Antimicrobial Resistance in US Healthcare

Michael Bell, M.D. Division of Healthcare Quality Promotion Centers for Disease Control and Prevention

Antimicrobial Resistance in US Healthcare

Release of CDC Report: Antibiotic Resistance Threats

in the United States, 2013

September 17, 2013

Thomas R. Frieden, MD, MPH Director,

Centers for Disease Control and Prevention

Antibiotic development is dwindling

Improving an,microbial use: •  Key factor

•  Promote implementa,on of targeted interven,ons

•  Conduct AU surveillance

•  Enhance communica,ons and messaging •  Communica,ons pla?orm(s)—Get Smart

•  Integra,on of inpa,ent and outpa,ent messages/campaigns

•  Consistent high-‐level messages

•  Agricultural use

•  Human use

•  Resistance ecology and the resistome

Carbapenem-resistant Enterobacteriaceae (CRE)

Multidrug-resistant organisms, including CRE, pose a significant public health threat • Most common type of CRE is resistant to almost ALL antibiotics • New and frightening resistance patterns emerging • CRE has spread across US – found in one state in 2001, now spread to 38 states

Outbreaks show importance of long-term care, acute care, and nursing homes as source of HAIs in hospitals • Regional prevention efforts effective in preventing infections (e.g., Chicago, Florida)

Facility characteris-c No. facili-es with CRE (2012)

No. facili-es performing surveillance

(2012)

(%)

All acute care hospitals 181 3,918 (4.6)

Short-‐stay acute hospital 145 3,716 (3.9)

Long-‐term acute care hospital 36 202 (17.8)

Facilities Reporting ≥ 1CRE, Jan.-Jun. 2012 (CAUTI and CLABSI)

Enteric diseases becoming increasingly resistant to antibiotics

Campylobacter resistance to ciprofloxacin

Salmonella resistance/

partial resistance to ciprofloxacin

Antibiotic prescriptions per 1000 persons of all ages according to state, 2010

Hicks LA et al. N Engl J Med 2013;368:1461-1462.a

Fighting back against antibiotic resistance

Implications of highly-resistant organisms

•  Limited treatment options •  Increased transmission risks to vulnerable populations •  Increase morbidity/mortality, LOS, hospital costs •  Drives more antimicrobial use •  Indicator of system failures; e.g., non-adherence to

recommended practices

Antimicrobial Resistance: Control Strategies in Healthcare

• Prevent infection • Eliminate infection • Use antimicrobials correctly • Prevent transmission


Prevent Infection 1. Vaccinate

•  Influenza vaccine for Healthcare Providers

•  Influenza & S. pneumonia vaccines for patients at risk, before discharge

Infectious Causes of Death: United States 1900-1996

1900 1920 1940 1960 1980

g  pneumonia, influenza, bronchitis g  HIV g  syphilis g  meningitis g  measles, diptheria, pertussis,scarlet fever g  diarrhea, typhoid fever g  tuberculosis g  other

Prop

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Vaccination prevents spread of drug-resistant S. pneumoniae infections

Antimicrobial Resistance: Control Strategies in Hospitals

Prevent Infection 1. Vaccinate... 2. Remove catheters as soon as possible!

•  Use catheters / invasive devices only when essential

•  Maintain proper catheter care

Scanning Electron Micrograph: Interior surface of IV Connector from Patient

“A” (asymptomatic)


Eliminate Infection 3. Obtain appropriate Cultures

•  Diagnose the infection •  Identify the pathogen •  Determine antimicrobial susceptibility


Eliminate Infection 3. Get some cultures 4. Treat to Cure

• Optimize regimen, dose, duration to eradicate the infection/pathogen

• Monitor response


Use Antimicrobials Correctly 5. Apply all available resources

• Seek expert input from infectious disease / pharmacy consultants

•  Implement local antimicrobial control programs

Antimicrobial Control Programs for Hospitals

•  Prescriber education •  Formulary restrictions •  Prior approval requirements to start/continue •  Standardization of antimicrobial order forms •  Pharmacy substitutions (e.g., IV to oral) •  On-line ordering & decision support •  Drug utilization evaluations •  Performance feedback

