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Antimicrobial Stewardship and Applications to Common Infections
1. Justin Kosar BSc., BSP
Lead – Antimicrobial Stewardship Pharmacist
Saskatoon Health Region
Lynette Kosar BSP, MSc
RxFiles Academic Detailing Program
PAS Conference May 2017
2. Objectives
• To understand the importance of antimicrobial
stewardship in everyday practice.
• To identify patients who could benefit from the
application of antimicrobial stewardship principles.
• To communicate why antibiotics may not be required
or the importance of using narrow spectrum first line
antibiotics for treating common infections to patients,
caregivers & prescribers.
3. To understandtheimportanceofantimicrobial
stewardshipineverydaypractice
• Antibiotics are overused particularly when
compared to other parts of Canada
• Particularly high usage in Saskatchewan!!
• Drug development is limited
• Resistance at a local, national and international
level will create real and lasting effects on the
ability to treat infections.
8. •Methicillin resistant Staphylococcus aureus (MRSA)
•Vancomycin resistant enterococci (VRE)
•MDR and extremely drug resistant (XDR) Tuberculosis
•Carbapenemase producing Enterobacteriaceae (CPE’s)
Examples:
•Klebsiella pneumoniae carbapenemases (KPC)
•New Delhi metallo-β-lactamase-1 (NDM-1)
Resistant organisms result in increased morbidity,
mortality and increased healthcare costs
SHEA et al. Infect Control Hosp Epidemiol. 2012;33(4):322-7.
Rising Antimicrobial Resistance
9. Map of NDM-1-positiveseepage(green)
and tap water(red) samplesin New Delhi
• Example of widespread
environmental reservoirs of
NDM-1 in India
• NDM-1 now endemic within
India and it is possible to
acquire NDM-1 outside of
hospitals
• At this point, it will be very
difficult to contain spread of
NDM-1
• Highlights the urgent need
to prevent emergence of
resistance
Slide credit: Public Health Ontario – ASP 101 – 2014 presentation
10. Antibiotics are not benign …
Clostridium difficile infection risk:
Largest risk compared to no antibiotics
• Clindamycin - OR 16.8 (7.5 - 37.8)
• Fluoroquinolones - OR 5.5 (4.3 - 7.1)
Lower association with
• Macrolides - OR 2.6 (1.9 - 3.6)
• Penicillin -OR 2.7 (1.8 - 4.2)
• Sulfonamides/Trimethoprim - OR 1.8 (1.3 - 2.4)
• No effect noted with tetracyclines - OR 0.9 (0.6 - 1.4)
Antimicrobial Agents and Chemotherapy 2013 (57; 5): 2326–32
11. Antibiotic: Potential harms
Common adverse effects
• Diarrhea
• Abdominal pain
• Nausea and vomiting
• Yeast infection
• Amoxicillin or Amox/clav vs. placebo NNH = 23
Rarer but increased severity
• Stevens Johnson Syndrome, TENS, other skin reactions,
photosensitivity etc.
• Possible QT prolongation (macrolides, fluoroquinolones)
• Increased risk for tendon rupture with fluoroquinolone
exposure
• Hyperkalemia induced complications – ACEi/ARBs with
TMP/SMX
12. An Evolving Antibiotic Mantra…
“Shorter is Better”
• NO evidence that taking antibiotics beyond the point at which a
patient’s symptoms are resolved reduces antibiotic resistance
• Longer than necessary courses of therapy result in MORE emergence of
antibiotic resistance
• In some cases, all that is achieved by treating an infection with
antibiotics for longer than the patient has symptoms is increased
selective pressure driving antibiotic resistance among our colonizing
microbial flora
• We should replace the old dogma of continuing therapy past resolution
of symptoms with a new, evidence-based dogma of “shorter is better”
Spellberg B. JAMA 2016
15. CASE 1
Mr. CAPpronzacki
A 70 year old man with T2DM and dyslipidemia presents to your pharmacy with a
prescription for moxifloxacin 400mg po daily for 10 days.
He describes a three day history of fever, dyspnea and productive cough with
yellow-green sputum.
NO recent antibiotics NO recent travel and NO pets
NO sick contacts Influenza vaccination received this year.
Current medications include metformin and atorvastatin.
He has a previous reaction to ciprofloxacin which necessitated discontinuation.
He is an ex-smoker, quit approximately 10 years ago and rarely consumes alcohol. He
does not use recreational drugs.
