From Handshakes to Rapid
Diagnostics: Advances in
Pediatric Antimicrobial Stewardship
Ronda Oram, MD
Medical Director, Antimicrobial Stewardship
Advocate Children’s Hospital
M. Ellen Acree, MD
Associate Medical Director, Antimicrobial
Stewardship
NorthShore University HealthSystem
Objectives
❑ Describe the role of handshake stewardship in
engaging with frontline providers and impacting
antibiotic prescribing
❑ Explain how the appropriate use of laboratory
resources can contribute to optimization of clinical
outcomes and reduce the spread of antimicrobial
resistance
❑ Choose empiric antibiotics for common pediatric
outpatient infectious syndromes, including pneumonia,
urinary tract infection and cellulitis
2
Outline
• Describe the power of antimicrobials and the development of antimicrobial resistance
• Discuss the principles of antimicrobial stewardship programs
• Discuss the success of antimicrobial stewardship interventions for inpatient and outpatient prescribing
• Discuss how laboratory tests contribute to diagnostic stewardship
• Describe how individual prescribers can contribute to antimicrobial stewardship efforts in the outpatient setting
3
Power of Antimicrobials
4
DiseaseDeath Pre-
Antimicrobials
Death with
Antimicrobials
Change in
Death
Community
pneumonia~35% ~10% -25%
Hospital pneumonia ~60% ~30% -30%
Heart valve infection ~100% ~25% -75%
Brain infection >80% <25% -60%
Skin infection 11% <0.5% -10%
Comparison: treatment of myocardial infarction with
aspirin or streptokinase -3%
1 IDSA Position Paper ‘08 Clin Infect Dis 47(S3):S249-65; 2IDSA/ACCP/ATS/SCCM Position Paper ‘10 Clin Infect Dis In Press; 3Kerr AJ. Subacute Bacterial Endocarditis. Springfield IL: Charles C. Thomas, 1955 & Lancet 1935 226:383-4; 4Lancet ‘38
231:733-4 & Waring et al. ‘48 Am J Med 5:402-18; 5Spellberg et al. ‘09 Clin Infect Dis 49:383-91 & Madsen ‘73 Infection 1:76-
81; 6‘88 Lancet 2:349-60
Slide credit: Adapted with modifications from IDSA, Public Policy & Government Relations
Antimicrobial Resistance
5
www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf
Update coming Fall 2019!!!
CDC-recognized threats
8
Urgent
• Clostridium difficile
• CRE
• Drug-resistant Neisseria gonorrhoeae
Serious
• MDR Acinetobacter
• ESBL-producing Enterobacteriaceae
• Vancomycin-resistant Enterococcus
• MDR Pseudomonas
• Methicillin-resistant S. aureus (MRSA)
• MDR S. pneumoniae
• MDR tuberculosis
• MDR Salmonella (typhi and non-typhoid)
• MDR Shigella
Concerning
• Vancomycin-resistant S. aureus (VRSA)
• Erythromycin-resistance Group A Streptococcus
• Clindamycin-resistant Group B Streptococcus
Respiratory S. pneumoniae Isolate
Resistant to Most Antibiotics
Outpatient Antibiotic Prescribing
❑ >47 million unnecessary prescriptions from offices and
EDs
11
https://www.cdc.gov/antibiotic-use/stewardship-report/pdf/stewardship-report-2018-508.pdf
Outpatient Antibiotic Prescribing
❑ 60% antimicrobial expenditures outpatient
❑ Antibiotic prescribing nationally has improved
▪ 5% decrease from 2011-2016
❑ 2016 – 270.2 million antibiotic prescriptions written
in the US
▪ 5 out of 6 Americans
❑ 74 million prescriptions for children
❑ Antibiotics - most commonly prescribed medication
in pediatrics
12
Outpatient Antibiotic Prescribing
https://www.cdc.gov/antibiotic-use/stewardship-report/pdf/stewardship-report-2018-
508.pdf13
Areas for Improvement
❑ Palms DL, et al. Comparison of Antibiotic Prescribing in Retail
Clinics, Urgent Care Centers, Emergency Departments, and
Traditional Ambulatory Care Settings in the United States. JAMA
Intern Med. 2018;178(9):1267–1269.
