Biofilms: The Expanding Threat & How to Win

Wava Truscott PhD. MBA. wava.truscott@gmail.com

Disclosure statement

Wava Truscott PhD, MBA▪ I have nothing relevant to this topic to disclose

Learning Objectives:

▪ Explain the advantages of being a member of a biofilm rather than a lone bacterium

▪ Describe the unique opportunities for biofilm success created by the presence of implants

▪ Identify how surgical staff can reduce the opportunities for biofilm formation

▪ Communicate what’s new discoveries in the world of treating biofilm infections

Biofilm Overview

Biofilm….

▪ Survival mechanism for bacteria

▪ Bacteria attach to surfaces, substrates, and each other forming communities within a tough gel-like coating: the matrix

− bacteria function together as a community

− growth rate and specific gene transcriptions are altered

− share genetic information/capability with bacteria in the community

− 50-5,000X more resistant to antimicrobials than free living bacteria

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Good: Harnessing Biofilms

▪ Water treatment – tremendous benefit (biological pre-treatment)

▪ Decay of dead plants and animals enabling reuse of their elements

▪ Cleanup oil & gasoline spills (bioremediation)

▪ Soil or aquifer clean up of contaminates

▪ Bio-leaching: 10 – 20% of copper mined in US extracted from low grade ore with biofilm help

▪ Microbial fuel cells to generate electricity from complex organic waste and renewable biomass

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Bad Biofilms: Harm Industry & Man

▪ Swamp Coolers

▪ Water pipes Legionella

▪ Cooled air filtration

▪ Poor manufacturing maintenance

▪ Poor housekeeping

Impede Optimal Function

▪ Navy: Biofilm & barnacles slow ships about 10%

▪ Up to 40% increase in fuel consumption

▪ Hull BUG: Underwater robot scrubs hull to:

− increase ship speed

− reduce fuel costs

− reduce down-time in dry dock

− reduced hull damage

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Contact Lenses

▪ Biofilm on lens case, contaminates lenses

▪ Crystal violet used to show biofilm

▪ Can cause mild to severe eye infections

Examples: Biofilms In Healthcare

Our Largest “good-guy” Biofilm

Colon Goblet Cells: Red Colon Villi

Colon VilliBottom layer thick, sluggish, protective

Top layer more fluid; full of symbiotic bacteria: biofilm of ~100 trillion bacteria of ~500 species

Vereecke, 2012

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Biofilms Associated With Infections

Subdivided into two main categories. Those that:

▪ Form on host tissues (epithelia, mucosal surfaces, teeth, etc.).

▪ Colonize abiotic surfaces such as indwelling medical devices (catheters, implanted prostheses, heart valves, ET tubes, etc.)

Biofilm Infections

▪ Sinusitis

▪ Tonsillitis

▪ Clostridium difficile

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Dental Disease

▪ Biofilm on the teeth is called dental plaque

1mm3 mature dental plaque contains > 108 bacteria!100,000,000 bacteria per cubic millimeter!

Biofilm Progression▪ 48 hours after a good tooth brushing

▪ Dental biofilm (plaque) is mature

▪ Waste from biofilm bacteria cause gingivitis = inflammation of gums: will destroy healthy tissue

− And that food for expanding biofilm colonies into the gums

▪ 72 hours, protective crystals (calcium + phosphate = calculus, tartar)

− Only remove with hygienist’s pick

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Cystic Fibrosis

▪ Thick mucus perfect for biofilm formation

− 1 in 2,000 Caucasian births

From Acute To Biofilm Infections: Need New Diagnostics, Prevention, Treatments

Until mid 20th CenturyAcute Infections caused hundreds of millions of deaths (tetanus, diphtheria, cholera, bubonic plague) until the new era of antibiotics that progressively conquered most acute infections

Batoni, Maisetta, Esin 2016

After mid 20th CenturyInfections characterized as alternating active symptomatic acute phases with quieter chronic phases refractive to antibiotics and causing disease by ill-defined mechanisms

More Diabetes With Aging Population,Food Choices, Obesity, Lack of Exercise

Role of diabetes:

▪ Impaired blood access: − blood glucose damages vessel walls

− fewer immune cells access to wound

− RBC impaired oxygen release – reducing quality of healing

− reducing PMN oxygen burst potency

− stiffened cell membranes impair diapedesis (movement through blood vessel to injury)

