biofilms on medical devices silke s. talsma, ph.d. c.r. bard, inc

Biofilms on Medical Biofilms on Medical DevicesDevices

Silke S. Talsma, Ph.D.Silke S. Talsma, Ph.D.C.R. Bard, Inc.C.R. Bard, Inc.

OutlineOutline

The biofilm problemThe biofilm problem

Antibiotic resistanceAntibiotic resistance

Biofilm on urinary cathetersBiofilm on urinary catheters

Biofilm on endotracheal tubesBiofilm on endotracheal tubes

The Biofilm ProblemThe Biofilm Problem

Biofilms are everywhereBiofilms are everywhere

Diseases caused by biofilmDiseases caused by biofilm

Device related infections Device related infections

Cystic fibrosisCystic fibrosis

Plaque; GingivitisPlaque; Gingivitis

Ear infectionEar infection

Bacterial endocarditisBacterial endocarditis

Chronic prostatitisChronic prostatitisThe Centers for Disease Control and the National Institutes of Health estimate that 65% to 80% of all chronic infections can be attributed to microbial biofilms.

What is a biofilm?What is a biofilm?

A collection of microorganisms on a A collection of microorganisms on a surface that is surrounded by an surface that is surrounded by an extracellular matrix made up of primarily extracellular matrix made up of primarily polysaccharide materialspolysaccharide materials

Stages of Biofilm FormationStages of Biofilm Formation

Bacteria switch from a free-floating (planktonic) Bacteria switch from a free-floating (planktonic) state where they function as individuals to a state where they function as individuals to a sessile state where they function as communitiessessile state where they function as communities

Biofilms move along the extraluminal or Biofilms move along the extraluminal or intraluminal surface of medical devicesintraluminal surface of medical devices

A closer look at biofilms A closer look at biofilms Extracellular MatrixExtracellular Matrix

• Microorganisms in biofilms are surrounded by a protective extracellular matrix

• Microorganisms in a biofilm can be 1,000 fold less susceptible to antibiotics than planktonic microorganisms

Bacteria are protected in a biofilmBacteria are protected in a biofilm

Antibiotic ResistanceAntibiotic Resistance

Antibiotic Resistance in BiofilmsAntibiotic Resistance in Biofilms

Antibiotics kill bacteria except the resistant ones, which multiply, and in the end there are more resistant than non-resistant bacteria

Tolerance in biofilms makes antibiotics lesseffective

Up to 1,000 fold less susceptible to antibiotics

Selection for bacteria that are more resistantto antibiotic

Spread of antibiotic resistance

Multiresistant BacteriaMultiresistant Bacteria2 million healthcare-associated infections occur every year; 70% of 2 million healthcare-associated infections occur every year; 70% of the pathogens causing them are resistant to at least one antibioticthe pathogens causing them are resistant to at least one antibioticNumbers of healthcare-associated as well as community associated Numbers of healthcare-associated as well as community associated MRSA are increasingMRSA are increasingHorizontal gene transfer is promoted in biofilms; therefore, it is Horizontal gene transfer is promoted in biofilms; therefore, it is possible that antibiotic resistance spreads more easily than in possible that antibiotic resistance spreads more easily than in planktonic populationsplanktonic populationsAntibiotic resistant bacteria are common in VAPAntibiotic resistant bacteria are common in VAP

AntimicrobialsAntimicrobials

Antibiotics => very specific, highly efficient, Antibiotics => very specific, highly efficient, prone to development of resistanceprone to development of resistance

Antiseptics, antimicrobials (for example Antiseptics, antimicrobials (for example silver) => broad spectrumsilver) => broad spectrum

Biofilms on Foley cathetersBiofilms on Foley catheters

Biofilms on Foley cathetersBiofilms on Foley catheters

Intraluminal contamination from theCollection bag

Extraluminal contaminationat the insertion site

Biofilms and infectionBiofilms and infection

The catheter is COLONIZED, the patient is The catheter is COLONIZED, the patient is INFECTEDINFECTED

Bacteria can survive/multiply in biofilm. Bacteria can survive/multiply in biofilm. Biofilm provides reservoir for bacteriaBiofilm provides reservoir for bacteria

Microorganisms are detached from the biofilm Microorganisms are detached from the biofilm and can infect a patientand can infect a patient

The presence of a biofilm strongly increases The presence of a biofilm strongly increases the likelihood that bacteria are available for the likelihood that bacteria are available for infectioninfection

Immune response to a biofilmImmune response to a biofilmThe bladder, ureter and urethra are lined with epithelial cells

Immune response to a biofilmImmune response to a biofilm1.1. Microorganisms colonize Microorganisms colonize

epitheliumepithelium2.2. Microorganisms manage to get Microorganisms manage to get

into tissue (either by damaging into tissue (either by damaging the tissue with toxin or by specific the tissue with toxin or by specific virulence mechanism)virulence mechanism)

3.3. Microorganisms multiply in tissue, Microorganisms multiply in tissue, spread into lymphatic organs, and spread into lymphatic organs, and eventually in bloodeventually in blood

4.4. Immune system mobilizes cells to Immune system mobilizes cells to eliminate bacteria = Inflammationeliminate bacteria = Inflammation

Incidence of CA-UTIIncidence of CA-UTI

Bacteriuria occurs in about 26% of Bacteriuria occurs in about 26% of patientspatientsSymptomatic UTI: 16-32% of those who Symptomatic UTI: 16-32% of those who are bacteriuricare bacteriuricBacteremia related to CAUTI: 3.6% of Bacteremia related to CAUTI: 3.6% of those with bacteriuria, attributable those with bacteriuria, attributable mortality 12.7%mortality 12.7%

(Saint, AJIC 2000;28:68-75.)(Saint, AJIC 2000;28:68-75.)

