Using Traditional and Innovative Risk Reduction Strategies to

Using Traditional and Innovative Risk Reduction Strategies to Reduce the Risk of SSIs in a Transparent and Evidence-Based Healthcare Environment Charles E. Edmiston Jr. , Ph. D. , CIC Professor of Surgery & Hospital Epidemiologist Department of Surgery Medical College of Wisconsin Milwaukee, Wisconsin USA edmiston@mcw. edu

Froedtert Hospital Infection Control Team 2011 - 2012 Chairman, Infection Control Committee Mary Beth Graham, MD Infection Control Coordinators Patti Wilson, BSN, CIC Pat Sadenwasser, BSN, CIC Amy Macke, BSN, CIC Microbiologists Nathan Ledeboer, Ph. D, DABMM Candy Krepel, MS, SMASCP, CIC Hospital Epidemiologist Charles Edmiston, Ph. D, CIC Administrative Support

“Risk Reduction Requires an Understanding of the Mechanistic Factors which Potentiate the Risk of Infection in the Surgical Patient Population”

2010 National Patient Safety Goals (NPGS) – The Joint Commission Health Care-Associated Infections • • • NPSG. 07. 03. 01: Implement evidence-based practices to prevent health care-associated infections due to multidrug-resistant organisms in acute care organizations (critical access facilities). NPSG. 07. 04. 01: Implement evidence-based practices to prevent central line-associated bloodstream infections (critical access and long-term care facilities). NPSG. 07. 05. 01: Implement evidence-based practices for preventing surgical site infections (critical care, ambulatory and office-based surgical facilities).

Evidence-Based Hierarchy

Mitigating Risk - Surgical Care Improvement Project (SCIP) – An Evidence-Based Approach • • Timely and appropriate antimicrobial prophylaxis Glycemic control in cardiac and vascular surgery Appropriate hair removal Normothermia in general surgical patients Is this the Holy Grail?

An Increase in Compliance With the Surgical Care Improvement Project Measures Does Not Prevent Surgical Site Infection in Colorectal Surgery Pastor et al. Diseases of the Colon & Rectum 2010; 53: 24 -30

“The report by Stulberg et al in this issue of JAMA is the largest study to date that fails to demonstrate an association between adherence to SCIP process measures and the occurrence of postoperative infections. The authors found no significant association between individual process measures or the all-or-none composite core measurement composed of all 3 measures for prophylactic antibiotic administration and postoperative infection. They report a modest association between adherence to a composite measure that included at least 2 of the 6 SCIP measures applied to an expanded SCIP population and postoperative infection. Despite substantial improvements in SCIP adherence over the 2 -year study period, postoperative infection rates actually increased. ” MT Hawn – Editorial JAMA

Does the Process Improve the Outcome? The author’s analysis suggest that, “…there was little or no association between compliance with most SCIP infection-related process measures and ACS NSQIP risk-adjusted outcome……. with the exception of administration of the appropriate antibiotic (SCIP-2). ” Ingraham et al. J Am Coll Surg 2010; 211: 705 -711

v. Taking a SCIP-Plus Perspective to Risk Reduction

v. Does increase BMI warrant a change in how we dose (prophylactic) our patients?

“Measured and dose-normalized subcutaneous cefoxitin concentrations and AUCs in the obese patients were significantly lower than in the normalweight subjects. There was an inverse relationship between cefoxitin tissue penetration (AUC tissue/ AUC plasma ratio) and body mass index. Tissue penetration was substantially lower in the obese patients compared to normal weight controls (p = 0. 05). ” “This occurred despite 2 -fold-higher cefoxitin dosage (1 to 2 gms). Diminished tissue antibiotic concentrations in morbid obesity may influence the incidence of SSIs. ” Toma et al. , Anesthetic Pharmacology and Preclinical Pharmacology 2011; 113: 730 -737

