Judicious Use and Antimicrobial Stewardship in Veterinary Medicine

Antimicrobial resistance (AMR) is primarily concerned with acquired resistance, which develops through bacterial mutation or the acquisition of new genes. This is distinct from innate resistance where a bacterium is naturally not susceptible to a drug.

AMR is a significant One Health problem, impacting:

• Animal Health: Infections become harder to treat.
• Human Health: Resistant bacteria can transmit between animals and humans.
• Economy: Treating resistant infections is more costly, increasing healthcare expenses.

National and international plans, collaborations, and regulations are in place to combat AMR, recognizing it as a major global health concern.

Veterinarians are identified as key players in antibiotic stewardship through:

• Promoting responsible antibiotic use.
• Educating pet owners and farmers.
• Resisting pressure to prescribe antibiotics when not clinically indicated (similar to human medicine challenges, e.g., viral infections). Using antibiotics only when necessary prevents selective pressure that drives resistance.

It's crucial to consider the bigger picture beyond the individual patient. Decisions made for one animal can impact the broader health of other animals, humans, and the environment (One Health approach).

Stewardship means using the right antibiotic, at the right time, the right dose, for the right duration.

The primary goals are to:

1. Optimize clinical outcomes for the individual patient.
2. Minimize the development of antimicrobial resistance.

This requires focusing on evidence-based medicine (when available) and practical risk assessment.

A robust treatment decision framework involves several key components:

Regulatory Framework

Regulations guide antimicrobial use, especially in food animals, due to concerns about residues and transmission of resistance to humans.

• FDA Oversight: Defines approved uses (treatment, control, prevention) and prohibits production uses (e.g., growth promotion). Medically important antibiotics are often moved from OTC to prescription/VFD status.
• State Boards: Provide oversight, enforcement, and may have specific CE requirements for stewardship.
• VCPR: A valid Veterinarian-Client-Patient Relationship is required for prescribing antibiotics.

Implementing a Stewardship Plan

While unique to each practice, key components include:

1. Bacterial Characteristics

• Local resistance patterns (Antibiogram data)
• Definitive diagnosis methods available
• Oxygen requirement (Aerobe vs. Anaerobe)
• Gram stain reaction (+/-)
• Spectrum of activity needed (Narrow vs. Broad)

2. Infection Site

Will the drug penetrate the site (e.g., urine concentration for UTIs, abscess penetration)?

3. Animal Species & Use

• Food animal vs. non-food animal (implications for ELDU, withdrawal times)
• Species-specific sensitivities or contraindications (e.g., oral antibiotics in hindgut fermenters like horses, rabbits)

4. Treatment Regimen Factors

• Route of Administration: Ensure the route allows the drug to reach necessary concentrations.
• Dosing Frequency: Consider client compliance. Can a once-daily (concentration-dependent) drug be used instead of multi-dose (time-dependent)?
• Cost: Ensure the client can afford the full course of therapy.

5. CNS Data

Disk diffusion, broth microdilution help determine if bacteria are Sensitive (S), Intermediate (I), or Resistant (R). Invaluable for choosing the narrowest spectrum effective drug.

6. Pharmacokinetics (PK) & Pharmacodynamics (PD)

• PK (Drug on Body): Absorption, Distribution, Metabolism, Excretion (ADME)
• PD (Body on Drug): Mechanism of action, drug effects
• Consider potential drug interactions (e.g., antagonism between bacteriostatic and bactericidal drugs)

ELDU regulations differ significantly between food and non-food animals. AMDUCA (Animal Medicinal Drug Use Clarification Act) provides the framework.

Non-Food Animals (Dogs, Cats, Rabbits)

Decision flow (simplified from AMDUCA):

1. Is there an approved animal drug labeled for the condition and species? If YES → Use as labeled.
2. If NO → Is there an approved animal drug (any species/condition) that could be used effectively extra-label? If YES → Use extra-label (with appropriate records, VCPR).
3. If NO → Can a compound be prepared by manipulating an approved animal or human drug? If YES → Compound from approved drug.
4. If NO → Consider compounding from bulk chemical substances (following FDA guidance).

Food Animals (Stricter Rules)

1. Is there an approved food animal drug labeled for the condition and species? If YES → Use as labeled.
2. If NO → Is there an approved food animal drug (any food animal species/condition) for extra-label use? If YES → Use extra-label (establish withdrawal time).
3. If NO → Can an approved human or non-food animal drug be used extra-label? If YES → Use extra-label (establish withdrawal time, ensure no residue risk).
4. If NO → Compounding is highly restricted and generally discouraged.

Antibiotics administered via feed for food animals require a Veterinary Feed Directive (VFD), not a standard prescription.

• A VFD is a "prescription" for medicated feed, issued by a veterinarian to a feed mill/distributor.
• Specifies the drug, concentration, duration, species, number of animals, and purpose (treatment, control, prevention).
• Prescriptions are limited to licensed pharmacies. VFDs allow veterinarians to oversee medicated feed use.
• This system brought feed-based antibiotics under veterinary oversight to improve stewardship.

Multiple agencies monitor antibiotic use, residues, and resistance:

• Federal: FDA, EPA, USDA
• Databases/Programs: Residue tracking, National/International monitoring (e.g., NARMS)

The FDA NARMS Strategic Plan focuses on:

• Expanding the One Health approach (human, animal, environment)
• Advancing detection technologies
• Strengthening collaboration and data sharing (national/international)
• Standardizing reporting formats
• Focusing on research for prevention and alternative treatments
• Studying the burden/impact of resistance and effectiveness of interventions

Initial Questions to Consider

• Confirm UTI vs. other differentials?
• Was CNS done last time? Was enrofloxacin actually used? Dose/duration?
• Will enrofloxacin work now? Other options?
• Can CNS be obtained this time?

Exam & Diagnostics

• Physical exam: No obvious abnormalities
• Records from other clinic unavailable (closed); associate unavailable
• Cystocentesis performed for in-house urinalysis (UA) & CNS testing proposed
• Client agrees to UA only
• UA Results: Positive for WBCs and Rods (bacteria) → Confirms likely UTI

Decision Point — Options Considered

Guideline Consultation (ISCAID UTI Guidelines)

• Case fits "Sporadic Bacterial Cystitis" (or potentially "Recurrent" if cautious).
• Recommendation: CNS recommended before prescribing. Systemic antibiotics are indicated.
• Initial empirical therapy (while awaiting CNS): Amoxicillin OR Trimethoprim-Sulfa (TMS).

• Improper and indicated antimicrobial use drives resistance.
• Overuse (e.g., treating bacteriuria without clinical signs) creates selective pressure.
• Veterinary guidelines are still evolving; consistency is challenging.
• Drug development lags far behind resistance emergence. Few novel antibiotic mechanisms approved since 2000.
• Current pipeline drugs often don't address multi-drug resistant gram-negative bacteria.

Improvements are happening through science and education, but challenges remain (similar issues exist in human healthcare).

• Veterinary Teaching Hospitals: Increasingly implementing stewardship committees and restrictions on "high priority" antibiotics (requiring justification/review, often by pharmacists).
• Guidelines: More evidence-based guidelines (like ISCAID UTI guidelines) are emerging, often recommending narrower-spectrum agents initially.

Vet On It CE · RACE Provider 50-29055 · Led by Science, Not Sponsors

These notes are supplementary study materials. They do not replace attending the live lecture or completing the post-course assessment.