Superbugs: why they are winning the war and what …...Superbugs: why they are winning the war and...

Superbugs: why they are winning the war and what we

can do about it Barbara DeBaun, RN, MSN, CIC

Improvement Advisor, Cynosure Health

Medical Surgical Nursing Conference

April 11, 2014

Objectives

Describe the top 3 urgent antimicrobial resistant threats in the US

Identify the CDC’s 4 core actions to prevent antibiotic resistance

Describe the mechanisms of antimicrobial drug resistance

Antibiotic Resistance Threats in the US

• More than 2 million people in the US become sick every year with an antibiotic resistant infection

• At least 23,000 people die as a result

Will antibiotics save us?

1. Given sufficient time and drug use, antibiotic resistance will emerge.

2. Resistance is progressive, evolving from low levels through intermediate to high levels.

3. Organisms resistant to one antibiotic are likely to become resistant to other antibiotics.

4. Once resistance appears, it is likely to decline slowly, if at all.

Levy SB. NEJM, 1998

Principles of Antimicrobial Resistance

Impact

Prolonged, costlier treatment

Extend length of stay

Additional doctor visits and healthcare use

Greater disability and death

Financial Impact

Difficult to calculate

May be as high as $20 billion in excess direct healthcare costs

Additional costs to society for lost productivity as high as $35 billion per

year (2008 dollars)

Use of Antibiotics

• Single most important factor leading to antibiotic resistance

• Antibiotics are the most commonly prescribed drugs used in human medicine

• 50% of antibiotics prescribed for people are not needed or are not optimally effective as prescribed

• Commonly used in food animals

Four Core Actions

Preventing Infections and Preventing Spread

Tracking Resistant Bacteria

Improving Use of Antibiotics

Developing New Antibiotics and Diagnostic Tools

1. Preventing Infections and Spread of Resistance

Avoid infections in the first place

Immunizations

Safe food preparation

Hand hygiene

Use of antibiotics only as directed and only when necessary

2. Tracking

CDC gathers data

Causes of infection

Risk factors

Specific strategies

3. Antibiotic Stewardship

Change the ways antibiotics are used

Stopping inappropriate and unnecessary use of antibiotics

Use only when needed

The right drug in the right way for the right amount of time

Antibiotic misuse adversely impacts patients Clostridium difficile

• Antibiotic exposure is the single most important risk factor for the development of Clostridium difficile associated disease (CDAD) • Up to 85% of patients with CDAD

have antibiotic exposure in the 28 days before infection

Chang HT et al. Infect Control Hosp Epidemiol 2007; 28:926–931.

Antimicrobials Predisposing to CDI

Very Commonly Related

Less Commonly Related

Uncommonly Related

Clindamycin

Ampicillin

Amoxicillin

Cephalosporins

Fluoroquinolones

Other penicillins

Sulfonamides

Trimethoprim

Cotrimoxazole

Macrolides

Carbapenems

Aminoglycosides

Bacitracin

Metronidazole

Teicoplanin

Rifampin

Chloramphenicol

Tetracyclines

Daptomycin

Tigecycline

Bouza E, et al. Med Clin North Am. 2006;90:1141-1163. Loo VG, et al. N Engl J Med. 2005;353:2442-2449.

Unnecessary Antimicrobial Use in Current or Recent CDI

• Up to 20% of CDI patients will have a recurrence

• At MN VAMC – 246 patients with new-onset CDI, 57% received additional antibiotics during CDI treatment • Antimicrobials assessed for appropriateness:

• 26% unnecessary totaling 45% non-CDI antimicrobial days

• Providers should be more cautious with treating recent CDI patients with antibiotics due to increased risk of recurrence

Shaughnessy, MK, WH Amundson, MA Kuskowski et al.;Infection Control and Hospital Epidemiology, Vol. 34, No. 2 (February 2013), pp. 109-116

Antimicrobial Stewardship Program Objectives

Minimize acquired resistance

Improve patient outcomes

Improve patient toxicities

Reduce treatment costs

CDC Publication March 2014

Core Elements: • Leadership Commitment • Accountability • Drug Expertise • Action • Tracking • Reporting • Education