Perioperative Antimicrobial Prophylaxis in Higher BMI (>30) Patients: Do We Achieve Therapeutic Levels? Percent Therapeutic Activity of Serum/Tissue Concentrations Compared to Surgical Isolate Susceptibility (2002 -2004/2006 -2009) to Cefazolin Following 2 gm (N = 38) and 3 gm (N = 40) Perioperative Dosing Regimen 2 -gma 3 -gmb Organism N Serum Tissue S. aureus 70 68. 6% 27. 1% 92 87. 5% 68. 5% S. epidermidis 110 34. 5% 10. 9% 156 64. 5% 49. 6% E. coli 85 75. 3% 56. 4% 101 92. 4% 86. 5% Kl. pneumoniae 55 80% 65. 4% 49 96. 8% 98. 4% a period covering 2001 -2003 b period covering 2006 -2009 a. Edmiston et al, Surgery 2004; 136: 738 -747 b. Edmiston et al. , In Press 2011: Surgical Infection

Effect of Maternal Obesity on Tissue Concentration Of Prophylactic Cefazolin During Cesarean Delivery Pevzner L, Edmiston CE, et al. Obstet & Gynecol 2011; 117: 877 -882

Percent (%) Perioperative Cefazolin Prophylaxis During Cardiovascular Surgery: Are Therapeutic Levels Impacted by BMI? * N = 10/Group *% therapeutic level versus BMI and cefazolin breakpoint Surgical Microbiology Research Laboratory 2011

v. Best Practice # 1: All surgical patients will receive a minimum dose of 2 gram unless their BMI is >30 – Then the correct dose is 3 grams Please Note: All surgical procedures at Froedtert Hospital are viewed as SCIP-eligible procedures

Risk Reduction Begins on the Front-End Quantitative Microbial Recovery from the Skin Surface* • Scalp 6. 0 Log 10 cfu/cm 2 • Axilla 5. 5 Log 10 cfu/cm 2 • Abdomen 4. 3 Log 10 cfu/cm 2 • Forearm 4. 0 Log 10 cfu/cm 2 • Hands 4. 0 -6. 6 Log 10 cfu/cm 2 • Perineum 7. 0 -11. 0 Log 10 cfu/cm 2 *Surgical Microbiology Research Laboratory 2010 – Medical College of Wisconsin, Department of Surgery

Mean Chlorhexidine Gluconate (CHG) Skin Surface Concentrations (µg/ml+SD) Compared to MIC 90 (5 µg/ml) for Staphylococcal Surgical Isolates Including MRSAa Subgroups (mean C, µg/ml) Pilotb 1 2 Groups (4%) (4% Aqueous) (2% Cloths) [C CHG/MIC 90] p-value Group A (20) evening (1 X) 3. 7+2. 5 24. 4+5. 9 436. 1+91. 2 0. 9 4. 8 87. 2 <0. 001 Group B (20) morning (1 X) 7. 8+5. 6 79. 2+26. 5 991. 3+58. 2 1. 9 15. 8 198. 2 <0. 0001 Group C (20) both (2 X) 126. 4+19. 4 1745. 5+204. 3 2. 5 25. 3 349. 1 <0. 0001 9. 9+7. 1 N = 90 b Pilot group N = 30 a Edmiston et al, J Am Coll Surg 2008; 207: 233 -239 Edmiston et al, AORNJ 2010; 92: 509 -518

Preadmission Showering/Cleansing Skin Preparations as a Pathway to Improving Patient Outcomes (Evidence-Based) • Reducing the risk of SSI in orthopaedic surgery • • Standardized precleansing initiative (CHG cloths) in total joint patients (night before/morning of surgery) 50% overall reduction in SSI Eiselt - Orthopaedic Nursing 2009; 28: 141 -145 • Bundling risk reduction strategies – Quality initiative • • • MRSA prescreening in orthopaedic, obstetric, bariatric patients – decolonization + precleansing with 2% CHG >60% overall reduction in SSI >75% reduction in MRSA SSI Lipke VL Hyott AS. AORNJ 2010’; 62: 288 -296 • Eradication of MRSA in orthopaedic patients • 60% reduction in MRSA infections • 40% reduction in MSSA infection Kim et al. J Bone Joint Surg 2010; 92; 1820 -1826

v. Best Practice # 2: All patients undergoing an elective surgical procedure will take a minimum of 2 CHG antiseptic shower/cleansings using a standardized regimen – The CHG must be supplied to the patient by the hospital

