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%

15

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

21

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

23

Antimicrobial Stewardship Assistance

Program - ASAP

24

Antimicrobial Stewardship Assistance

Program - ASAP

25

Handshake Stewardship

26

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

27

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

30

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

32

Broad Spectrum Days of Therapy

33

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.

37

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

38

Diagnostic Stewardship - Collection

❑ Sample collection, transport to avoid contamination

▪ Periurethral cleansing before midstream urine

▪ Avoid blood draws from indwelling lines

39

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

40

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

49

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

51

Recommendations for Treatment

AOM and Sinusitis

52

• 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

56

• 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

59

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?

64

65