ANTIMICROBIAL
STEWARDSHIP
MERIN VARGHESE, MD
PHYSICIAN, NGPG INFECTIOUS DISESASE
CHAIR AND PHYSICIAN LEAD, NGHS ANTIMICROBIAL STEWARDSHIP COMMITTEE
• NO FINANCIANCIAL DISCLOSURES
Objectives
• Define antimicrobial stewardship program
• Purpose of antimicrobial stewardship program
• Understanding B-lactam allergieswith respect to antimicrobial
stewardship
THE BUGS ARE WINNING…
Antimicrobial Resistance is a Growing
Problem
• More than 2.8 million antibiotic-resistant infections occur in the U.S.
each year.
• More than 35,000 people die as a result, according to CDC’s 2019
Antibiotic Resistance Threats Report.
• The estimated national cost to treat infections caused by six
multidrug-resistant germs frequently found in health care can be
substantial—more than $4.6 billion annually
https://www.cdc.gov/drugresistance/national-estimates.html
ANTIMICROBIAL RESISTANCE
Problem Statement
AHRQ SAFETY PROGRAM FOR LONG-TERM CARE: HAIs/CAUTI Centers for Disease Control and Prevention. Antibiotic Resistance Threats in the United States, 2013.
SHARING THE RESTISTANCE
SHARING THE RESISTANCE
HOW ANTIMICROBIAL RESISTANCE
SPREADS
https://www.cdc.gov/narms/faq.html
ANTIMICROBIAL RESISTANCE
THREATS
BUGS FIGHTING BACK
ANTIMICROBIAL STEWARDSHIP
• Per Infectious Disease Society of America (IDSA) –
• Antimicrobial stewardship is an activity that promotes
• Appropriate selection of antimicrobials
• Appropriate dosing of antimicrobials
• Appropriate route and duration of antimicrobial therapy
GOALS OF ANTIMICROBIAL
STEWARDSHIP
What is antimicrobial stewardship?
Antibiotic stewardship refers to a set of commitments and activities
designed to “optimize the treatment of infections while reducing
the adverse events associated with antibiotic use.”
The goal is…
• to have the RIGHT DRUG
• for the RIGHT PERSON
• over the RIGHT TIME FRAME
AHRQ SAFETY PROGRAM FOR LONG-TERM CARE: HAIs/CAUTI
GOALS OF ANTIMICROBIAL
STEWARDSHIP
• Primary goal
• Optimize clinical outcomes while minimizing unintended consequences of
antimicrobial use
• Unintended consequence
• Toxicity
• Selection of pathogenic organisms such as C. difficile
• Emergence of resistant pathogens
• Secondary goal
• Reduce healthcare costs without adversely impacting the quality of care
PREVENT ANTIMICROBIAL
RESISTANCE • Infection prevention IS
antimicrobial stewardship!
• Tracking infection prevention
data has double value
• Hospital acquired infection
prevention
• Informs antibiotic stewardship
programs
• Improving antibiotic prescribing
• Bacteria are constantly evolving,
requiring the need for new
antibiotics
Source: Centers for Disease Control and Prevention. Antibiotic Resistance Threats in the United States, 2013.
AHRQ SAFETY PROGRAM FOR LONG-
TERM CARE: HAIs/CAUTI
WE MUST WORK TOGETHER…
• Working relationship between infection control and antimicrobial
management.
• Selection of antimicrobials from each class of drugs that does the
LEAST collateral damage
• Collateral damage
• Methicillin-resistant Staphylococcus aureus
• Extended spectrum B-lactamase (ESBL)
• Clostridioides difficile (C. difficile)
• Vancomycin-resistant enterococci (VRE)
• Metalloenzymes & other carbapenemases
• Appropriate de-escalation when culture results are available
DRUGS CAN’T KEEP UP
NGHS ASP Structure
Acute Care Campuses
Microbiology
Gainesville
Braselton
Medical
Barrow Quality
Staff
Lumpkin
Skilled Nursing
Limestone
Lanier Park
Antimicrobial
Nursing Stewardship Pharmacy
Program
Outpatient
NGPG Urgent Care
NGPG Clinics
Senior Information
Leadership Technology
Infection Reports to:
Control
Pharmacy & Therapeutics Committee
Infection Control Committee
NGMC Quality Committee
TODAY’S FOCUS
What is antimicrobial stewardship?