The Increasingly Modern Medicine Brings New Hope and More Threats

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Vascular Catheters

▪ 5-6 million Central Lines placed annually

▪ > 5% infections

▪ >250,000 central line-associated infections (CLABSI)

▪ Approximately 20% attributable death rate

Cirioni O J Infect Dis 2006;193:180-186; CDC MMRW 2002;10:1-28

Biofilm On Septum of Needless ConnectorEmphasizing The Must Do: To “Scrub The Hub”

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Vastly Increasing Threat: Implant Associated Biofilms

▪ Tissue surrounding implants-reduced blood vessels so:

− fewer white blood cells delivered to implant surface

− less antibiotics and other drugs delivered

▪ White blood cells that do make it there have:

− reduced ability to capture bacteria

− reduced ability to kill bacteria

− damage tissues surrounding implant providing:

• additional organic food source for biofilm

• creates damaged areas great for “outpost biofilm reservoirs”

▪ Unfortunately, antibiotic resistance is occurring just as just as our incoming patient population is increasingly vulnerable to infection

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Keeping Things Straight

▪ Pins, screws, wires

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So Vulnerable

• Stringent adherence to antiseptic regimens

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So Vulnerable

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Restoring Function – Relieving Pain

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Biofilm Formed On Implants Both Hands

▪ Implants in both hands acquired biofilm infection

▪ Implants had to be removed; all bacteria killed before new implants

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Foiled Immune ResponseTo Biofilm Forming On Implant Surface

Frustrated white blood cells spit out their oxygen burst that doesn’t phase the biofilm but instead hurts healthy surrounding tissue making food debris and hiding places to start off-shoot biofilms in the surrounding tissues

▪ Osteomyelitis Secondary to biofilm on implant to stabilizers

▪ Predisposing:

− open fractures

− internal fixation devices

− prosthetic implant devices

− chronic soft tissue infection (secondary to implant biofilm as bacteria “burrow” into surrounding soft tissue: form biofilm pathogen reservoirs)

▪ Multiple organisms but S. aureus and S. epidermidis most prevalent

Osteomyelitis

Biofilms LOVE Implants

Stent

Heart Valve

Plate & Screws

TreatedSpacers

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Dr William Costerton coined the term & delved into “Biofilm” at Univ. of Calgary, Alberta Canada & Montana State Univ., Bosman Montana

How Do Biofilms Form?What are Their Characteristics?

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Stages to a Mature Biofilm

Dirckx P. Center for Biofilm Engineering at Montana State University, Bozeman Montana

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Stage 1. Bacteria Attach to a Surface

▪ Surface conditioned with proteins, blood, dead cells

▪ If surface not favorable, will let go

▪ Mere touch of favorable surface triggers change: • fimbriae• pili• flagella• adhesion proteins

▪ Sends out signals attracting others

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Stage 2. Irreversible Adhesion

▪ Decide favorable conditions, they increase:

• production of protein adhesins & attach tenaciously

• pumping out polysaccharides (“goo!”)

• exponential cell division = rapid population growth!

Stage 3. Aggregation – Community Formation

▪ Function responsibility influenced by location in biofilm

− periphery = defensive

− upper levels = harvest food

− lower levels = get rid of waste

− bottom level = adherence to surface

▪ Bacteria pump out more goo: attachment & elastic stretch so strong survives outside of jet in flight!

Stage 4. Maturation: Complex Community

▪ Bacteria communicate changes in environment from their post and alter behavior if needed

▪ eDNA, enzymes (digesting and cutting antibiotics), food, minerals dispersed throughout the matrix during the construction and maintenance of the construction process

A.

B.

C.www.cs.Montana.edu

Stage 5. Dispersal

▪ Creation and release of free floating, single celled “children” called pioneer or planktonic bacteria to start

− new colonies− local infections− remote infections − systemic infections− embolic complications

▪ Planktonic bacteria are the most vulnerable to biocides▪ Recurrent symptoms (e.g. sinus; implant biofilm

infections)

7 days2 days6 hoursLegionella

39Animation sequences by Biolumination Studios: http://www.bioluminationstudios.com

Putting It All Together

Putting It All Together

Animation sequences by Biolumination Studios: http://www.bioluminationstudios.com40

Putting It All Together

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Biofilm Infection & Treatment Profile