Checklist for Core Element for Hospital ASP

Antimicrobial Surgical Prophylaxis

PERIOPERATIVE ANTIBIOTICS AT SMMC

SURGICAL PROCEDURE

RECOMMENDED ANTIBIOTIC OPTIONS

Cardiac (CABG, Pacemakers, AICDs) or Vascular

Cefazolin***

If β-lactam allergy: Vancomycin or Clindamycin

Orthopedic (Hip/Knee arthroplasty) and Podiatry

Cefazolin***

If β-lactam allergy: Vancomycin or Clindamycin

Gastric (PEG placement or revision) or Biliary

Cefazolin***

Cefazolin + Metronidazole

Cefoxitin If β-lactam allergy: Vancomycin or Clindamycin

Colorectal Cefazolin + Metronidazole

Cefoxitin alone

If β-lactam allergy: Clindamycin + Gentamicin

Gynecologic (Hysterectomy, Pubovaginal sling)

Cefazolin

Cefoxitin


Urologic: Prostate biopsy

Cipro- or Levofloxacin

Cefazolin

Penile prosthesis insertion, removal, revision

Cefazolin + Gentamicin

Piperacillin/Tazobactam


1) CHOOSE AN ANTIBIOTIC 2) DOSE IT CORRECTLY

Cefazolin (redose in OR with 1g at 4hr)

Standard preop dose in OR: 2g, then1-2g q8h

In other areas (Cath Lab, IR, etc.) preop dose is 1-2g, then 1-2g q8h (use 2g if >80kg)

Vancomycin (do not redose in OR)

If <80kg: 1g q12h If 80-100kg: 1.2g q12h If >100kg: 1.5g q12h

Clindamycin (redose in OR at 6hr)

900mg q8h

Metronidazole (do not redose in OR)

500mg q8h

Cefoxitin (redose in OR at 2hr)

2g q6h

Gentamicin (do not redose in OR)

5mg/kg AdjBW preop only

(no postop doses) Call Pharmacy (x4921) if dosing questions

WHEN TO START THE PREOP DOSE:

Most antibiotics should be infused within 1hr of incision time. Vancomycin must be infused more slowly: start within 2hrs of incision time. Patients on therapeutic antibiotics before

surgery should get an extra dose of the

RECOMMENDED ANTIBIOTIC (FROM TABLE

1) within 60min before incision.

WHEN TO REDOSE IN OR:

Redose antibiotic if significant blood loss, or if

procedure is long duration (see Table 2 above

for when to redose).

3) STOP PERIOPERATIVE

ANTIBIOTICS WITHIN 24HR*

* For Cardiothoracic Surgery, perioperative

antibiotics should be stopped within 48 hrs.

For many outpatient procedures, no post-

operative antibiotics may be needed.

Call José Eguía, MD (Director of Infectious

Diseases) if questions: Bpr. 372-0367

*** Vancomycin may be added to the regimen IF the

following MRSA risk factors are documented in the

chart PREoperatively by the MD/DO/PA/NP:

prior MRSA infection or colonization

recent hospitalization/SNF stay within 1 year

chronic dialysis

chronic wound care

Rev. 4/13. Based on 2013 ASHP/IDSA/SIS/SHEA guidelines:

Bratzler, AmJHealthSystPharm 2013; 70: 195-283.

Consistent with CMS/Hospital OQR Specifications 1/1/13.

4. New Drugs and Diagnostic Tests

Antibiotic resistance occurs as part of a natural process in which bacteria evolve

Resistance can be slowed but not stopped

New drugs are needed but are few and far between

Three Categories of Threats

Urgent

Serious

Concerning

Concerning Threats

Vancomycin-resistant Staphylococcus aureus (VRSA)

Erythromycin-resistant Group A Streptococcus

Clindamycin-resistant Group B Streptococcus

Serious Threats

• Multidrug-resistant Acinetobacter

• Drug-resistant Campylobacter

• Fluconazole-resistant Candida

• Extended spectrum β-lactamase producing Enterobacteriaceae (ESBL)

• Vancomycin-resistant Enterococcus (VRE)

• Multi-drug resistant Non-typhoidal Salmonella

• Drug-resistant Salmonella Typhi

• Drug-resistant Shigella

• Methicillin-resistant Staphylococcus aureus (MRSA)

• Drug-resistant Streptococcus pneumoniae

• Drug-resistant tuberculosis

• Multi-drug resistant Pseudomonas aeruginosa

Urgent Threats

Clostridium difficile

Carbapenem-resistant Enterobacteriaceae (CRE)

Drug-resistant Neiserria gonorrhoeae

Neisseria gonorrhoeae

Causes gonorrhea (STD)

