Download Preeti Jaggi, MD

Outpatient Antimicrobial Stewardship
Preeti Jaggi, M.D.
Associate Professor of Pediatrics
Nationwide Children’s Hospital
Antimicrobial Stewardship
Overuse Under‐use
Correct dose, Minimize cost
Objectives
• History of resistance of organisms
• Besides resistance, are there other adverse effects of antibiotics in children?
• Does decreasing antimicrobial use in the community work to decrease resistance?
• Does parent expectation affect inappropriate prescribing?
• What has worked in the outpatient setting to decrease prescribing of antibiotics
Part 1
Antibiotics
Every Rose has its Thorn
Courtesy of Stan Shulman
Alexander Fleming
• "The greatest possibility of evil in self‐medication is the use of too small doses so that instead of clearing up infection the microbes are educated to resist penicillin and a host of penicillin‐fast organisms is bred out which can be passed to other individuals and from them to others until they reach someone who gets a septicemia or pneumonia which penicillin cannot save." (New York Times June 26, 1945) Penicillin Binding Protein
or PBP 2a
Chambers and DeLeo. Nat Rev Microbiol 7(9), 629-641. 2009
Every time you prescribe, think about the first and last patient you will treat in your career
Has microbial resistance impacted the way you treat patients? 1970: AOM, pneumonia,
sulfa/EES
1980: S. pneumo meningitis
Ampicillin alone
1964: urinary infection
sulfa
1990: SSTI
1st generation ceph
Urgent Threats • Carbapenem‐resistant Enterobacteriaceae (CRE)
• Drug‐resistant Neisseria gonorrhoeae Serious Threats • Methicillin‐resistant Staphylococcus aureus (MRSA)
• Drug‐resistant Streptococcus pneumoniae • Drug‐resistant tuberculosis Infect Control Hosp Epidemiol 2009; 30:1211‐1217
Antibiotic Resistance
• CDC estimates that at least 23,000 people die annually in the United States as a result of an infection with an antibiotic‐resistant organism and more than 2 million are sickened. • UK study‐ 300 million cumulative premature deaths by 2050, with a loss of up to $100 trillion (£64 trillion) to the global economy.
Arias and Murray, NEJM 2015
Antimicrobial stewardship • Antibiotics are the second most commonly used class of drugs in the United States
• More than $8 billion spent on anti‐infectives annually
• 25‐40% of all hospitalized patients receive antibiotics
• 50% of antimicrobial use is either unnecessary or inappropriate
• Children: 10‐20 courses of antibiotics before 18y
Besides resistance and C. difficile infections, any other adverse effects from antibiotics?
Blaser, Nature, 2011
Blaser, Science 2016
Systemic Consequences of Decreasing Microbial Diversity of Normal Flora? • Changes in microbiome
– Linked to obesity?
– Linked to auto‐immune illness?
• Inflammatory bowel disease
• Celiac
• Juvenile arthritis
– Linked to asthma and/or allergies
• Asthma
• Food or other allergies
Antibiotics and Obesity
• Sub therapeutic antibiotics at a young age promotes growth
– Livestock
– Animal studies
– Malnourishment
– Does early life exposure to antibiotics promote weight gain and increases risk of obesity? Lassiter C. J Dairy Sci. 1955; Cho, Nature 2012; Trehan, NEJM 2013,
2016
Antibiotics and Weight Gain
• Malnutrition
• Developing countries
• Developed nations
– BMI was higher in boys at 2 years in those receiving broad spectrum agents at <6 months
– Dose dependent, antibiotics in infancy associated with obesity at 3‐5 years
– Weight was not higher at age 7 for those receiving antibiotics at <6 mo, 250 g at 24 months
Gough EK BMJ, Saari et al, Pediatrics, 2015, Bailey JAMA peds 2014, Gerber 2016
Antibiotics and Allergy
Longitudinal data from 30,060, ages<7 years
Matched case‐control study Food allergies and other. Children with three or more antibiotic orders greater odds of: • Milk allergy (OR 1.78; 95% CI 1.28‐2.48), non‐
milk food allergy (1.65; 1.27‐2.14) and other allergies (3.07; 2.72‐3.46)
•
•
•
•
Hirsch, AG Clin Exp Allergy, 2016
Antibiotics and Asthma?
• All children born 1996–2004 and diagnosed with asthma by age 3 were identified; for each case, one matched control was selected. (n = 6,690 pairs).
• Maternal use of any antibiotics during pregnancy associated increased risk of asthma in the offspring [(OR) = 1.31 (95% confidence interval (CI): 1.21–1.42)]. • Strongest association was observed for cephalosporins [OR = 1.46 (95% CI 1.30–1.64)]. • Child's use of antibiotics during first year of life associated with an increased risk of asthma [OR = 1.60 (95% CI 1.48–1.73)]. Metsala, Clinical and Experimental Immunology, 2014
Antibiotics and Auto‐Immune Illness
Disease
Incidence
Inflammatory Bowel 1.2 per 10,000 person‐years
Disease
Juvenile Arthritis
6‐15 per 100,000
Diabetes
20 per 100,000
Antibiotics and Juvenile Arthritis
• Nested case‐control study in UK. • Newly diagnosed JIA compared with matched healthy controls. • Any antibiotic exposure associated with increased rate of developing JIA (OR 2.1,95% CI 1.2‐3.5). • Dose dependent (OR >5 antibiotic courses: 3.0 [95% CI 1.6‐5.6])
• Strongest for exposures within 1 year of diagnosis
Horton, Pediatrics, 2015
Proportion of subjects developing IBD according to age and antianaerobic
antibiotic exposure status.
