Great Plains Veterinary Educational Center Breakpoint Clinical Considerations Dee Griffin...

Great Plains Veterinary Educational CenterGreat Plains Veterinary Educational Center

Breakpoint Clinical Breakpoint Clinical ConsiderationsConsiderations

Dee Griffin

[email protected] http://gpvec.unl.edu


An An antibiotic breakpointantibiotic breakpoint is a maximum is a maximum MIC threshold for predicting successful MIC threshold for predicting successful

antibioticantibiotic therapy … therapy … During the antibiotic dosing interval, organisms with an MIC at or below this threshold are expected to be inhibited as a minimum expectation or, better still, to be killed. This applies only to the immunocompetent patient whose host defenses will then provide the necessary antibacterial activity to resolve the infection.


RESPIRATORY DISEASE RESPIRATORY DISEASE

This is where we start …This is where we start …


……


Cattle Cattle are are Prey Prey AnimalsAnimals

• It’s in their genetic heritage not to look sick

• Finding sick cattle early … is not in our genetic heritage


Seek & TreatSeek & Treat … Less Than Perfect … Less Than Perfect


ADG Pulled vs Not-PulledADG Pulled vs Not-Pulled

0.00

0.50

1.00

1.50

2.00

2.50

3.00

3.50

4.00

Replicate 1 Replicate 2

Ave

rage

Dai

ly G

ain

(lbs)

Pulled Not Pulled

P = .0054

P = .0128

2.86

3.413.28

3.85


Dealing With DiseaseDealing With Disease• Find Sick Cattle Early

Temp Day 1(Aug AM)

Ave = 105.0SD = 1.8

0.0

2.0

4.0

6.0

8.0

10.0

12.0

1 2 3 4 5 6 7 8 9 1 0 1 1 1 2 1 3 1 4 1 5 1 6 1 7 1 8 1 9 2 0 2 1 2 2

Appetite & Appetite & DepressionDepression


Respiratory DiseaseRespiratory Disease• Cost money …

• Cost performance …


Offal Data RecorderOffal Data RecorderNormal

Lung

Minor Purple

Major Purple

Minor Adhere

Major Adhere

Missing Lung

Green Eosin

Contam. Condemn Normal

Heart

Contam. Condemn

Epi-Para Carditis

Railed Out

Other .

NO

Pregnancy

RAILED OUT

Normal

Intestines

Contam. Condemn

Peritonitis Adhere

Ulcer Ruptured

Other .

Normal

Kidney

Sm White Spots

Large Spots

Rough Surface

Other .

Normal

Liver

Minor Abscess

Major Abscess

Flukes Liver

Telang Liver

Para Scars

Contam. Condemn

Other .

Trolley ID Animal ID

SubmitEDIT Cancel

YES

Active LN Condemned

Contam. Condemn


LungsLungs Lungs … MOST will NOT be associated with condemnation

Minor Adhesions Look Like … Spider Web Strands



Note the Skirt is adhered to the lung.



Note the Skirt is adhered to the lung.

Note: Lung was condemned … this is good evidence there was an active infection

(could also record as “Active LN”)

Note: Most of both sides are missing.


(could also record as “Active LN”) Note: Part of Lung is still in the chest




(could also record as “Active LN”)

Note: Young Lesions are Bloody


Stripped PluraStripped PluraSevScr Lesion PS+%

9 M3 75%

9 M3other 71%

9 P3 38%

9 M2 33%

10 Aall 33%

allM 30%

all3 29%

7 CC3 23%

18 P1&2+M 20%


Lung LesionsLung Lesions


Lung Lesions Cost PerformanceLung Lesions Cost Performance

0.00

1.00

2.00

3.00

4.00

Ave

rag

e D

aily

Gai

n (

lbs)

No Lesions Minor Lesions Major Lesions

3.52 a

3.40 a 2.77

b

3.92 ab 3.42

b 2.87 a

P = . 0245 P = . 0204

Buhman, NU-GPVEC 2001


Data from Different SourcesData from Different SourcesDescription ADG Marbling Ref

No Rx vs 2 RX - 0.37 ~ - 100 Missouri

No Rx vs 2 RX - 0.45 ~ - 100 Colorado

No Rx vs 2 RX - 0.35 - 34 JAVMA

Health vs Sick - 0.54 - 23 / -35 Texas

Health vs Sick - 0.46 --- Smith

Lung Lesions - 0.34 - 11 Bryant

Lung Lesions - 0.06 --- Bryant

Lung Active - 0.90 - 30 Bryant

Lung All/Severe - .06/30 - 31 / - 78 GPVEC


Dealing with Dealing with Respiratory DiseaseRespiratory Disease


Select appropriate high quality productsSelect appropriate high quality products

• Most commonly, BRD has a head start in high-stressed young commingled cattle.