14https://www.cdc.gov/antibiotic-use/stewardship-report/pdf/stewardship-report-2018-508.pdf
Areas for Improvement in Children
❑ Fleming-Dutra KE, et al. Variations in Antibiotic and Azithromycin
Prescribing for Children by Geography and Specialty-United States,
2013. Pediatr Infect Dis J. 2018 Jan;37(1):52-58.
❑ Azithromycin often prescribed when not recommended
or not the first-line drug by guidelines
❑ 2016 - 67 million antibiotics prescribed to children
▪ Amoxicillin 35%
▪ Azithromycin 18%
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Antimicrobial Stewardship
❑ In 2014, CDC recommended all
hospitals implement Antimicrobial
Stewardship Programs (ASP) to
combat antimicrobial resistance
and adverse drug reactions
❑ Limited number of ASPs in
pediatric centers
❑ In 2016, CDC published elements
of Outpatient Antimicrobial
Stewardship
❑ Limited number of outpatient
programsHersh AL, et al. Infect Control Hosp Epidemiol 2009;30:1211-1217.
Newland JG, et al. Infect Control Hosp Epidemiol 2014;35:265-271.
CDC: ASP Core Elements
Leadership
• Dedicate necessary personnel, financial and information technology resources
• CRITICAL TO SUCCESS
Accountability
• Appoint single leader responsible for program outcomes
• Physician involvement demonstrated to be highly effective
Drug Expertise
• Appointing a single pharmacist leader responsible for working to improve antibiotic use
Education
• Educating healthcare providers about resistance and encouraging optimal prescribing patterns
Action
• Implement policies and Interventions to Improve antibiotic use
Tracking
• Monitoring the antimicrobial stewardship program, which may include information on antibiotic prescribing and resistance patterns
Reporting
• Regularly report findings to healthcare providers and other relevant staff
Aims of Antibiotic Stewardship
❑ Improve antibiotic
prescribing
❑ Optimize clinical
outcomes
❑ Minimize unintended
consequences (e.g. C.
difficile infection)
❑ Slow the progression of
antimicrobial resistance
Diagnosis Drug Dose Duration Discharge
5 D’s of Antimicrobial
Stewardship
Prescribing Antibiotics Incorrectly Can Lead to
Patient Harm
❑ Direct patient harm▪ Treatment failure, poor outcomes with inadequate
regimens
▪ C. difficile colitis
▪ Development of MDRO colonization and infection
▪ Adverse Drug Events
▪ Excess cost
❑ Indirect patient harms▪ Horizontal spread of MDRO colonization and infection
❑ Regulatory burden▪ Reporting of C. difficile colitis, MDRO
▪ Compliance with performance measures
Solutions – Inpatient vs. Outpatient
❑ Inpatient▪ Restriction/pre-authorization
▪ Prospective audit and feedback
▪ Handshake stewardship (2)
❑ Outpatient▪ Patient education on when antibiotics are needed
▪ Peer comparison on prescribing practices
▪ Accountable justification
❑ Both▪ Diagnostic stewardship (3)
▪ Clinical practice guidelines and pathways (1)
▪ Penicillin allergy
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Electronic Guidelines for Antimicrobial Prescribing
• Empiric use guidelines
• 2011 PR
• 2017 OL
• Beta lactam allergy guidelines
• Surgical prophylaxis guidelines
• Vancomycin dosing guidelines
• Pediatric CAP antimicrobial
guidelines
• NICU system guidelines
• Appendicitis guidelines
Antimicrobial Stewardship Assistance
Program - ASAP
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Antimicrobial Stewardship Assistance
Program - ASAP
24
Antimicrobial Stewardship Assistance
Program - ASAP
25
Handshake Stewardship
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ACTION: One of the Core Elements of ASPs
❑ Prior authorization: providers call stewards for
permission to use certain antimicrobials
❑ Prospective audit and feedback: stewards review list
of certain antimicrobials at certain time frames and
contact providers with feedback, usually by phone or
EMR
❑ Handshake stewardship is a unique prospective audit
and feedback program
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Handshake Stewardship
❑Relies on communication and trust between the ASP members and
providers
❑Rounding-based service with review of all antimicrobials prescribed
for pediatric inpatients 5 days a week
❑ ID MD and ID pharmacist round with prescribers to provide in person
real time feedback and education
❑During stewardship rounds, recommendations are given to
prescribers, who may then opt to accept or reject recommendations.