White 1997 CID Frank 1997 CPQHC Evans 1998 NEJM

Method prior approval prior approval computer assisted

Time 1 year 1 year 1 year

Antimicrobial Cost Savings 32% overall 15%/patient-day 31% overall 22%/patient-day 71%/patient**

Resistance ↓ B-lactam ↓ quinolone ↓ MRSA colonization ↓ bacteremia* not assessed ↓ adverse events ↓ susceptibility mismatch

Intervention

Optimizing Antimicrobial Use

* enterococcal / selected gram negative pathogens **excludes cases where MD used independent judgement

Antimicrobial Resistance: Control Strategies in Hospital

Use Antimicrobials Correctly 5. Seek and accept expert input 6. Ａｐｐｌｙ　ｙｏｕｒ Antibiogram

• Use Local Data to direct empiric treatment •  Focus antibiograms

•  infection site •  healthcare setting / unit •  patient characteristics •  duration of hospitalization


Use Antimicrobials Correctly 7. Target only the pathogen...

• Apply a narrow spectrum regimen ASAP


Use Antimicrobials Correctly 7. Target the pathogen... 8. Stop antimicrobials...

•  Stop antimicrobials when infection is not diagnosed or is unlikely

•  Stop antimicrobials when cultures are negative


Use Antimicrobials Correctly 9. Don’t treat contaminants

• Use proper antisepsis for blood cultures • Do not culture catheter tips • Avoid culturing through lines

Pseudobacteremia

Impact •  accounts for ~50% of all positive cultures •  increases lab costs •  increases antimicrobial use (vancomycin) •  increases length of stay •  average cost of a false-positive blood culture: $4500

Pseudobacteremia

>90% probability of a True Bacteremia

•  S. aureus •  E. coli •  Enterobacteriaceae •  P. aeruginosa •  S. pneumoniae •  C. albicans

<5% probability of a True Bacteremia

•  Corynebacterium spp. •  Propionibacterium acnes •  Bacillus spp.

Pseudobacteremia

10-20% likely to be True Bacteremia •  coagulase-negative Staphyloccoci

•  patient risk factors ? •  prosthetic devices ? •  check # positive / # ordered •  compare antibiograms / fingerprints


Prevent Transmission 11. Isolate infection at the source…

• Adhere to Standard Precautions • Apply appropriate isolation, e.g., for patients with

uncontained infectious body fluids

VRE Survival on Hands and Environmental Surfaces

Noskin et al ICHE 1995;16:577

Source Gloved fingers Ungloved fingers Stethoscope Countertops Telephone Handwashing 5 secs (water) 30 secs (water & soap)

VRE survival time >60 min >60 min 30 min 5-7 days 60 min VRE Titer No decrease Eliminated VRE

Outbreak NY MD IN

Barrier Precautions*

á 28% to 92%

initial 64%

á 22% to 88%

Vancomycin Use

---

â 59% ---

Colonization â 50% no significant change â 80%

Infection â 35% 0 infections

VRE

Impact of HICPAC Guidelines after VRE Outbreaks (CDC)

* compliance with HICPAC “glove/gown” recommendations: ICHE 95;16:105-13

Antimicrobial Resistance: Control Strategies in Hospitals

Prevent Transmission 11. Isolate infection at the source… 12. Ｅｎｓｕｒｅ　ｈａｎｄ　ｈｙｇｉｅｎｅ

•  Administrative support •  Observation and feedback

Percent EIN Respondents Encountering MDR GNB in Last Year By Region

Pacific 48%

Mountain 44%

WN Central

60% EN

Central 59%

New England

66%

WS Central

64%

ES Central

50%

S Atlantic 66%

Mid Atlantic 76%

Red ≥ 70%

Orange 60-69%

Yellow 50-59%

Blue < 50%

What's Up With Community-acquired S. aureus? Moran NEJM 2006:355:666

Competitive Sports Arch Int Med 1998:158:895 MMWR 2003;55:793 Native Americans ICHE 2003;24:397 JAMA 2001;286:1201 School children JAMA 1997;279:593 Familial Transmission JAMA 1999;2;82:1038 Prison Inmates