Durable Cure & DARTDurable Cure & DART• The goal:

– 1) A first-time treated animal is more likely to become a high-performing, profitable animal ;

– 2) That animal stays with its group mates and does not suffer a disease relapse.

• D.A.R.T. – An acronym for four areas that MUST be thoroughly

assessed and monitored, – especially high stress or high risk of disease. – Depression, Appetite, Respiratory index & Temperature.


Durable Cure & DARTDurable Cure & DART• Depression is rated on four levels:

– Normal, mild, moderate and severe. – A normal animal is alert and moves with its group

mates. – Mild depression may include signs like droopy ears

or head, but the animal is easily stimulated into normal behavior.

– Moderate depression means an animal appears listless and acts sore. It responds to stimulation but does not behave like its group mates.

– An animal with severe depression is too weak to walk and looks close to dying.


Durable Cure & DARTDurable Cure & DART• Appetite:

– One of the first signs of many systemic diseases, such as respiratory, intestinal or severe reproductive infections can be loss of appetite.

– Animals are going off feed when they fail to show interest in feed.

– Watch your animal’s response to feed deliver. – If they do not appear interested something may be

wrong. – Try to catch animals before they have been off feed

long enough to lack fill and appear - gaunt.


Durable Cure & DARTDurable Cure & DART• Respiratory Index:

– An additional sign of many systemic diseases is an irregular breathing pattern.

– This is especially true if the animal is suffering from respiratory disease.

– Its respiratory rate can be accelerated, its effort to take breaths can be exaggerated, and the depth of its breaths can be noticeably different.

– Essentially, an animal's respiratory index is abnormal when its rate, depth and effort differ from those of its normal group mates.


Durable Cure & DARTDurable Cure & DART• Temperature:

– The normal temperature of a healthy cow or calf is approximately 102.5° F.

– The temperature can is influence not only by disease, but by the animal’s environment, housing, and temperament.

– Remember if appropriate; adjust your definition of normal temperature to account for these factors.


How Sick Cattle EatHow Sick Cattle Eat

• Pull any new calf that is slow to come to the bunk

• Look for sick cattle shortly after putting out feed.


Sick: Intake vs. TempSick: Intake vs. Temp

Intake & Temp Response To IBR ChallengeAdapted from Hutchenson, Cole & Mock 1985

0

5

10

15

20

25

30

35

-7 -5 -3 -2 -1 0 1 2 3 4 5 6 7 8 9 10

Intake

Temp


Subclinical AcidosisSubclinical Acidosis

3.5

4

4.5

5

5.5

6

6.5

7

8 10 12 14 16 18 20 22 24 2 4 6 8 10 12 14 16 18 20 22 24 2 4 6 8

Time

0

5

10

15

20

25

30

35

40

Feed

pH


Understand the Problem … Understand the Problem …

Diagnoses & Cause ?


Vets have a symbiotic relationship with NutsVets have a symbiotic relationship with Nuts

•Vets … Work with

MEDS

•Nuts … Work with

RATS

Very important to understand the relationship Very important to understand the relationship between cattle health and nutrition !!!between cattle health and nutrition !!!


