Epidemiology and Healthcare Associated Infection: What does the future hold ?

1. Epidemiology and Healthcare Associated Infection: What does the future hold? Denise Gravel, PhD(c) August 29, 2014 University of OttawaDepartment of Epidemiology & Community MedicineSummer Institute 2014 CIPARS INTEGRATED AMR RESULTS 2012

2. Overview • Review of healthcare-associated infections • Antimicrobial resistant organisms: why are they important • Current research focus • Examples studies in healthcare epidemiology

3. Introduction • Healthcare-associated infections (HAI) are infections that patients acquire while receiving treatment for medical or surgical conditions and are the most frequent adverse event during care delivery • formerly « nosocomial » and/or « hospital acquired » • Burden remains unknown because of the difficulty in gathering reliable data • surveillance is complex and requires the use of standardized criteria • availability of diagnostic facilities • expertise to conduct it and interpret the results Horan TC, Andrus M, Dudeck MA. Am J Infect Control.2008; 36(5):309–332.

4. Common HAI, in order of relative frequency • Urinary tract infections (UTI) • 80% Catheter-associated (CAUTI) • Prevalence 4.3% • Pneumonia (HAP) • 30% Ventilator-associated (VAP) • Prevalence 2.7% • Surgical site infections (SSI) • Prevalence 2.7% • Blood stream infections (BSI) • 40% Central venous catheter associated (CVC-BSI or CLBSI) • Clostridium difficile infection (CDI) • Prevalence 1.5% Children, in addition to the above • Necrotizing enterocolitis (NEC) • Viral respiratory infections and gastroenteritis (VRI/VGE) Gravel et al. Am J Infect Control.2009

5. Impact of HAI on healthcare delivery • Lengthened hospital stays, • Delays in new admissions • Risk of wide propagation of infection & increased mortality • Units/facilities closed due to isolation/quarantine policy • Increased use of diagnostic tests & expensive treatments • Undermining of governments efforts to improve the healthcare system, e.g. • access, • quality, and • wait times

6. Burden of illness of HAI • In Europe: • 16 million extra-days of hospital stay, • 37 000 attributable deaths, and contribute to an additional 110 000 every year. • annual financial losses approximately € 7 billion, direct costs only. • In the USA, • approximately 99 000 deaths were attributed to HAI in 2009 • annual economic impact was estimated at approximately US$ 6.5 billion in 2010. • Several studies showed that increased length of stay between 5 and 29 days. Stockholm,European Centre for Disease Prevention and Control, 2012 Klevens RM et al. Public Health Reports, 2007,122:160–166. Scott RD, Direct Medical Costs of HAI, CDC, 2009

7. What about Canada? “Each year in Canada over 220,000+ HAIs result in 8,500-12,000 deaths… rates are rising. HAI are the fourth leading cause of death in Canada.” “One in eight patients hospitalized in Canada will developed a HAI. Deaths directly related to C.difficile have increased by 5 fold the past decade.” • The healthcare-associated methicillin-resistant Staphylococcus aureus infection rate increased more than 1,000% from 1995 to 2009. • About 80% of common infections are spread by healthcare workers, patients and visitors. Direct medical costs associated with HAI exceeded $CDN200 million annually in 2009 Clostridium difficile infection (CDI) alone was CDN$46.1 million MRSA was estimated at CDN$36.3 million Surgical site infections (SSI) at CDN$24 million Zoutman et al, AJIC 2003; 31(5): 266-272 CPHO 2013 Report CPSI, The Economics of Patient Care, 2012

8. Estimated attributable per inpatient costs of HAI* *Based on US$ adjusted by 2007 CPI for inpatient services **Average attributable costs based on reported studies from 1997-2005 †Increments of $1000 ‡Based on reported studies prior to the emergence of hypervirulent NAP1 Gravel, D. 2011 unpublished

9. Increasing Attention to AMR Dame Sally Davies, Chief Medical Officer for England: 'Antibiotic resistance is like climate change in that we're doing it to ourselves. But there are no sceptics' 'as big a risk as terrorism’ Dr. Arjun Srinivasan, Associate Director Centers for Disease Control and Prevention: “There have been covers of magazines about the end of antibiotics, question mark; I would say you can change the title to the end of antibiotics, period”

10. AMR now causes more deaths in US than all other infectious diseases combined. CDC Source: CDC, Antibiotic Resistance Threats in the United States, 2013

11. The drivers of AMR • Examples include: • Salmonella heidelberg • Carbapenem-resistant Enterobacteriaceae (CRE) (e.g., NDM-1) • Methicillin-resistant Staphylococcus aureus (MRSA) • Vancomycin-resistant Enterococci (VRE) • Multidrug resistant tuberculosis (MDR-TB) • Neisseria gonorrhoeae • Escherichia coli (E.coli) • Clostridium difficile (C. difficile) • Candida spp. andAspergillus Demographic changes Climate change Healthcare Trade Globalization Travel Human Behaviour Antimicrobial Resistance Agriculture and Veterinary Practices Environmental Sources ANTIMICROBIAL RESISTANCE IN CANADA: WORKING TOWARDS A COMMON UNDERSTANDING

12. Why is AMR a global concern? • AMR kills • Prolonged illness & greater risk of death. • AMR hampers the control of infectious diseases & healthcare gains • Potential spread of resistant microorganisms to others. • AMR increases the cost of health care • Need for more expensive & lengthy treatments in healthcare settings • AMR jeopardizes healthcare gains to society • Without effective antimicrobials, the success of treatments such as organ transplantation, cancer chemotherapy & major surgery would be compromised. • AMR threatens health security and damages economies & trade • Global trade & travel – AMR organisms spread rapidly to distant countries & continents. • AMR threatens a return to the pre-antibiotic era • Health-related UN Millennium Development Goals set for 2015 in jeopardy. Source: http://www.who.int/mediacentre/factsheets/fs194/en/

