part 1 - framing the discussion on sterile...

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Part 1 - Framing the Discussion on Sterile Surfaces

The Importance of Antimicrobial Incise Drapes and Sterile Surface in

Managing the Risk of Surgical Wound Infections

Patrick J. Parks M.D. Ph.D.

3M Health Care

St.Paul, Minnesota

Commercial Identification

“Povacrylex”– 3M™DuraPrep™ Surgical Solution (Iodine Povacrylex [0.7% available iodine] and Isopropyl

Alcohol, 74% w/w) Patient Preoperative Skin Preparation “Antimicrobial Impregnated Incise Drape”

– 3M™ Ioban™2 Antimicrobial Incise Drape “Ethanol/Chlorhexidine”

– ChloraPrep® (Chlorhexidine Gluconate 2% w/v and Isopropyl Alcohol 70% v/v) Antiseptic Skin Prep. ChloraPrep is a registered trademark of Allegiance Corporation [Enturia product, now part of Cardinal Health]

“Cyanoacrylate”– InteguSeal Microbial Sealant is a registered trademark of Kimberly-Clark Worldwide, Inc.

Betadine® Solution– Betadine® Solution is a registered trademark of The Purdue Frederick Company.

IF commercial labels appear, they appear as they are given in the cited literature. All data presented have appeared or are scheduled to appear in peer-reviewed

publications.

3M, DuraPrep, Ioban, and Steri-Drape are trademarks of 3M.

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Outline

Framing the discussion

– The relationship of contamination to infection

• Sources of infection

• Local factors

• Implants as a special case

• Biofilm formation

Reducing contamination and infection

• Antisepsis

• Sterile surface formation

Future

Wound Contamination and Wound Infection

“It ought to be axiomatic by now that reducing bacterial contamination reduces infection.”*

* Raahave,D., Wound contamination and postoperative infection. A review. Dan. Med. Bulletin (1991) 38:481-485.

Defining the Risk of Surgical Site Infection

==

Dose of Bacterial Contamination

Virulence

Resistance of the host (patient)

XRisk of Surgical Site Infections

Resistance of the host (patient)+ Antibiotics+ Local factors

SSI improved from 14.3% to 8.7%

Forbes et al.,J Am Coll Surg (2008) 207:336-341.

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Host Defenses

“Adequacy of host immune defenses is the primary factor determining whether wound contamination progresses into a clinical infection.”*

* Sessler, D.I., “Nonpharmacologic prevention of surgical wound infection.” Anesthesiol.Clin.(2006) 24:279-297.

Resistance of the Host

“Local” factors– Under control of SURGEON

Avoid seroma

Avoid tissue necrosis

Minimal trauma to tissue

– Inherent PATIENT risk factors Neumayer,L. et al. J.Am.Coll.Surg.(2007) 204:1178-

1187

Genetic factors (vit D receptor, MMP1 in THR failure) Malik, MHA et al. Ann.Rheum.Dis.(2007) 66:116-1120.

Defining the Risk of Surgical Site Infection:All surgeries

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Sources of Wound Contamination and Routes of Transmission

Patient’s skin

Theatre personnel

Instruments

Adjacent area Floor

Ventilation

Wound

Theatre air

Body, incisionand wound drapes

Watertightclothing

Gloves

Clothing

Masks

Mouthhands

Body

Source of Bacteria

Where do bacteria come from?Air Whyte et al., J. Hosp. Infect. (1991) 18:93-107.

Brown,A.R., et al., J.Hosp.Infect.(2001) 48:117-131.Edminston, CE et al., Surgery (2005) 138:573-582.

Staff skin Huebner,J. Annu.Rev.Med. (1999) 50:223-236.

Patient skin vonEiff, et al., Eur.J.Clin.Microbiol.Infect.Dis. (1999) 18:843-846.

Brown,A.R., et al., J.Hosp.Infect.(2001) 48:117-131. (ultraclean air systems present)

Garvin,K.L. and Urban,J.A., Total hip infectionsin Musculoskeletal Infections (2003) pp. 241-293.

Defining the Risk of Surgical Site Infection:Source of Organisms

Clean and Clean Contaminated surgery:Skin organisms are a major source of infecting organisms.*

*Taylor,G.J. et al., Perioperative wound infection in elective orthopaedic surgery. J.Hosp.Infec.(1990) 16:241-247.

