Rational Antimicrobials 4

Question 1

host factors when choosing an antimicrobial

Answer 1

-age
-disease status
- target site factors

Question 2

do age and disease change PK and PD?

Answer 2

Age and disease produce changes to PK rather than PD !!

Question 3

changes in drug choices due to geriatric or neonate considerations

Answer 3

• Geriatric animals more likely to have disease and require multiple drug therapy
• Immature nature of the neonatal body systems:
  > greater bioavailability
  > greater volume of distribution
  > slower elimination

Question 4

3 most important disease factors for AM choice

Answer 4

• kidney disease
• hepatic disease
• heart failure

Question 5

what can occur if an infection is in a difficult to reach place?

Answer 5

Difficult to penetrate tissues (cells); can yield therapeutic failure or promote resistance

Question 6

factors of a hostile infection site environment

Answer 6

• inoclulum size
• purulent debris
• reduced pH (inflammation
• low O2 tension

Question 7

after administering therapy, when should we look for improvement or decline?

Answer 7

§ improvement/decline should be seen within 24-48 hrs

Question 8

should we assess the given therapy? how and why?

Answer 8

Assessment of therapy should continue during treatment period
§ nonspecific and specific methods; success of treatment; resistance

Measurement of antibacterial drugs in blood; if available !
§ reduce toxicity concerns with aminoglycosides
§ reduce costs with expensive drugs
§ determination of individuals blood drug levels
§ optimization of dosage regimen for efficacy § minimize resistance

Question 9

common reasons for therapeutic failure and what we should do

Answer 9

Therapeutic failure due to several causes; often drug selection, dosage regimen or host factors or other underlying disease
§ warrants reassessment of case

Question 10

Prophylaxis and Operative Wound Classification, and what we should do?

Answer 10

Clean—generally no prophylaxis
Clean-contaminated—prophylactic antimicrobials
Contaminated—prophylactic antimicrobials
Dirty—therapeutic antimicrobials

Question 11

Basis of antimicrobial drug choice

Answer 11

• likely microorganisms and susceptibility patterns
• drug pharmacokinetics and toxicity in species of interest

Question 12

most common antimicrobials for dog/cat, equine, ruminants for prophylaxis

Answer 12

> Dog/Cat—cefazolin most commonly used
Equine—cefazolin +/- gentamicin
Ruminants—ceftiofur versus penicillin

Question 13

Timing and duration of prophylaxis

Answer 13

at least 30 min before incision…. within 24 hours after surgery

Question 14

Metaphylaxis - what is it and when do we do this? what assumptions do we make?

Answer 14

Administration of antimicrobials to herds at high risk of a disease outbreak
- transporting; long transit times and transit shrinkage
- crowding and stress; commingled of unknown origin
- age of animals; immune status
- source history of disease eg BRD
- metaphylaxis is not vaccination

• Assume that “at risk” animals harbor pathogens
  > Treatment with any product labeled for disease would be acceptable based on rational assumption

Question 15

Some antimicrobial choices for feedlot cattle for metaphylaxis?

Answer 15

• tilmicosin
• oxytetracycline
• florfenicol
• tulathromycin

Question 16

goal of metaphylaxis

Answer 16

Goals of therapy–prevent outbreak, not infection

Question 17

why should we use prudent antimicrobial choice?

Answer 17

Judicious/Prudent antimicrobial use should be pursued for animal and public health concerns
- definition: “optimal selection of drug, dose and duration of therapy along with reduction of excessive and inappropriate use, as a means of slowing resistance”

Question 18

General guidelines for prudent antimicrobial use

Answer 18

Use the most efficacious antibacterial appropriate for the situation
§ using an antibacterial rationally will NEVER yield more resistance than
inappropriate use of an antibacterial

Use a dosing regimen that maximizes the antibacterial agent’s efficacy
§ concentrations at the site of infection below the MIC favor resistance
§ too short a treatment period favors resistance

Establish a strong likelihood of bacterial infection before using antibacterials
§ avoid use of antibacterials to “cover” or “just in case”

Question 19

Suggested categorization of antimicrobials

Answer 19

1st line/Primary
- Used as initial treatment with known or suspected bacterial infection
> Penicillin, amoxicillin, most cephalosporins, TMS, tetracyclines

2nd line/ Secondary
- Used when C/S testing, plus patient and infection factors, indicate that no 1st-line drug are reasonable
> FQ’s, 3rd generation cephalosporins, ticarcillin, piperacillin, aminoglycosides

3rd line/Tertiary
- Used in serious, life-threatening infections with the support of C/S testing; no 2nd-line drugs indicated; infection is treatable
> Carbapenems (imipenem-cilastatin), vancomycin, linezolid

Question 20

Following drugs, families of drugs, and substances are prohibited for extra-label use in food-producing animals in Canada

Answer 20

• chloramphenicol
• clenbuterol
• diethylstilbesterol (DES)
• nitroimidazoles (eg. metronidazole)
• nitrofuranzone

Question 21

tissue drug residues: concerns related to withdrawl times

Answer 21

• Adulteration of the food supply with antimicrobial agents has been a growing source of concern
  > antimicrobial resistance
  > hypersensitivity (allergic) reactions
  > contamination of milk with antimicrobials can affect starter cultures (cheese, sour cream, buttermilk)

Question 22

Violative residues ie. higher than the maximum allowable limits in edible foodstuffs can result from…..

Answer 22

• Failure to observe approved meat/milk WDT on the drug label
• ELDU and failure to establish a new WDT
• Unintentional administration of drugs, or food additives
  > eg. error at the feed mill mixing the drug with complete feed

Question 23

what counts as extra-label drug use?

Answer 23

§ Changing dose
§ Changing indication
§ Changing route
§ Changing amount injected per site
§ Changing frequency

Question 24

what bodies oversee veterinary drug approval policy and residue monitoring/surveillance?

Answer 24

-Drug use in veterinary medicine is regulated by Health Canada
> Health Canada-Veterinary Drugs Directorate….drug approval policy
> Canadian Food Inspection Agency……residue monitoring/surveillance

Question 25

A violative residue occurs when …

Answer 25

an edible animal product eg. meat, milk or eggs has drug residues in excess of the maximum allowable limit (MRL), aka tolerance in the USA

Question 26

Most commonly cited antimicrobial culprits for drug residues

Answer 26

• Sulfonamides (sulfamethazine)
• Penicillin
• Oxytetracyclines
• Long acting preparations commonly implicated

Question 27

The primary parameter used by veterinarians to prevent violative tissue residues in food producing animals is:

Answer 27

the length of the withdrawal time

Question 28

what is withdrawl time?

Answer 28

“withdrawal time is the interval between the last treatment with the compound and the time when the animal can be marketed (meat, eggs or milk)”

Question 29

how should we address withdrawl times when using extra-label drugs in food producing animals?

Answer 29

…seek advice on extended WDTs !!

Canadian Global Food Animal Residue Avoidance Databank (CgFARAD)
> Ron Johnson (co-Director, OVC, University of Guelph)
> Trisha Dowling (co-Director, WCVM, University of Saskatchewan)
> University based national program; non-profit service to practitioners
> Primary source for scientifically-based guidance regarding safe WDTs for
ELDU and chemical intoxications in food-producing animals