Why Should We Consider Chlorhexidine Gluconate (CHG)? • Persistent antimicrobial activity for up to 6 hours 1, 5 • Documented residual activity and repeat applications will maximize antimicrobial effect 2, 5 • Rapid bactericidal action 3, 5 • Has good to excellent activity against gram-positive and gramnegative bacteria 4, 5 • CHG activity is not adversely impacted by either blood or tissue proteins 5 1. Larson E, APIC guidelines for infection control practice: guideline for use of topical antimicrobial agents. Am J Infect Control. 1988; 16(6): 253 -65; 2. Paulson D, Am J Infect Control. 1993; 21: 205 -9; 3. Denton GW, Chlorhexidine. In Seymour S. Block (Ed. ) Disinfection, sterilization, and preservation. 4 th Ed. , Lea & Febiger, Williams & Wilkins, Media PA, 1991: 279; 4. Mangram AJ, et al. , Guideline for prevention of surgical site infection, 1999. Centers for Disease Control and Prevention, Hospital Infection Control Practices Advisory Committee, Atlanta GA. ; 5. Edmiston CE et al. Am J Infection Control 2007; 35: 89.

DESIGN: Multi Center: A PROSPECTIVE, RANDOMIZED, MULTICENTER CLINICAL TRIAL OF 2% CHLORHEXIDINE GLUCONATE / 70% ISOPROPYL ALCOHOL (Alc-CHG) VS POVIDONEIODINE (PI) FOR PREVENTION OF SSI Michael E. Debakey Veterans Affairs Medical Center, Ben Taub General Hospital, Houston, Veterans Affairs Medical Center, Boston, Medical College of Wisconsin, Milwaukee, Veterans Affairs Medical Center, Atlanta, Baylor College of Medicine, Houston • Patients > 18 years, undergoing clean-contaminated procedures (gastrointestinal, thoracic, urologic and gynecologic) • N = 849 surgical patients: 409 Alc-CHG vs 440 PI • 1: 1 randomization • Patients monitored for 30 days post-op • Overall rate of SSI was significantly reduced in Alc-CHG vs PI groups: 9. 5% vs 16. 1%, p=0. 004 • Significant difference for both superficial incisional site rate: 4. 2% A-CHG vs 8. 6% PI (p=0. 008) and deep incisional: 1% A-CHG vs 3% PI (p=0. 05) • No significant adverse events noted during the study in either group • Alc-CHG superior to PI in reducing the risk of SSI in clean-contaminated procedures New England Journal of Medicine 2010; 362: 18 -26

v. Best Practice # 3: Alcohol/chlorhexidine gluconate represents the state-of-the-art skin antiseptic agent Please Note: Froedtert services using Alcohol/CHG for skin antisepsis: general, vascular, CT, orthopaedic, urology, neurosurgery, OB/GYN, hepatobiliary, solid organ transplant

Utilizing Innovative Impregnated Technology to Reduce the Risk of Surgical Site Infections J Am Coll Surg 2006; 203: 481 -489

Mean Microbial Recovery from Standard Polyglactin 910 Sutures (V) and Triclosan-Coated Polyglactin 910 Braided Sutures (VT) Mean colony forming units (cfu)/cm suture V VT N=10 p<0. 01 102 105 S. aureus (MRSA) 102 105 S. epidermidis E. coli RP 62 A Exposure Time 2 Minutes Edmiston et al, J Am Coll Surg 2006; 203: 481 -489

Braided Monofilament Zones of Inhibition - S. aureus (MRSA) Edmiston et al. , J Am Coll Surg 2006; 203; 481 -489; 2011 Mechanistic Benefits of Antimicrobial Sutures • Reduce risk of wound contamination • Reduction in device contamination • Elution of antiseptic agent within the wound bed

Are Sutures Really a Nidus for Infection? Staphylococcus epidermidis Incisional Wound Infection Surgical Microbiology Research Laboratory, Milwaukee - 2005

Percent Sutures Recovered from Infected Cases and Mean Microbial Recovery from Explanted Absorbable / Non-Absorbable Microbial Recovery (log cfu/cm Percent Infected Devices* suture) Cases 10 Polydioxanone (fascia, n=18) Poliglecaprone (skin, fascia, n=13) Polyglactin (fascia, n=14) Polypropylene (fascia, n=37) Nylon (fascia, n=11) Nylon (skin, n=65) 5/18 38. 5% 6. 3 27. 7% 5/13 28. 5% 5. 9 4/14 22/37 59. 5% 36. 4% 9. 2% 6/65 6. 9 4/11 5. 6 4. 9 5 *29/65 (44. 6%) nylon skin sutures were culture positive but not infected [mean microbial recovery = 1, 674 (3. 2 log 10 cfu/cm suture)]; NS between non-infected and infected nylon sutures

