline for the prevention of CRIReference: CDC Guideline for the prevention of CRI--2002. Frequency of isolation is2002. Frequency of isolation is

approximate and changes over time. Data presented is for 1991approximate and changes over time. Data presented is for 1991--1999 period.1999 period.

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PathogenesisPathogenesis

Migration of skin organisms from the insertion site intoMigration of skin organisms from the insertion site intothethe cutaneouscutaneous catheter tract with colonization of thecatheter tract with colonization of thecatheter tip is the most common route of infection forcatheter tip is the most common route of infection forperipherally inserted, short term catheters.peripherally inserted, short term catheters.

Contamination of the catheter hub contributesContamination of the catheter hub contributessubstantially tosubstantially to intraluminalintraluminal colonization of longcolonization of long--termtermcatheters.catheters.

Occasionally catheters may becomeOccasionally catheters may become hematogenouslyhematogenouslyseeded from another focus of infection.seeded from another focus of infection.

RarelyRarely infusateinfusate contamination leads to CRBSIcontamination leads to CRBSI

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Types of Vascular Catheter RelatedTypes of Vascular Catheter RelatedInfections: Localized or SystemicInfections: Localized or Systemic

Colonized CatheterColonized Catheter--Significant microbial growth from the device tip,Significant microbial growth from the device tip,subcutaneous segment, or hub (asymptomatic)subcutaneous segment, or hub (asymptomatic)

PhlebitisPhlebitis--Erythema/induration/tenderness/painErythema/induration/tenderness/pain near exit site.near exit site. Exit Site infectionExit Site infection--Erythema/induration/tenderness/painErythema/induration/tenderness/pain with orwith or

without pus within 2 cm of exit site.without pus within 2 cm of exit site. ExudateExudate and positiveand positivemicrobiological culture.microbiological culture.

Tunnel InfectionTunnel Infection--Erythema/induration/tendernessErythema/induration/tenderness >2 cm of exit site>2 cm of exit sitealong the subcutaneous tract.along the subcutaneous tract.

Pocket InfectionPocket Infection--Infection in the subcutaneous pocket of anInfection in the subcutaneous pocket of aninplantableinplantable port.port.

CRBSICRBSI--Bloodstream Infection.Bloodstream Infection.

Note: Exit site, tunnel and port infections are soft tissue infeNote: Exit site, tunnel and port infections are soft tissue infection alongction alongthe external surface of the catheter and may or may not involvethe external surface of the catheter and may or may not involveCRBSICRBSI

Ref. HallRef. Hall et.alet.al. Diagnosis and Management of Long. Diagnosis and Management of Long--term CVC Infections, J.term CVC Infections, J. VascVasc IntervInterv RadiolRadiol. 2004;15:327. 2004;15:327--334334

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Site of Catheter InsertionSite of Catheter InsertionInfluences Risk of InfectionInfluences Risk of Infection

The density of skin flora at the catheterThe density of skin flora at the catheterinsertion site is a major risk factor forinsertion site is a major risk factor forCatheter Related Blood Stream InfectionCatheter Related Blood Stream Infection(CRBSI).(CRBSI).

CDC Guideline recommends that CVC beCDC Guideline recommends that CVC beplaced in aplaced in a subclaviansubclavian site instead of asite instead of ajugular of femoral site to reduce infectionjugular of femoral site to reduce infectionrisk.risk.

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An Adaptive EnemyAn Adaptive Enemy--AntibioticAntibioticResistant Clinical IsolatesResistant Clinical Isolates

Many of the bacteria causing catheter relatedMany of the bacteria causing catheter relatedinfections, and infections in general areinfections, and infections in general areantibiotic resistant, making treatment difficult.antibiotic resistant, making treatment difficult.

Bacteria are very adaptive to adverseBacteria are very adaptive to adverseenviromentsenviroments. Unnecessary and over use of. Unnecessary and over use ofantibiotics has created a significant increase inantibiotics has created a significant increase inantibiotic resistant microbes.antibiotic resistant microbes.

Use of inappropriately low levels of antibioticsUse of inappropriately low levels of antibioticsselects for the most resistant species.selects for the most resistant species.

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Resistance to AntimicrobialResistance to AntimicrobialAgentsAgents

MethicillinMethicillin resistantresistant StaphylococcusStaphylococcus aureusaureus(MRSA) and(MRSA) and StaphStaph.. epidermidisepidermidis (MRSE) are(MRSE) areprevalent in clinical settings and responsible forprevalent in clinical settings and responsible formany device related infections.many device related infections.

