Biofilms on Medical Devices Silke S. Talsma, Ph.D. C.R. Bard, Inc.

Outline The biofilm problem Antibiotic resistance Biofilm on urinary catheters Biofilm on endotracheal tubes

The Biofilm Problem

Biofilms are everywhere

Diseases caused by biofilm Device related infections Cystic fibrosis Plaque; Gingivitis Ear infection Bacterial endocarditis Chronic prostatitis The 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? A collection of microorganisms on a surface that is surrounded by an extracellular matrix made up of primarily polysaccharide materials

Stages of Biofilm Formation Bacteria switch from a free-floating (planktonic) state where they function as individuals to a sessile state where they function as communities

Biofilms move along the extraluminal or intraluminal surface of medical devices

A closer look at biofilms Extracellular 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 biofilm

Antibiotic Resistance

Antibiotic Resistance in Biofilms Tolerance in biofilms makes antibiotics less effective Up to 1,000 fold less susceptible to antibiotics Selection for bacteria that are more resistant to antibiotic Spread of antibiotic resistance Antibiotics kill bacteria except the resistant ones, which multiply, and in the end there are more resistant than non-resistant bacteria

Multiresistant Bacteria 2 million healthcare-associated infections occur every year; 70% of the pathogens causing them are resistant to at least one antibiotic Numbers of healthcare-associated as well as community associated MRSA are increasing Horizontal gene transfer is promoted in biofilms; therefore, it is possible that antibiotic resistance spreads more easily than in planktonic populations Antibiotic resistant bacteria are common in VAP

Antimicrobials Antibiotics => very specific, highly efficient, prone to development of resistance Antiseptics, antimicrobials (for example silver) => broad spectrum

Biofilms on Foley catheters

Biofilms on Foley catheters Intraluminal contamination from the Collection bag Extraluminal contamination at the insertion site

Biofilms and infection The catheter is COLONIZED, the patient is INFECTED Bacteria can survive/multiply in biofilm. Biofilm provides reservoir for bacteria Microorganisms are detached from the biofilm and can infect a patient The presence of a biofilm strongly increases the likelihood that bacteria are available for infection

Immune response to a biofilm The bladder, ureter and urethra are lined with epithelial cells

Immune response to a biofilm Microorganisms colonize epithelium Microorganisms manage to get into tissue (either by damaging the tissue with toxin or by specific virulence mechanism) Microorganisms multiply in tissue, spread into lymphatic organs, and eventually in blood Immune system mobilizes cells to eliminate bacteria = Inflammation

Incidence of CA-UTI Bacteriuria occurs in about 26% of patients Symptomatic UTI: 16-32% of those who are bacteriuric Bacteremia related to CAUTI: 3.6% of those with bacteriuria, attributable mortality 12.7% (Saint, AJIC 2000;28:68-75.)

Microbiology of CA-UTI

Biofilms 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 tubes

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

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

Biofilms on endotracheal tubes Pooled secretions above the cuff Oral Biofilm Intraluminal contamination from the ventilator or suction catheter

Oral 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 tubes ICU patients were swabbed to determine the colonization of the upper and lower Respiratory and GI regions Mouth/Oropharynx Upper GI tract Lower Respiratory Tract Inner lumen of ETT Gram negative bacteria Gram positive bacteria Feldman et al., 1999

Biofilms on endotracheal tubes Etiology shifts over intubation period: initially endogenous flora, later on exogenous, harder to treat microorganisms intubation > 80% of intubated patients are extubated by day 10 < 5 days ≥ 5 days Streptococcus pneumoniae Haemophilus influenzae AB sensitive Staphylococcus aureus MRSA Enterobacteriaceae (e.g. Klebsiella, E. coli) AGBN (Pseudomonas, Acinetobacter) Early onset Late onset

When Biofilms spread into the lower respiratory tract, they can cause VAP Microaspiration at the cuff Accumulation in the carina Aerosolization from the inside of the tube into the lung

Biofilms 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

Summary Microorganisms form biofilms on surfaces such as medical devices Biofilms provide protection for microorganisms and make them more resistant to antibiotic treatment National organizations recommend bundle strategies to prevent device related infections