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

CIPARS INTEGRATED AMR RESULTS 2012 1

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

OverviewReview of healthcare-associated infections

Antimicrobial resistant organisms: why are they important

Current research focus

Examples studies in healthcare epidemiology

IntroductionHealthcare-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.

Common HAI, in order of relative frequency

1. Urinary tract infections (UTI)• 80% Catheter-associated (CAUTI)• Prevalence 4.3%

2. Pneumonia (HAP)• 30% Ventilator-associated (VAP)• Prevalence 2.7%

3. Surgical site infections (SSI)• Prevalence 2.7%

4. Blood stream infections (BSI)• 40% Central venous catheter associated (CVC-BSI or CLBSI)

5. 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

Impact of HAI on healthcare deliveryLengthened hospital stays, Delays in new admissions Risk of wide propagation of infection & increased

mortalityUnits/facilities closed due to isolation/quarantine

policyIncreased use of diagnostic tests & expensive

treatmentsUndermining of governments efforts to improve

the healthcare system, e.g. access, quality, and wait times

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, 2012Klevens RM et al. Public Health Reports, 2007,122:160–166.Scott RD, Direct Medical Costs of HAI, CDC, 2009

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 millionZoutman et al, AJIC 2003; 31(5): 266-272CPHO 2013 ReportCPSI, The Economics of Patient Care, 2012

Estimated attributable per inpatient costs of HAI* Site Low estimate** High estimate Total infections Low adjusted

overall cost†High adjusted overall cost

CAUTI $862 $1,007 19,373 $16,700 $19,509

VAP $19,633 $28,508 4,561 $89,546 $130,025

SSI $11,874 $34,670 12,952 $153,792 $449,046

BSI $7,288 $29,156 3,829 $27,908 $103,980

CDI‡ $6,408 $9,124 6,758 $43,305 $61,660

$256,959 $508,423

*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

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”

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AMR now causes more deaths in US than all other infectious diseases combined. CDC

Source: CDC, Antibiotic Resistance Threats in the United States, 2013

The drivers of AMR

ANTIMICROBIAL RESISTANCE IN CANADA: WORKING TOWARDS A COMMON UNDERSTANDING

Demographic changesClimate changeHealthcare

Trade Globalization Travel

Human Behaviour

Agriculture and Veterinary Practices

Environmental Sources

Antimicrobial Resistance

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. and Aspergillus

Why is AMR a global concern?1. AMR kills

Prolonged illness & greater risk of death.

2. AMR hampers the control of infectious diseases & healthcare gains Potential spread of resistant microorganisms to others.

3. AMR increases the cost of health care Need for more expensive & lengthy treatments in healthcare settings

4. AMR jeopardizes healthcare gains to society Without effective antimicrobials, the success of treatments such as organ

transplantation, cancer chemotherapy & major surgery would be compromised.

5. AMR threatens health security and damages economies & trade Global trade & travel – AMR organisms spread rapidly to distant countries &

continents.

6. 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/

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)

Only 5% of the drugs in the development pipeline are antibiotics

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Silver. 2011. Clin Micro Rev. 24:71-109

Penicillins

Carbapenems

Cephalosporins

The Beta-Lactam Antibiotics

TEM-1, SHV-1

ESBLsTEM/SHV-variantsCTX-M

Carbapenemases

Expended 1930s

Expended late 1970s

Expended in 1990s-2000s

Research Focus over the years1970s: 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;

Research: Future Focus2010s: advancing healthcare epidemiology using

business cases, patient safety, and performance improvement methodscombatting ESKAPE pathogens —Enterococcus faecium,

Staphylococcus aureus, Klebsiella species, Acinetobacter baumannii, 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/AMRcost effectiveness studies

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Source: INSPQ February 2006

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

The effect of hospital-acquired infection with C.difficile on length of stay in hospitalForster et al. CMAJ 2012

A: Kaplein-Mayer curves adjustedB: with C.difficile as time-varyingD: with baseline risk of death

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%

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

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

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 effectCatheter placed into a

large vein, tip is lodged in the right atrium

Sites of insertion: right and left subclavian, internal jugular and femoral veins

An intervention to decrease catheter-related bloodstream infections in the ICUPronovost et al, NEJM 2006procedure cart for central line insertionadherence 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

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

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

2006 2009 2010 20110.00

0.50

1.00

1.50

2.00

2.50

3.00

National and Regional CVC-BSI rate per 1,000 days in Medical, Surgical, and Mixed Adult ICUs 2006, 2009-2011

West Central East Overall

Targeted vs Universal Decolonization to Prevent ICU InfectionHuang et al. NEJM 2013Cluster-randomized trial in 74 ICUs (43 hospitals) in

CaliforniaHospitals 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

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?

Questions? Comments?