1. Breakpoint Clinical Considerations
Dee Griffin

2. An antibiotic breakpoint is a maximum MIC threshold for predicting successful antibiotic 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.

3. RESPIRATORY DISEASE
This is where we start …

4. …

5. Cattle are Prey Animals
It’s in their genetic heritage not to look sick
Finding sick cattle early … is not in our genetic heritage

6. Seek & Treat … Less Than Perfect

7. ADG Pulled vs Not-Pulled

8. Dealing With Disease
Find Sick Cattle Early
Appetite & Depression

9. Respiratory Disease
Cost money …
Cost performance …

10. Offal Data Recorder Normal NO Submit EDIT Cancel YES Lung Minor Purple
Major Purple
Minor Adhere
Major Adhere
Missing Lung
Green Eosin
Contam. Condemn
Heart
Epi-Para Carditis
Railed Out
Other NO
Pregnancy
RAILED OUT
Intestines
Peritonitis Adhere
Ulcer Ruptured
Kidney
Sm White Spots
Large Spots
Rough Surface
Liver
Minor Abscess
Major Abscess
Flukes Liver
Telang Liver
Para Scars
Trolley ID
Animal ID
Submit
EDIT
Cancel
YES
Active LN Condemned
Offal Data Recorder
Contam. Condemn
Offal Inspection – Viscera Defect Recorder
Six sets of observations will be taken
Lungs, Liver, Heart, Intestines, Kidneys, and Pregnancy
Enter the observation for each of these organ
The EDIT button allows you to change entries.
The CANCEL button allows you to cancel an entry
The SUBMIT button ends the data entry and brings up the ID of the next animal.

11. Lungs Minor Adhesions Look Like … Spider Web Strands
Lungs … MOST will NOT be associated with condemnation
Lungs … MOST will NOT be associated with condemnation
Major Purple: Lung Areas will be depressed purple areas as large or larger than the small lung lobes close to the trachea.
Minor Adhere: These are spider web strands or tags of adhesions on the surface of the lung
Minor Adhesions Look Like … Spider Web Strands

12. Lungs Lungs … MOST will NOT be associated with condemnation
Major Adhere: These are thick tags of adhesions on the between the lung lobes or on the surface of the lung
Missing Lung: Part of the lung is missing … almost always the parts close to the trachea. If the missing lung part is associated with an active infection the inspector will condemn the lung.
Note the Skirt is adhered to the lung.

13. Lungs Lungs … MOST will NOT be associated with condemnation
Note: Lung was condemned … this is good evidence there was an active infection (could also record as “Active LN”)
Note the Skirt is adhered to the lung.
Note: Most of both sides are missing.
Lungs … MOST will NOT be associated with condemnation
Missing Lung: Part of the lung is missing … almost always the parts close to the trachea. If the missing lung part is associated with an active infection the inspector will condemn the lung.
Generally, the missing part of the lung will be found in the animals chest cavity. Which will cause the pleura to be stripped out.
Note: Lung was condemned … this is good evidence there was an active infection (could also record as “Active LN”)
Note: Part of Lung is still in the chest

14. Lungs Lungs … MOST will NOT be associated with condemnation
Note: Lung was condemned … this is good evidence there was an active infection (could also record as “Active LN”)
Lungs … MOST will NOT be associated with condemnation
Active LN Condemn: Are lungs with active infections as judged by the lymph nodes (LN) being swollen and inflamed.
Green Eosin: Are greenish blood spots in the lung. These are usually the size of a dime or nickel. The larger the spot the bloodier it will appear. As the the lesion ages it becomes smaller and more greenish.
Note: Young Lesions are Bloody

15. Stripped Plura

16. Lung Lesions

17. Lung Lesions Cost Performance
Buhman, NU-GPVEC 2001

18. Data from Different Sources
Description
ADG
Marbling
Ref
No Rx vs 2 RX
- 0.37
~ - 100
Missouri
- 0.45
Colorado
- 0.35
- 34
JAVMA
Health vs Sick
- 0.54
- 23 / -35
Texas
- 0.46
---
Smith
Lung Lesions
- 0.34
- 11
Bryant
- 0.06
Lung Active
- 0.90
- 30
Lung All/Severe
- .06/30
- 31 / - 78
GPVEC

19. Dealing with Respiratory Disease

20. Select appropriate high quality products
Most commonly, BRD has a head start in high-stressed young commingled cattle.

21. Durable Cure & DART The goal: D.A.R.T.
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.

22. Durable 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.

23. Durable 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.

24. Durable 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.

25. Durable 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.

26. How Sick Cattle Eat Pull any new calf that is slow to come to the bunk
Look for sick cattle shortly after putting out feed.