28
Hurst AI et al PIDJ 2016:35(10):1104
Handshake Stewardship Goals
Improve antimicrobial prescribing
Minimize unintended consequences
Reduce antimicrobial DOT
Reduce costs
Inaugural
Rounds
July 9,2018
Reduction in
antimicrobial
days of therapy
by
11%
Handshake Stewardship Process
❑ All antimicrobials at ACH PR are reviewed, 5 days a week
❑ ID pharmacist and/or ID pharmacy resident and ID MD
❑ In person rounds with recommendations
❑ Data entered into MIDAS
❑ Total time usually 3-4 hours for ID pharmacist and MD
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This material has been used in the course of internal quality improvement pursuant to the Medical Studies Act, 735 ILCS 5/8-2105.
Handshake Antimicrobial Stewardship (HAMS)July 2018- May 2019
5006 pediatric admissions
1233 (25%) unique patients reviewed
2869 antimicrobial courses reviewed
851 interventions made
87%
ACCEPTED
Days of Therapy DOT
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Broad Spectrum Days of Therapy
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Good Catches and Wins
❑ Patient with Pseudomonas growing in culture not receiving anti
pseudomonal therapy
❑ NBN using outdated order set for newborn sepsis with 48 hours of empiric
antibiotics, antibiotic dosing not updated
❑ CNS culture thought to be final negative and antibiotics were d/c but review
by AMS showed growth of pathogen
❑ NICU patient going to surgery but inappropriate surgical prophylaxis
ordered, correct antibiotics given prior to procedure
❑ Oseltamivir continued in critically ill patient with rapid flu negative, PCR
positive for flu
❑ Anaerobic culture bottles not being used in older patients > 12 y as is
consistent with ACH policy
❑ Residents are calling AMS Team to discuss empiric antibiotics before they
are started!!!
Diagnostic Stewardship
35
https://apps.who.int/iris/bitstream/handle/10665/251553/WHO-DGO-AMR-2016.3-
eng.pdf;jsessionid=8826AA007860D7394EF177ABD7E9501F?sequence=1
Diagnostic Stewardship
❑ Positive tests when pretest likelihood of infection of low are confusing!
▪ False positives, colonization ➔ unnecessary antibiotic use
▪ Underuse and overuse of testing can lead to incorrect diagnoses and inappropriate treatment
❑ Aims
❑ Improve clinical care
❑ Reduce false positives
❑ Less overdiagnosis, unnecessary antibiotic use, shorter lengths of stay
36
Diagnostic Stewardship
❑ Definition: Modifying the process of ordering,
performing and reporting diagnostic tests to improve
the treatment of infections and other conditions.
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Diagnostic Stewardship - Ordering
❑ Order tests with high pretest probability
▪ Urine – test only when symptoms suggest urinary tract infection
▪ CDI – recent antibiotic use, > 3 loose stools/d, duration >24
hours, no recent stool softeners, avoid tests of cure
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Diagnostic Stewardship - Collection
❑ Sample collection, transport to avoid contamination
▪ Periurethral cleansing before midstream urine
▪ Avoid blood draws from indwelling lines
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Diagnostic Stewardship - Reporting
❑ Report results in a format that guides appropriate practice
❑ Comments with result
❑ “Multiple organisms indicating likely contamination”
❑ “No pyuria, culture not performed”
❑ “Toxin negative, PCR positive – indicating possible colonization rather than disease”
❑ Selective reporting of antibiotic susceptibilities
❑ Display preferred antibiotics
❑ Cascade reporting
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Rapid Diagnostics
❑ Molecular testing
❑ Under the diagnostic stewardship umbrella
❑ Goal of appropriate, timely therapy
❑ Opportunity for ASP and microbiology to work together
41
Bloodstream Infections (BSI)
❑High rates of morbidity and mortality
❑Delays in antimicrobial therapy result in poor clinical outcomes
❑Traditional organism identification methods are time-consuming
Kothari A, et al. Clin Infect Dis. 2014;59(2):272-278.Kumar A, et al. Crit Care Med 2006;34:1589-1596.
