when your antibiotic choice makes a difference · when your antibiotic choice makes a difference...
TRANSCRIPT
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When Your Antibiotic Choice Makes a Difference
First
What are veterinarians being
asked to do?
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What is “Stewardship”?
2. Is there a non‐antibiotic alternative which will appropriately prevent, control, or treat this disease challenge?
3. Selection of an antibiotic which has been demonstrated to be safe and effective for this purpose
4. Assuring use of the antibiotic as shown to be safe and effective
Yes…
1. Responsibility for appropriate diagnostics and establishment of an accurate and functional case definition
5. Is this antibiotic intervention still necessary?
While…
A difference in treatment outcome based on treating or not treating?
A difference in treatment outcome based on treating with one drug vs. another?
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AnimalDisease Outcome
DiseasePathogen
Location
Antimicrobials
Anti-inflammatory?
diffusionpHions
proteinsbiofilms
susceptibility
virulence
inoculum
age
other disease
genetics
Therapy
total vs. free?
pharmacokineticsregimen
pharmacodynamics
Physiological state
Husbandry
Immunity
diagnostics
case definition
Progression
nutrition
environment
stress
biosecurity
body temperature
hydration
acid/base
production level
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32.1%
53.6%
66.9%
85.9%
0.0% 10.0% 20.0% 30.0% 40.0% 50.0% 60.0% 70.0% 80.0% 90.0% 100.0%
CCFA Strep Zoo
CCFA all cases
Treated
Control
Treatment successes
Treatment successes Failures
Failures
Horses treated with ceftiofur crystalline free acid (CCFA, Excede®), either all cases treated, or the subset of all cases positive for Streptococcus equi subspecies zooepidemicus (Strep Zoo)
Does CCFA work as well in the Strep Zoo (+) cases as in all cases?
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0% 100%
Clinical success rate according to protocol criteria
(-)
(+) 75%
25%
FailureSuccess Difference attributable to therapy
ARR (Attributable Reduction in Risk) = 75% - 25% = 50%
NNT (Number Needed to Treat*) = 100% / 50% = 2*to make a difference in one animal according to the protocol criteria
32.1%
53.6%
66.9%
85.9%
0.0% 10.0% 20.0% 30.0% 40.0% 50.0% 60.0% 70.0% 80.0% 90.0% 100.0%
CCFA Strep Zoo
CCFA all cases
Treated
Control
All cases: ARR is 86% - 54% = 32%, NNT is 100%/32% = 3
Strep Zoo (+) subset: ARR is 67% - 32% = 35%, NNT is 100%/35% = 3
Treated successes
Treated successes
Untreated control successes
Untreated control successes
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32.1%
53.6%
66.9%
85.9%
0.0% 10.0% 20.0% 30.0% 40.0% 50.0% 60.0% 70.0% 80.0% 90.0% 100.0%
CCFA Strep Zoo
CCFA all cases
Treated
Control
Failures in both groups
Failures in both groups
Difference due to CCFA
Difference due to CCFA
Untreated control successes
Untreated control successes
Treated successes
Treated successes
The difference due to the drug (NNT) is the same in the overall group of cases and in the Strep zoo (+) subset. The difference in treatment success is due to the decrease in untreated control success.
Why not just focus on % reduction in failures?• The NNT tells us the actual difference in clinical
outcome due to administering a specific drug regimen in a population of animals with thisdisease.
• The NNT not only reflects the drug efficacy, it also reflects the self cure rate of the population with this disease and the stated criteria for declaring an animal diseased and cured. Note: The cure rate is based on criteria we set, which are
applied equally to the treated and untreated groups.
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DeDonder KD, Apley MD. A review of the expected effects of antimicirobials in bovine respiratory disease treatment and control using outcomes from published randomized clinical trials with negative controls. Vet Clin North Am Food Animal Practice 31 (2015) 97-111
Treatment Success: Controls vs. Treated
Median = 24%
Median = 71%
Median NNT = 2
Median
Upper Quartile
Lower Quartile
Maximum value (excluding outliers
Minimum value (excluding outliers
N = 31 trials
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Mortality: Controls vs. Treated
Median = 17%
Median = 1%
Median NNT = 6N = 25 trials
Morbidity After Treatment for Control of BRD: Controls vs. Treated
Median = 48%
Median = 22%
Median NNT = 5N = 18 trials
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AnimalDisease Outcome
DiseasePathogen
Location
Antimicrobials
Anti-inflammatory?
diffusionpHions
proteinsbiofilms
susceptibility
virulence
inoculum
age
other disease
genetics
Therapy
total vs. free?
pharmacokineticsregimen
pharmacodynamics
Physiological state
Husbandry
Immunity
diagnostics
case definition
Progression
nutrition
environment
stress
biosecurity
body temperature
hydration
acid/base
production level
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Tul Comp ARR NNT
61.8% 32.2% 29.6% 3
81.9% 72.0% 9.9% 10
80.3% 62.8% 17.5% 6
92.9% 77.7% 15.2% 7
67.1% 32.0% 35.1% 3
Median 6
51.0% 25.0% 26.0% 4
53.2% 23.2% 30.0% 3
79.4% 63.6% 15.8% 6
76.5% 53.0% 23.5% 4
73.0% 67.0% 6.0% 17
77.6% 60.6% 17.0% 6
76.5% 43.1% 33.4% 3
87.9% 70.2% 17.7% 6
80.0% 62.5% 17.5% 6
87.8% 74.7% 13.1% 8
Median 6
Tul Comp ARR NNT
0.0% 0.8% 0.8% 125
0.4% 0.8% 0.4% 250
0.8% 1.2% 0.4% 250
0.3% 1.9% 1.6% 63
3.4% 13.6% 10.2% 10
Median 125
6.0% 21.0% 15.0% 7
1.1% 5.1% 4.0% 25
1.0% 0.0% 1.0% 100
0.9% 3.4% 2.5% 40
0.0% 1.0% 1.0% 100
0.0% 3.2% 3.2% 31
0.9% 3.2% 2.3% 43
0.0% 0.0% 0.0% Inf
2.5% 2.5% 0.0% inf
5.6% 10.8% 5.2% 19
Median 42
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N = 98 trials
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Resistance??
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Kansas State Diagnostic Lab isolates
Kansas State Diagnostic Lab isolates
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Kansas State Diagnostic Lab isolates
Kansas State Diagnostic Lab isolates
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Kansas State Diagnostic Lab isolates
Kansas State Diagnostic Lab isolates
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Kansas State Diagnostic Lab isolates
Kansas State Diagnostic Lab isolates
Tulathromycin % MIC by Year
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Individual Susceptibility Data
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
2009 2010 2011 2012 2013
Percent of Isolates ‐Su
sceptible
Oxytetracycline
Tilmicosin
Enrofloxacin
Spectinomycin
Ceftiofur
Florfenicol
0%
10%
20%
30%
40%
50%
60%
0 1 2 3 4 5 6
Percent of Isolates for Given Year
Number of Resistant Interpretations per Individual Isolate
2009 (55)
2010 (155)
2011 (179)
2012 (160)
2013 (240)
Pan‐Susceptible
Multidrug Resistant