Transcript Appropriate Use of Antimicrobials

Appropriate Use of
Antimicrobials:
New Recommendations
Thomas M File, Jr MD MSc MACP
FIDSA FCCP
Chair, Infectious Disease Division
Summa Health System, Akron, Ohio;
Professor of Internal Medicine,
Chair ID Section
Northeast Ohio Medical University
Rootstown, Ohio
•
Antimicrobial Resistance:
Public
Health
Crisis
The discovery of potent antimicrobial agents was one of
the greatest contributions to medicine in the 20th
century.
• Now THREATENED due to Resistance
• Antibiotic resistance:
a
threat to global health security
May, 2013
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Perhaps the single most important
action needed to greatly slow down
the development and spread of
antibiotic-resistant infections is to
change the way antibiotics are used..”
IDSA Call-to-Action:
Bad Bugs, No Drugs
No. of new antimicrobials
As resistance increases . . . number of new
antimicrobials diminishes
IDSA. Infectious Diseases Soc. Of Am. Bad Bugs, No Drugs.
Available at: www.idsociety.org/badbugsnodrugs.html.
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Antimicrobial overuse: US
• 160 million prescriptions/yr for antibiotics (25,000 tons)*
o 30 prescriptions/100 persons/year
• ½ for humans; ½ for animals
• Animal use linked to
human infection
• IDSA and others lobbying
congress to reduce use in
agriculture
resistance and
o The Preservation of Antibiotics for Medical Treatment Act
o
“end use of antibiotics for growth promotion, feed efficiency, and routine disease prevention
purposes in animal agriculture and to ensure that these precious drugs are being used wisely in all
settings.”
Wenzel and Edmond, NEJM, 343,2000
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PART OF SOLUTION
“If best infection control practices and antibiotic
stewardship were nationally adopted, more than
600,000 infections and 37,000 deaths could be
prevented over 5 years.”
— MMWR Aug 2015
File TM Jr, et al. Clin Infect dis. 2014; 59 (Supple 3): S93-96.
MMWR. August 14, 2015 / Vol. 64 / No. 31 / Pg. 837 - 864; ND 544 – 561.
Acute Respiratory Tract Infections
• Most Common reason for antimicrobials
o Many are NOT appropriate
• Many infections
Common ColdAcute Bronchitis
Ear Infection (Otitis)Chronic Bronchitis (smokers)
SinusitisPneumonia
Pharyngitis
o
Challenge
o What infections warrant antimicrobial therapy?
o What etiology (viral vs bacterial)?
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Who of the following patients
warrant antibacterial therapy?
1.
2.
3.
4.
5.
35 year old afebrile, non-smoking male with mild nasal
congestion and non-productive cough for three days
20 year old afebrile college student with non-exudative
acute sore throat
35 year old afebrile female with signs of acute sinusitis
of three days duration
55 year old smoking male with diabetes and acute fever
and cough
All of the above
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Who of the following patients
warrant antibacterial therapy?
35 year old afebrile, non-smoking male with mild nasal
congestion and non-productive cough for three days—
VIRAL BRONCHITIS; NO ANTIBIOTICS
2. 20 year old afebrile college student with non-exudative
acute sore throat-VIRAL PHARYNGITIS; NO
ANTIBIOTICS
3. 35 year old afebrile female with signs of acute sinusitis
of three days duration-VIRAL SINUSITIS; NO
ANTIBIOTICS
4. 55 year old smoking male with diabetes and acute
chills, fever, chest pain, and cough with new thick green
phlegm-X RAY= PNEUMONIA; YES ANTIBIOTICS
1.
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Antibiotic Prescriptions: US (source CDC)
Source: CDC
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JAMA May 2016
CONCLUSIONS AND RELEVANCE In the United States in 2010-2011, there was an estimated
annual antibiotic prescription rate per 1000 population of 506, but only an estimated 353
antibiotic prescriptions were likely appropriate, supporting the need for establishing a goal
for outpatient antibiotic stewardship. REDUCE ABX by 31%
JAMA Int Med; Online Oct 2016
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Antimicrobials for Colds—Why?