Hospital Transmission of CA-MRSA

•  Hospital transmission of CA-MRSA among post-partum women, NY (Saiman L, CID, 2003;37:1313-9)

•  CA-MRSA in a NICU, TX (Healy CM, CID, 2004;39:1460-6)

•  CA-MRSA in hospital nursery and maternity units, NY (Bratu S, EID, 2005;11:808-13) •  Nasal carriage in HCW 3/189, HA-MRSA

Clostridium difficile Colitis

C. diff infections declined sharply after revision of antibiotics guidelines

University Hospital Lewisham, London, 2005-07

Source: Talpaert et al. J. Antimicrob Chemother 2011;66: 2168-74.

C. difficile-associated disease prevention

•  Use antibiotics correctly

•  Use Contact Precautions for patients with known or suspected CDAD •  Place patients in private rooms, if no private rooms – cohort

•  Perform Hand Hygiene – alcohol based rub or soap and water – Consider using only soap and water in outbreak setting

•  Use gloves when entering patients’ rooms and during patient care

•  Use gowns if soiling of clothes is likely

•  Dedicate equipment whenever possible

•  Continue these precautions until diarrhea ceases

•  Implement an environmental cleaning and disinfection strategy: •  Adequate cleaning and disinfection of environmental

surfaces and reusable devices, especially items likely to be contaminated with feces and surfaces that are touched frequently

•  Use of EPA registered hypochlorite-based disinfectant for environmental surface disinfection after cleaning.

•  Infection control practices in LTC and home settings are similar to those in traditional health-care settings.

C. difficile-associated disease prevention

•  Includes infection control, laboratory and surveillance recommendations.

•  Review microbiology data to ensure there are no unrecognized cases.

•  Use active surveillance cultures in response to clinical cases to assess for transmission.

Investigation of Carbapenem Resistant Klebsiella Pneumoniae in Hospital A, Puerto Rico, 2008

• On September 11, 2008, the PRDOH notified CDC of an outbreak of CRKP infections in patients at hospital A in Ponce, PR and requested CDC’s support in conducting an outbreak investigation.

Timeline

• April 2008 – Initial recognition of increased number of CRKP cases

• May-July 2008 – Implemented strict hand hygiene and education

• August 2008 – ICU visitation hours limited, old ICU closed because of increased cases in the unit

• September 2008 – Facility requests assistance from PRDOH and CDC.

Investigation Activities § Active case finding

§  Laboratory records obtained back to 2006 § Active surveillance to identify colonized patients in

MICU/SICU, diabetic ward § Observe/audit infection control practices

“Resistance”

Infected

Colonized

EPI-CURVE SINCE 2006 ALL CASES OF CRKP IDENTIFIED AS HOSPITAL-ACQUIRED, COMMUNITY-ONSET, OR

SURVEILLANCE

Preliminary Findings, Confidential

0 1 2 3 4 5 6 7 8 9

Hospital-Acquired, Community-Onset, and Active Surveillance Cases Jan 2006 - Sept 2008

Surveillance

Community-Onset

Hospital-Acquired

CHARACTERISTICS OF 26 HOSPITAL- ACQUIRED CRKP CASES

Mean Age 69 years

Median hospital LOS before + culture 16 days

Median ICU LOS before + culture 4.5 days

Presence of foley catheter 79% (n=19)

Mechanical Ventilation 46% (n=12)

Median Vent days prior to + culture 14 days

Central line 50% (n=12)

Point Prevalence

•  Rectal swabs were obtained from all patients currently hospitalized on SICU and diabetic ward- 20-30 patients.