Contaminated surgery“There was no significant correlation between intraoperative

tissue bacterial density and subsequent wound infection, or contaminating and infecting bacteria.*”

*Becker,G.D., Welch, W.D. Quantitative bacteriology of intraoperative wound tissue in contaminated surgery. Head Neck. (1990) 12:293-297.

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Skin Microbiology

Humans carry between 100 (“2 logs”) and100 000 (“5 logs”) organisms per sq cm on their skin

Number depends on site on body and individual Most common organisms include

– Staph. Epidermidis (coagulase neg staph)– Staph. Aureus– Propionibacterium species (anaerobe)

Staphylococci Prefer Implant Surfaces

Llinos G Harris, R Geoff Richard, Staphylococci and implant surfaces: a review. Injury (2006) 37:S3-S14.

Skin Microflora has Become Complex

“We examined the diversity of the skin biota from the superficial volar left and right forearms in six healthy subjects using broad-range small subunit rRNA genes (16S rDNA) PCR-based sequencing of randomly selected clones. For the initial 1,221 clones analyzed, 182 species-level operational taxonomic units (SLOTUs) belonging to eight phyla were identified*.

*Z Gao, C Tseng, Z Pei and MJ Blaser. Molecular analysis of human forearm superficial skin bacterial biota. PNAS (2007) 104: 2927-2932.

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Skin Biofilm Forming Bacteria are Common

Multiple biofilm forming bacteria, some previously unknown!– Lysobacter species

KE Dempsye, MP Riggion, A Lennon, VE Hannah, G Ramage, D Allan and J Bagg. Identification of bacteria on the surface of clinically infected and non-infected prosthetic hip joints removed during revision arthroplasties by 16S rRNA gene sequencing and by microbiological culture Arthritis Research & Therapy (2007) 9: 1-11.

Biofilms

All bacteria make biofilm

Foreign & devitalized tissue can succumb to biofilm formation if exposed to bacteria

Slide courtesy of Dr. Ed McPherson, USC Orthopaedics

Costergan, W. MSIS 2000

Characteristics

Biofilms

Biofilms– Sugars (Extracellular polysaccharides)

– Proteins (Bacterial and Host)Planktonic bacteria Planktonic bacteria

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Infection in Implant SurgeryMolecular measurement methods are critical!

“Our results indicate that the incidence of prosthetic jointinfection is grossly underestimated by current culture detection methods*.”

*Tunney,M.M., et al., Detection of prosthetic hip infection at revision arthroplasty by immunofluorescence microscopy and PCR amplification of the bacterial

16S rRNA gene. J.Clin.Microbiol. (1999) 37:3281-3290.

Where incidence is correct (Norway, Sweden, Denmark), impact may be underestimated.

– Infection during first implantation increases risk of failure ofrevision*.

*Anguita-Alosno,P. et al., Prosthetic joint infection. Expert Rev.AntiInfect.Ther. (2005) 3: 797-804.

Implant Infection Summary:

There is NO minimum critical density for infection since:– Each patient has a unique immune system

– Each patient has different risk factors

– Surgery is different for each patient

– Bacteria have different levels of virulence

– Bacteria may form biofilms

– Common pathogens (staph) preferentially attach to common implant materials

Outline

Framing the discussion

The relationship of contamination to infection

Sources of infection-patient skin

Local factors-host response

Implants as a special case-high morbidity

Biofilm formation-common critical factor

Reducing contamination and infection

Antisepsis

Sterile surface formation

Future

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Part 2 - Antisepsis and the Reduction of Wound Bacterial Count

Skin Microbiology:Risk of Surgical Site Infections

==


Virulence


X

Reducing Contamination:

There are two ways to reduce local contamination– Antibiotics

– Antiseptics

SG

Stratum corneum

Dermis

Transient flora

Resident flora

26

SG

Stratum corneum

Dermis

Transient flora•Low in number on clean unexposed skin

•Do not reproduce

•Attached weakly

•Easily removed

27

SG

Stratum corneum

Dermis

Resident flora• Grow

• Reproduce

• Attach firmly

• Difficult to remove

SG

Dermis

Antiseptics work

here

NOT here

Patients’ Skin Flora

Skin antimicrobials/antiseptics are required to provide 2 to 3 log reduction in skin flora.