Presence of Biofilm on Selected Sutures from Non-Infected and Infected Cases 100 100 Presence of Biofilm (%) SUTURES Nylon a Braided b Monofilament c 62. 5 Non-Infected Cases (Nylon = 16) a a 16 Infected Cases Superficial SSI Deep Incisional SSI (N = 8) non-infected nylon suture segments were randomly selected for microscopy infected braided suture segments were randomly selected for microscopy c 12 infected monofilament suture segments were randomly selected for microscopy b 4

Making an Evidence-Based Argument for Antimicrobial (Triclosan) Coated Sutures Safety 1. Ford et al. Intraoperative handling and wound healing…… Surg Infect 2005; 3: 313 Clinical Efficacy 2. Edmiston et al. Bacterial adherence to surgical sutures: …Surgery 2006; 203: 481. 3. Rozzelle at al. Antimicrobial sutures for wound closure in CSF shunt surgery…… J Neurosurg 2008; 42: 111 4. Pico et al. Incisional closure following appendectomy in children…. Pediatric Surg 2008; 21: 199 5. Justinger et al. Antimicrobial coating of abdominal closure sutures and infection…. . Surgery 2009; 145: 330 6. Mingmalairak et al. Efficacy of antimicrobial coated sutures in reducing SSI following appendectomy. J Med Assoc Thai 2009; 92: 770 7. Chao-ping et al. Comparison of two absorbable sutures for abdominal wall closure. J Clin Rehab Tissue Eng Research 2009; 13: 4045 8. Galal et al. Impact of using triclosan-antibacterial sutures on incidence of surgical site infection. Am J Surgery 2011; 202: 133 -138 Economic Benefit 9. Fleck et al. Triclosan-coated sutures for reduction of sternal wound infection…. Ann Thor Surg 2007; 84: 232 10. Stone et al. Healthcare saving associated with reduced infection in CSF shunt procedures…. Pediatric Neurosurg 2009; 46: 19 -24

Antimicrobial Suture Technology – Emerging Evidence of Clinical Efficacy • An Accumulation of Evidence-Base Outcome Data 16 Published clinical studies (12 independent investigator initiated) • 9 RCTs (Randomized Controlled Trials) • 6 NRCTs (Non-Randomized Controlled Trials) • 1 Economic Evaluation of a Trial Previously Reported (Stone et al) • 10 + studies in progress • Independent initiated as well as industry funded • Including robust hypothesis-testing RCTs • Multiple specialties (CV, GS, Ortho, Breast) • Multiple international venues

Meta-Analysis – Random Effects Model - p = 0. 0012

v“Although use of antimicrobial sutures is not a routine practice, the benefits are becoming increasingly apparent. Recent evidence-based clinical studies have demonstrated both the clinical and economic benefit of this technology. ” APIC 2010 Orthopaedic Risk Reduction Guidelines – However, it should never be viewed as a “Magic a thoughtful, Bullet” but rather a component of evidence-based risk reduction stratgey

v A Special Consideration: Device. Related Breast Infections – Building an Evidence-Based Intervention

Considering the Risk and Microbial Epidemiology of Breast Infections: Non. Device versus Device-Related • Operative closure and SSI in women undergoing breast conserving therapy (N=580) -11. 7% (superficial) vs. 5. 2% (full-thickness) Indelicato et al, Surgery 2007; 141: 645 • Economic burden N=949): mastectomy with immediate reconstruction (implant) – 12. 4% vs. mastectomy only – 4. 4% vs. breast reduction – 1. 1% Suboptimal antimicrobial prophylaxis modifiable risk factor Olsen et al, J Am Coll Surg 2008; 207: 326 • Breast augmentation (N=3, 002) – 1. 1% (<1. 0%-2. 5%): modifiable risk factor – drains Araco et al, Aesthetic Plastic Surgery 2007; 31: 325