Finding Sick Cattle Finding Sick Cattle

EarlyEarly… may be an … may be an

impossible jobimpossible job


Prevention … is key Prevention … is key Treatment salvages only part of the lossTreatment salvages only part of the loss

• Immune preparation

• Treatment timing


What You Need to Know &Think About What You Need to Know &Think About When Selecting AntibioticsWhen Selecting Antibiotics

The objective will be to help folks better understand:

1) how antibiotics work … clinically2) antibiotic classes … & what makes them different3) how to think through developing treatment protocols4) understand dose management & resistance

development5) how to select a proper antibiotic for different diseases6) how the other things given sick cattle can influence an

antibiotic's effectiveness7) how to know when to switch8) which antibiotic would make a better choice when a

switch is need if an animal doesn't respond9) when to quit 10) potential residue considerations & management


7 Antibiotic Use Myths7 Antibiotic Use Myths … Dr. Mike Apley… Dr. Mike Apley

1. Two antibiotics work twice as well as one2. You must give an IV to get a quick response3. If they have not responded to the first, switch to another4. Aggressive is good. If they don’t look better in 24 hours,

add the next drug in the rotation to the first treatment5. The hotter they are, the sicker they are, so make drug

choices based upon rectal temperature6. Adding supportive drugs will improve response7. Vaccination at time of treatment improves response


What happened?What happened?

… a look at the Sequence… a look at the Sequence

Example:Example:Respiratory SystemRespiratory System


Disease sequence of events:Disease sequence of events:• Susceptible animal exposed.

• Incubation is the period (time) from the first replication of the disease causing biological agent until sufficient compromise of the target organ(s) occurs causing loss of function of the target organ(s).

• Primary viral BRD this averages 3 days.

• Secondary bacterial BRD averages 3 to 5 days behind the initial viral infection.


Disease sequence of events:Disease sequence of events:• Inflammation occurs in stages. • Early, the body diverts white blood cells and

blood in to the affected area typically causing swelling of tissue, both cells and spaces between cells.

• As the inflammation continues, loss of function of the affected tissue occurs.

• Late stage of inflammation is involved in the body trying to clean up, remove, or repair / reconstruct the damaged tissue.

• The late stage of inflammation is the first stage of recovery. … begins 7 to 10 days … last for weeks


how the antibiotics workhow the antibiotics work

• Antibiotic – mold, 1928• Protect molds from bacteria• No effect on viruses or normal body cells• Two types -static (slows) & cidal (kills)• Four mechanisms

– Cripples cell wall– Interferes with protein synthesis– Confuses metabolic processes– Blocks DNA / RNA synthesis

• Different bacteria … require different mechanisms to stop them …


antibiotic resistance mechanisms antibiotic resistance mechanisms • Decrease Cell Wall Uptake / Perm

– Aminoglycosides• Efflux

– Macrolides, fluoroquinolones, tetracyclines• Enzymes Induced

– Aminoglycosides, florfenicol, beta-lactams• Altered Target Binding Sites

– Ribosome …macrolides, lincosamides– Wall Protein … beta-lactams, glycopeptides– DNA … fluoroquinolones

• Gene Resistance– Plasmids … b-lact, tetra, macro, linco, fluro,

sulfa– Transposons … beta-lactams, glycopeptides– Chromosome … beta-lactams, fluoroquinolones


Antimicrobial groups approved for cattle:

Antibiotic Class Antibiotic Within Class ResistanceMechanism Lipid Solubility ~ Protein

Binding %

Aminocyclitols Spectinomycin PS Low Low

Aminoglycosides Gentamicin, Neomycin PS Low 20-25%

Beta-lactams Penicillin G, Ampicillin, Ceftiofur CW Low P&A 20, Cef 80+

Chloramphenicol derivatives Florfenicol PS High 60

Fluoroquinolones Enrofloxacin, Danofloxacin GR High Low

Lincosamides Lincomycin PS High 55-75

Macrolides Erythromycin, Tilmicosin, Tylosin PS High 70-80

Sulfonamides Sulfa - dimethoxine, methazine, chlorpyridazine MP Low SM 70, SDM 80-85

Tetracyclines Oxytetracycline, Chlortetracycline PS Intermediate OTC 20-25, CTC 65

CW crippling production of the bacterial cell wall that protects the cell from the external environment

PS interfering with protein synthesis by binding to the machinery that builds proteins, amino acid by amino acid

MP wreaking havoc with metabolic processes, such as the synthesis of folic acid, that bacteria need to thrive

GR blocking genetic replication by interfering with synthesis of DNA and RNA


PK / PD RelationshipsPK / PD Relationships


Antibiotic MovementAntibiotic Movement


What Does This Mean? What Does This Mean?