VancomycinVancomycin resistantresistant enterococcienterococci (VRE) which(VRE) whichare gram positiveare gram positive coccicocci, are a growing problem., are a growing problem.

Antibiotics are ineffective against yeasts.Antibiotics are ineffective against yeasts.CandidaCandida biofilmsbiofilms are resistant to most antifungalare resistant to most antifungalagents. Bacteria inagents. Bacteria in biofilmsbiofilms are markedlyare markedlyresistant to antimicrobial agents.resistant to antimicrobial agents.

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Understanding the Role ofUnderstanding the Role ofBiofilmsBiofilms in Catheter Relatedin Catheter Related

Infections (CRI)Infections (CRI)

UnderstandingUnderstanding biofilmsbiofilms is essential to establishingis essential to establishingstrategies relative to their prevention/treatment.strategies relative to their prevention/treatment.

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BiofilmBiofilm: Definition: Definition

AA biofilmbiofilm is a complex aggregation ofis a complex aggregation ofmicroorganisms marked by the excretionmicroorganisms marked by the excretionof a protective and adhesive matrix.of a protective and adhesive matrix.

MatrixMatrix--enclosed microbial populationsenclosed microbial populationsadherent to each other and/or to surfacesadherent to each other and/or to surfacesand interfaces.and interfaces.

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Microbial Biofilm on a Medical Device

~1 {------]

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Microorganisms Can colonize both the internaland external surfaces of the IV Catheter

Bacterial colonies

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STEP 1: Bacteria enter the catheter in a free floating or planktonic form.Characterized by high susceptibility to antimicrobials. Cells are unprotected.This usually occurs between 0 -4 hours.STEPS 2-4: Bacteria adhere to the catheter surface and grow/multiply into anorganized community known as a biofilm. Characterized by high resistance toantimicrobials. Cells surrounded by glycocalyx matrix. Biofilm begins to formafter ~4 hours.

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Examples ofExamples of biofilmbiofilm shedding and movementshedding and movement

Adherent/biofilm bacteria have the ability to shed cells and move

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Cell-cell communication: This is called quorum sensing. The ability ofa bacterial colony to sense its size and regulate its activity in response.

Behave like a tissue. It is an intercellular signaling mechanism thatdepends on cell density.

BiofilmBiofilm BehaviorBehavior

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Biofilm Resistance to Antimicrobial Treatments

Slow diffusion ofantimicrobial through theglycocalyx matrix

Cells divide into manydifferent forms with variableantimicrobial susceptibility

Environment within thebiofilm has variable oxygenconcentration and pH whichaffects antimicrobial activity.

Low metabolically active“persister” cells allow forbiofilm regrowth afterantimicrobial is used up.

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CRBSICRBSI--Difficult to DiagnoseDifficult to Diagnose

Clinical signs (fever/chills) are sensitive but not specificClinical signs (fever/chills) are sensitive but not specificfor diagnosis. Other indicators, such as catheterfor diagnosis. Other indicators, such as catheter--sitesiteinflammation, are specific but not sensitive.inflammation, are specific but not sensitive.

SemiquantitativeSemiquantitative (roll(roll--plate technique) and quantitativeplate technique) and quantitative(i.e.(i.e. sonicationsonication) used traditionally for past 27 years.) used traditionally for past 27 years.Require catheter removal.Require catheter removal.

Differential time toDifferential time to positivitypositivity--Method to diagnose CRIMethod to diagnose CRIwithout removing the catheter.without removing the catheter.

Defined as the difference in the time it takes for a bloodDefined as the difference in the time it takes for a bloodculture draw through the CVC and a culture drawn fromculture draw through the CVC and a culture drawn froma peripheral vein to become positive.a peripheral vein to become positive.

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Treatment of a CRBSITreatment of a CRBSI

Antibiotics,Antibiotics, AntifungalsAntifungals, and Device, and DeviceRemovalRemoval

Drug resistance.Drug resistance.

May need more than one antibiotic.May need more than one antibiotic.

Hypersensitivity.Hypersensitivity.

Costly and not always effective.Costly and not always effective.

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Best Approach is PreventionBest Approach is Prevention

Providing aseptic barrier and antisepticProviding aseptic barrier and antisepticagent for skin preparation.agent for skin preparation.

Providing continuous protection postProviding continuous protection postinsertion by treating our CVC with agentsinsertion by treating our CVC with agentswhich are both safe and efficacious.which are both safe and efficacious.

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$$1,000,0001,000,000 QuestionQuestion

Can we do betterCan we do better ??

IfIf yesyes,, whatwhat ??

