Dr. Colette Cozean

1. Dr. Colette Cozean • PhD in BioMedical Engineering (Ohio St.), Masters in Electrical Engineering (Ohio St.), J.D. (Concord Law School) • Senior management positions with Pfizer, Baxter, American Hospital Supply • Author of more than 100 peer-reviewed papers, holds more than 50 patents • Reviewer for National Institute of Health

2. Failures of Current Hand Hygiene, and the Search for Solutions Colette Cozean, PhD

3. Summary • Promise of Alcohol Sanitizers • Failure of Alcohol Sanitizers • Reasons for Failure • The Ideal Product • Potential Solutions

4. Promise of Alcohol Sanitizers • Alcohol Sanitizer showed more complete kill against bacteria than soap and water • Alcohol is much more convenient, with the potential to decrease time spent while increasing compliance

5. Results of Alcohol Sanitizers • After more than 10 years of alcohol sanitizer use, 5% of patients get an HAI, 90,000 deaths • Studies – 7 comparison studies between handwashing and alcohol sanitizer in medical • 4 Studies show alcohol increases infections • 2 Studies report improvement in HAIs with alcohol • 1 Study shows no difference in surgical site infections • Fendler et al, The Impact of hand sanitizer use on infection rates in an extended care facility, AJIC, 30:4, 226-33, 2002 • Hilburn et al, Use of alcohol hand sanitizer as an infection control strategy in an acute care facility, AJIC, 31:2, 109-116, 2003 • Rupp M et al, Prospective, Controlled, Cross‐Over Trial of Alcohol‐Based Hand Gel in Critical Care Units, Infection Control and Hospital Epidemiology; 29:1, 2008 • Larsen E et al, Effect of Antiseptic Handwashingvs Alcohol Sanitizer on Health Care–Associated Infections in Neonatal Intensive Care Units, Arch PediatrAdolesc Med. 2005;159(4):377-383

6. Evaluating Clinical Trials • Is it blinded? • Is it randomized? • Is it a crossover design? • Are there any potential confounding factors? • Is it large enough to be statistically significant? • Who sponsored the study?

7. University of Iowa Study • 3 ICUs, crossover (multiple) study, 3,000+ pts, compared CHG handwash vs. alcohol sanitizer, sponsored by Calgon-Vestal • Shown significant increase in HAIs with alcohol Doebbeling BN, Stanley GL, Sheetz CT, et al. Comparative efficacy of alternative handwashing agents in reducing nosocomial infections in intensive care units, New England Journal of Medicine, 1992; 327: 88-93

8. New York Presbyterian Hospital Study • Nearly 3,000 pts, 2 NICUs, crossover, comparison with 2% CHG handwash • Increase in HAIs of 27.3% overall, and in 4/5 categories, sponsored by 3M (Avagard) Larsen E et al, Effect of Antiseptic Handwashingvs Alcohol Sanitizer on Health Care–Associated Infections in Neonatal Intensive Care Units, Arch PediatrAdolesc Med. 2005;159(4):377-383

9. University of Nebraska • Two-year study, 2 ICUs, crossover, monitored compliance and HAIs, sponsored by GOJO, compared against PCMX soap • No improvement noted with addition of alcohol sanitizer • Worse than baseline in 4/6 categories, equivalent in 1/6, improvement in 1/6. • Rupp M et al, Prospective, Controlled, Cross‐Over Trial of Alcohol‐Based Hand Gel in Critical Care Units, Infection Control and Hospital Epidemiology; 29:1, 2008

10. Surgical Site Infection Study • Study in 6 surgical centers, randomized, crossover (multiple) 4,000+ pts • Compared alcohol vs. CHG or iodine as a surgical scrub in between patients, when hands were not visibly soiled • No difference between handwashing and alcohol rub (2.48% vs. 2.44%), concluded alcohol was equivalent. • Sponsored by Rivardis Laboratories • Parienti JJ et al, Hand-rubbing with an aqueous alcoholic solution vs. traditional surgical hand-scrubbing and 30-day surgical site infection rates: a randomized equivalence study, JAMA, 2002; 288:722-727

11. Extended Care Facility Study • Showed a 30% decrease, sponsored by GOJO • Compared against a PCMX soap, not CHG or other top-tier antimicrobial • No crossover design • Significant differences between control and experimental groups • Exp. group only in residential wards • Control group on main floor, with cafeteria, dialysis, recreation/activity area, and rehab room – all common areas where germs can be transmitted • Control group (1:8.5 staff/pt), Exp. group (1:4.5) Fendler et al, The impact of alcohol hand sanitizer use on infection rates in an extended care facility, AJIC, 30:4, 226-233, 2002

12. Ortho Surgery Study • Showed 36% decrease, sponsored by GOJO • Also compared against PCMX soap • No crossover design • Gave additional education to staff, including in-service, posters, brochures, and reminders, that were not given to controls • Gave patients individual bottles of hand sanitizer and additional education • Only performed in orthopedic surgery suite, not in general ward (SS infections and UTIs) Hillburn et al, Use of alcohol hand sanitizer as an infection control strategy in an acute care facility, AJIC, 31:2, 109-166, 2003

14. Results in Hospitals • Improves compliance and skin condition • No improvement in HAIs • Never shown in a crossover study to offer improvement • Never shown in any trial to be better than top-tier antiseptic handwashes (CHG, iodine, etc.), only PCMX • “PCMX had the weakest immediate and residual activity of any of the agents studied…studies (2) demonstrated the immediate and residual activity of PCMX was inferior to both CHG and povidone-iodine.” – CDC Hand Hygiene Guidelines, 2002