0

1

2

3

“Dry” “Moist”

M

MM

M

D M

D

Patient Antisepsis

Iodine compounds– Slow release to avoid irritation

Povidone ‘carrier’ Povacrylex film former

Chlorhexidine– Superior for intravenous lines

Alcohols– Combined for rapid effect

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Skin Flora Counts after Chlorhexidine/Alcohol Preparation

“Skin preparation with ethanol/ chlorhexidine is unable to suppress the physiological skin flora for the duration of a heart operation*.”

*KÜHME,T, et al., Wound contamination in cardiac surgery. A systematic quantitative and qualitative study of bacterial growth in sternal wounds in cardiac surgery patients APMIS (2007) 115, 1001–1007.

Skin Flora Counts AFTER Isopropyl Alcohol

1

10

100

1000

10000

100000

1000000

1 10 100 1000 10000 100000 1000000 10000000

CFUs per square cm BEFORE skin preparation

CF

Us

per

sq c

m A

FT

ER

pre

p

Acceptable antiseptic

action

STAPH EPIDERMIDIS CFUs AFTER Iodophor

1

10

100

1000

10000

1 10 100 1000 10000 100000 1000000 10000000

CFUs per sq cm BEFORE skin preparationCF

Us

per

sq c

m A

FT

ER

(S

epi

)

Acceptable antisepsis

A.B. Cronquist, K. Jakob, L.Lai, P. Dellla Latta, and E.L. Larson. “Relationship between skin microbial counts and surgical site infection after neurosurgery.” Clin.Infect. Dis 33, no. 8(2001): 1302-08. Keywords: clinical study/infection/ioban/postoperative/PP

io009/skin preparation/skin

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==

Dose of Bacterial Contamination Virulence


X

What ‘dose’ is acceptable to AVOID infection?

1. N.P.O'Grady, M.Alexander, E.P.Dellinger, J.L.Gerberding, S.O.Heard, D.G.Maki, H.Masur, R.D.McCormick, L.A.Mermel, M.L.Pearson, I.I.Raad, A.Randolph, and R.A.Weinstein. "Guidelines for the prevention of intravascular catheter-related infections." Infect.Control Hosp.Epidemiol. 23, no. 12(2002):759-69.Keywords: adherence/catheters/central venous catheter/chlorhexidine clinical/clinical trial/Clinical Trials/guideline/infection/infections/outcome PPio062/review/Risk/skin/skin preparation/synthesis Abstract: BACKGROUND: Although many catheter-related bloodstream infections (CRBSIs) are preventable, measures to reduce these infectionsare not uniformly implemented. OBJECTIVE: To update an existing evidenced-based guideline that promotes strategies to prevent CRBSIs. DATA SOURCES: The MEDLINE database, conference proceedings, and bibliographies of review articles and book chapters were searched for relevant articles. STUDIES INCLUDED: Laboratory-based studies,controlled clinical trials, prospective interventional trials, and epidemiologic investigations. OUTCOME MEASURES: Reduction in CRBSI, catheter colonization, or catheter-related infection. SYNTHESIS: The recommended preventive strategies with the strongest supportive evidence are education and training of healthcare providers who insert and maintain catheters; maximal sterile barrier precautions during central venous catheter insertion; use of a 2% chlorhexidine preparation for skin antisepsis; noroutine replacement of central venous catheters for prevention of infection; and use of antiseptic/antibiotic-impregnated short-term central venous catheters if the rate of infection is high despite adherence to other strategies (ie, education and training, maximal sterile barrier precautions, and 2% chlorhexidine for skin antisepsis). CONCLUSION: Successfulimplementation of these evidence-based interventions can reduce the risk for serious catheter-related infection. Publication Types: • Guideline

Clinical and Experimental Thresholds

Dose % Infected System Comment Reference5.60 >90 Rabbit Osteomyelitis Li et al 2007

6 70 Mouse Inoculated at implantation Merritt et al 19794 30 Mouse Inoculated at implantation Merritt et al 19792 0 Mouse Inoculated at implantation Merritt et al 19792 Human Suture Elek 19571 Human Calculated Charnley

Dose % Infected System Comment Reference9 50 Rabbit cobalt chrome Petty et al8 50 Rabbit polyethylene Petty et al6 50 Rabbit PMMA Petty et al4 50 Rabbit polymerizing PMMA Petty et al

