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
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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
❑ “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
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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
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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
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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!!
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Additional References
• Morgan DJ, Malani P, Diekema DJ. Diagnostic Stewardship—
Leveraging the Laboratory to Improve Antimicrobial Use. JAMA.