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11/6/2017
1
Antibiotic Mindfulness - Becoming Better Stewards of a Precious Resource
Paul J. Carson, MD, FACP
Dept. of Public Health,
Management of Infectious Diseases
© 2013 Template and icons provided by The Advisory Board Company.
What Is Stewardship?
Merriam-Webster:
“The careful and responsible management of something entrusted to one's care”
“The responsible overseeing and protection of something
considered worth caring for and preserving”
“Because infectious diseases
have been largely controlled in the United States, we can now close the book on infectious diseases.”
- William Stewart, MD
U.S. Surgeon General, 1967
Conspicuous Consumption
• 5 out of every 6 Americans will receive a course of antibiotics annually
• 160-258 million antibiotic Rx (≈ 3 million kg) / yr
• Avg American child will receive 10-20 courses of antibiotics before age 18
• Not atypical for a 2 y.o. to have spent ≈ 3 mos of their life on antibiotics
Wenzel RP and Edmond MB. N Engl J Med. 2000;343:1961-1963
Spellberg and Bartlett. N Engl J Med. 2013; 368;299-302
Hicks and Taylor. N Engl J Med. 2013; 368; 1461-1462© 2013 Template and icons provided by The Advisory Board Company.
Antibiotics Across the Health Care Spectrum
Nursing Home
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Estimated 50 million unnecessary
outpt antibiotic prescriptions / yr
CDC
A Tale of Two Countries:Rate of Outpatient Antibiotic Use, 2014
835 / 1000 population / yr 328 / 1000 population / yr
Geographic Variability in HEDIS Measures Related to Appropriate Antibiotic Use
Children diagnosed with VURI not receiving an antibiotic, 2008-2012
Adults with acute bronchitis not receiving an antibiotic, 2008-2012
Roberts RM. Am J Manag Care. 2016;22(8):519-23 © 2013 Template and icons provided by The Advisory Board Company.
Antibiotic Prescribing Increases with Fatigue
© 2013 Template and icons provided by The Advisory Board Company.
Overuse of Antibiotics in Nursing Homes
• 5 million people will pass through a NH each year
• 1.6 million long-term residents in 20,000 NHs
70 - 80% will
receive an antibiotic each year
50% of antbiotics
will be unnecessary
or inappropriate
• 2 million will receive unnecessary or inappropriate antibiotics
© 2013 Template and icons provided by The Advisory Board Company.
Trends in Hospital Antibiotic Use from 2002-2006
Hecker MT, et al. Arch Intern Med2003:163:972-978
Pakyz AL, et al. Arch Intern Med. 2008;168(20):2254-2260
Vancomycin 43%
Carbapenems 59%
Piperacillin- 84%
Tazobactam
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© 2013 Template and icons provided by The Advisory Board Company.
Trends in Hospital Antibiotic Use from 2002-2006
Hecker MT, et al. Arch Intern Med2003:163:972-978
Pakyz AL, et al. Arch Intern Med. 2008;168(20):2254-2260
30 - 50% of Antibiotic UseUnnecessary or Inappropriate
April 2010
CDC Hazard Level for Antibiotic Resistance Threats - 2013
Concerning Serious Urgent
VRSA MRSA Clostridium difficile (C. diff)
Ery-R GABHS VRE Carbapenem-R Enterobacteriaceae
Clinda-R GBBHS MDR-Pseudomonas Drug-resistant N. gonorrhoeae
ESBL-Enterobacteriaceae
DR-Campylobacter
DR-Salmonella
Fluconazole-R Candida sp
MDR-Acinetobacter
MDR/XDR TB
Approved Antibiotics in U.S. 1983 - 2015
0
2
4
6
8
10
12
14
16
# of
New
Abx
Frequency of ADEs due to Antibiotics in Outpatient Setting
� Up to 1:4 will experience some ADE with an antibiotic
� 142,505 estimated emergency department visits/year due to untoward effects of antibiotics (~ 1:1000 abx prescriptions)
� Antibiotics account for 19.3% of drug related adverse events
� 78.7% for allergic events
� 19.2% for adverse events (e.g. diarrhea, vomiting)
� Approximately 50% due to penicillin & cephalosporin classes
� 6.1% required hospital admission
2004-2005 NEISS-CADES project
Bourgeois, et al. Pediatrics. 2009;124;e744-50
Linder. Clin Infect Dis. 2008 Sep 15;47(6):744-6Vangay, et al. Cell host & Microbe 2015;17;553-64
Shehab N et al. Clin Infect Dis. 2008;47:735
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© 2013 Template and icons provided by The Advisory Board Company.