MALDI-TOF MS
❑ Matrix assisted laser desorption/ionization time of
flight utilizes mass spectrometry to rapidly and
accurately identify isolated organisms
▪ Reduces time to identification by 1.2-1.5 days
▪ Combined with antimicrobial stewardship interventions
demonstrates improved clinical and financial outcomes
Time to optimal therapy
Blood cultures analyzed via BacT/ALERT Microbial
Detection System (bioMérieux, Durham, NC)
Positive cultures evaluated every 2 hours; gram stain
performed if positive
Positive gram stain results reported in
CareConnection and called to RN
MALDI-TOF performed, pharmacist paged with
result and provides prospective antimicrobial
stewardship recommendations to
provider 24/7
Guidelines for the management of patients with
positive blood cultures developed
Beganovic M, et al. J Clin Microbiol
2017;55:1437-1445.
Microbiology Workflow with real-time AMS response
MALDI-TOF Intervention Project--Results
❑ Improved time to optimal antimicrobial therapy in patients with positive blood cultures
❑ Time to microbiologic clearance, length of hospital stay, length of ICU stay improved with estimated cost savings of $6,000,000
❑ Program now in place at all Advocate sites
❑ 2500 patients impacted in 2018
67%
reduction
in
mortality
YOUCan Be an Antibiotic Steward
• You are seeing a 10yo male in your office. He has had persistent nasal drainage for 10 days. He had a fever for the first two days of illness, which seemed to resolve, however the fever has now returned. He is 102.5 in the office and has right-sided facial pain on exam. You diagnose him with acute sinusitis. He has no reported drug allergies. Which antibiotic do you recommend?
• Azithromycin
• Levofloxacin
• Clindamycin
• Amoxicillin-clavulanate
Case Vignette
48
• Approximately one half of
AOM and URIs are due to viral
etiologies
• The time course and
symptoms of viral and
infection etiologies are similar
• Antibiotics are not indicated in
all patients with AOM and URI
• Watchful waiting for 3 days is
appropriate for non severe
symptoms in most children in
order to make the correct
diagnosis
Upper Respiratory Infections
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AAP Guidelines – 2013
• High-dose amoxicillin 90 mg/kg/day divided q 12
– Exclusions
• Amoxicillin within 30 days
• Concurrent purulent conjunctivitis
• Penicillin allergy
• Use an antibiotic with β-lactamase coverage if
– Amoxicillin in the past 30 days
– Concurrent purulent conjunctivitis
– History of recurrent AOM unresponsive to amoxicillin
Recommendations for Treatment
AOM and Sinusitis
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Recommendations for Treatment
AOM and Sinusitis
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• You are seeing a 10yo male with acute sinusitis. He has no reported drug allergies. Which antibiotic do you prescribe?
1. Azithromycin
2. Levofloxacin
3. Clindamycin
4. Amoxicillin-clavulanate
• Antimicrobial therapy is warranted for children with sinusitis who either have a severe onset or a worsening course. For children with non-severe or persistent illness with ≥ 10 days of symptoms, either observation for an additional 3 days or antimicrobial therapy is indicated. When antibiotic therapy is indicated, amoxicillin alone or with clavulanate is preferred.
Case vignetteAnswer
53
• You are seeing a 3 yo vaccinated male in your office with a fever to 101.4 and cough. Physical exam is suggestive of pneumonia, and a CXR confirms a right lower lobe infiltrate. You diagnose bacterial pneumonia. Which of the following is true regarding outpatient antimicrobial recommendations for community acquired pneumonia in children?