27. Sick: Intake vs. Temp

28. Subclinical Acidosis

29. Understand the Problem …
Diagnoses & Cause ?

30. Vets have a symbiotic relationship with Nuts
Work with
MEDS
Nuts …
Work with
RATS
Very important to understand the relationship between cattle health and nutrition !!!

31. Finding Sick Cattle Early … may be an impossible job

32. Prevention … is key Treatment salvages only part of the loss
Immune preparation
Treatment timing

33. What You Need to Know &Think About When Selecting Antibiotics
The objective will be to help folks better understand:
1) how antibiotics work … clinically
2) antibiotic classes … & what makes them different
3) how to think through developing treatment protocols
4) understand dose management & resistance development
5) how to select a proper antibiotic for different diseases
6) how the other things given sick cattle can influence an antibiotic's effectiveness
7) how to know when to switch
8) which antibiotic would make a better choice when a switch is need if an animal doesn't respond
9) when to quit
10) potential residue considerations & management

34. 7 Antibiotic Use Myths … Dr. Mike Apley
Two antibiotics work twice as well as one
You must give an IV to get a quick response
If they have not responded to the first, switch to another
Aggressive is good. If they don’t look better in 24 hours, add the next drug in the rotation to the first treatment
The hotter they are, the sicker they are, so make drug choices based upon rectal temperature
Adding supportive drugs will improve response
Vaccination at time of treatment improves response

35. What happened? … a look at the Sequence
Example: Respiratory System

36. 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.

37. 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

42. how 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 …

43. 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

44. Antimicrobial groups approved for cattle:
Antibiotic Class
Antibiotic Within Class
Resistance
Mechanism
Lipid Solubility
~ Protein
Binding %
Aminocyclitols
Spectinomycin PS
Low
Aminoglycosides
Gentamicin, Neomycin
20-25%
Beta-lactams
Penicillin G, Ampicillin, Ceftiofur CW
P&A 20, Cef 80+
Chloramphenicol derivatives
Florfenicol
High 60
Fluoroquinolones
Enrofloxacin, Danofloxacin GR
Lincosamides
Lincomycin
55-75
Macrolides
Erythromycin, Tilmicosin, Tylosin
70-80
Sulfonamides
Sulfa - dimethoxine, methazine, chlorpyridazine MP
SM 70, SDM 80-85
Tetracyclines
Oxytetracycline, Chlortetracycline
Intermediate
OTC 20-25, CTC 65
crippling production of the bacterial cell wall that protects the cell from the external environment
interfering with protein synthesis by binding to the machinery that builds proteins, amino acid by amino acid
wreaking havoc with metabolic processes, such as the synthesis of folic acid, that bacteria need to thrive
blocking genetic replication by interfering with synthesis of DNA and RNA

45. PK / PD Relationships

46. Antibiotic Movement

48. What Does This Mean? What Value is This?

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

51. Pen G Dose Curves

52. Ceftiofur Dose Curves

53. Ceftiofur Sensitivity (VADS)
P. multocida (498)
MIC
Incidence
Cumulative
0.5
99.20% 1
0.40%
99.60% 2
0.20%
99.80% 4
0.00% 8 16
100.00%
M. haemolytica (481)
MIC
Incidence
Cumulative
0.5
99.38% 1
0.21%
99.58% 2
0.00% 4
99.79% 8 16
100.00%

54. Ceftiofur Sensitivity (VADS)
H. somni (208)
MIC
Incidence
Cumulative
0.5
98.56% 1
1.44%
100.00% 2
0.00% 4 8 16
S. typhimurium (66)
MIC
Incidence
Cumulative
0.5
75.76% 1
21.21%
96.97% 2
1.52%
98.48% 4
0.00% 8 16
100.00%

55. Oxytet Dose Curves

56. Oxytet Sensitivities (VADS)
P. multocida (498)
MIC
Incidence
Cumulative
0.25
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)
MIC
Incidence
Cumulative
0.25
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%

57. Oxytet Sensitivities (VADS)
H. somni (208)
MIC
Incidence
Cumulative
0.25
36.54%
0.5
23.08%
59.62% 1
3.37%
62.98% 2
0.00% 4
2.88%
65.87% 8
13.46%
79.33% 16
20.67%
100.00%
S. typhimurium (66)
MIC
Incidence
Cumulative
0.25
0.00%
0.5
1.52% 1 2
13.64%
15.15% 4
3.03%
18.18% 8 16
81.82%
100.00%

58. Macrolide Dose Curves

59. BIGGEST FACTOR … TIMING!!! Animal’s ability to help fight back
why an antibiotic may seem to work on some sets of cattle and not others
Source, Source, & Source
BIGGEST FACTOR … TIMING!!!
How much of a head start ???
Animal’s ability to help fight back
Differences in bugs …
Diagnosis ???