Results in discharge and inflammation at the urethra, cervix, pharynx or rectum

Is 2nd most common reported notifiable infection in the US

820,000 estimated infections/year

Drug-resistant Neisseria Gonorrhoeae

246,000 drug resistant cases/year

Resistant to cefixime, ceftriaxone, azithromycin and tetracycline

CDC recommendation for treatment is ceftriaxone PLUS either azithromycin OR doxycycline as first-line treatment

Carbapenem-resistant Enterobacteriaceae (CRE) • Two most common types of CRE

are Klebsiella sp. and E. coli

• Resistant to all or nearly all antibiotics

• 50% mortality in patients with CRE bloodstream infections

• More than 9,000 healthcare-associated infections/year

• Identified in 44 states

Enterobacteriaceae & Spread of Carbapenemase-producing CRE in U.S. Common cause of healthcare and community

infections

Resistance to many antibiotics has developed over the last several decades, but carbapenems have remained a treatment option

Carbapenem resistance rare before 2000

Emergence of new “carbapenemases” has resulted in spread of CRE across the U.S.

KPC – Klebsiella pneumoniae carbapenemase

NDM – New Delhi metallo-β-lactamase

Epidemiologically Important

Common cause of infection

Multi-drug resistant - limited treatment options

Capable of transferring resistance

High mortality rates for invasive infections

Potential to spread out of healthcare settings

CRE Vital Signs: Key Points CRE are increasing

1% to 4% overall

Over 10% of Klebsiella are CRE

Most Hospitals don’t see CRE regularly

4% of hospitals

18% of LTACHs

Most CRE are still healthcare -associated


• Gram positive, spore forming rod

• Obligate anaerobe

• Toxin A and Toxin B • Required to cause disease • Clostridium difficile infection (CDI,

formerly CDAD)

• Most common cause of healthcare-associated diarrhea • Fecal-oral transmission • Can be community-associated


• 70% of <1 year olds are colonized

• By age 2, ‘normal’ colonic flora is established

• 2-5% of healthy adults have C. difficile colonization of the colon

• 20-40% of hospitalized adults are colonized with C. difficile


• Causes life threatening diarrhea

• 250,000 infections/year

• 14,000 deaths/year

• At least $1 billion in excess medical costs/year

• Occurs mostly in persons who have been exposed to recent antibiotics and healthcare


• A more potent strain emerged in 2000

• New strain is resistant to fluoroquinolones

• Deaths related to C. difficile increased 400% between 2000 and 2007

• Nearly half occur in people <65

• More than 95% of deaths occur in people 65 and older

Pathogenesis of CDI

Key steps

• Acquisition of C. difficile

• Alteration of colonic flora

• Growth of C. difficile and elaboration of toxins

• Poorly understood additional factor (s?)

CDI Risk Factors

• Antimicrobial exposure

• Acquisition of C. difficile

• Advanced age

• Underlying illness

• Immunosuppression

• Tube feeds

• ? Gastric acid suppression

Major Modifiable Risk Factors

Major Modifiable Risk Factors

Antibiotic Exposure

Acquisition of C. difficile

CDC Prevention Strategies

• High levels of scientific evidence

• Demonstrated feasibility

• Some scientific evidence

• Variable levels of feasibility

Core Strategies Supplemental

Strategies

Environmental Cleaning

Core Supplemental

• Cleaning and disinfection of equipment and environment

• Consider sodium hypochlorite in outbreak or hyper endemic settings

• Routinely assess adherence to protocols and adequacy of cleaning

• Reassess adequacy of room cleaning and address issues

• Use sodium hypochlorite (bleach) – containing agents

www.cdc.gov/ncidod/dhqp/id_CdiffFAQ_HCP.html Dubberke et al. Infect Control Hosp Epidemiol 2008;29:S81-92 Cohen et al. Infect Control Hosp Epidemiol 2010;31

Saving Lives: One Room At A Time

• Reward System • EVS voted on name • PR and Employee Relations

• Certificate, pin • Name in Microscope

• EVS management • Call/email when 100% • Monthly list of names by time clock • Pictures from pin ceremony by time

clock

• IP • Quarterly pin ceremony

• Medical director and/or IP director shake their hand

Source: WakeMed, Raleigh, NC

Contact Precautions

Core Supplemental • Gloves/gowns on room entry

• Private room (preferred) or cohort with dedicated commodes

• Dedicated equipment

• Maintain for duration of diarrhea

• Measure compliance

• Extend use of Contact Precautions beyond duration of diarrhea (hospitalization)