Matthew P. Kronman et al. Pediatrics 2012;130:e794-e803
©2012 by American Academy of Pediatrics
Diabetes
• Danish cohort study, with 1, 503 cases (DM by age 15)
• Broad‐spectrum antibiotics were associated with an increased rate of type 1 diabetes in children delivered by C‐section (HR 1.70; 95% CI 1.15 to 2.51) but not in vaginally delivered children. Clauson, Plos One 2016
Other associations
• Stress may alter the microbiome
• Questionable association with antibiotics and celiac disease and eczema
• Depressed microbiome associated with colonization of resistant potential pathogens
Part 1: Summary
• We prescribe more antibiotics in the US versus Europe and more in the Midwest than the West
• Most antibiotic prescribing is in outpatients
• Emerging evidence in humans that microbiome disruptions may predispose to future chronic conditions
• Increasing resistance impacts clinical management
Some good news…
Decreasing use in the community can reduce resistance
Frequency of Resistance to Erythromycin among Group A
StreptococcalTotal
Isolates
from Throat-Swab
Pus Samples
in Finland
Consumption
of Macrolideand
Antibiotics
by Outpatients
in Finland from
in 1990 and in 1992 1976
through
1996.
through
1995.
Seppälä H et al. N Engl J Med 1997;337:441-446.
Part 2: Inappropriate Prescribing National Estimates of Inappropriate Prescriptions
Fleming‐Dutra, JAMA 2016
Gerber, JPIDS, 2015
How do we do in Ohio?
Partners for Kids (PFK)
Accountable Care Organization
• Physician & NCH
partnership
• Accepts clinical and
financial risk for patients
• Serves 330,000 pediatric
Medicaid recipients
• 34-county region in
Central/Southeast Ohio
Kelleher et al. Pediatrics 2015
Gleeson et al. JAMA Pediatr
2014
Prescriptions by Age
No. of prescriptions by age
No. of PFK members by
age
>25% of antibiotics are prescribed to children aged < 3y
Prescriptions for children associated with a medical encounter
Exclusions: complex & chronic conditions; antibiotics in prior 30 days; encounter in prior 30 days for that family; additional bacterial diagnoses
Upper Respiratory Symptoms
(Viral + Bacterial)
UR Symptom
Prescribing
Index
Lower Respiratory Symptoms
(Viral + Bacterial)
Skin & Soft Tissue Symptoms (Non‐infectious + Bacterial)
Urinary Symptoms
(Non‐infectious + Bacterial)
Prescribing Index For uncomplicated children with upper
respiratory complaints
Viral URI
Sinusitis Common Conditions in Pediatrics
• Group A streptococcal pharyngitis
• Acute bacterial rhinosinusitis
• Urinary tract infection
Non-Group A streptococcal causes of
pharyngitis (the other 70-85% of pharyngitis)
Bacteria
Beta-hemolytic
streptococci: Group C, G
Corynebacterium diptheriae
Arcanobacterium haemolyticum
Neisseria gonorrhoeae
Uncommon:Chlamydophila
pneumoniae
Chlamydia trachomatis
Mycoplasma pneumoniae
Francisella tularensis
Coxiella burnetti
Yersinia enterocolitica
Yersinia pestis
Viruses
Epstein-Barr
Adenovirus
Enterovirus
Herpes simplex
Influenza
Parainfluenza
Rhinovirus
Coronavirus
Respiratory syncytial
Why do we treat for GAS pharyngitis?
• Prevention of rheumatic fever • Shortens symptoms by about one day
• To some extent, to prevent suppurative complications
• IDSA guidelines: Children 3 and older should be tested, clinical and epidemiologic features not consistent with a viral etiology (cough, hoarseness, rhinorrhea, oral ulcers)
• Need confirmatory testing, 1st line PCN or amox
Streptococcal Testing
2402 (8%) prescriptions were for children aged < 3
years
Schematic characterization of the natural history and time course of fever and respiratory
symptoms associated with an uncomplicated viral upper respiratory infection (URI) in
children (courtesy of Dr Ellen Wald)
Chow A W et al. Clin Infect Dis. 2012;cid.cir1043
© The Author 2012. Published by Oxford University Press on behalf of the Infectious
Diseases Society of America. All rights reserved. For Permissions, please e-mail:
[email protected].
Sinusitis UTI Testing
Factors Associated with Inappropriate Prescribing
• Parent expectations
• Clinician perception of parent expectations
• Clinician fatigue
Parental expectations
• Parent vs. physician expectations about need for antibiotics
• Survey of parents before appointments for child’s cold symptoms in LA (38 pediatricians/543 parents) • Parents: 70% Antibiotics needed, 36% physicians
• Physicians 7% more likely to make a bacterial diagnosis and 21% more likely to prescribe antibiotics when they perceived that antibiotics were expected.