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The Risk of Bloodstream Infection in AdultsThe Risk of Bloodstream Infection in AdultsWith Different Intravascular Devices:With Different Intravascular Devices:

A Systematic Review of 200 Published ProspectiveA Systematic Review of 200 Published ProspectiveStudiesStudies

DENNIS G. MAKI, MD; DANIEL M. KLUGER, MD; AND CHRISTOPHER J.DENNIS G. MAKI, MD; DANIEL M. KLUGER, MD; AND CHRISTOPHER J.CRNICH, MDCRNICH, MD

MayoMayo ClinClin Proc. • September 2006;81(9):1159Proc. • September 2006;81(9):1159--11711171

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Summary ofSummary of IVD’sIVD’s bloodstreambloodstreaminfections relative riskinfections relative risk

Review of 200 published prospectiveReview of 200 published prospectiveobservational or clinical trials publishedobservational or clinical trials publishedbetween January 1, 1966 and July 1,between January 1, 1966 and July 1,20052005

MetanalysisMetanalysis

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The most “preventable” classes ofThe most “preventable” classes ofnosocomialnosocomial infectionsinfections22

IVD’sIVD’s infections have an associated mortalityinfections have an associated mortalityof approximately 35%of approximately 35%

Increased morbidity and length of hospitalIncreased morbidity and length of hospitalstay calculated at 24 days for those whostay calculated at 24 days for those whosurvive any bacteremia.survive any bacteremia.33--44

Can be reduced by more than 65% by usingCan be reduced by more than 65% by usingrelatively straightforward infection controlrelatively straightforward infection controlproceduresprocedures 66--88

2. Harbarth S, Sax H, Gastmeier P. The preventable proportion of nosocomial infections: an overview of published reports. J Hosp Infect. 2003;54:258- 266.3. Pittet D.Tarara D.Wenzel RP. Nosocomial bloodstream infection in critically ill patients: excess length of stay, extra costs, and attributable mortality.JAMA.1994;271:1598-1601.4. O’Grady NP, Alexander M, Dellinger EP, et al, Healtcare Infection Control Practices Advisory Committee. Guidelines for the prevention of intravascular catheter-relatedinfections. Infect Control Hosp Epidemiol. 2002; 23:759-769.5. Berwick DM, Calkins DR, McCannon CJ, Hackbarth AD. The 100,000 lives campaign: setting a goal and a deadline for improving health care quality. JAMA. 2006;295:324-327.6. Sirio CA, Segel KT, Keyser DJ, et al. Pittsburgh Regional Healthcare Initiative: a systems approach for achieving perfect patient care. Health Aff. 2003;22:157-165.7. Centers for Disease Control and Prevention. Reduction in central lineassociated bloodstream infections among patients in intensive care units— Pennsylvania, April 2001-March 2005. MMWR MorbMortal Wkly Rep. 2005;54;1013-1016.8. Berenholtz SM, Pronovost PJ, Lipsett PA, et al. Eliminating catheterrelated bloodstream infections in the intensive care unit. Crit Care Med. 2004;32:2014-2020.

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InIn otherother wordswords((basedbased onon thisthis metaanalysismetaanalysis ofof

somesome 25,00025,000 CVCsCVCs )) IfIf 44 outout ofof 100100 patientspatients willwill developdevelop bloodblood

streemstreem infectioninfection

11--22 patientspatients willwill developdevelop intointo sepsissepsis

CanCan wewe realyrealy preventprevent 11 patientpatient fromfromdevelopingdeveloping sepsissepsis ??

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50%50% infectioninfection reductionreduction filterfilter

MedicatedMedicated catheterscatheters

ChlorhexidinChlorhexidin--silversilver ––sulfadiazinsulfadiazin

MinocyclinMinocyclin--rifampinrifampin

PeripherallyPeripherally insertedinserted centralcentral catheterscatheters

TunneledTunneled catheterscatheters

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NEJM StudyNEJM Study

Darouiche RO, et al.

A comparison of twoAntimicrobial -

impregnated centralvenous catheters.

N Engl J Med. 1999

Jan 7;340(1):1-8.

NOTE: Bothcatheters had similarefficacy forapproximately first10 days. MRcatheters were 1/3as likely as CS to becolonized, and 1/12(0.3% vs. 3.4%) aslikely to result inCRBSI

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OurOur Focus:InfectionFocus:Infection PreventionPrevention

““When meditating overWhen meditating overa disease, I nevera disease, I neverthink of finding athink of finding aremedy for it but,remedy for it but,instead, search for ainstead, search for ameans to prevent it.”means to prevent it.”

Louis PasteurLouis Pasteur