16. Pre-treatment stewardship
points to consider …
• While NP swabs and cultures are not immediately
available, review can an allow for earlier antibiotic
stopping or switching if necessary
• Review medication profiles to see if antibiotics
associated with higher S.pneumoniae resistance
have been prescribed – consider switching to
another agent
17. Diagnose
community-acquired
pneumonia (CAP)
Risk stratify based on clinical judgment
AND
objective scoring tool
Scoring Tool Advantages Disadvantages
CURB-65 • Ease of use, well-validated
• Faster than PSI
• Equal sensitivity to PSI
• Higher specificity than PSI
• Does not directly assess
underlying disease
• Requires bloodwork (ie.
urea)
CRB-65 • Ease of use, well-validated
• Faster than PSI
• Does not requires urea
• Does not directly assess
underlying disease
Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the
management of community-acquired pneumonia in adults.
Clin Infect Dis 2007; 44:S27-72.
Lim WS, van der Eerden MM, Laing R, et al. Defining community acquired pneumonia severity on presentation to hospital: an international derivation
and validation study. Thorax 2003; 58: 377-82.
18. Diagnosis of
community-
acquired
pneumonia
(CAP)
Risk stratify based
on clinical
judgment
Objective Scoring
Tool CRB-65
AND
Confusion
Respiratory rate >
30 breaths/min
SBP < 90 mmHg
or dBP < 50
mmHg
Age > 65 years
Assign 1 point for each:
Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the
management of community-acquired pneumonia in adults.
Clin Infect Dis 2007; 44:S27-72.
Lim WS, van der Eerden MM, Laing R, et al. Defining community acquired pneumonia severity on presentation to hospital: an international
derivation and validation study. Thorax 2003; 58: 377-82.
19. 0 points
Low Risk
30d mortality =
1.2%
1-2 points
Intermediate
Risk
30d mortality =
8.2%
3-4 points
High Risk
30d mortality =
31%
OUTPATIENT
Respiratory viruses
Streptococcus pneumoniae
Haemophilus influenzae
INPATIENT
(or close outpatient monitoring)
Respiratory viruses
Streptococcus pneumoniae
Haemophilus influenzae
Legionella spp.
ICU
(or observation unit)
Respiratory viruses
Streptococcus pneumoniae
Haemophilus influenzae
Legionella spp.
Staphylococcus aureus
Gram-negative bacilli
Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the
management of community-acquired pneumonia in adults.
Clin Infect Dis 2007; 44:S27-72.
Lim WS, van der Eerden MM, Laing R, et al. Defining community acquired pneumonia severity on presentation to hospital: an international derivation
and validation study. Thorax 2003; 58: 377-82.
23. When is coveragefor atypicalpathogensneeded?
• Atypicals are thought to represent approximately 15% of CAP and
may be more common some populations
• M. pneumoniae in young, otherwise healthy adults – although
typically also self resolving without antibiotics
• C. pneumoniae in:
• LTC residents
• Immunocompromised
• Multiple comorbidities
• However – an acute onset of C. pneumoniae is less likely
• Listeria sp. – in returning travellers – usually present as non-CAP
• If no atypical coverage is initiated empirically – MAY consider
adding atypical coverage if patients symptoms do not improve in 3-
5 days or if symptoms worsen
24. Do we always need to cover
atypicals?
Bottom Line: For patients with suspected or proven
community acquired pneumonia requiring ward
hospitalization (CURB-65 score 1-2), a beta-lactam
monotherapy strategy was non-inferior to a beta-
lactam plus macrolide combination strategy and
fluoroquinolone strategy.
Postma DF, van Werkhoven CH, van Elden LJR, et al. Antibiotic treatment strategies for community-acquired pneumonia in
adults. N Engl J Med 2003; 372:1312-23.
25. Management considerations
DURATION OF TREATMENT
• Treat for a minimum of 5 days and afebrile for at
least 48 hours
• Meta-analyses (15 RCTs n=2,796; 5 RCTs
n=1,303) compared treatment durations of > 7
days vs. ≤ 7 days
• NO DIFFERENCE in clinical success rates in
ambulatory patients.
27. BACK TO OUR CASE
Point ….
- Covers atypical organisms
- Easy once daily admin.
- Short course therapy
Counterpoint …
- Often don’t require atypical
coverage in uncomplicated CAP
- Lower coverage for typical
pathogens
- BID admin for other options
- Overly broad spectrum
- ? Resistance promotion
- Also short course (e.g. doxy)
• You contact the prescriber,
advising them of the previous
fluoroquinolone allergy and
suggest a different therapy.
• He prescribes Azithromycin
500mg x 1 then 250mg po
daily x 4 days.
• What do you do????
28. Having the talk …
You state that you would
recommend something
narrower for a couple of
reasons.
1) Most likely pathogen is
Streptococcus
pneumoniae given his
symptomology
2) Mr. K is otherwise an
uncomplicated CAP with a
CRB65 score of 0 and
should be trialed with a
more narrow spectrum
agent.
The prescribing physician
takes your call but still
wonders what you have
against azithromycin.
1) His symptoms are keeping
him from activity and he
wants to get better
quickly – I want a “big
gun” to cover all
possibilities.