• “Patient pressures”
o Patient satisfaction correlates with
quality of patient-doctor intervention,
not prescription1
•“Prevent bacterial superinfection”
o Several controlled studies showed
no benefit for URI/colds2
1Hamm
RM, et al. J Fam Pract. 1996;43:56-62.
2Rosenstein N, et al. Pediatrics. 1998;101:181-184.
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Appropriate antimicrobial usage:
For optimal outcomes and reduce resistance
•‘Antimicrobial Avoidance’ when not indicated
•3 ‘Ds’
o Right
DRUG
• Guidelines
• Local resistance patterns
• Patient risk stratification
o Right
DOSE
• Pharmacokinetics/Pharmacodynamics (PK/PD)
o Right
DURATION
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
A cough and sneeze; NO antibiotics please!!

Antibiotics cure bacterial infections, NOT viral infections such as: colds
and flu, most coughs and runny noses

Antibiotics are the only drug where use in one patient can impact the
effectiveness in another

If everyone does not use antibiotics well, we will all suffer the
consequences

Unnecessary antibiotics are harmful!!!
Get Smart: Know When Antibiotics Work. Available at: www.cdc.gov/getsmart. Accessed 5 July 2012.
CDC: Division of Healthcare Quality Promotion
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Harm of using
unnecessary antibiotics
• Annual direct costs are $6.5 billion in US
• Annual indirect costs are $30 billion in US
• Antibiotics are responsible for 1 of every 5
emergency department visits for drug-related
complications
o Complications
occur in 5-25%
• Antibiotic-associated diarrhea caused by
Clostridium difficile is the most common serious
complication responsible for 29300 deaths in the
US per year
Harris et al. Ann Intern Med. Jan 2016;
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Interventions to Improve
Appropriate Antibiotic Use
for Acute Respiratory Tract Infections
•“Watchful Waiting Strategy”
•Electronic Decision Support
•clinic-based education interventions
•multifaceted intervention that combined a
clinical
•algorithm, clinical tutor training, and provider
education
Agency for Healthcare Research and Quality; 2015
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• Acute respiratory tract infection (ARTI) is the
most common reason for antibiotic prescription in
adults.
• Antibiotics are often inappropriately prescribed
for patients with ARTI.
• This article presents best practices for antibiotic
use in healthy adults (those without chronic lung
disease or immunocompromising conditions)
presenting with ARTI.
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Ann Intern Med. 2016; pub before print Jan 19, 2016
Antibiotic Prescribing Strategies
Variable
Acute Bronchitis
Pharyngitis
Acute
Rhinosinusitis
Common Cold
Definition
Cough up to 6
wks (often non
productive); often
Sore throat
usually 1 wk
Nasal congestion +;
1-28 days
Mild URI, up to 14
d
common cold
Causes
Viruses 90%;
Mycoplasma,
Chlamydophila
Most viral;
Streptococcus
15%; other
Viral > 90%; 2nd
bacterial 2%
All viral
Benefit
ABX*
NO
If Strep, may
shorten, prevent
RF**
Limited
NO
Harm of
ABX*
Adverse effects;
rash; C diff;
anaphylaxis
Adverse effects;
rash; C diff;
anaphylaxis
Adverse effects;
rash; C diff;
anaphylaxis
Adverse effects;
rash; C diff;
anaphylaxis
*ABX=Antibiotics; RF=Rheumatic Fever
Ann Intern Med. 2016; pub before print Jan 19, 2016
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Antibiotic Prescribing Strategies: RTIs
Am College Physicians Recommendations
• Reducing unneeded ABX will improve care, lower costs and
help reduce ABX resistnace.
• In most patients, symptoms improve in 1-2 weeks; coughs
may last 6 weeks.