13. Why is antimicrobial resistance a concern in Canada? • AMR is a global threat to the prevention and control of infectious diseases • It is complex and multi-faceted • The loss of effective antibiotics will undermine our ability to fight infectious diseases • Increasing morbidity and mortality throughout world • Less effective antimicrobials for treatment of infectious diseases • Longer, more severe illnesses / complications in vulnerable populations • Increasing costs to the health care system (i.e. hospitalization, wait time, complex treatments) • Investment in development of new antibiotics is decreasing • Research, development and commercialization to bring a new antibiotic to market is costly and may take years to develop. • Potential return to a pre-antibiotic era treatment options for a number of resistant infections are running out (i.e. multi-drug resistant gonorrhea)

14. Only 5% of the drugs in the development pipeline are antibiotics Silver. 2011. Clin Micro Rev. 24:71-109

15. The Beta-Lactam Antibiotics Expended 1930s TEM-1, SHV-1 Penicillins Expended late 1970s Carbapenemases ESBLs TEM/SHV-variants CTX-M Carbapenems Expended in 1990s-2000s Cephalosporins

16. Research Focus over the years • 1970s: establishing evidence for infection prevention and control programs • 1980s: focussed on risk factors for HAI • understanding device associated HAI • 1990s: focussed on antimicrobial resistance • outcomes research • preventing infections in health-care personnel; • 2000s: focussed on prevention in an era of increasing complexity of medical care • preventing bloodstream infections, surgical site infections, and pneumonia associated with healthcare • infection prevention in special populations, pediatric, geriatric, and immunocompromised patients; • infection control in nonhospital settings, including long-term care, home health care, and ambulatory care;

17. Research: Future Focus • 2010s: advancing healthcare epidemiology using business cases, patient safety, and performance improvement methods • combatting ESKAPE pathogens —Enterococcus faecium, Staphylococcus aureus, Klebsiella species, Acinetobacterbaumannii, Pseudomonas aeruginosa, and Enterobacter species. • optimizing the implementation of infection control interventions that are known to be effective • modelling interventions: understanding what works and how • health care costs of HAI/AMR • cost effectiveness studies

18. Source: INSPQ February 2006

19. The effect of hospital-acquired infection with C.difficile on length of stay in hospitalForster et al. CMAJ 2012 • Retrospective observational cohort design using a hospital administrative database: reviewed 136,877 admissions • Association between C.difficile infection and time to discharge • Kaplan-Meier and Cox proportional hazards regression models controlling for baseline risk of death and accounting for time-varying effect of onset of CDI Clostridium difficile: anaerobic, spore-forming, gram-positive bacillus, Resists disinfection, Persists in the environment

20. The effect of hospital-acquired infection with C.difficile on length of stay in hospitalForster et al. CMAJ 2012 A: Kaplein-Mayer curves adjusted B: with C.difficile as time-varying D: with baseline risk of death

21. Surgical Mask vs N95 Respirator in preventing Flu in Healthcare WorkersLoeb et al. JAMA 2009 • Randomized controlled trial of 446 nurses in ER, medical and pediatric units from 8 acute care hospitals • Non-inferiority of surgical mask to N95 respirator • Primary outcome: lab-confirmed flu • Non-inferiority was met if lower limit of 95%CI for reduction in incidence was < -9%

22. Surgical Mask vs N95 Respirator in preventing Flu in HCWLoeb et al. JAMA 2009

23. Surgical Mask vs N95 Respirator in preventing Flu in HCWLoeb et al. JAMA 2009

24. An intervention to decrease catheter-related bloodstream infections in the ICUPronovost et al, NEJM 2006 • Cohort study in 108 ICUs in Michigan, comparing BSI rates before, during, and 18-months after implementing IPC interventions • Calculated rate per 100 catheter-days X 3months, adjusted using generalized linear latent and mixed model with Poisson distribution • Nested clustering for BSI within hospital, within geographic regions plus third level clustering potential ICU effect Catheter placed into a large vein, tip is lodged in the right atrium Sites of insertion: right and left subclavian, internal jugular and femoral veins

25. An intervention to decrease catheter-related bloodstream infections in the ICUPronovost et al, NEJM 2006 • procedure cart for central line insertion • adherence to recommended guidelines • hand washing • sterile gloves & gown • mask and cap • sterile drape (preferably full body drape) • chlorhexidine-based skin prep • maintenance of sterile field • use of subclavian site and tunnelled, cuffed catheter • authorizing nurses to stop any procedure that did not follow catheter insertion guidelines • daily assessment of the need to continue central line use

26. An intervention to decrease catheter-related bloodstream infections in the ICUPronovost et al, NEJM 2006

27. Rates in Canada following implementation of “Safer Health Care Now!” initiative

28. Targeted vs Universal Decolonization to Prevent ICU InfectionHuang et al. NEJM 2013 • Cluster-randomized trial in 74 ICUs (43 hospitals) in California • Hospitals were assigned to: 1. MRSA screening and isolation, 2. targeted decolonization, 3. universal colonization • Proportional hazards models were used to assess differences in infection rates, clustering to hospital Decolonization: BID intranasal mupirocin x 5 days with daily bathing chlorhexidine

29. Targeted vs Universal Decolonization to Prevent ICU InfectionHuang et al. NEJM 2013 Universal decolonization was more effective than targeted decolonization or screening/isolation in reducing MRSA clinical infections and bloodstream infections from any pathogen Question: Is it cost effective?

30. Questions? Comments?