Limits of Current Hand Hygiene, and the Search for Solutions. Jesse Cozean

Transcription

1 Limits of Current Hand Hygiene, and the Search for Solutions Jesse Cozean

2 Jesse Cozean, MBA Headed Research and Development at Abela Pharmaceuticals, consultant with Innovative BioDefense Designed and overseen more than 10 clinical trials Received FDA approval for Phase III clinical trials Co-author of 1 of 4 randomized, controlled hospital clinical trials with hand sanitizer Holds 4 patents in drug and hand hygiene nationally and others throughout the world Author of 4 peer-reviewed hand hygiene articles, published author Winner of the Fighting Ebola Grand Challenge for innovative technology to prevent viral illness

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, , 2002 Hilburn et al, Use of alcohol hand sanitizer as an infection control strategy in an acute care facility, AJIC, 31:2, , 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 Handwashing vs Alcohol Sanitizer on Health Care Associated Infections in Neonatal Intensive Care Units, Arch Pediatr Adolesc Med. 2005;159(4):

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

7 University of Iowa Study Change with Alcohol Overall +33.4% UTI +40.0% Skin Infections +93.0% GI Infections +436% 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 Change with Alcohol Overall +27.3% Bloodstream +23.0% Pneumonia +29.4% Skin Infections +77.4% CNS +6.0% Conjunctivitis -15.8% 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 Handwashing vs Alcohol Sanitizer on Health Care Associated Infections in Neonatal Intensive Care Units, Arch Pediatr Adolesc Med. 2005;159(4):

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 handscrubbing and 30-day surgical site infection rates: a randomized equivalence study, JAMA, 2002; 288:

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, , 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, , 2003

13 Randomized/ Crossover Confounding Factors Valid Comparison Product Conducted in Hospital Setting Doebbeling Yes No Yes Yes Calgon-Vestal Increase of 33% Sponsor Result Larsen Yes No Yes Yes Avagard Increase of 27% Parienti Yes No Yes No Rivardis No difference Rupp Yes No No Yes GOJO Slight increase Fendler No Yes No No GOJO Decrease of 30% Hillburn No Yes No No GOJO Decrease of 36%

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 longterm care facilities in northern New England: December 2006 to March 2007, American Journal of Infection Control, 39 (4) , 2011

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 Our Research 94% of HCWs report major concerns with their hand sanitizer, ranging from dryness (65%), irritation (32%), and cracking of hands (26%) Overall hand feel of 6.8 (scale of 1-10, 10 being worst possible) 87% of HCWs apply lotion 3 or more times daily to try and reduce dryness and irritation 77.7% of HCWs report dryness or irritation with alcohol hand sanitizers makes compliance more difficult

23 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 nonenveloped viruses

24 3. Lack of efficacy against viruses Alcohol sanitizers relatively ineffective against nonenveloped viruses Researchers at Emory University showed that rinsing the hands with water alone was more effective than using an alcohol sanitizer against Norovirus

25 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

26 The Ideal Sanitizer Fast-acting Ideal Sanitizer Alcohol Sanitizer Effective against bacteria Effective against viruses Persistent Less effective than water rinse No persistence Non-irritating (compliance) 40-50% compliance % of HCWs report contact dermatitis

27 Other Alternatives Non-alcohol sanitizers Alcohol-plus sanitizers

28 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 HibiClens (4% CHG)* High skin irritation Acinetobacter baumannii 1 min Bacteroides fragilis 10 minutes Some persistence Enterococcus faecalis Enterococcus faecium Staphylococcus aureus Staphylococcus epidermis Staphylococcus saprophyticus Streptococcus pyogenes 10 minutes 10 minutes 10 minutes 3 min 3 min 10 minutes

29 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

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

31 Dermal Moisture after 100 Uses Day 1 Day 2 Day 3 Day 4 Day 5

32 Skin Irritation Skin Irritation after 5 Day Dermal Test BZT (0.2%) CHG (0.75%) PCMX (1.0%) Triclosan (0.3%) CHG (4.0%)

33 Non-alcohol sanitizers Ideal Alcohol CHG Triclosan QATs Fast-acting Bacteria Viruses Persistence Non-irritating

34 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)

35 Fast-acting Bacteria Viruses Persistence Non-irritating Overall Comparison Ideal Alcohol Non-alcohol Alcohol + (CHG, QAT)

36 CDC Recommendations Selection committees must consider factors that can affect the overall efficacy of such products, including the relative efficacy of 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.

37 Our Research Clinical study of 3,000+ patients comparing persistent hand sanitizer against soap Clinical study in schools observing illness outbreaks and illness absenteeism among students and staff Comparison of time-kill curve of alcohol and non-alcohol products Largest hand hygiene study ever conducted, hospitals throughout the US and internationally Fighting Ebola Grand Challenge, clinical study in West Africa and both clinical and in-vitro lab testing