• Specific Recommendations:
No ABX for acute bronchitis ( only if pneumonia)
o Test patients with pharyngitis for Grp A Strep; only prescribe ABX
if confirmed (Oral penicillin V, 250 mg QID or 500 mg BD 10 d; Oral amoxicillin,
o
1000 mg QD or 500 mg BD for 10 d; IM benzathine penicillin G X1)
Should not prescribe ABX for sinus infection unless severe
symptoms or symptoms lasting 10 days (Oral amox/Clav, 500/125 mg
TID; Oral amoxicillin, 875/125 mg;Oral amoxicillin, 500 mg TID 5 to 7)
o Do not prescribe ABX for the common cold
o
Harris et al. Ann Intern Med. 2016; 164: 425-
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• Trial to assess impact of 3 interventions for URI, Influenza,
Acute Bronchitis; based on EMRs:
1. Suggested Alternatives (decongestants)
a. Patient Education/instructions
2. Accountable Justification
3. Peer Comparison
• Results:
• Reduced ABX in all
• Significant with Justification and Peer Comparison
• No significant harm (repeat visit for bacterial infection)
Meeker et al. JAMA Feb 9, 2016
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From American/s Knowledge of and Attitudes towards Antimicrobial Resistance. From Pew Health Group
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Patient Instructions (Meeker et al JAMA 2016)
Your doctor has diagnosed you with a non-specific upper
respiratory infection. This is also called the “common
cold.” The symptoms of a cold include watery eyes,
runny nose, nasal stuffiness, sneezing, scratchy or sore
throat, fatigue, fever, muscle aches, and cough. Most
colds last 1 to 2 weeks. Although you may feel bad, the
common cold almost never causes serious illness.
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Patient Instructions (Meeker et al JAMA 2016)
Colds are caused by viruses. After you have caught a cold
virus, it takes 2 or 3 days for you to develop symptoms.
You can avoid getting and spreading colds by washing
your hands frequently, avoiding other people with colds,
avoiding touching your face, and coughing or sneezing
into a tissue.
You cannot treat cold viruses directly, but you can treat
the symptoms. Your doctor may have made
recommendations for medications to help treat your
symptoms
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Patient Instructions (Meeker et al JAMA 2016)
Antibiotics: Do not help colds. Antibiotics are not
effective against viruses that cause colds. If you use
unnecessary antibiotics, you run the risk of having diarrhea
and yeast infections, having an allergic reaction, and
increasing your risk of having an infection later with
antibiotic-resistant bacteria. Colored nasal discharge or
sputum is a frequent symptom of the common cold and
does not necessarily indicate a bacterial infection. You
should contact your doctor if: Your symptoms have not
improved after 14 days; You develop a fever (above
102)F), confusion, difficulty breathing, severe
headache, severe fatigue, or rash
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Vaccines to reduce antimicrobial use
Vaccines to Prevent Respiratory
Impact of pneumococcal vaccine Diseases
• Pneumococcal vaccine (“pneumonia
vaccine”)
o
o
Conjugate (Prevnar™
Polysaccharide (Pneumovax)™
• Influenza vaccine
o
Many types
• Pertussis (Tdap; tetanus, diptheria,
acellular pertussis)
• VERY IMPORTANT to maintain good
health!!
Kyaw et al, NEJM, 2006,354,1455-63
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Antimicrobials for RTIs:
Choosing Wisely
•Avoid ABX for Viral Respiratory Infections
o Strategies:
• Use diagnostic tests (e.g. Strep for pharyngitis)
o
Better point of care tests to come
• Apply clinical criteria
o
e.g no improvement after 10 days for sinusitis
• Educate pts (information sheets)
• ‘Watchful waiting’
• ‘alternative’ prescriptions
• EMR justification
•Use Appropriate Drug; Dose; Duration
o Guidelines
•Vaccinate
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Hospital Antimicrobial Stewardship:
Definition
“An ongoing effort…to optimize antimicrobial use in
order to improve patient outcomes, ensure costeffective therapy, and reduce adverse sequelae of
antimicrobial use (including antimicrobial resistance)”
Secondary goal: Reduce costs
Dellit T, et al. Clin Infect Dis. 2007;44:159-177.