What Value is This? What Value is This?


the different classes of antibiotics … the different classes of antibiotics … & … what makes them different& … what makes them different


Pen G Dose CurvesPen G Dose Curves


Ceftiofur Dose CurvesCeftiofur Dose Curves


Ceftiofur Sensitivity (VADS)Ceftiofur Sensitivity (VADS)P. multocida (498)

MIC Incidence Cumulative

0.5 99.20% 99.20%

1 0.40% 99.60%

2 0.20% 99.80%

4 0.00% 99.80%

8 0.00% 99.80%

16 0.20% 100.00%

M. haemolytica (481)


0.5 99.38% 99.38%

1 0.21% 99.58%

2 0.00% 99.58%

4 0.21% 99.79%

8 0.00% 99.79%

16 0.21% 100.00%


Ceftiofur Sensitivity (VADS)Ceftiofur Sensitivity (VADS)H. somni (208)


0.5 98.56% 98.56%

1 1.44% 100.00%

2 0.00% 100.00%

4 0.00% 100.00%

8 0.00% 100.00%

16 0.00% 100.00%

S. typhimurium (66)


0.5 75.76% 75.76%

1 21.21% 96.97%

2 1.52% 98.48%

4 0.00% 98.48%

8 0.00% 98.48%

16 1.52% 100.00%


Oxytet Dose CurvesOxytet Dose Curves


Oxytet Sensitivities (VADS)Oxytet Sensitivities (VADS)P. multocida (498)


0.25 15.46% 15.46%

0.5 30.52% 45.98%

1 10.44% 56.43%

2 3.01% 59.44%

4 1.41% 60.84%

8 2.81% 63.65%

16 36.35% 100.00%

M. haemolytica (481)


0.25 4.37% 4.37%

0.5 40.54% 44.91%

1 2.49% 47.40%

2 0.83% 48.23%

4 2.70% 50.94%

8 14.55% 65.49%

16 34.51% 100.00%


Oxytet Sensitivities (VADS)Oxytet Sensitivities (VADS)H. somni (208)


0.25 36.54% 36.54%

0.5 23.08% 59.62%

1 3.37% 62.98%

2 0.00% 62.98%

4 2.88% 65.87%

8 13.46% 79.33%

16 20.67% 100.00%

S. typhimurium (66)


0.25 0.00% 0.00%

0.5 1.52% 1.52%

1 0.00% 1.52%

2 13.64% 15.15%

4 3.03% 18.18%

8 0.00% 18.18%

16 81.82% 100.00%


Macrolide Dose CurvesMacrolide Dose Curves


why an antibiotic may seem to work on why an antibiotic may seem to work on some sets of cattle and not otherssome sets of cattle and not others

Source, Source, & SourceSource, Source, & Source

• BIGGEST FACTOR … TIMING!!!– How much of a head start ???

• Animal’s ability to help fight back

• Differences in bugs …

• Diagnosis ???


how the other things we give sick cattle how the other things we give sick cattle can influence an antibiotic's effectivenesscan influence an antibiotic's effectiveness

• The stress caused by some products does more damage than their benefit – Injection site irritation ???

– Restraint for IV injection … IV-ing ability

• Product interferes with antibiotic– Sulfa’s and folic acid (a “B” vitamin)


““May Help … What It Don’t Hurt”May Help … What It Don’t Hurt”


Injection Sites … New ConcernsInjection Sites … New Concerns


Knots aren’t BadKnots aren’t Bad


PTI (Post Treatment Interval) EconomicsPTI (Post Treatment Interval) Economics


PK & PD ComparedPK & PD Compared


Dose Price ComparedDose Price Compared


PTI Example PTI Example …… Draxxin Draxxin

Percent treatment Success, re-treatments &BRD associated chronic and mortalities.