• Presumptive isolation

• Universal glove use on units with high CDI rates

• Intensify assessment of compliance

Tips on prevention of transmission

Special Contact Precautions

CONTACT PLUS Precautions

CONTACT PLUS

Signage

Yellow Caddy

• Floor “STOP” sign decal

• Filled with gowns, gloves

Safe Zone

Hand Hygiene

Core • Hand hygiene based on CDC or

WHO guidelines

• Soap and water preferentially in outbreak or hyper endemic settings

• Measure compliance

Supplemental • Soap and water for hand hygiene

before exiting room of a patient with CDI

• Intensify assessment of compliance

Soap or Hand Sanitizer Debate

Diagnostic Testing

Core Supplemental

• Laboratory-based alert system for immediate notification of positive test results

• Evaluate and optimize testing for CDI

Evaluate and Optimize Testing for CDI • Toxin A/B enzyme immunoassays have low sensitivities

(60-80%) • Despite high specificity, poor test ordering practices (i.e.

testing formed stool) may lead to false positives • Consider more sensitive diagnostic paradigms but apply

judiciously • Restrict testing to unformed stool only • Focus testing on patients with > 3 unformed stools

within 24 hours • Repeat testing no more than every 5-7 days if negative

• Require expert consultation for repeat testing within 5 days

• Test of cure is not recommended

Peterson et al. Ann Intern Med 2009;15:176-9. Cohen et al. Infect Control Hosp Epi 2010; 31 (5): 431-455.

Screening for CDI

Lab Tests for CDI

• 2014: NHSN requires reporting type of test used at your facility for CDI reporting

• PCR=90% sensitive, 96% specific

• EIA significantly lower for detection

FV Tenover, JCM 48:3719, 2010 54

Charts and Tarts

SHEA/IDSA Compendium

• Perform testing on unformed stool

• Do not test asymptomatic patients or for “test of cure”

• Stool culture is most sensitive test

• Toxigenic culture is the gold standard for CDI testing

• EIA is suboptimal for diagnostic testing

• GDH followed by cell cytotoxicity or toxigenic culture is a potential option for testing (2-step procedure)

• rtPCR may be the optimal test-more data needed

• Repeat testing is of limited value

• SH Cohen et al, ICHE 31:431-55, 2010

56

Stool Collection Guidelines

If it ain’t loose, it’s of no use If the stick stands, the test is banned

58 Source: UCSF

CDI Therapy Goals

Inhibition of C. difficile growth

(vegetative forms)

Preservation or reestablishment of

colonic flora

• Antibiotics do not affect spores

• Prevent relapse

• ?Prevent shedding/contamination/transmission

Slide courtesy of S. Parodi

CDI Treatment Principles

• Stop offending antibiotic if possible – 25% respond without further therapy

• Oral therapy preferred

• Treat initial episode for 10-14 days

• Mean time for diarrhea to stop: ~2.0 to 4.0 days • Treat for ~4 days before declaring failure

• Do not perform “tests of cure”

Cohen et al. Clin Infect Dis 2010;31(5) Slide courtesy of S. Parodi

SHEA-IDSA Guideline: CDI Treatment

• Discontinue offending antibiotic agent as soon as possible • Increases likelihood of CDI recurrence

• When severe or complicated CDI is suspected, initiate treatment immediately

• If toxin assay is negative, tailor treatment to clinical picture

• Avoid antiperistaltics as they may precipitate complications

Cohen SH et al. Clin Infect Dis 2010;31(5):431-455.

SHEA-IDSA Guideline: CDI Treatment

• Mild-to-moderate: • Metronidazole 500mg PO TID for 10-14 days

• Severe: • Vancomycin 125 mg PO QID for 10-14 days

• Severe, complicated: • Vancomycin 500mg PO QID or Vancomycin 500mg in 100ml NS PR q6hours

+/-

• Metronidazole 500mg IV q6hours

• Consider subtotal colectomy (elevated lactate and WBCs associated with increase mortality)

Cohen SH et al. Clin Infect Dis 2010;31(5):431-455.

Oral Vancomycin vs Metronidazole in Mild and Severe Disease

Clinical Cure in

Severe Disease* (n=69)

Metronidazole Vancomycin P = NS

90

98

0

10

20

30

40

50

60

70

80

90

Per

cen

t o

f P

atie

nts

100

Metronidazole Vancomycin P = 0.02

67

97

0

10

20

30

40

50

60

70

80

90

Pe

rce

nt

of

Pat

ien

ts

100

Clinical Cure in Mild Disease (n=81)


Zar FA, et al. Clin Infect Dis. 2007;45:302-307.