Risks with Use of the Quinolones
Van Der Linden. JAMA Int Med 2003
Gowtham. Ann Fam Med. Apr 2014Chien-Chang. JAMA Int Med 2015
McCusker. Emerg Infect Dis 2003Tacconelli. JAC 2008
Condition Relative Risk
Achilles tendon rupture
Current exposure overallAge 60-79Age > 80
4.3 (95% CI, 2.4-7.8)6.4 (95% CI, 3.0-13.7)
20.4 (95% CI, 4.6-90.1)
Serious arrhythmia 2.43, 95% (CI, 1.6–3.8)
Death 1-5 d after Levofloxacin 2.49 (95% CI, 1.7–3.6)
Aortic dissection 2.43 (95%CI, 1.8 - 3.2)
C. Diff infection 12.7 (95% CI, 2.6–61.6)
Risk of acquiring MRSA3.0 (95% CI 2.5 to 3.5)
(c/w 1.8 RR for other abx)
� 2nd line abx for pneumonia and UTIs with a black box warning
� Over 23 million prescriptions of quinolones / yr in U.S. (mostcommonly prescribed class)
� Over 2,000 lawsuits filed for injuries in 2011
Human Microbiome
1013 Human Cells
1014 Bacterial Cells
Diversity of Bacteroides Species in GutAfter 7 day Course of Clindamycin
Microbiology (2010), 156, 3216–3223
“Dysbiosis”
� Obesity
� Auto-immune dz
� Metabolic syndrome
� Diabetes
� IBD
� Asthma
� Allergy
� Autism
© 2013 Template and icons provided by The Advisory Board Company.
Mice given low dose penicillin
before weaning become obese
Germ free mice exposed to the
microbiome of the obese mice
become obese
Do These Antibiotics Make Me Look Fat??
Cox et al. Cell 2014
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JAMA Pediatr. 2014;168(11):1063-1069
� Prevalence of colorectal adenomas on screening colonoscopy in
the Nurses Health Study based on > 2mos of antibiotic exposure at a younger age
� 36% increased risk if received age 20-39
� 69% increased risk if received age 40-59
Are doctors just
being stupid?
Or Evil? Risks of not recognizing
and treating early sepsis
Risks of over-
diagnosis and
treatment
We must come to the belief that casually
writing for an antibiotic is not a benign act! © 2013 Template and icons provided by The Advisory Board Company.
Call for Antimicrobial Stewardship -Preserve a Precious Resource
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What Is Antimicrobial Stewardship?Right Drug, Right Dose, Right Duration, Right Time, Every Time
Antibiotic Benefits
Resolution of Infxn
Morbidity & mortality
Antibiotic Risks
ADEs
C diff
Abx resistance
Antibiotic Expenditures in U.S. by Treatment Setting, 2009 Total Cost $10.7 billion)
61%
34%
5%
Community Hospital Nursing Home
1. Does my patient really need an antibiotic?
2. If I am going to give an antibiotic, what
is the most appropriate choice?
3. Can I revisit the situation in a couple
days to assess clinical progress, cultures,
and ability to adjust my antibiotics?
4. Have I set an appropriate duration of
therapy?
Antibiotic Time-Out
1. Does my patient really need an antibiotic?
2. If I am going to give an antibiotic, what
is the most appropriate choice?
3. Can I revisit the situation in a couple
days to assess clinical progress, cultures,
and ability to adjust my antibiotics?
4. Have I set an appropriate duration of
therapy?
Antibiotic Time-Out
Respiratory Infections are the # 1 Reason for Office Visits
165
119
65
51
28
0
20
40
60
80
100
120
140
160
180
Respiratory
infections
Hypertension Disorders of
lipid
metabolism
Diabetes
mellitus
Depressive
disorder
Source: Verispan PDDA 2004
Nu
mb
er
of
co
mm
on
off
ice v
isit
s (
millio
ns)
Nearly Two-thirds of all Oral Solid Antibiotic Prescriptions are for Sinusitis and Bronchitis
21.5
19.3
9.6
7.6
5.2
0
5
10
15
20
25
Sinusitis Bronchitis Pharyngitis Pneumonia Otitis media
Pe
rce
nt
ora
l s
olid
an
tib
iotic
us
e
Source: SDI, FANDxRx. Based on all tablets/capsule antibiotics for the 52 weeks ending April 6, 2005
Telithromycin (Ketek®) is indicated for acute exacerbations of chronic bronchitis, acute bacterial sinusitis and mild-to-moderate community-acquired pneumonia
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How Do You Clinically Distinguish
Bacterial Sinusitis
From a VURI??