Re - Treatments BRD

Success 1st 2nd 3rd C M

7 day 85.9 9.2 2.8 0.8 0.4 0.8

10 day 85.3 12.4 1.6 0 0 0.8

14 day 88.8 9.2 1.2 0 0.4 0.4

253 allocated in all treatment intervals … Non-BRD removals: 7 day (5), 10 (2), 14 (3)

Average daily gain mean and range in poundsAverage daily gain mean and range in pounds LS Mean Median Range

7 day 2.7 2.72 (-0.18 , 4.14)

10 day 2.72 2.73 (0.64 , 4.46)

14 day 2.55 2.57 (-0.79 , 4.14)


PTI Example PTI Example …… The deal is it changes the flowThe deal is it changes the flow

Cumulative 1st Re-Treatments

0

20

40

60

80

100

120

7

10

14


how to select a proper antibiotic for how to select a proper antibiotic for different diseases … will focus on BRDdifferent diseases … will focus on BRD

• Pneumonia … Ab penetration not as much of a problem early as late

• Bugs that live in cells … need Ab that crosses cell walls

• Animal’s that are over whelmed & can’t help the drug by fighting back … – cidal Ab may be better than static Ab

• Can’t defend the use of Pen G (especially LA Pen) & Sulfa in BRD Rx programs

• CAUTIONCAUTION – Generics … & AVOID Bathtub mixes

• Neomycin & Gentamicin … violate BQA & reason


how to know when to switchhow to know when to switch

• 1st … and very important … assess the “stress” effect of the Ab– gut fill, soreness, tissue temp, etc– don’t switch because of stress effect

• Monitor animal NOT temp!!!– Don’t let the thermometer do your thinking– Use temp to confirm your visual

assessment

• Give the Ab 48 hours … @ MIC 90


which antibiotic would make a better choice which antibiotic would make a better choice when you need to switch … poor responsewhen you need to switch … poor response

• Re-check the diagnosis … – & evaluate the treatment extras being used

• Use previous lab work … – animals that die may be the most valuable

• If the infection is winning … get meaner– Cidal Ab KILL bugs … good selection– Ab that penetrate … good selection– Ab that minimizes stress effect … may be good

• Have faith in the treatment plan … stick to it !


why an antibiotic may seem to work on why an antibiotic may seem to work on some sets of cattle and not otherssome sets of cattle and not others

• BIGGEST FACTOR … TIMING!!!– How much of a head start ???

• Animal’s ability to help fight back

• Differences in bugs …

• Diagnosis ???

• … When to Quit and Let Go


when to quitwhen to quit• Consider two things …

1) How long ago did the “stress” start ???• Auction market … days received + 3 days

2) How long have you been treating animal?

• … Quit when you win… temp down, gaining weight for 48 hours

• If 1 is over 21days & 2 is over 7days … QUITQUIT• If 2 is greater than 10 … QUITQUIT


when to quitwhen to quit

letting goletting go


http://gpvec.unl.eduhttp://gpvec.unl.edu


Food Animal Therapeutic Food Animal Therapeutic Management is Not Management is Not Complete Until The Complete Until The Residue Potential Is Residue Potential Is

Considered & ManagedConsidered & Managed


A Producers Guide for Judicious Use of Antimicrobials in CattleA Producers Guide for Judicious Use of Antimicrobials in Cattle (As Adopted by the NCBA.)(As Adopted by the NCBA.)

1. Prevent Problems: Emphasize appropriate husbandry and hygiene, routine health examinations, and vaccinations.2. Select and Use Antibiotics Carefully: Consult with your veterinarian on the selection and use of antibiotics. Have a

valid reason to use an antibiotic. Therapeutic alternatives should be considered prior to using antimicrobial therapy. 3. Avoid Using Antibiotics Important In Human Medicine As First Line Therapy: Avoid using as the first antibiotic those

medications that are important to treating strategic human or animal infections. 4. Use the Laboratory to Help You Select Antibiotics: Cultures and susceptibility test results should be used to aid in the

selection of antimicrobials, whenever possible. 5. Combination Antibiotic Therapy Is Discouraged Unless There Is Clear Evidence The Specific Practice Is Beneficial:

Select and dose an antibiotic to affect a cure. 6. Avoid Inappropriate Antibiotic Use: Confine therapeutic antimicrobial use to proven clinical indications, avoiding

inappropriate uses such as for viral infections without bacterial complication. 7. Treatment Programs Should Reflect Best Use Principles: Regimens for therapeutic antimicrobial use should be

optimized using current pharmacological information and principles. 8. Treat the Fewest Number of Animals Possible: Limit antibiotic use to sick or at risk animals. 9. Treat for the Recommended Time Period: To minimize the potential for bacteria to become resistant to

antimicrobials. 10. Avoid Environmental Contamination with Antibiotics: Steps should be taken to minimize antimicrobials reaching the

environment through spillage, contaminated ground run off or aerosolization.11. Keep Records of Antibiotic Use: Accurate records of treatment and outcome should be used to evaluate therapeutic

regimens and always follow proper withdrawal times.12. Follow Label Directions: Follow label instructions and never use antibiotics other than as labeled without a valid

veterinary prescription. 13. Extralabel Antibiotic Use Must follow FDA Regulations: Prescriptions, including extra label use of medications must

meet the Animal Medicinal Drug Use Clarification Act (AMDUCA) amendments to the Food, Drug, and Cosmetic Act and its regulations. This includes having a valid Veterinary-Client-Relationship.

14. Subtherapeutic Antibiotic Use Is Discouraged: Antibiotic use should be limited to prevent or control disease.


Antibiotic MRL (Tolerance)Antibiotic MRL (Tolerance)


Test to Reg. DifferencesTest to Reg. Differences• Note: From the USDA-FSIS Domestic

Residue Plan “Blue Book” page 10. “beta-lactams (quantitated as penicillin-G; penicillins and cephalosporins are not differentiated within this category). Therefore ceftiofur will be false positive and not differentiated from penicillin. (last publication released 2005)

• http://www.fsis.usda.gov/PDF/2005_Blue_Book_Vet_Drugs_%20Dom_Tables_1_thru_6B.pdf


Ben. Pen. Residue Potential Ben. Pen. Residue Potential


What can be done to protect our What can be done to protect our producers … & ourselves?producers … & ourselves?

• Use FAST (PHAST) before “high-Use FAST (PHAST) before “high-residue-risk” cattle are sold …residue-risk” cattle are sold …

• Will the test work “pre-harvest”?– Based on everything I know and have done

in my lab … it will work as well as LAST

• If the urine doesn’t inhibit the test … it is not likely tissue juices from the kidney will inhibit the test … a couple of potential exceptions …


Testing Urine Isn’t Tough …Testing Urine Isn’t Tough …


Antibiotic Residue Avoidance StrategyAntibiotic Residue Avoidance Strategy1. Identify all animals treated.2. Record all treatments: Date; animal’ ID; dose given; route of

administration; the person who administered the treatment; withdrawal time (WD).

3. Strictly follow label directions for product use.4. Use newer technology antibiotics when possible.

a. Reduce unwanted depot effect. Select low volume products when available.

b. Select generic medications and vaccines with EXTREME CAUTION. c. Avoid inferior products. They may cause performance loss or

damage quality.5. Select with short WD when antibiotic choice is equivalent.6. Never give more than 10 cc per IM injection site.7. Avoid Extra Label Drug Use (ELDU) of antibiotics.

a. Use label dose and route of administration.8. Avoid using multiple antibiotics at the same time.9. Don’t mix antibiotics in the same syringe, especially if given IM

or Sub-Q.


Antibiotic Residue Avoidance StrategyAntibiotic Residue Avoidance Strategy10. Check ALL medication/treatment records before marketing:

a. Don’t market cattle with less than 60 WD without examining the treatment history.

b. Extend the WD time if the route or location of administration is altered.

1. Example; the WD for ear route of administration ceftiofur will be over 120 days if given SQ in the neck.

2. Example; tissue irritation will cause the WD for Banamine to be over 30 days if given IM or Sub-Q instead of IV.

c. Extend the withdrawal time for multiple medications given by summing their label recommended WD.

1. Example; if the 1st medication has a 10 day WD and the 2nd medication has a 28 day WD, assign a 38 day. WD.

2. Example; if 1st medication has a 10 day WD and is repeated in three days, assign a 20 day WD.


Antibiotic Residue Avoidance StrategyAntibiotic Residue Avoidance Strategyd. Extend the WD for all penicillin given at doses which exceed the

label dose1. Example; the WD for Procaine Pen G given at 3 CC per CWT IM or Sub-Q

is over 30 days 2. Example; the WD for Procaine Pen G given at 4 CC per CWT IM or Sub-Q

is over 30 days 3. Example; the WD for Long Acting Pen G given at 3 CC per CWT IM or

Sub-Q is over 120 days 4. Example; the WD for Long Acting Pen G given at 4 CC per CWT IM or

Sub-Q is over 180 days 1. Testing urine test may not detect injection site residues and will test

positive by the USDA-FSIS.e. Never inject gentamicin or neomycin. The estimated WD is over

24 months 1. Testing urine test may not detect a kidney that will test positive by the

USDA-FSIS.