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Joint Commission Antimicrobial Stewardship
Standards
Effective January 1, 2017
1. Leaders establish antimicrobial stewardship as priority.
2. Educate staff about antimicrobial resistance and antimicrobial
stewardship practices.
3. Educate patients and families regarding the appropriate use of
antibiotics.
4. The hospital has an AS multidisciplinary team that includes:
IDphysician, Infect Control, Pharmacist(s), Practitioner.
5. The ASP includes the CDC Core Elements of Hospital ASP.
6. The ASP uses organization-approved multidisciplinary protocols
(ex: policies and procedures).
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https://www.jointcommission.org/
CDC Core Elements of Hospital ASP
1. Leadership Commitment: Dedicating necessary human, financial and
information technology resources.
2. Accountability: Appointing a single leader responsible for program
outcomes. Experience with successful programs show that a physician
leader is effective.
3. Drug Expertise: Appointing a single pharmacist leader responsible for
working to improve antibiotic use.
4. Action: Implementing at least one recommended action, such as systemic
evaluation of ongoing treatment need after a set period of initial treatment
(i.e. “antibiotic time out” after 48 hours).
5. Tracking: Monitoring antibiotic prescribing and resistance patterns.
6. Reporting: Regular reporting information on antibiotic use and resistance to
doctors, nurses and relevant staff.
7. Education: Educating clinicians about resistance and optimal prescribing.
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http://www.cdc.gov/getsmart/healthcare/implementation/core-elements.ht
March, 2015
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Diagnostic Tests for Etiology
• Standard culture methods (blood, sputum)
–
Low yield, time to results
• Gram stain, urinary antigen testing
–
S pneumoniae, Legionella spp
• Newer molecular tests (PCR, MALDI-TOF)
–
–
Potential for more rapid diagnosis, greater sensitivity
Allows for pathogen-directed therapy
• Biomarkers (Procalcitonin)
• Differentiate Bacterial vs virus
• Timely response to bacterial load
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PCR, polymerase chain reaction; MALDI-TOF, matrix-assisted laser desorption/ionization Time of Flight mass spectrometry
Diagnostic testing: Time to ID
• Rapid diagnostic tests
o PNA FISH,
PCR, MALDI-TOF
Goff DA, et al. Pharmacother. 2012;32:677-88.
• Retrospective chart review to assess impact of introduction of FilmArray
Multiplex PCR technology on surrogate and clinical outcomes in bacteremic
patients at Akron City Hospital
• 87 patients in post-implementation group vs. 93 in pre-implementation
• Active ASP in place
• Findings:
o Mean time to optimal therapy was reduced from 30.6 to 1.7 hours (P<0.001)
o 30 day readmission rate was reduced from 29.3% to 4.3% (P<0.001)
o Inpatient mortality rate was reduced from 18.8% to 8.6% (P=0.046)
o Cost per day of antimicrobial therapy per patient was $14.20 less in the
intervention group compared with the pre-intervention group ($24.80 vs.
$10.60; P=0.012)
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Blount PL et al. Poster. Summa Health Post-Graduate Day 2016, Akron. June 4, 2016.
Use of Procalcitonin for Antimicrobial
Stewardship for RTIs
PCT < 0.1
ug/ml
Bacterial
Infection
VERY
UNLIKELY
NO
ANTIMICROBIALS
Consider repeat 6-24hrs
based on clinical status
PCT 0.10.25 ug/ml
Bacterial
infection
UNLIKELY
NO
ANTIMICROBIALS
Use of ABX based on
clinical status (‘unstable’)
& judgment
YES
ANTIMICROBIALS
Repeat PCT day 3, 5, 7 (for
Duration)
Bacterial
YES
infection
ANTIMICROBIALS
VERY LIKELY
CONSIDER STOP ABX
when 80=90% decrease; if
PCT remains high consdier
treatment failure
PCT > 0.25- Bacterial
0.5 ug/ml
infection
LIKELY
PCT > 0.5
ug/ml
File TM Jr. Clin Cherst Med. 2011; modified from
Schuetz P. et al. Eur Respir J 2011;37(2): 384–92.