Acute Uncomplicated Rhinosinusitis –Antibiotics Only If:
� Symptoms lasting > 10 days, or
� 3-4 days of severe symptoms or high fever, or
� “Double-sickening” – start worsening after initial improvement
Guidelines from the AAO-Head and Neck Surgery 2015
17 million
Antibiotic
Prescriptions
Annually in U.S.
95% of patients
at Sanford with
acute uncompli-
cated sinusitis
Acute Bronchitis: Meta-Analysis of Abx v. Placebo
Cochrane Review 2012
N = 875
Acute Suppartive Otitis Media Otitis Media with Effusion
AAP Recommendations for Watchful Waiting in AOM
� Child > 6 mos old
� Non-severe AOM
� Unilateral disease
� Mild pain < 48 hrs
� Temp < 102.2 degrees F
� Consideration with parent for watchful waiting for
48-72 hrs
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Pharyngitis
• Grp A Strep Only in:
– 37% of children
– 18% of adults
• No antibiotics without a positive test
Appropriate Antibiotic
Condition 1st Line Antibiotic 2nd Line Antibiotic
Acute Otitis Media Amoxicillin Cefdinir, Cefprozil
Acute Bacterial Sinusitis Amoxicillin
Amoxicillin clavulanate
Doxycycline
Pharyngitis Penicilliin V
Benzathine Penicillin
Cephalexin
Clindamycin
© 2013 Template and icons provided by The Advisory Board Company.
Urinary Tract Infection – What is It?
© 2013 Template and icons provided by The Advisory Board Company.
Asymptomatic Bacteriuria = UTI
� Common, esp. elderly women and compromised pts
� 20-50% of treated “UTI” is actually Asx Bacteriuria
� Ratio of asx bacteriuria to symptomatic UTI in LTC is > 100:1
� Good evidence that Rx gives no benefit and causes harm (ADEs, resistance, more UTI)
© 2013 Template and icons provided by The Advisory Board Company.
UTI is #1 reason for Abx in LTCFs
Problem: What constitutes symptoms in an elderly, incontinent, and demented patient with limited ability to communicate?
ASB is common as are atypicalpresentations for infection.
© 2013 Template and icons provided by The Advisory Board Company.
Do “UTIs” Cause That? -Myths, Legends, and Reality:
� Unexplained falls
� Weakness
Kallin K, et al. J Family Practice 2004:53;41‐52
Campbell AJ. BMJ2008;337:a2320
Juthani‐Mehta M. J Am Geriatr Soc 2009;57:963‐70
Nicolle, L. J Amer Geri Soc 2009;57:113‐49Rituparna, D. Infect Control and Hosp Epid 2011;32:84‐6
Gupta K. JAMA 2014;311:844‐54.
Sundvall PD.BMC Family Practice 2011, 12:36
Juthan‐Mehta M. JAMA2014;312:1687‐8
Evidence for this is
overall poor quality
� Change in urine character
� Delirium
� Change in mental status
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UTI Pathway to Assist with Antibiotic Usefor Sub-Acute Care, LTC & Nursing Home Facilities
STOP
WAIT
GO
START: Suspected UTI. What are the patient’s symptoms?
Mental Status Changes (resident seems “off”), Foul Smelling Urine,
OR Urine Color Changes (dark or cloudy)
Antibiotics and Urine Culture NOT INDICATED, further eval’n and monitoring required
Seek alternative causes changes (e.g. dehydration, medications, environmental
changes, metabolic problems, bleeding, cardiovascular, stroke, etc.)
PLACE RESIDENT ON CLOSE MONITORING PROTOCOL
Increased fluid intake (unless contraindicated)
Monitor & document I/Os and VS every shift for next 24h
New or Changing Urinary Symptoms (Urgency, frequency, suprapubic pain, gross hematuria, CV angle tenderness, incontinence, persistent foul urine)
ORSigns of Sepsis (100 - 100 - 100)
THEN take a clean catch urine (per protocol) and send for UA and/or C&S
© 2013 Template and icons provided by The Advisory Board Company.