Antibiotic Residue Avoidance StrategyAntibiotic Residue Avoidance Strategyf. USDA-FSIS. Don’t market cattle with suspected liver or kidney

damage without examining the treatment history.g. Don’t market cattle with antibiotic injection site knots without

examining the treatment history.h. Screen the urine for antibiotics of all cattle identified in steps a-

d above. It is best to use broad spectrum microbial inhibition test such as the Pre-Harvest Antibiotic Screening Test (PHAST), a microbial growth inhibition test which uses B. megaterium as the test organism. Test sensitivity relative to FDA-CVM violative residue tolerances (Maximum Residue Limit or MRL)


Save a Cow …

Eat a Vegetarian

Good Luck To YouGood Luck To [email protected] http://gpvec.unl.edu


Thanks for having me … & Thanks for having me … & we would love to have you come see us…we would love to have you come see us…

...where agriculture & all it’s people

make a difference


The Ear Is A Busy PlaceThe Ear Is A Busy Place


Comparison of two drugs for treatment of a Comparison of two drugs for treatment of a gram-negative bacterial infectiongram-negative bacterial infection

• Drug A- fluoroquinolone; – Cmax: 6 mg/L … T1/2: 4 hr … 24 hr AUC: 70 mg-hr/L– MIC90: 2 mg/L

• Drug B: cephalosporin; – Cmax: 32 mg/L … T1/2: 2 hr … 24 hr AUC: 27 mg-hr/L– MIC90: 4 mg/L

• Which is the “better” drug?– Fluoroquinolone: 24 hr AUC:MIC90 = 70/2 = 35– Cephalosporin: %T>MIC90 = 6 hr/8 hr interval = 75%

• Therefore, in this case …– cephalosporin is superior to the quinolone


Comparing Antimicrobial Activity In VivoComparing Antimicrobial Activity In Vivo

• Comparing MICs– Assumes similar pharmacokinetics– Assumes similar pharmacodynamics

• (apples vs. oranges)

• Comparing MICs vs. “breakpoints”– Crude estimates– Assumes higher breakpoint/MIC ratio is better

• Comparing PK/PD measures


Establishing MIC BreakpointsEstablishing MIC Breakpoints

• Breakpoint established arbitrarily =>• Drug used clinically =>• Breakpoint revised• Appropriate PK/PD identified for class =>• Magnitude of PK/PD for efficacy established

=>• Antibiotic PK profile measured =>• Breakpoint revised


Building ResistanceBuilding Resistance


Antimicrobial Model Antimicrobial Model • Successful treatment of infection involves the

interactions of host, drug and bacteria

Host Drug

Bacteria s

PharmacokineticsTissue penetration

• Susceptibility of pathogens• PK/PD relationship

• PAE• Killing rate• Other metrics

Immune system

?

??

?

• The factors not being considered may represent potential limitations.


Appropriate Pharmacokinetic/Pharmacodynamic Appropriate Pharmacokinetic/Pharmacodynamic Measures to Assess Antimicrobial Activity In VivoMeasures to Assess Antimicrobial Activity In Vivo

Drug Conc -Cidal Activity PAE PK/PD

Measures

Beta-lactam Fixed Minimal T>MIC

Macrolide Fixed Some T>MIC

Azalide Fixed Longer AUC:MIC

Aminoglycoside Linear Some AUC:MIC


Please know, Please know, We take our responsibility We take our responsibility to use antibiotics properly to use antibiotics properly

very seriously …very seriously …

Great Plains Veterinary Educational Center Breakpoint Clinical Considerations Dee Griffin...

Documents

Transcript of Great Plains Veterinary Educational Center Breakpoint Clinical Considerations Dee Griffin...