Staphylococcus aureus

Staphylococcus epidermidis

1. S.D.Elek and P.D.Conen. "The virulence of Staphylococcus pyogenes for man. A study of the problem of wound infections." Br.J.Exp.Path. 38,(1957):573-76. Keywords: infection/infections/PPss040/Staphylococcus aureus/surgicalsite infection/virulence/wound infection2..Li,D, Gromov,K, Soballe,K, Puzas,JE, O'Keefe,RJ, Awad,H, Drissi,H, Schwarz, EM. Quantitative mouse model of implant associated osteomyelitis and the kinetics of microbial growth, osteolysis, and humoral immunity. J. Orthop.Res (2008) 26: 96-105.3. Merritt,K., Shafer,JW, Brown, SA. Implant site infection rates with porous and dense materials. J. Biomed. Mater. Res. (1979) 13: 101-108.4. Bannister, G, Prevention of infection in joint replacement Curr. Orthopaed. (2002) 16:426-433

Case Control Study: TKA/THA and Bacterial Density

N=52 both groups

0

200

400

600

800

1000

1200

1400

1600

1800

Operative Site Back

InfectedControl

p=0.01

p=0.02

Bacterial density (CFU/sq cm)

1. J.A.Urban, S.Hinrichs, H.Song, B.P.Hasley, and K.L.Garvin. "Skin bacterial counts in patients with a history of infected total joint arthroplasty.“ Amer.Acad.Orthop.Surg. Poster Pres.,(2001).Keywords: biomaterials/implant/joint/PPio021/skin preparation/skin/surgical site infection

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Outline

Framing the discussion The relationship of contamination to infection

Sources of infection-patient skin Local factors-host response Implants as a special case-high morbidity Biofilm formation-common critical factor

Reducing contamination and infection Antisepsis

Antisepsis does NOT form sterile surfaceThreshold for infection ~100 organisms (per sq

cm) Sterile surface formation

Future

Part 3 - Levels of Evidence Supporting Sterile Surface Value

Levels of Evidence for Antiseptics

In vitro – Kill rate

– Minimum bacteriocidal level

– Minimum inhibitory (bacteriostatic) level

– Bacterial capture/immobilization

In vivo– Reduction in wound contamination rate

– Reduction in surgical site infection rate

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In Vitro Kill Rate: Povacrylex

Organisms placed on top of dried Povacrylex film (% Microbial kill)

MBCs for Povacrylex and Betadine

Povacrylex Solution

Povacrylex

Bacterial ImmobilizationNatural consequence of film formation

Povacrylex Solution + Bacteria Povacrylex Solution Control

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Levels of Evidence: Film Formers

In vitro – Kill rate

– Minimum bacteriocidal level

– Minimum inhibitory level– Bacterial

capture/immobilization

In vivo– Reduction in wound

contamination rate

– Reduction in surgical site infection rate

Cyanoacrylate Povacrylex

No activity Meets standards

No activity <16 μg/ml

(6020 μg/mlavailable)

No activity As above

Captures bacteria Captures bacteria

Towfigh, S et al Arch Surg (2008)

143:885-891.

Jacobson, C et al Clin Orthop Rel Res(2005)439:32-

37.

No data Swenson,B. et al. (2008)

ABSTRACT TITLE: The effects of preoperative skin preparation on postoperative wound infection: a prospective study comparing three skin preparation protocols

AUTHORS: Brian R. Swenson, Traci Hedrick, Hugo Bonatti, Rosemaire Metzger, Timothy L. Pruett, Robert G. Sawyer

RESULTS: 3209 operations were included in the 18 month study. In subgroup analysis most of the difference in SSI rates were seen in clean-contaminated cases. SSI rates by prep received were: Betadine® 4.8%, ChloraPrep® 8.2%, and DuraPrep™ 4.8%, p=0.0035.

Period 1(Betadine®)

n=987

Period 2(ChloraPrep®)

n=994

Period 3(DuraPrep™)

n=1228p value

Any SSI 63 (6.4%) 71 (7.1%) 48 (3.9%) 0.0024

Superficial 43 (4.4%) 48 (4.8%) 32 (2.6%) 0.015

Deep 6 (0.6%) 4 (0.4%) 1 (0.01%) 0.088

Organ/Space 14 (1.4%) 19 (1.9%) 17 (1.4%) 0.56

Sterile Surface Formation

Formation of sterile surface by addition of antimicrobial impregnated incise drape reduces contamination and risk of infection.

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==


Virulence


X

900 prosthetic joint infections in >12,000 patients.