Antibiotic stewardship refers to a set of commitments and activities designed to
“optimize the treatment of infections while reducing the adverse events associated
with antibiotic use.”
The goal is…
• to have the RIGHT DRUG
• for the RIGHT PERSON
• over the RIGHT TIME FRAME
TODAY’S FOCUS
• Penicillin allergy
PENICILLIN ALLERGY
• Up to 10% of the general population and 15% of hospitalized patients
list penicillin as an allergy.
PENICILLIN ALLERGY
https://www.cdc.gov/antibiotic-use/community/pdfs/penicillin-factsheet.pdf
PENICILLIN ALLERGY
• Penicillin “allergic” patients are more likely to
• Received fluroquinolones, vancomycin, clindamycin
• Harbor drug resistant organisms such as MRSA and VRE
• Develop C diff colitis
• Increased mortality
• Experience --
• treatment failure, infection recurrence, death from MSSA bacteremia
• treatment failure in gram negative bacteremia
• a delay in empiric antimicrobial treatment
• a surgical site infection
PENICILLIN ALLERGY
• Pencillin “allergic” patients are more likely to
• Develop new antibiotic “allergies” with alternative therapies
• Have an allergic reaction to vancomycin than cefazolin
• Have side effects or toxicities from second-line therapies
PENCILLIN ALLERGY
• Penicillin allergic patients have higher drug costs
• Higher outpatient antibiotic costs per patient
• $300 more per patient per day of inpatient antibiotic therapy
• $1253 more in length of stay costs per patient per admission
• Penicillin allergic patients have longer hospital stays
• 10% longer hospital stays, estimated cost of $21.5 million per year.
PENICILLIN ALLERGY: ACCURATE
DIAGNOSIS?
• Less than 10% of these allergies are confirmed when tested
• Childhood viral rashes are often misdiagnosed as drug rashes
• Only 7-16% of kids with “drug allergy” during an infection later test positive to
the drug.
• Even if a patient is truly allergic, most people “outgrow” penicillin
allergy
• Over 50% of people with confirmed allergy to penicillin ‘lose their allergy’
after 5 years
• Over 80% will lose it in 10 years
BETA LACTAMS
CEPHALOPSORIN VS PENICILLIN
• Overall cross-reactivity based on multiple studies is actually very low:
• Reported (but unconfirmed) penicillin allergy: 0.1%
• Confirmed penicillin allergy: 2%
• Above exclude patients with penicillin anaphylaxis
PENICILLIN ALLERGY
OUR EFFORTS
• Cascading susceptibilities
• Drug desensitization
• Drug challenge
Cascading Susceptibilities
• Definition
• a strategy of reporting antimicrobial susceptibility test results in which
secondary (e.g., broader-spectrum, more costly) agents may only be reported
if an organism is resistant to primary agents within a particular drug class
Old
New
Graded Challenge/Test Doses
1%/10%/20% Monitoring
Ampicillin 20 mg IV once
• Vital signs every 30 minutes
Observe for 30 minutes • Rescue meds available
(diphenhydramine, epinephrine,
methylprednisolone)
Ampicillin 200 mg IV once
Observe for 30 minutes • Update allergy profile after challenge
Ampicillin 2000 mg IV once
Observe for 30 minutes
Scheduled Maintenance Dosing
Graded Challenge (GC)
• Non-life threatening reaction and using agent with similar side chain
• Severe Type1 IgE mediated allergy and using Agent with dissimilar side-
When to Use chain
• Severe-delayed reactions such as SJS or DRESS
Contraindications • When a reaction is likely (a recent reaction to the same agent)
• Tests for existence of true allergy
Pros/Cons • Allows allergy de-labeling
Desensitization
18 step process Monitoring
1. Ampicillin IV Desensitization Protocol (Goal dose 2 grams)
1. 0.01 mg (0.01mg/mL) IV once in 50 mL of 0.9% NS
• Requires 1:1 nursing ratio