2) Tell me more about this
ranking system???
3) Amoxicillin – that’s not
strong enough.
29. CAP - Clinical Pearls
• S. pneumoniae remains most common bacteria for CAP even
in patients with comorbidities
• Rapid viral testing for respiratory pathogens can reduce the
use of inappropriate antibiotics – check/ask about testing
• Atypical coverage is not always necessary
• Fluoroquinolones should be reserved for patients with true
beta lactam allergies AND ideally medical comorbidities
• Five to seven days of therapy is likely sufficient for out-patient
management of CAP
30. Objection:
I want a “big gun” to get rid of my patients symptoms.
Response:
Every antibiotic when used appropriately is a “big gun”. As for the
patient the most likely causative organisms for pneumonia is still
Streptococcus pneumoniae – and it has better sensitivity to amoxicillin
than a macrolide.
Objection:
I would like to cover for atypicals as well.
Response:
Strep. pneumoniae accounts for up to 50% of CAP (due to bacteria). As
the patient is quite stable how would you feel about trialing amoxicillin
to see if they get better over the next couple of days?
Objection:
I wanted to give the patient amoxicillin but they insisted on wanting
azithromycin because amoxicillin didn’t work last time.
Response:
Perhaps they were having a viral illness. I think that with the patient still
being stable we should trial amoxicillin. I’d be happy to speak to them
about why this antibiotic is appropriate.
32. • 15 year-old boy with acute sore throat
• Mother is very upset:
● the locum who is filling in for her regular physician
wouldn’t prescribe an antibiotic, & instead took a throat
swab
● it’s Friday; swab won’t be processed until next week
● she shows you her son’s throat, & says, “Look at all that
pus! It’s clearly a bacterial infection.”
● great-uncle had acute rheumatic fever due to strep throat
● she asks you to recommend another physician… one that
will prescriber an antibiotic
WHAT DO YOU DO?
The case of the Friday night sore
throat ….
33.
34. Digging deeper…
Her son had an acute onset of his symptoms last night
• oral temperature of 38.5 °C
• no cough
• swollen cervical nodes
• tonsillar exudate can be appreciated
• no allergies to medications
• no medications have been tried for symptom
management
• still able to eat and drink without difficulty and has no
other concerns other than an acutely sore throat.
Modified Centor score = 4
35. Antibiotics and pharyngitis
• The real culprit:
• 80-90% of adults DO NOT require antibiotics as infection likely due to
viruses
• Why you don’t need to treat right away …
• Turn around time for throat swabs may take up to a few days.
Antibiotics started within 9 days of symptom onset will prevent
rheumatic fever
• When to treat:
• Patients who qualify for throat swab with symptoms AND return
positive should receive an antibiotic
• If antibiotics are started empirically – ensure the agent is
discontinued if throat swab is negative.
• Symptom management remains key to helping in any case (viral
or bacterial)
38. Friday night cont’d. – What
would do you do??
• Acknowledge son does look unwell. Provide reassurance and
education that you agree with the locum.
• While the patient has a positive Centor score – the watchful
waiting approach is still valid.
• Centor score 4 = 50% chance of Group A Strep – BUT … also a
50% chance of not (e.g. viral illness)
• Risk of complications is low and can be mitigated up to 9 days
post symptom onset of actual bacterial infection
• REMEMBER – even a positive swab only detects for presence
of Group A strep – NOT symptoms.
• Recommend ibuprofen for the throat pain, throat lozenges,
warm liquids, and lots of rest.
39.
40.
41. Keys to stewardship success – providers
• Be informed
• Access local antibiograms for objective data on resistance patterns
• Refresh your antibiotic knowledge on a regular basis (RxFiles, CE’s etc.) –
if you don’t use it you loose it.
• Follow up on patient culture results when you think you can make a
difference.
• Ask about symptoms – its easier to speak to prescribers when you have a
full understanding of the patients symptoms and timelines.
• Use common references to bacterial spectrum of activity and relevant
PK/PD
• Ask about role of diagnostics – have you done an x-ray? swab ?
• Be clear on your recommendations
• Have a plan for an alternate therapy or substantiate why no therapy is
required – both to patients and providers
• Be honest
• If you don’t understand something around testing/diagnosis – ask the
prescriber – the best decisions are the ones made through collaboration.
42. Keys to stewardship success – patients
• Be clear on your reasons for your recommendations
• Show them scoring tools (e.g. Center score) on which you’re basing
your conclusions
• Ask the right questions
• Listen to the timeline of events and other accompanying
symptoms
• Ask about symptoms (presence or absence)
• Use antibiograms as another tool.
• Dispel myths
• Allergies versus intolerances
• Predisposition to allergic conditions is inherited NOT the specific
allergies.