•  2 patients had unrecognized colonization with CRKP.

•  Point prevalence of unrecognized cases: 6.6- 10%

Infection control observations

•  Staff entering rooms without donning a gown, occasionally no gloves or hand hygiene

•  Reuse of gloves between rooms with no hand hygiene.

•  Exiting rooms without removing gowns

•  Touching patients and equipment without PPE

•  Inconsistent PPE use during wound care, respiratory care

INFECTION CONTROL ASSESSMENT BASED ON 50 HOURS OF OBSERVATION

Hand Hygiene Contact Precautions

Staff Type Entry Exit Entry Exit

Nurse (145) 46% 61% 57% 76%

Physician (31) 48% 60% 33% 33%

Proposed algorithm for Klebsiella pneumoniae Carbapenemase (KPC) -producing Organisms in Acute Care Facilities

Prospective lab review (-)

(+)

Monitor for new cases

Point prevalence survey (-)

(+)

Maintain active surveillance until no new cases

New clinical case

Isolate patient and perform one round of point prevalence survey

Modified Hodge test:

New Diagnostics for Carbapenemase Detection - Examples

Test Methodology Enzymes Detected Carbapenemase Result CarbaNP Nitrocefin-based

carbapenemase test

All carbapenemases

Positive or negative for carbapenemase

MALDI-TOF Mass Spec All carbapenemases

Positive or negative

Check-Points PCR KPC NDM IMP VIM OXA-48

Positive or negative

BD Diagnostics

PCR KPC NDM OXA-48

Positive or negative and which enzyme is present

The PCR tests and chromogenic agars could be applied to CRE rectal screens, but no FDA-approved tests

Number (%) of CRE Not Meeting Case Definition after Reference Testing (CDC)

(n=46)

Organism Type

No. (%) that did not meet case

definition

No. (%) carbapenemase positive by PCR

(n=46)

E. coli 3/7 (43%) 1 (14%)

Enterobacter spp. 11 /25(44%) 7 (28%)

K. pneumoniae 1 /14 (7%) 11 (79%)

CDC CRE Toolkit – 2012

q  Facility-level recommendations

q  Regional prevention strategy for health department implementation

http://www.cdc.gov/hai/organisms/cre/cre-toolkit

Adherence

•  Administrative involvement • Staffing support • Resource allocation

•  Systematic implementation •  Observation and enforcement •  Culture change

Methicillin-resistant Staphylococcus aureus Prevention Initiative in Pittsburgh

•  Prevention strategies focused on preventing transmission •  Remove barriers to adherence with infection control precautions •  Monitor transmission and infection rates •  Unit-specific feedback

•  Initial pilot in two hospitals •  Sustained >50% reductions in MRSA infection rates within

intervention units

MRSA Infection Incidence by Year in an Intervention Unit

Overall Rates Pre-intervention = 1.48 infections/1,000 pt days Post-intervention = 0.68 infections/1,000 pt days 54% reduction, p=.04

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0 0.5

1 1.5

2

2000 2001 2002 2003 2004 2005

Muder et al. SHEA 2005

Chicago Antimicrobial Resistance Project (CARP)

•  Hand Hygiene Program •  Standardized, interactive educational sessions •  Promotion by local opinion leaders •  Promotional materials (personal bottle of hand-rub, pens, etc.) •  Adherence measurement and feedback

•  Intervention to Improve Antimicrobial Use •  Training sessions on infection diagnosis and treatment •  Management algorithms developed with input from clinicians •  Feed back provided to clinicians

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Antimicrobial Utilization and

Incidence of Targeted Resistant Isolates

MRSA, VRE, quinolone-resistant E. coli, ceftazidime-resistant Klebsiella sp and imipenem-resistant Pseudomonas sp

Key Elements for Infection Prevention

•  Leadership •  Protocols, resources, and systems in place •  Performance measurements with feed back •  Collaboration •  Cultural change:

Infection control and prevention is everyone’s responsibility.

