Rational Antimicrobials 4 Flashcards
host factors when choosing an antimicrobial
-age
-disease status
- target site factors
do age and disease change PK and PD?
Age and disease produce changes to PK rather than PD !!
changes in drug choices due to geriatric or neonate considerations
- 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
3 most important disease factors for AM choice
- kidney disease
- hepatic disease
- heart failure
what can occur if an infection is in a difficult to reach place?
Difficult to penetrate tissues (cells); can yield therapeutic failure or promote resistance
factors of a hostile infection site environment
- inoclulum size
- purulent debris
- reduced pH (inflammation
- low O2 tension
after administering therapy, when should we look for improvement or decline?
§ improvement/decline should be seen within 24-48 hrs
should we assess the given therapy? how and why?
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
common reasons for therapeutic failure and what we should do
Therapeutic failure due to several causes; often drug selection, dosage regimen or host factors or other underlying disease
§ warrants reassessment of case
Prophylaxis and Operative Wound Classification, and what we should do?
Clean—generally no prophylaxis
Clean-contaminated—prophylactic antimicrobials
Contaminated—prophylactic antimicrobials
Dirty—therapeutic antimicrobials
Basis of antimicrobial drug choice
- likely microorganisms and susceptibility patterns
- drug pharmacokinetics and toxicity in species of interest
most common antimicrobials for dog/cat, equine, ruminants for prophylaxis
> Dog/Cat—cefazolin most commonly used
Equine—cefazolin +/- gentamicin
Ruminants—ceftiofur versus penicillin
Timing and duration of prophylaxis
at least 30 min before incision…. within 24 hours after surgery
Metaphylaxis - what is it and when do we do this? what assumptions do we make?
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
Some antimicrobial choices for feedlot cattle for metaphylaxis?
- tilmicosin
- oxytetracycline
- florfenicol
- tulathromycin
goal of metaphylaxis
Goals of therapy–prevent outbreak, not infection
why should we use prudent antimicrobial choice?
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”
General guidelines for prudent antimicrobial use
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”
Suggested categorization of antimicrobials
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
Following drugs, families of drugs, and substances are prohibited for extra-label use in food-producing animals in Canada
- chloramphenicol
- clenbuterol
- diethylstilbesterol (DES)
- nitroimidazoles (eg. metronidazole)
- nitrofuranzone
tissue drug residues: concerns related to withdrawl times
- 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)
Violative residues ie. higher than the maximum allowable limits in edible foodstuffs can result from…..
- 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
what counts as extra-label drug use?
§ Changing dose
§ Changing indication
§ Changing route
§ Changing amount injected per site
§ Changing frequency
what bodies oversee veterinary drug approval policy and residue monitoring/surveillance?
-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
A violative residue occurs when …
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
Most commonly cited antimicrobial culprits for drug residues
- Sulfonamides (sulfamethazine)
- Penicillin
- Oxytetracyclines
- Long acting preparations commonly implicated
The primary parameter used by veterinarians to prevent violative tissue residues in food producing animals is:
the length of the withdrawal time
what is withdrawl time?
“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)”
how should we address withdrawl times when using extra-label drugs in food producing animals?
…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