Microbiology of CA-UTIMicrobiology of CA-UTI

Biofilms on Foley cathetersBiofilms on Foley catheters

Prevention:

• trained personnel, aseptic technique

• handwashing

• Closed system

• proper securement

• Assess if Foley catheter is still necessary

CDC recommendations: http://www.cdc.gov/ncidod/dhqp/gl_catheter_assoc.html

Biofilms on endotracheal tubesBiofilms on endotracheal tubes

Biofilm on endotracheal tubesBiofilm on endotracheal tubes

In addition to microorganisms and microbial secretions In addition to microorganisms and microbial secretions there are also other components, such as mucus, there are also other components, such as mucus, blood cells, pollen particles etc...blood cells, pollen particles etc...

Biofilms on endotracheal tubesBiofilms on endotracheal tubesMucus is part of the host immune system, it Mucus is part of the host immune system, it traps particles such as bacteria, also traps particles such as bacteria, also prevents tissues from drying out.prevents tissues from drying out.In the healthy body, mucus is swept away In the healthy body, mucus is swept away by cilia, and for the most part swallowed by cilia, and for the most part swallowed and digested.and digested.Removal of mucus by natural mechanisms Removal of mucus by natural mechanisms does not occur in the intubated patient and does not occur in the intubated patient and it can accumulate above the cuff, or inside it can accumulate above the cuff, or inside the ET tubethe ET tubeCough reflex does not work effectively in Cough reflex does not work effectively in intubated patient, so if mucus particles with intubated patient, so if mucus particles with bacteria reach the lower respiratory tract, bacteria reach the lower respiratory tract, they can grow and spread and lead to they can grow and spread and lead to infectioninfection

Biofilms on endotracheal tubesBiofilms on endotracheal tubes

Pooled secretionsabove the cuff

Oral Biofilm

Intraluminal contamination fromthe ventilator or suction catheter

Oral biofilmOral biofilm

• In a healthy adult, the oral cavity is colonized by more than 500 different kinds of bacteria (most of them are normal flora and do not cause harm).

• In the intubated patient, natural defense mechanisms, such as saliva production and swallowing are impaired

• Oral hygiene of intubated patients is difficult, because access is limited and it requires a substantial amount of nursing time

• If microorganisms are not sufficiently removed from the tooth surface, they colonize and form a biofilm (Plaque)

• If the plaque is not removed, the secretions in the biofilm (acids and sugars) can cause inflammation and damage to the teeth and gums (gingivitis)

Biofilms on endotracheal tubesBiofilms on endotracheal tubes

Feldman et al., 1999

Mouth/Oropharynx

Upper GI tract

Lower Respiratory Tract

Inner lumen of ETT

ICU patients were swabbed to determine the colonization of the upper and lowerRespiratory and GI regions

Gram negative bacteriaGram positive bacteria

Biofilms on endotracheal tubesBiofilms on endotracheal tubes

Etiology shifts over intubation period: initially Etiology shifts over intubation period: initially endogenous flora, later on exogenous, harder to treat endogenous flora, later on exogenous, harder to treat microorganismsmicroorganisms

intubation> 80% of intubatedpatients are extubatedby day 10

< 5 days ≥ 5 days

Streptococcus pneumoniaeHaemophilus influenzaeAB sensitive Staphylococcus aureus

MRSAEnterobacteriaceae (e.g. Klebsiella, E. coli)AGBN (Pseudomonas, Acinetobacter)

Early onset Late onset

When Biofilms spread into the lower When Biofilms spread into the lower respiratory tract, they can cause VAPrespiratory tract, they can cause VAP

Microaspiration at the cuffMicroaspiration at the cuff

Accumulation in the carinaAccumulation in the carina

Aerosolization from the insideAerosolization from the inside

of the tube into the lungof the tube into the lung

• Oral/Nasal colonization

• External migration

• Micro-leakage past cuff

• Colonization of bronchi & lungs

• Tracheal suctioning colonizesinternal surface

• Inoculation of lungs withmucous-biofilm encased bacteria

• Oral/Nasal colonization

• External migration

• Micro-leakage past cuff

• Colonization of bronchi & lungs

• Tracheal suctioning colonizesinternal surface

• Inoculation of lungs withmucous-biofilm encased bacteria

• Oral/Nasal colonization

• External migration

• Micro-leakage past cuff

• Colonization of bronchi & lungs

• Tracheal suctioning colonizesinternal surface

• Inoculation of lungs withmucous-biofilm encased bacteria

Biofilms on endotracheal tubesBiofilms on endotracheal tubes

Prevention - The IHI Ventilator Bundle

• Elevated bed position => avoids contamination by gastric reflux

• Daily sedation vacations and assessment of readiness to extubate

• peptic ulcer disease prophylaxis

• deep venous thrombosis prophylaxis

•Silver-coated endotracheal tube reduced the incidence of VAP in a

Multicenter clinicial trial (Kollef et al. 2008: JAMA 300(7):805-13.)

VAP bundle: http://www.ihi.org/IHI/Topics/CriticalCare/IntensiveCare/Changes/ImplementtheVentilatorBundle.htm

SummarySummary

Microorganisms form biofilms on surfaces Microorganisms form biofilms on surfaces such as medical devices such as medical devices

Biofilms provide protection for Biofilms provide protection for microorganisms and make them more microorganisms and make them more resistant to antibiotic treatmentresistant to antibiotic treatment

National organizations recommend bundle National organizations recommend bundle strategies to prevent device related strategies to prevent device related infectionsinfections