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• Observational, historical control to assess impact of PCT in ICU
• 50 patients with PCT at initial suspicion of infection and 48 hrs 50 Control pts--same
time frame, diagnosis, gender, age, APACHE II
• Active ASP in place
• Findings:
o Duration of ABX decreased by 3.3 days (p=0.0238)
o Duration in hospital decreased by 4.3 days (p=0.029)
o Readmission to hospital decreased by 16% (p=0.055)
o Mortality 2% vs 4% (p=0.5)
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Common Principles of
Antimicrobial Stewardship
•
Avoid Antimicrobials if not warranted
o
•
? Value of delayed prescription for RTIs
Appropriate agent (based on susceptibility)
o
Avoid discordant therapy
•
De-escalation
•
Dose Optimization
o
Based on renal function, weight, MIC
•
Stop ABX if not warranted
•
Reduce duration
•
Switch to oral
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82 y/o female transferred from LTCF with fever, decrease
mental status; WBC-15,000. Exam unremarkable. Has
long-term foley catheter: + pyuria; Treated initially with
ciprofloxacin. Day #3 lab reports culture with > 100,000
E. coli resistant to ciprofloxacin but susceptible to all
other agents tested. What is the appropriate choice
now? Stop ciprofloxacin and start:
A.
B.
C.
D.
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Cefepime
Ampicillin
Piperacillin/tazobactam
Imipenem
De-escalation
• Susceptibility results used to more specifically
target microbiological results; narrowing the
antibiotic spectrum by changing from a broad
spectrum agent to a narrow spectrum agent or by
eliminating a drug from combination therapy.
• Should ideally occur as soon as possible, but within
48 hours of the availability of culture results.
• Benefits include
•
•
•
•
reduced bacterial resistance,
decreased incidence of bacterial, viral, and fungal
superinfections,
limited exposure to unnecessary drug therapy and the
associated risks
decreased costs.
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Duration of Therapy: How low
to go (Clinically resolving)
Infection
Duration (days)
Meta-analysis
Duration (days)
Guideline
Cystitis (uncomplicated)
3 = 5-10 for clin cure; 5-10
better bact erad (Milo et al
3 days (Gupta et al. IDSA 2009)
Cochrane 2004)
Pyelonephritis(uncomplicated)
≤7 = longer (Eliakim-Raz J
7 (Gupta et al IDSA 2009)
Antim Chem 2013)
Intra-ABD (surgical drainage)
4-7 days (Afebrile, WBC normalizing,
Bowel sounds)[IDSA 2010]
VAP
7-8 = 10-15 (Dimopoulos
Chest 2013; Pugh et al. Cochrane
2011-except Non Fermenters
CAP
AECOPD
7-8 days (? 14 for Pseudomonas)
[ATS/IDSA 2005]
5-7 days (IDSA/ATS 2007)
5 days = 7-10(Falagas.
J
Antimicrob Chemother 2008)
Cellullitis (uncomplicated)
Sinusitis (Max)
5 days (IDSA 2014)
≤7 = >7, adults ( Falagas.
Cochrane 2009)
5-7days (IDSA 2012)
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Antimicrobial Stewardship: Summary
• ASSISTS appropriate patient care to improve
outcomes for your patients
o Not to be considered as source of critical review
• Summa Experience
o Reduced LOS
o Reduced Cost ($740,000
over first 4 years)
o Reduced Mortality (ICU)
o Possible enhanced patient satisfaction
• Antimicrobial Stewardship
A Win Win Program
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