1. Cefdinir has excellent activity against S. pneumoniae and is an appropriate choice as first line therapy
2. High dose amoxicillin (90 mg/kg/day) divided tid is the preferred first line treatment
3. Azithromycin can be used as first line for either bacterial or atypical infection because the once daily dosing is preferred for compliance
4. Amoxicillin-clavulanate is first line for bacterial pneumonia because amoxicillin is not broad enough
Case vignette
54
Community Acquired Pneumonia
• Viral causes of CAP are most common but are difficult to distinguish from bacterial
• S. pneumoniae is the most common bacterial etiology
• Broad spectrum but less effective antibiotics are often prescribed in favor of narrow spectrum agents
• Oral cephalosporins have short half lives, are poorly absorbed and are highly protein bound, resulting in poor serum concentrations
• Amoxicillin is superior to oral cephalosporins
• More frequent dosing of amoxicillin provides more killing time with potential for improved outcomes
55
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• You are seeing a 3 yo vaccinated male with bacterial
pneumonia. Which of the following is true:
1. Cefdinir has excellent activity against S. pneumoniae and is
an appropriate choice as first line therapy
2. High dose amoxicillin (90 mg/kg/day) divided tid is the
preferred first line treatment
3. Azithromycin can be used as first line for either bacterial or
atypical infection because the once daily dosing is preferred
for compliance
4. Amoxicillin-clavulanate is first line for bacterial pneumonia
because amoxicillin is not broad enough
Case vignetteAnswer
57
• S. pneumoniae remains the most common cause of CAP.
• Amoxicillin is superior to oral cephalosporins and is the drug of choice for S. pneumoniae.
• Oral cephalosporins have short half lives, are poorly absorbed and are highly protein bound, resulting in poor serum concentrations to provide effective killing.
• Amoxicillin reaches higher serum levels and is less protein bound, resulting in concentrations that produce effective killing, particularly when dosed at 90 mg/kg divided tid.
• Azithromycin has poor activity against S. pneumoniae and is not considered first line therapy. Amoxicillin-clavulanateis not indicated unless beta lactamase producing organisms are suspected such as H. influenzae or M. catarrhalis.
Case VignetteAnswer
58
Common Conditions - Pharyngitis
• ~20% of asymptomatic children can be colonized with GAS
• Clinical guidelines have been developed but are uncommonly applied when deciding who should be tested and receive antibiotics
• Sore throat plus 2 or more from below → Send RADT– Absence of cough
– Presence of tonsillar exudates/swelling
– Fever
– Presence of swollen/tender anterior cervical nodes
– Age 3-15
• Consistently applying guidelines, avoiding RADT in children with viral symptoms can prevent unnecessary antibiotics for strep carriers who have a viral infection
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Duration of Antibiotic Therapy
Less is More
Penicillin Allergy
61
Conclusions
• Improving antibiotic prescribing is a patient safety and
public health priority
• Antibiotic stewardship programs can optimize
antibiotic use, optimize the treatment of infections, and
reduce adverse events
• Growing antibiotic stewardship programs to the
outpatient setting is integral to improving prescribing
and reducing antibiotic resistance
• All medical providers can be antimicrobial stewards!!
62
Additional References
• Morgan DJ, Malani P, Diekema DJ. Diagnostic Stewardship—
Leveraging the Laboratory to Improve Antimicrobial Use. JAMA.
2017;318(7):607–608. doi:10.1001/jama.2017.8531
• https://www.cdc.gov/antibiotic-use/community/for-hcp/outpatient-
hcp/pediatric-treatment-rec.html
• CDC. Antibiotic Use in the United States, 2017:Progress and
Opportunities. Atlanta, GA: US Department of Health and Human
Services, CDC: 2017.
• https://apps.who.int/iris/bitstream/handle/10665/251553/WHO-DGO-
AMR-2016.3-
eng.pdf;jsessionid=8826AA007860D7394EF177ABD7E9501F?sequ
ence=1
Thank You!
Questions?
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