MRSA 28% of infections.

Lipsky, BA et al. Inf Ctl Hosp Epidemiol. (2007) 28:1290-1298.


Skin Microbiology:Risk of SSI

With Antimicrobial impregnated incise Drape

Staph Aureus

↓ MRSA

Coagulase neg Staph.

Corynebacterium sp.

Without Antimicrobial impregnated incise Drape

Staph Aureus

MRSA

Coagulase neg Staph.

Corynebacterium sp.

Hemolytic strep. sp

E. faecalis

Enterococcus spp.

Proteus mirabilis

Burholdia cep.*Dohmen, PM Influence of skin flora and preventive measures on

surgical site infection during cardiac surgery. Surg. Infec. (Larchmt) (2006) 7 Suppl 1: S13-S17.

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Sterile Surface Formationand Virulence

Use of an iodophor impregnated incise drape – Reduces density of MRSA in wounds

– Reduces density of multiple ‘less virulent’pathogens

Antimicrobial Impregnated Incise Drape Reduces Wound Contamination

Fairclough, J.A. et al., The prevention of wound contamination by skin organisms by the pre-operative application of an iodophor impregnated plastic adhesive drape. J Int Med Res. 1986;14(2):105-9.

Jacobson, C. et al., Prevention of wound contamination using DuraPrep solution plus Ioban2 drapes. Clin Orthop Relat Res. (2005)439:32-7.

Meta-Analysis References

Hagen KS, Teston-Auran J. A comparison of two skin preps used in cardiac surgical procedures. AORN J (1995) 62: 393-402.

Pinheiro SMC,Mafra S, Couto BRGM, Starling CAF. Woven drape versus adhesive drape impregnated with PVPI: comparison of surgical infections incidence. S54, SHEA 1997 Meeting Abstract.

Segal CG and Anderson JJ. Preoperative skin preparation of cardiac patients. AORN J (2002) 76: 821-828.

Dewan PA, VanRu AM, Robinson RG, Skeggs GB, Fergus M. The use of an iodophor impregnated plastic drape in abdominal surgery- a controlled clinical trial. Aust NZ J Surg (1987) 57: 859-863.

Yoshimura Y, Kubo S, Hirohaski K, et al. Plastic iodophor drape during liver surgery: operative use of an iodophor impregnated adhesive drape to prevent wound infection during high risk surgery. World J Surg (2003) 27: 685-688.

Dahlin LG, Granfeldt H, Hultkvist H. A multimodel approach for reducing wound infections after sternotomy. Interactive Cardiovasc. Thor. Surg. (2004) 3: 206-210.

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Meta-Analysis: Antimicrobial Impregnated Incise Drape Reduces Risk

Outline

Framing the discussion Reducing contamination and infection AntisepsisAntisepsis does NOT form sterile surfaceThreshold for infection ~100 organisms (per sq cm)

Sterile surface formation-REDUCES Exposure to virulent strains (MRSA) Exposure to multiple organisms with different virulence levelsWound contaminationRisk of surgical site infection

Future

Future

“Prediction is difficult…………especially the future.” (Neils Bohr)

Vaccination against most common pathogens

Antimicrobial impregnated incise drapes containing different or multiple antiseptics

Reduction in wound damage through– Incise drape modification to improve healing

– Minimal incision/invasive surgery

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Summary

Wound contamination is important in reducing risk of infection for high morbidity surgery:

– Implant/indwelling devices

Risk of infection is the result of a balance of factors

– Local host response– Bacterial virulence– Bacterial contamination

Timely antibiotics can reduce contamination and infection

Antiseptics are critical but incomplete Sterile surface formation can reduce risk of

wound contamination and wound infection

Patrick J. Parks M.D. Ph.D. Credentials

M.D. School of Medicine 1978

Case Western Reserve University

Cleveland, Ohio

Ph.D. Department of Biomedical Engineering 1977

(bio materials track)

Case Western Reserve University

Cleveland, Ohio

B.S.Ch. E. Department of Chemical Engineering 1972

University of Pittsburgh

Pittsburgh, Pennsylvania

Education

Acknowledgements

Egil Lingaas M.D.Ph.D. Shelley-Ann Walters MS Stat David O’Sullivan, Ph.D. Laura Lyden Karen Zaruba Ken Kato, Ph.D.

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Thank you

part 1 - framing the discussion on sterile...

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