▪ Infections can often be low profile (mild symptoms), early on

▪ More mature biofilms: planktonic pioneers are released− symptoms surge upwards

− antibiotics may initially work (kill planktonic & periphery bacteria)

− biofilm community rebuilds

− symptoms return bacteria may grow more tolerant

▪ Mounting survivor resistance; up to 5,000X antibiotic needed

▪ Usually requires removal of associated implanted devices

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Catheters & Tubes

▪ Central Venous Catheters▪ Hemodialysis catheters▪ Pulmonary artery catheters▪ Arterial catheters▪ Urinary catheters▪ Peritoneal catheters▪ Umbilical catheters▪ Tracheostomy tubes

▪ Enteral feeding tubes

▪ Gastrostomy tubes

▪ Nasogastric tubes

▪ Endotracheal tubes

▪ Peritoneal dialysis

▪ Drainage tubes

▪ Endoscope Lumen

Endotracheal tube for patient’s on ventilation

What Is The Biofilm’s Role in Antibiotic Resistance?

Blue dye representing antibiotic or disinfectant

diffusion through matrix gel

Biofilm Bacteria Excel In Resistance▪ Antibiotics & disinfectants diluted as diffuse through matrix

▪ Enzymes dispersed into matrix: cut & degrade antimicrobials

▪ Both encourage dormant bacterial resistance genes to express

− weak threats switch bacteria’s physiology to re-activate defensive factors and multiply them

− resistance genes passed to neighbors & next generation

− 10 to 5,000X more resistant than free pathogens

− deeper into matrix, antimicrobials encounter metabolically slow bacteria that rarely uptake food or antimicrobials

VRES. aureus

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More Resistance Strategies

▪ Incapacitates White Cells that might penetrate matrix

− Poor phagocytic (capture) capability

− Poor killing capability

WBC (Macrophages here) trying to attack biofilm bacteria

Bacteria in biofilm (stained pink here)

WBC (Neutrophil large red balls) gets in through water channels but cannot kill much

Bacteria: A Survival Success Story (Vertical)

Depends on many variables, but an example

Time from First survivor

Number of Bacteria

One survivor 120 minutes 240 minutes 4

1 hour 82 hours 643 hours 5124 hours 4,0965 hours 32,7686 hours 262,1447 hours 2,097,152!!

I, Peter Pathogen, survived antibiotic and found a nice surface with a wonderful organic food supply tissues and fluids! Starting my own Biofilm with all new kids!:

“Peter Pathogen’s Antibiotic-Resistant Protected Pavilion!”

More Recently: Next Level of Understanding Biofilms

Habitat FormationFlemming 2016

Flemming 2016

Flemming 2016

VBNC: Viable But Non-Culturable Cells

Initiating VBNC state depends on species: − starvation − pH − food preservatives− light − electric field − oxygen limitation − low temperature − copper − salinity alterations− aerosolization

Flemming 2016

Cheaters:Quorum sensing mutants

Ex: Some Vibrio choleraDo not respond to communication to participate in the “public good”.

Some communicate only enough to force others to contribute enzymes, digested food, eDNA, etc. but do not contribute back when “instructed” to.

Flemming 2016

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Catheter-Associated Urinary Tract Infections (CAUTI): Biofilm & More

▪ 25% patients receive urinary catheter

▪ 95% urinary tract infections: catheter-associated

▪ > 800,000 hospital acquired CAUTI in US yearly

▪ Bacteria like Proteus mirabilis produce enzyme urease: − breaks down urea to to ammonia, carbonate: alkaline pH

− magnesium & calcium phosphate crystals formed; block urine flow

Sedor J. The Urologic Clinics Of North America. 1999;26:821-828

Current Research Activities Preventing Biofilm Formation, or

Destroying Those Formed

Implant Removal, Debridement, Antibiotic Depots

▪ Soft tissue surrounding implant biofilm contain bacteria encapsulated as reservoirs for future infection/biofilms

▪ Depots: spacers, beads, granules, cement: with antibiotics

▪ PMMA: poly methyl methacrylate

▪ CaSO4: calcium sulfate

▪ Antimicrobial loaded cement: − PMMA are not absorbable: beads must remove after use; not

optimal antimicrobial dispersion, lower concentration delivered; further reduced when coated with bodily fluids

Upper Right Arm

Implantation At 3 months At 5 months

Mirzayan

▪ CaSO4 granules, beads in cement:

▪ Absorbable

▪ Dispenses antibiotics in higher concentration

▪ No reduced dispersion if coated with bodily fluids

▪ However, does not have PMMA strength

CaSO4

Antimicrobial Coated Catheters, Drains, Implants; And Sprays

▪ Because of expense, usually recommended for longer indwelling patients

▪ Helpful in preventing biofilm formation and infection (e.g silver) initially

▪ Longer term, however, shows minimal prevention primarily due to coating active agents with organic fluid in use, and:

▪ Reduced antimicrobial concentration with time

▪ Some success with nebulized antibiotics at intervals (e.g. endotracheal tubes)

Antibodies Against Pilli

▪ Antibodies against flagella of Pseudomonas inhibited biofilm formation (Adams)

▪ Antibodies against Pili of Haemophilus influenza

▪ Note: similar success by others with anti-fimbriae and anti-flagella

Adams 2015;

Biofilm Naïve serum

Antibodies to Pilli

From above From above

Profile of biofilm

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Device Reprocessing ▪Biofilms increased in CSPD if:

– endoscopes (ES) not dried

– organic debris present (food source)

– scratched during reprocessing

– etched by harsh chemicals

– mixed metals in ultrasonic cleaner

– poorly rinsed = detergents

– hard water minerals (rinse water, steam)

– multiple reprocessing of single use items

– rough handling

– oils not removed

– poor assembly dead spaces

– particles not removed

– particles added: lint, hair

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Surface Traits That Impact Biofilms▪ shape, topography▪ rough vs smooth surface ▪ charge (bacteria are negatively charges)▪ hydrophobicity (bacteria attracted to hydrophobic)▪ hydrodynamics▪ etchings, scratches▪ crevices, edges▪ screws: continually reprocessed (start to pit)▪ stainless steel increased biofilm over titanium▪ wet vs dry lumen▪ any organic debris left on/in any device▪ lint, detergent particles, saline (becomes salt crystals)▪ any corroded portions of device

Incapacitating Ability of Bacteria to Communicate

▪ Pseudomonas biofilm on:

1. Standard untreated polyurethane

2. Usnic acid treated polyurethane – disrupts communication and ability to organize community

(1) (2)

Francolini I, Norris PM, Stooldley P. Montana State University, Bozeman MT62

Antibodies AgainstDNABII Proteins

We know eDNA:

▪ is distributed throughout biofilm matrix

▪ DNABII protein holds eDNA pieces together providing structural integrity throughout EPS matrix (like framing a house)

▪ When DNABII “king-pin” structure destroyed, bacteria released and become free-floating

▪ Add Antibiotic: sensitive bacteria killed

Novotny L, et al. Antibodies against DNA-binding tips of DNABII proteins

Mouse lung pneumonia: Pseudomonas colored green released from broken down biofilm matrix

Electric Field + Antibiotic

▪ Apply a safe extremely low voltage of alternating Direct Current (DC and Alternating Current (AC) while applying antimicrobial

▪ Killed all bacteria of P. aeruginosa biofilm & E. coli biofilm

Kim YW 2014 Intern Conf on Miniaturized Sys Chem & Life Sciences

Control: no treatment Antibiotic only Alternating AC & DCAntibiotic plus

Alternating AC & DC

+Antibiotic

AC - DC

Phage Therapy ▪ Phage aka. bacteriophage: viruses that kill bacteria, harmless to humans

▪ Like human viruses, they come in different shapes and sizes

ClassicT-Phage

Lytic Bacteriophage Attacking E. coli

▪ Injection of genetic code to Lysis (break open) 20-40 minutes

▪ Burst size ranges from 50-200 new bacteriophage

E. coli

E. coli

DNA protein capsid

“Holie” Matrix!!

Or:▪ Attach antibiotics to phage as transporters

▪ After biofilm matrix disruption by phage-associated enzymes dispersin B or depolymerases, add antibiotic

▪ Add phage + extra sterile enzyme onto implant during surgery

▪ Add lysogenic (temperate phage) that add polymerase production gene into bacteria

What Can We Do Now?