15. Other Medical Trials • Study of 61 long-term care facilities, sponsored by the CDC, largest multi-center look at medical infections ever done. • Showed that facilities that rely on alcohol sanitizers were six times more likely to have an illness outbreak (Norovirus) than ones relying on soap and water alone. • Only study unfunded by sanitizer company, and truly “real-world” situation • Blaney D et al, Use of alcohol-based hand sanitizers as a risk factor for norovirus outbreaks in long-term care facilities in northern New England: December 2006 to March 2007, American Journal of Infection Control, 39 (4) 296-301, 2011 • CDC, Vessel Sanitation Program, http://www.cdc.gov/nceh/vsp/surv/gilist.htm

16. Reasons for Failure • Alcohol sanitizers kill bacteria faster and more completely than soap and water. They are more convenient and more widely used. • Why have we not seen the anticipated drop in infection and illness?

17. Persistence “Antiseptic handwash….[should be] broad-spectrum, fast-acting, and if possible persistent.” CDC Guidelines, 2002 “Persistence, defined as prolonged activity, is a valuable attribute that assures antimicrobial activity during the interval between washings, and is important to a safe and effective healthcare personnel handwash” FDA Tentative Final Monograph, 1994

18. 1. Lack of Persistence “Alcohols are rapidly germicidal when applied to the skin, but they have no appreciable persistent (i.e., residual) activity.” CDC Hand Hygiene Guidelines, 2002 • Kills the bacteria on the skin, but hands can immediately become recontaminated by the next surface or patient touched. • Compliance has to be perfect in order to eliminate risk of transmission

19. CDC Hand Hygiene Research Agenda Determine if preparations with persistent antimicrobial activity reduce infection rates more effectively than do preparations whose activity is limited to immediate effect CDC Hand Hygiene Guidelines, 2002, “Hand Hygiene Research Agenda”

20. 2. Lack of Compliance Because HCWs <health care workers> may wash their hands….as many as 30 times per shift, the tendency of products to cause skin irritation and dryness is a substantial factor that influences acceptance, and ultimate usage CDC Hand Hygiene Guidelines, 2002

21. 2. Lack of Compliance • Studies show that healthcare workers only comply with hand hygiene protocols 40-50% of the time • CDC studies have shown that 25% of HCWs have contact dermatitis from their hand hygiene products. Other studies put this number closer to 50%. Overall, 85% of HCWs have reported skin problems • Without persistence, each failure leaves the patient and worker open to pathogen transmission. • Erasmus V et al. Systematic Review of Studies on Compliance with Hand Hygiene Guidelines in Hospital Care, Infection Control and Hospital Epidemiology, 31(3) 2010 • CDC Guidelines for Hand Hygiene, 2002

22. 3. Lack of efficacy against viruses • Approximately 22% of HAIs are viral, though we typically think of them as bacterial • Alcohol sanitizers are relatively ineffective against non-enveloped viruses

23. 3. Lack of efficacy against viruses • Researchers at Emory University showed that rinsing the hands with water alone was more effective than using an alcohol sanitizer against Norovirus

24. Failures of Alcohol Sanitizers • Lack of Persistence • Every failure to use product leaves HCW exposed • Lack of Compliance • Drying effects of alcohol cause skin irritation, reducing usage and compliance • Lack of Efficacy against Viruses • Viruses cause 22% of HAIs, and a high percentage of visitor illnesses (flu, colds, stomach flu, etc.). Alcohol sanitizers less effective than water rinse against many non-enveloped viruses

25. The Ideal Sanitizer

26. Other Alternatives • Non-alcohol sanitizers • Alcohol-plus sanitizers

27. CHG • “Immediate efficacy occurs more slowly than that of alcohols” – CDC Guidelines • “It has in-vivo efficacy against enveloped viruses…but substantially less activity against non-enveloped viruses” - CDC • High skin irritation • Some persistence

28. Triclosan • Serious health concerns, lawsuits against FDA and Dial, unable to pass the new FDA regulations governing soaps • Slower immediate activity than alcohol • Relatively ineffective against gram-negative bacteria, even resulting in contamination • High skin irritation • Persistent

29. QATs • Slow-killing (2+ minutes) • Relatively weak against gram-negative bacteria • Good antiviral activity • Persistent • Well-tolerated on the skin

31. Skin Irritation

32. Non-alcohol sanitizers

33. Alcohol-Plus Products • Use a combination of alcohol (immediate kill) and another antimicrobial (persistence) • Avagard (61% ethanol, 1% CHG), ChloraPrep (70% isopropyl alcohol, 2% CHG) • Surgicept (70% alcohol, BZK, CHG) • Typically used only as surgical scrubs, increase skin irritation (alcohol + additional irritating ingredient)

34. Overall Comparison

35. CDC Recommendations “Selection committees must consider factors that can affect the overall efficacy of such products, including the relative efficacyof antiseptic agents against various pathogens and acceptance of hand hygiene products by personnel. Because HCWs may wash their hands….as many as 30 times per shift, the tendency of products to cause skin irritation and dryness is a substantial factor that influences acceptance, and ultimate usage” “An antiseptic…(should be) broad-spectrum, fast-acting, and if possible, persistent.”