Mangione‐Smith, Pediatrics 2004
Parents of children<6, n=1500, Survey data
Vaz, Pediatrics, 2015
Are Clinician’s Perceptions Correct?
• Providers poor at determining parental expectation for antibiotics
• Parents not expecting antibiotics‐ Physicians
correct 73%
• Parents expecting antibiotics‐ Physicians
correct 41%
Mangione‐Smith R et al Pediatrics 1999
Clinician Fatigue
Linder, JAMA Internal Medicine, 2014
Summary of Part 2
• Most antibiotics prescribed to children are for upper respiratory complaints
• Heterogeneity among frequencies of prescriptions
• Under‐utilize appropriate diagnostic testing for UTI and streptococcal pharyngitis
• Factors that affect prescribing
– Parental expectation, perception of expectation
– Fatigue
Part 3: Poster
• RCT 5 outpatient adult clinics in LA
• Signed commitment letter with photo in exam rooms
• One year observation period total, with intervention in 12 weeks at height of cold and influenza season
• 20% decreased inappropriate prescribing in experimental vs. control arm
Meeker, JAMA Internal Medicine, 2014
Durability of Benefits of an Outpatient Antimicrobial Stewardship Intervention After Discontinuation of Audit
and Feedback
JAMA. 2014;312(23):2569-2570. doi:10.1001/jama.2014.14042
Figure Legend:
Standardized Rates of Broad-Spectrum Antibiotic Prescribing Before, During, and After Audit and Feedback. The estimate
of interest is the treatment × time interaction term, representing the relative changes in trajectories before and during the
intervention. Error bars indicate 95% CIs.
Date of download: 9/2/2016
Copyright © 2016 American Medical
Association. All rights reserved.
From: Durability of Benefits of an Outpatient Antimicrobial Stewardship Intervention After Discontinuation of
Audit and Feedback
JAMA. 2014;312(23):2569-2570. doi:10.1001/jama.2014.14042
Figure Legend:
Standardized Rates of Broad-Spectrum Antibiotic Prescribing Before, During, and After Audit and Feedback. The estimate
of interest is the treatment × time interaction term, representing the relative changes in trajectories before and during the
intervention. Error bars indicate 95% CIs.
Date of download: 9/2/2016
Copyright © 2016 American Medical
Association. All rights reserved.
From: Durability of Benefits of an Outpatient Antimicrobial Stewardship Intervention After Discontinuation of
Audit and Feedback
JAMA. 2014;312(23):2569-2570. doi:10.1001/jama.2014.14042
Figure Legend:
Standardized Rates of Broad-Spectrum Antibiotic Prescribing Before, During, and After Audit and Feedback. The estimate
of interest is the treatment × time interaction term, representing the relative changes in trajectories before and during the
intervention. Error bars indicate 95% CIs.
Date of download: 9/2/2016
Copyright © 2016 American Medical
Association. All rights reserved.
Nudging Antibiotic Prescribing
• Cluster randomized trial among 47 adult primary care practices in Boston and LA
• Randomized to 0 or 3 of the following:
‐Suggest alternatives
‐Accountable justification
‐Peer comparison
•All received education
Meeker, JAMA 2016
• Suggested alternatives: EHR‐based intervention. “Antibiotics are not generally indicated for [this diagnosis]. Please consider the following prescriptions, treatments, and materials to help your patient”
• Accountable justification: EHR prompt asked each clinician to justify, in a free text response, his or her treatment decision. Triggered for both antibiotic‐inappropriate diagnoses and potentially antibiotic‐appropriate acute respiratory tract infection diagnoses • Peer comparison: Email‐based intervention. Clinicians were ranked from highest to lowest inappropriate prescribing rate. “Top Performers” or “Not a Top Performer”
Combine explanations for why antibiotics are not needed with positive treatment recommendations
Strategy
Examples
Why antibiotics are “The strep test is negative, meaning your sore throat is caused by a virus, not needed
and antibiotics won't help.”
“You have a chest cold, and antibiotics won't help.”
Positive treatment recommendations
Contingency plan
Delayed antibiotic prescriptions
“Taking ibuprofen and drinking plenty of fluids will help you feel better.”
“Honey can actually soothe your child's cough and help her sleep better.”
“If you are not better in three or four days, call or come back and we can reassess the need for antibiotics then.”
“If your child is still sick in a week or if he develops a fever, come back and see me.”
“Your child has an ear infection that will likely clear up on its own. Just in case it doesn't, here is an antibiotic prescription. Fill this prescription in two days if the ear still hurts, or earlier if your child gets worse. Feel free to call me with any questions.”
Fleming Dutra, Am Fam Physician, 2016
Summary of Part 3
What Helps to Decrease Prescribing
• Feedback, peer comparison are key to decreasing overall use
• Poster in the office to set expectations • Recognition of fatigue at the end of the day
• ‘Get smart’resources from CDC • Combine positive and negative treatment recommendations
Courtesy of Stan Shulman
What else can we do?
Thank you! Questions?