62. The stress caused by some products does more damage than their benefit
how the other things we give sick cattle can 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)

63. “May Help … What It Don’t Hurt”

64. Injection Sites … New Concerns

65. Knots aren’t Bad

66. PTI (Post Treatment Interval) Economics

67. PTI (Post Treatment Interval) Economics

68. PK & PD Compared

69. Dose Price Compared

70. PTI Example … 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
10 day
85.3
12.4
1.6
14 day
88.8
1.2
253 allocated in all treatment intervals … Non-BRD removals: 7 day (5), 10 (2), 14 (3)
Average daily gain mean and range in pounds
LS Mean
Median
Range
7 day
2.7
2.72
(-0.18 , 4.14)
10 day
2.73
(0.64 , 4.46)
14 day
2.55
2.57
(-0.79 , 4.14) 7
Animal 0320 was euthanatized 30 Oct 2005; necropsy indicated brain edema and hyperemia.
Animal 0066 died 16 Nov 2005; necropsy indicated cardiac failure due to chronic hardware.
Animal 1010 died 06 Dec 2005; necropsy indicated polio.
Animal 1104 was treated (Nuflor) 14 Dec 2005 for lameness and subsequently euthanatized 16 Dec 2005.
Animal 0012 removed from analysis because of protocol deviation 10
Animal 0457 died 8 Nov 2005; necropsy indicated petechial hemorrhages throughout abdomen.
Animal 0527 removed from analysis because of protocol deviation 14
Animal 0035 was treated (Nuflor) 23 Nov 2005 for foot rot. Animal 0046 was treated (Nuflor) 23 Nov 2005 for foot rot. Animal 0474 was treated (tetracycline, dexamethasone) 14 Dec 2005 for polio.

71. PTI Example … The deal is it changes the flow
Cumulative 1st Re-Treatments 7
Animal 0320 was euthanatized 30 Oct 2005; necropsy indicated brain edema and hyperemia.
Animal 0066 died 16 Nov 2005; necropsy indicated cardiac failure due to chronic hardware.
Animal 1010 died 06 Dec 2005; necropsy indicated polio.
Animal 1104 was treated (Nuflor) 14 Dec 2005 for lameness and subsequently euthanatized 16 Dec 2005.
Animal 0012 removed from analysis because of protocol deviation 10
Animal 0457 died 8 Nov 2005; necropsy indicated petechial hemorrhages throughout abdomen.
Animal 0527 removed from analysis because of protocol deviation 14
Animal 0035 was treated (Nuflor) 23 Nov 2005 for foot rot. Animal 0046 was treated (Nuflor) 23 Nov 2005 for foot rot. Animal 0474 was treated (tetracycline, dexamethasone) 14 Dec 2005 for polio.

72. how to select a proper antibiotic for different 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
CAUTION – Generics … & AVOID Bathtub mixes
Neomycin & Gentamicin … violate BQA & reason

73. how 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

74. Re-check the diagnosis … Use previous lab work …
which antibiotic would make a better choice when 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 !

75. … When to Quit and Let Go BIGGEST FACTOR … TIMING!!!
why an antibiotic may seem to work on some 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

76. when 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 … QUIT
If 2 is greater than 10 … QUIT

77. when to quit
letting go

80. Food Animal Therapeutic Management is Not Complete Until The Residue Potential Is Considered & Managed

81. A Producers Guide for Judicious Use of Antimicrobials in Cattle (As Adopted by the NCBA.)
Prevent Problems: Emphasize appropriate husbandry and hygiene, routine health examinations, and vaccinations.
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.
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.
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.
Combination Antibiotic Therapy Is Discouraged Unless There Is Clear Evidence The Specific Practice Is Beneficial: Select and dose an antibiotic to affect a cure.
Avoid Inappropriate Antibiotic Use: Confine therapeutic antimicrobial use to proven clinical indications, avoiding inappropriate uses such as for viral infections without bacterial complication.
Treatment Programs Should Reflect Best Use Principles: Regimens for therapeutic antimicrobial use should be optimized using current pharmacological information and principles.
Treat the Fewest Number of Animals Possible: Limit antibiotic use to sick or at risk animals.
Treat for the Recommended Time Period: To minimize the potential for bacteria to become resistant to antimicrobials.
Avoid Environmental Contamination with Antibiotics: Steps should be taken to minimize antimicrobials reaching the environment through spillage, contaminated ground run off or aerosolization.
Keep Records of Antibiotic Use: Accurate records of treatment and outcome should be used to evaluate therapeutic regimens and always follow proper withdrawal times.
Follow Label Directions: Follow label instructions and never use antibiotics other than as labeled without a valid veterinary prescription.
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.
Subtherapeutic Antibiotic Use Is Discouraged: Antibiotic use should be limited to prevent or control disease.