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Biofilm Formed On Implants Both Hands▪ Implants in both hands acquired biofilm infection

▪ Implants had to be removed; all bacteria killed before new implants

Culprit: Remote infection

Prevent this cause of implant biofilm by ensuring all remote infections treated and resolved before surgery

▪ Mermel: 5 cardiac surgery patients with SSI − surgeon onychomycosis: fungus of nail − Pseudomonas hideout in fungus branches− nail removed, treated, infections stopped

▪ Malani: 27 sternal infections after CABG − 11 cases Candida albicans

− 16 cases Pseudomonas aeruginosa

− both from thumbnail fungus of same circulating nurseNote: 4 of these infections took 48 to 150 days to appear!

▪ McNeil: 16 of 185 median sternotomy patients: Pseudomonas from Scrub Nurse thumbnail fungus

− 7 mediastinitis− 5 deep sternal infection− 2 superficial sternal wound − 1 prosthetic valve endocarditis− 1 sepsis

Biofilm Hiding Among Fungus Branches

702-13% adults have onychomycosis (nail fungus); 90% of the elderly

Recommend coat with antiepic and cover before surgery

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Royer: Bloodstream Infections Reduced

▪ After blood draw, retained blood provided breeding ground for biofilm formation

▪ Opaque valves do not show residual blood▪ Switched to clear housing▪ 10mL flush did not clear blood; 20 mL did ▪ 5 fold reduction in BSI

Poster: Royer T: VHA MRSA Prevention Forum; Orlando FL Nov 5-6, 2007

Breast Implant Contractures

▪ Implant capsular contractures: hard scar tissues walling off threat

▪ Surgeon certain particles attracted onto implant surface and there − distract local immune response & hide bacteria − enable few bacteria contaminating site to form a micro-biofilm− subclinical infection

(Pajkos AB, 2003; Netscher D, 2004; Mladick RA, 2005; Netscher DT, 2005)Capsule:

Implant removed

Breast Implants

▪ He was still convinced in spite of disbelievers▪ Performed all breast implant surgeries:

− lint-free− powder-free gloves− no touch implant− no touch patient skin (even though prepped)

Mladick RA. Plast Reconstr Surg 2005;(14):26-27//Keller funnel

Eight years without a single capsular contraction!

▪ Little things (lint, powder, other particles matter!)▪ Principle applies to all implants!!

Implant static cling

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Distraction

Crime Of Distraction: Great Break for Biofilm• Things that strongly attract the attention of the immune system

– become the center of attention so microorganisms are ignored and can multiply

germ

Significantly Reduced Infection Threshold

Elek▪ Wound: no particles = 10 million bacteria (107) to cause infection▪ Wound: with suture fragment = 100 bacteria (102) to cause infection

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1. Macrophage attention to larger lint & particulate threats2. Neutrophils deplete oxidative burst defending these larger threats3. WBCs ignore the few Pseudomonas nearby (immune distraction)4. The few contaminating bacteria become many5. Infection initiated (threshold reduced-takes fewer bacteria to infect)

Jaffray▪ Wound: no particles = 1,000 (103) = 1/10 animals infected▪ Wound: 2mg sterile particulates = 1,000 (103) = 9/10 infected

Reduced # bacteria needed for infection by 100,000X!

Increased number of “patients” infected from 10% to 90%!

Immune Distraction

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Lint & Particulate Sources▪ Poorly cleaned devices: tissues, fat, blood ▪ Linting sterilization wrap▪ Gasket seals oxidizing on containers or devices▪ Sweaters, fleece vests in SPD room▪ Devices dried with/on linting materials▪ Hair, lint, debris from staff and traffic▪ Corrugated cardboard, newspapers, tissues▪ Rigid containers not washed clear of debris▪ OR: gowns, hair, drapes, back table cover,

sterilization wrap, glove powder

90% cellulose fibers10% polyester (melted edges)

White Wipe Swipe: Wrapping Table In The Sterile Processing Department

Inadequate Instrument Processing

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Poorly Reprocessed Electrodes ▪ Electroencephalogram electrodes not properly cleaned

▪ Residual dried on biofilm provided

− protection of entrapped virus − prevented adequate sterilization

▪ Several patients acquired hepatitis B (HBV)

▪ $27.5 million legal settlement against neurologist & hospital

Mackay B CMAJ 2002; 166(7):943

Stage Six: Fortified Endoscope Biofilm

▪ Studies by Pajkos, 2004; Alpha, 2010; Ofstead 2017: after following IFUs, clean results not always 100% successful

▪ Once an area of organic debris is missed: − organisms attach and multiply forming classic biofilm− endoscope is processed through disinfectant− disinfectants (esp. aldehydes) “fix” (like glue) organics to

surface along with biofilm resident bacteria inside− endoscope goes back into use− process continues with fresh organics & bacteria repeatedly− each layer increases the formidable protective shielding

▪ Fixed layered biofilm is much, much harder to remove and for disinfectants to penetrate

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If Delayed: Biofilm Starts, Expands, Layers

▪ (A) Communities (biofilm) of healthy multiplying bacteria – left over weekend before processing

▪ Bacteria, organic debris food supply + matrix dry onto surfaces “like cement” live bacteria inside

▪ (B) Dried organic debris & biofilm after reprocessed; but microorganisms still alive!!