*>2 points with 1 point for each: Age >60, Temp >38.3, Alb <2.5, WBC >15,000 ; 2 points for pseudomembranous colitis or treatment in an ICU.

Recurrence Treatment Options

• First recurrence (7-10 days) often treated with initial therapy • Metronidazole not used beyond first recurrence due to risk of neurotoxicity

• Chronic, relapsing pattern • Pulsed vancomycin

• Probiotics – limited evidence

• Fecal (donor stool) transplant

Cohen SH et al. Clin Infect Dis. 2010;31(5):431-455; Surawicz CM et al. Am J Gastroeneterol. 26 Feb 2013. .

Why Fecal Microbiota Therapy?

• Impede growth of exogenous bacteria

• Compete for binding sites on the colon

• Production of antimicrobial factors

• Normal flora utilize nutrients > efficiency

=

Colonization Resistance

Bakken Anaerobe 2009;15:285 Slide courtesy of S. Parodi

Administration

• Route: 77% enema/colonoscopy

• Number: 50% One infusion (1 – 48)

• Amount: 71% ≥200 mL (25 – 1500 mL)

• Diluent: 62% Saline • Water, Pasteurized cow’s milk, Yogurt, Psyllium + Saline

• Time from Prep to Administration • 47% immediate

Van Nood Euro Surveill 2009;14(34):1 Gough Clin Infect Dis 2011;53(10):994 Slide courtesy of S. Parodi

Resolution/Relapse Success Number and Type of Procedure

Gough Clin Infect Dis 2011;53(10):994 Slide courtesy of S. Parodi

Resolution/Relapse Success Preparation Characteristics


Resolution/Relapse Success Donor Status


Duodenal FMT vs. Vancomycin for Recurrent CDI

Patients randomized to Standard PO Vancomycin (500mg QID x 14 days), Standard PO Vancomycin + bowel lavage, Vancomycin

500mg PO QID x 4 days + bowel lavage + duodenal FMT

End point was resolution of CDAD without relapse at 10 weeks

Study was stopped after interim analysis

van Nood et al. NEJM 2013;368(5)

Duodenal FMT vs. Vancomycin for Recurrent CDI

• Of 16 patients who received FMT, 13 (81%) resolution of CDAD after 1 FMT (P<0.001 with other treatments) • Of remaining 3 patients, 2 had resolution of CDAD after 2nd

FMT from different donor

• Of 13 patients who received Standard PO Vancomycin, 4 (31%) resolved CDAD

• Of 13 patients who received Standard PO Vancomycin + bowel lavage, 3 (23%) resolved CDAD

• Conclusion – FMT significantly more effective than PO Vancomycin treatment alone

van Nood et al. NEJM 2013;368(5)

Unanswered Questions

• When should transplant be done? • Acute/Fulminant Disease? • Which relapse?

• Optimal route

• Standardized donor screening

• Pretreatment of the CDI patient • PPI or not?

• Are there other benefits • Spore shedding after transplant • Colonization resistance if re-exposed to antibiotics


February 2014 FDA Draft Guidance

• FMT will not require IND approval if: • Informed consent is obtained from the patient or his or her legally authorized

representative.

• The FMT product is obtained from a donor known to either the patient or the licensed health care provider treating the patient.

• The stool donor and stool are screened and tested for the specific purpose of providing the product to the specific patient

FMT Protocol

• Patient chooses donor

• Informed consent

• Donor blood and stool tested for: • HAV, HBV, HCV, HIV, Treponema pallidum • C. difficile, stool culture, ova and parasites

• NGT, colonoscope or enema, H2 blocker

• Donor produces sample

• Placed in enteral feeding bag, diluted and warmed to body temperature

• Pre-procedure sedation

• Transplant

Preparation of donor stool sample before stool transplantation.

Aas J et al. Clin Infect Dis. 2003;36:580-585

© 2003 by the Infectious Diseases Society of America

Preparation of stool transplant recipient and description of the transplantation procedure.

Aas J et al. Clin Infect Dis. 2003;36:580-585

© 2003 by the Infectious Diseases Society of America

Approaches to Prevent CDI

Gerding D N , Johnson S. CID 2010;51:1306-1313

Summary/Next Steps

[email protected]

Superbugs: why they are winning the war and what …...Superbugs: why they are winning the war and...

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