82. Antibiotic MRL (Tolerance)

83. Test 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)

84. Ben. Pen. Residue Potential

85. What can be done to protect our producers … & ourselves?
Use FAST (PHAST) before “high-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 …

86. Testing Urine Isn’t Tough …

87. Antibiotic Residue Avoidance Strategy
Identify all animals treated.
Record all treatments: Date; animal’ ID; dose given; route of administration; the person who administered the treatment; withdrawal time (WD).
Strictly follow label directions for product use.
Use newer technology antibiotics when possible.
Reduce unwanted depot effect. Select low volume products when available.
Select generic medications and vaccines with EXTREME CAUTION.
Avoid inferior products. They may cause performance loss or damage quality.
Select with short WD when antibiotic choice is equivalent.
Never give more than 10 cc per IM injection site.
Avoid Extra Label Drug Use (ELDU) of antibiotics.
Use label dose and route of administration.
Avoid using multiple antibiotics at the same time.
Don’t mix antibiotics in the same syringe, especially if given IM or Sub-Q.

88. Antibiotic Residue Avoidance Strategy
Check ALL medication/treatment records before marketing:
Don’t market cattle with less than 60 WD without examining the treatment history.
Extend the WD time if the route or location of administration is altered.
Example; the WD for ear route of administration ceftiofur will be over 120 days if given SQ in the neck.
Example; tissue irritation will cause the WD for Banamine to be over 30 days if given IM or Sub-Q instead of IV.
Extend the withdrawal time for multiple medications given by summing their label recommended WD.
Example; if the 1st medication has a 10 day WD and the 2nd medication has a 28 day WD, assign a 38 day. WD.
Example; if 1st medication has a 10 day WD and is repeated in three days, assign a 20 day WD.

89. Antibiotic Residue Avoidance Strategy
Extend the WD for all penicillin given at doses which exceed the label dose
Example; the WD for Procaine Pen G given at 3 CC per CWT IM or Sub-Q is over 30 days
Example; the WD for Procaine Pen G given at 4 CC per CWT IM or Sub-Q is over 30 days
Example; the WD for Long Acting Pen G given at 3 CC per CWT IM or Sub-Q is over 120 days
Example; the WD for Long Acting Pen G given at 4 CC per CWT IM or Sub-Q is over 180 days
Testing urine test may not detect injection site residues and will test positive by the USDA-FSIS.
Never inject gentamicin or neomycin. The estimated WD is over 24 months
Testing urine test may not detect a kidney that will test positive by the USDA-FSIS.

90. Antibiotic Residue Avoidance Strategy
USDA-FSIS. Don’t market cattle with suspected liver or kidney damage without examining the treatment history.
Don’t market cattle with antibiotic injection site knots without examining the treatment history.
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)

91. DGriffin@GPVEC.UNL.EDU http://gpvec.unl.edu
Save a Cow …
Eat a Vegetarian
Good Luck To You

92. we would love to have you come see us…
Thanks for having me … &
we would love to have you come see us…
...where
agriculture & all it’s people
make a difference

93. The Ear Is A Busy Place

94. Comparison of two drugs for treatment of a gram-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

95. Comparing 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

96. Establishing 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 =>

100. Building Resistance

102. Antimicrobial Model
Successful treatment of infection involves the interactions of host, drug and bacteria
Host
Drug
Bacteria s
Pharmacokinetics
Tissue penetration
Susceptibility of pathogens
PK/PD relationship
PAE
Killing rate
Other metrics
Immune system ? 
The factors not being considered may represent potential limitations.

103. Appropriate Pharmacokinetic/Pharmacodynamic Measures to Assess Antimicrobial Activity In Vivo
Drug
Conc -Cidal Activity
PAE
PK/PD Measures
Beta-lactam
Fixed
Minimal
T>MIC
Macrolide
Some
Azalide
Longer
AUC:MIC
Aminoglycoside
Linear

104. Please know,
We take our responsibility to use antibiotics properly very seriously …