MDRO Prevention: Baseline Activities for ALL Healthcare Settings

Administrative measures •  Designate MDRO prevention an institutional priority

•  Implement notification systems for reportable MDROs

•  Designate Hand hygiene adherence an institutional priority with monitoring and feedback


MDRO education

•  Provide MDRO education during orientation and education updates

•  Include MDRO education in pre-post-medical education


Antibiotic stewardship

•  Stop unnecessary antibiotic use

•  Verify prescribed antibiotics are active against clinical isolates

•  Form multi-disciplinary committee to:

•  Review antibiotic utilization patterns •  Compare susceptibility trends •  Provide appropriate antimicrobial formulary

Antibiotic stewardship is an effective strategy to prevent and reverse resistance

Facility benefits Antibiotic best practices

Antibiotic stewardship

programs are a win-win

•  Decrease antibiotic resistance

•  Decrease C. difficile infections

•  Decrease costs

•  Improve patient outcomes

1. Ensure all orders have dose, duration, and indications

2. Get cultures before starting antibiotics

3. Take an “antibiotic timeout,” reassessing antibiotics after 48-72 hours

•  A University of Maryland study showed one antibiotic stewardship program saved $17M over 8 years

•  Antibiotic stewardship helps improve patient care and shorten hospital stays

Stewardship Program Key Elements

•  Commitment: dedicated human, financial, information technology resources

•  Single leader responsible for program implementation and outcomes as well as pharmacist leader

•  Tracking antibiotic prescribing and resistance patterns

•  Clinician education •  Reporting antibiotic prescribing & resistance

information to MDs & other key staff regularly •  Implemtation of recommended actions to improve

antibiotic prescribing (e.g., antibiotic time out)


Surveillance

•  Establish lab-based systems to detect and communicate evidence of MDROs

•  Prepare/review susceptibility reports

•  Target specific MDROs for systematic monitoring

•  Define thresholds for intensified control


Precautions

•  Observe Standard Precautions for all patients

•  Prioritize known MDRO patients for single rooms

•  Implement Contact Precautions on case-by-case basis


Environmental measures

•  Routine cleaning/disinfection

Discontinuation of MDRO Contact Precautions •  Follow guidelines on case-by-case basis

Intensified MDRO Control Measures Administrative measures

•  Consult with experts on assessment, design and implementation of MDRO measures

•  Evaluate system factors that may be contributing to problem

•  Develop systems to identify MDRO patients

Intensified MDRO Control Measures

Administrative measures •  Provide feedback to clinicians on intervention outcomes •  Implement intensive monitoring of selected indicators

Education •  Facility-wide campaigns •  Educate on MDRO trends, process improvement

measures, and outcomes


Enforced antibiotic stewardship • Restrict selected antimicrobials that are

contributing to increased MDRO prevalence


Surveillance •  Calculate/analyze target MDRO prevalence

•  Perform active surveillance cultures of at-risk populations (locally defined)

•  Establish protocols for saving isolates for typing

•  Culture HCWs if epidemiologically implicated as possible transmission source


In acute care settings •  Implement Contact Precautions upon room entry • Patient placement – single rooms when available

In LTCFs, ambulatory and home care • Use Hand Hygiene, gloves routinely •  Implement contact precautions on case-by-case basis


Environmental measures •  Patient-dedicated equipment

•  Prioritize MDRO room-cleaning • Dedicated personnel • Enhanced cleaning and disinfection • Target “high touch” areas

•  Environmental cultures if indicated epidemiologically

•  Vacate and clean units as last resort


Decolonization (e.g. MRSA nares) • Guided by expert consultation • Decolonize HCWs only if epidemiologically

implicated

GA state - Trained Pharmacists and Physicians §  Opportunity: HAI capacity grant from the Association

of State and Territorial Health Officials (ASTHO) •  Created stewardship training programs focused on hospital

physicians and pharmacists v 82 pharmacists attend in person training v 75 physicians and clinicians attend webinars