2. 0.02 mg (0.01 mg/mL) IV once in 50 mL of 0.9% NS once, 15 min after previous dose • ICU admission likely required
3. 0.04 mg (0.01 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose
4. 0.08 mg (0.01 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose • Airway box at bedside
5. 0.16 mg (0.1 mg/mL)IV once in 50 mL of 0.9% NS, 15 min after previous dose
6. 0.32 mg (0.1 mg/mL) IV once in 50 mL of 0.9% NS , 15 min after previous dose
• Vital signs every 30 minutes
7. 0.64 mg (0.1 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose • Rescue meds available
8. 1.2 mg (0.1 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose
9. 2.4 mg (10 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose (diphenhydramine, epinephrine,
10. 4.8 mg (10 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose
11. 10 mg (10 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose
methylprednisolone)
12. 20 mg (10 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose • Desensitization establishes a temporary
13. 40 mg (10 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose
14. 80 mg (10 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose tolerance so allergy on profile is relevant and
15. 160 mg (250mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose
16. 320 mg (250 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose
should remain there
17. 640 mg (250 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose
18. 1600 mg (250 mg/mL) IV once 50 mL of 0.9% NS, 15 min after previous dose
Desensitization
• Anaphylaxis within the past 5 years
When to • Failed PCN skin test
• Failed Graded Challenge
Use • Allergic reaction is highly likely
• SJS, DRESS, other delayed reactions
Contraindications
• Allows treatment if true IgE mediated allergy
• Short-term tolerability
Pros/Cons • Does not mitigate (Type II-IV) delayed reactions
• Time and resource intensive
Graded Challenge vs Desensitization
Graded-Challenge Desensitization
Method 2-3 doses every 30 min 10+ doses every 15-30 min
Rational Test of tolerance Establishes tolerance despite allergy
Immune modification No Yes (temporary)
Effect of Therapy None Must repeat/restart
Interruption
Indication If unlikely to have severe If Type1 IgE mediated allergy is likely
allergy
Outcome (if successful) Allergy can be removed Allergy remains
Site of care Ambulatory Practice Intensive Care/Specialty Unit
Any Inpatient Unit Allergist’s Office
Nursing Home
Solensky. Immunol Allergy Clin N Am 24 (2004) 425–443
Solensky. Ann Allergy Asthma Immunol 2010;105:259
Is The Risk Worth It?
• Risk of life-threatening reaction to beta lactams in those with
reported allergies – very low if they are screened for mild reactions
and antimicrobials are chosen carefully.
• With the use of LIFE THREATENING infection - MUCH HIGHER when
ALTERNATIVE agents are used.
• C. difficile colitis kills about 29,000 per year
• Fatal drug induced anaphylaxis (1999-2010) – antibiotics were identified as
culprits in 585 deaths (12 year period).
https://www.sciencedirect.com/science/article/pii/S0091674914011907?via%3Dihub
THANK YOU
REFERENCES
• Cdc.gov
• https://www.sciencedirect.com/science/article/pii/S009167491401190
7?via%3Dihub
• Solensky. Immunol Allergy Clin N Am 24 (2004) 425–443.
• Solensky. Ann Allergy Asthma Immunol 2010;105:259
• https://www.publichealthontario.ca/apps/asp-strategies/data/pdf/ASP
_Strategy_Cascading_Microbiology_Reporting.pdf
• https://www.researchgate.net/figure/The-Partners-Penicillin-and-Ceph
alosporin-Hypersensitivity-Pathway-These-pathway_fig2_316781890
• https://www.ryah.ca/2014/09/29/animal-health-week-antibiotic-respo
nsible-and-appropriate-use/
• https://www.istockphoto.com/illustrations/antibiotic-resistance