Empiric Antimicrobial Management of UTI
Syndrome Antibiotic Duration Comments
Uncomplicated
Cystitis
Nitrofurantoin
100 mg bid5 days
First choice, low resistance,
Avoid if GFR < 30
TMP-SMX DS bid 3 daysAvoid if regional resistance >
20% or recent use
Fosfomycin 3 gm Single doseMinimal resistance, avoid if any
suspicion of pyelo
Cipro or Levo
250 mg bid3 days
2nd line agents, should be
reserved if can’t take above
Pyelonephritis
- Outpatient
- Inpatient
- Cipro 500 mg bid
- IV FQ, CP or ES-PCN
7 days
Definitive therapy should be
based on C&S data. Consider carbapenem if ESBL risk is
high
Complicated
Cystitis
Pyelonephritis
- Cipro 500 mg bid
- IV CP, ES-PCN, FQ
5-10 days
5-14 days
Need to empirically cover for
pseudomonas and consider
ESBL. Definitive rx based on
C&S data
© 2013 Template and icons provided by The Advisory Board Company.
Antibiotic Resistance Trends in E. coli Urinary Isolates
n = 12,253,679
Sanchez GV. Antimicrob Agents Chemother 2012
51
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SSTI - Infection not Really Present
� No documentation other than skin changes - no fever, no WBC, no pain
Dependent Rubor
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SSTI - Infection not Really Present
� No documentation other than skin changes - no fever, no WBC, no pain
Acute Edema / Expansion
Syndrome
© 2013 Template and icons provided by The Advisory Board Company.
SSTI - Infection not Really Present
� No documentation other than skin changes - no fever, no WBC, no pain
Stasis dermatitis and
Stasis ulcerationLipodermatosclerosis
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© 2013 Template and icons provided by The Advisory Board Company.
Empiric Rx of Cellulitis
�Purulent or Wound
� Usually staphylococcal
� MRSA will account for ~ 50% depending on your
community
�Non-purulent
� usually due to beta-hemolytic
strep
55
© 2013 Template and icons provided by The Advisory Board Company.
Empiric Antibiotic Choices for SSI
�If Strep likely
� IV start with cefazolin (2gm IV q 8 hrs) or ceftriaxone (1gm IV)
�Continue with p.o. cephalexin or dicloxacillin
• Don’t shortchange the dose.... Minimum 500 mg qid, can give up
to 1gm qid in the obese
�If S. aureus likely
� IV start with vancomycin
�Continue with p.o. Zyvox or cephalexin + TMP-SMX or Minocycline
1. Does my patient really need an antibiotic?
2. If I am going to give an antibiotic, what
is the most appropriate choice?
3. Can I revisit the situation in a couple
days to assess clinical progress, cultures,
and ability to adjust my antibiotics?
4. Have I set an appropriate duration of
therapy?
Antibiotic Time-Out
© 2013 Template and icons provided by The Advisory Board Company.
Duration of Therapy
It May Be Shorter Than You Think!
Disease Duration of Treatment (days)Short Long
Pharyngitis 3-6 10
Acute Sinusitis 5 10
COPD exacerbation < 5 > 7
CAP 3-5 7-10
HCAP, HAP < 8 10-15
Cellulitis 5-6 10
UTI – Cystitis 5 days (macrodantin)3 days (TMP-SMX, quinolones)
7
UTI – Pyelonephritis 5 days (quinolones) 14 days (TMP-SMX, or
Beta lactam)
Peritonitis 4-7 days after source control 10
Altimimi S. Cochrane Database 2012
Spellberg B. JAMA Int Med 2016
The art of medicine is to amuse the patient while nature cures the disease
Voltaire
“A desire to take medicine is, perhaps, the greatest
feature which distinguishes man from animals”
Sir William Osler
“One of the first duties of the physician
is to educate the masses not to take
medicines”
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© 2013 Template and icons provided by The Advisory Board Company.
Patient Education Resources
� CDC’s Get Smart Patient Education (office posters, fact sheets, viral “prescription pads”
� https://www.cdc.gov/getsmart/community/materials-references/print-materials/hcp/index.html
� ABIM/Consumer Reports Choosing Wisely patient education handouts (excellent!)
� http://consumerhealthchoices.org/depth-antibiotics/