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B

A

Dried-out, cemented on surface, the organic debris “Like dried Jerky with live bacteria inside!”

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Pre-clean per endoscope reprocessing guidelines Using Manufacturers IFU

“Immediately after removing the endoscope from the patient, wipe the insertion tube with the wet cloth or sponge soaked in the freshly prepared

enzymatic detergent solution.”

Bolander S 2005 SGNA Standards of Infection Control in Reprocessing of Flexible Gastrointestinal Endoscopes

Also guidelines from:

AORNAAMICDC

IAHCSMMCBSPD

Next Critical Biofilm Prevention StepTransport: Immediately after Pre-cleaning:

▪ Place endoscope coiled in safe container free from items that could damage the unit

▪ Cover with enzyme solution/foam/spray to degrade organics so can more easily be cleaned

▪ Keep wet/moist to prevent drying onto surface (cover with towel/lid)

▪ Mark Contaminated/Biohazard

▪ Enzymes: Protease for proteins, Amylase for carbohydrates; Lipase for fats. (However appropriate detergents/surfactants do just as well for fats)

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Protease Amylase

ProteinsBroken down To amino acids Carbohydrates

Broken down to sugars

Lipase

Fats

Broken down to lipids

Biofilms: Flexible Endoscopes

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Primary causes:

▪ Not wiped/flushed at site immediately after use ▪ Left too long before SPD cleaning (dried on) ▪ Organics missed; fixed by disinfectant, layering▪ Leak test not performed (damaged seals: biofilms love)▪ Tap water used as rinse water▪ Not properly and thoroughly dried▪ Poor repair jobs▪ Automatic Endoscope Reprocessors (AER):

Biofilms contaminated scopes & caused infections

• Under trays • Tubing • Detergent tank

• Water bottles • Connectors• AER not disinfected

• Pump Contaminated

• Filter overgrown

AER Biofilms sites resulted in infections

Water Based Biofilm Infections

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▪ Tap water safe to drink but not rinse endoscopes Patient infections and full outbreaks:

− Acinetobacter

− Burkholderia

− Legionella

− Mycobacterium

− Pseudomonas

− Serratia

− Stenotrophomonas

▪ Biofilms form in pipes, faucet heads, drains

33 patient 145 infection

Mycobacterium, Pseudomonas, Legionella,

Acinetobacter, Serratia, Stenotrophomonas, Burkholderia

Contaminated Water: Aerosolized, Liquid or Ice have Caused SSIs

▪ Contaminated solutions for processing endoscopes

▪ Cardioplegia solutions

▪ Dialysis equipment (usually rinse water)

▪ Disinfectants

▪ Hospital tap water

▪ Hydrotherapy pools

▪ Peritoneal dialysis fluids

▪ Respiratory equipment and humidifiers

▪ Splashes after contacting contaminated sink, drain

▪ Stagnant lip of water in aeration faucet head

▪ Water dispensers

▪ Water/ice used to cool eye solutions

▪ Water-based patient warming devices (esp. + pressure)

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Summary▪ Biofilms: Highly organized, well defended, microbial communities

▪ Biofilm bacteria much more resistant to antimicrobials than individual bacteria and share resistance genetics with community

▪ There is a lot of research to prevent formation and destroy those formed

▪ Delayed cleaning, residual organics, rinsing with tap water, and incomplete drying all increase biofilm risk

▪ Lint, debris, dead biofilm chunks, increase risk of biofilm formation and infection by immune distraction

▪ Most effective way to reduce biofilm impact now is prevention

DUJS Nov 21, 2009

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Addressing Biofilm Prevention Now!

You’re Staff Are Proud of it

Joint Commission Approves of It!

Accounting Loves it

Patients Couldn’t Be Happier!