Considering the Risk and Microbial Epidemiology of Breast Infections Microbial Etiology Percent • • Methicillin-sensitive Staphylococcus aureus 41. 9 (35)a Methicillin-resistant Staphylococcus aureus 16. 3 (22) • • Coagulase-negative staphylococci 7. 0 (11) Streptococcal sp. 4. 7 (<2. 0) • • Gram-negative 8. 0 (<6. 0) Pseudomonas aeruginosa 18. 6 (<7. 0) • • Polymicrobial 16. 3 (<12) No growth a. MCW 9. 3 (<6. 0) implant experience (2000 -2009) Olsen et al, J Am Coll Surgery 2008; 207: 326 “Is cefazolin sufficient in breast implant surgery“ – Feldman et al, Plast Reconstr Surg 2010; 126: 779

Staphylococcal Biofilm - Surgical Microbiology Research Laboratory 2006 - Medical College of Wisconsin

Building an Evidence-Based Risk Reduction Strategy for Breast Reconstruction – A 6 Point Strategy • • • CHG shower or cleansing - EB Augment antibiotic dosing – 2 to 3 grams - EB Alc/CHG perioperative antisepsis – EB Antimicrobial (CHG) dressing post JP insertion - TBD CHG irrigation (0. 05%) - TBD Antimicrobial closure technology - EB Improving Patient Outcome Requires One To “Think Different”

The Mechanistic Etiology of a Surgical Site Infection – Let Me Count the Ways • • The patient’s own endogenous flora – skin antisepsis Intrinsic versus extrinsic considerations - Inadequate sterilization/disinfection - Breaks in sterile technique - Nasopharyngeal shedding - Microperforation of surgical gloves

Looking at the Risk of Surgical Site Infections from a New Mechanistic Perspective Surgical Glove Perforation and the Risk of Surgical Site Infection – Analysis of 4147 Surgical Cases • Compared to a control group logistic regression model documented a higher likelihood of SSI in procedures in which surgical gloves were perforated and errors had occurred in antimicrobial prophylaxis (adjusted OR, 4. 2; 95% CI, 1. 7 -10. 8; P=0. 003). Misteli et al. Arch Surgery 2009; 144: 553 -558 Bacteria Passage Following Surgical Glove Perforation Over a 4 month interval the microperforation rate of the outer layer ranged from 4. 7% to 28% - allowing bacterial passage across the surgical glove into the surgical wound. • Harmob et al. Am J Infect Control 2010; 38: 154 -158

Integrated Antimicrobial Surgical Glove Technology Outer mechanical layer Middle layer including the antimicrobial liquid in droplike compartments Inner mechanical layer Skin (hand) Sonntag et al. , Nature Materials 2004; 3: 311 -315 Krikorian R, J Hosp Infect 2007; 66: 339 -345

cfu/ml Mean Microbial (S. aureus) Recovery (cfu/ml) at 10 and 45 Minutes Post Surgical Glove Microperforation* 418 351 292 p<0. 005 NS 24. 5 180 p<0. 05 p<0. 005 1. 4 *N = 24 gloves per group Daeschlein and Edmiston – Am J Infect Control 2011; 39: 98 -103

Why Should an Antimicrobial Surgical Glove be Viewed as a Risk Reduction Strategy Viewing Risk from a Mechanistic Perspective • • • Microperforation rates exceed 25% in selective surgical services Microbial rebound (hand) occurs in all surgical cases Perforation rates highest in non-dominant hand (thumb and index finger) Wound bed vulnerable to contamination – hyperglycemia and corticosteroids diminish wound defenses Biomedical devices at high risk for contamination – 40% of SSI discovered beyond 30 days

v. Caveat - Surgical site infections represent a complex and multifactorial process - the mechanistic etiology is quite often elusive, requiring innovative solutions

v. Era of Surgical Transparency – NHSN and CMS (308 d Participation and Consent Document)

A New Era of Transparency – A Surgeon’s Perspective • 4 -year colorectal infection rate = 24. 5% (Surgery 2007; 142: 704) • Operative closure and SSI in women undergoing breast conserving therapy = 5. 2 to 11. 7% (Surgery 2007; 141: 645) • SSI risk factors in inflammatory bowel patients undergoing colorectal procedures = >15% (Diseases Colon & Rectum 2007; 50: 331) • Post-cesarean surgical site infection rate – 8. 9% (post-discharge) vs 1. 8% at hospital discharge (Acta Obstet Gynecol 2007; 86: 1097) Thinking outside of the box – impact of BMI, diminished granulocytic cell function

The Pogo Effect – “Yep, we have met the enemy and he is us”