•  Measurement: v Assessment tool developed with CDC v Focus group with pharmacists

•  New Partners: Atlanta Chapter of the Society of Hospital Medicine, Atlanta Infectious Disease Society, Georgia Society of Health System Pharmacists, and Medical Association of Georgia

What We Learned about Leadership and Management

§  22 of 48 facilities had a multidisciplinary committee focused on antibiotic use

v 16 (72%) reported physician or pharmacist leader for stewardship activities

v 6 (27%) have neither physician nor pharmacist leaders v 2 (9%) did not meet regularly

What We Learned about Guidelines

§  Does facility have facility-specific guidelines to assist with antibiotic selection for … (% Yes)?

Focus Group: The Role of the State in Stewardship

§  What can the state do to promote/enhance hospital stewardship efforts? •  More training and a stipend to facilitate attendance

§  What are your initial thoughts on the Honor Roll program? •  A “good starter” for stewardship activities •  Needs flexibility to recognize different resource levels

Our Next Steps §  Issue Call for Action for Antibiotic Stewardship from

DPH Commissioner §  Launch Honor Roll for Antibiotic Stewardship

•  Defines State Expectations for Antibiotic Stewardship for Hospitals

•  Two Tiers of Stewardship: v Level 1: Engagement (Leadership Support, Defined Multi-Disciplinary

Team, Staff Education) v Level 2: Implementation (Level 1 Activities plus Implementation of

Stewardship Intervention and Data Collection to Demonstrate Impact) v Honor Roll Requires Completion of Assessment Tool and annual

renewal

§  Offer Additional Pharmacist Training and Stipends to Hospitals to Support Participation

Acknowledgements Georgia Department of Public Health Matthew Crist Cherie Drenzek Stephanie Lambert (former intern) Lauren Lorentzson Michele Mindlin Ashley Moore Michelle Nelson Melissa Tobin D’Angelo Nadine Oosmanally

Georgia Antibiotic Stewardship Subcommittee Jesse Jacob, MD, MS, Emory University Hospital, co-chair Renee Watson, RN, CIC, Children’s Healthcare of Atlanta, co-chair Angelina Davis, PharmD, MS, BCPS (AQ-ID) WellStar Health System Denise Flook, RN, CIC, Georgia Hospital Association Kimberly Hazelwood, PharmD, Georgia Department of Public Health Sheena Kandiah, MD, Emory University Hospital

Armando Nahum, SafeCare Campaign Cindy Prosnak, RN, CIC, Georgia Medical Care Foundation Craig Smith, MD, University Health System, Augusta

Centers for Disease Control and Prevention Loria Pollack Ronda Sinkowitz-Cochran Heidi Gruhler Arjun Srinivasan Susan Fuller Turquoise Griffith Association of State and Territorial Health Officials Catherine Cairns Virginia Dolen

Health plan performance for appropriate use measures, 2012

Measure 2012 national average (%)

Best-performing plan (%)

Worst-performing plan (%)

Avoidance of Antibiotics in Adults with Acute Bronchitis

20.62 71.59 (Health plan A)

7.41 (Health plan B)

Appropriate Testing for Children with Pharyngitis

81.04 96.64 (Health plan C)

46.51 (Health plan D)

Appropriate Treatment for Children with URI

84.64 99.3 (Health plan E)

44.7 (Health plan F)

Interna-onal Collabora-on

•  Evolving role (esp. re: GHS) •  TATFAR secretariat

•  Possible expansion of TATFAR beyond EU •  Increasing orienta,on toward objec,ves within

recommenda,ons •  WHO—Geneva: Ongoing rela,onship

•  Rela,onship with PAHO

•  Possible bilateral rela,onships (Canada, Mexico)

Centers for Disease Control and Prevention 1600 Clifton Road NE, Atlanta, GA 30333

Phone: 1-800-CDC-INFO (232-4636)/TTY: 1-888-232-6348 E-mail: [email protected] Web: www.cdc.gov

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Antimicrobial Resistance in US Healthcare