06: Antibacterials

Who invented the first microscope

Antonie van Leeuwenhoek

Specific terms that are encompassed by the umbrella terms antibiotics/antimicrobials

Antibacterials, antivirals, and antifungals

Globally, which industry carries the greatest burden for AB stewardship

Vet med, we use 80% of the ABs globally

Most frequently sold class of ABs in production medicine

Tetracyclines make up 2/3 of ABs sold in PA medicine

Definition of broad spectrum AB

There is some efficacy on both G+ and G- bacteria, but it will not work on everything!

β-lactam mechanism of action

Inhibits cell wall synthesis via inhibiting production of or cross linking peptidoglycan

3 main classes of β-lactams

• Penicillins

• Cephalosporins

• Carbapenems

Glycopeptide mechanism of action

Inhibits cell wall synthesis

Polymyxin mechanism of action

Binds up lipid A region of LPS and disrupts cell membranes

Why are polymyxins typically topicals

Lower threshold for toxicity with systemic administration

Classes of ABs that target bacterial ribosomes

• Aminoglycosides

• Lincosamides

• Macrolides

• Phenicols

• Tetracyclines

Advantage of using an AB that targets bacterial ribosomes

Great for bacteria with plasma membrane or cell wall modifications or for intracellular bacteria

Fluoroquinolone mechanism of action

Binds to DNA gyrase and inhibits DNA replication

Type of bacteria that fluoroquinolones are not great for

Anaerobes

Nitroimidazoles mechanism of action

Targets nucleic acids and inhibits repair

Type of bacteria that nitroimidazoles are best for

Anaerobes

Nitrofurans mechanism of action

Also targets nucleic acids

Classes of ABs that block folic acid metabolism

Sulfonamides and trimethoprim

Why does blocking folic acid metabolism work as an antibacterial

Bacteria have to synthesize their own folic acid, they cannot source it externally

Antimicrobials that are prohibited for food animal use

• Chloramphenicol

• Fluoroquinolones

• Glycopeptides

• Nitroimidazoles

• Nitrofurans

Antimicrobials that are restricted for use in food animals

Cephalosporins and sulfonamides

Two general mechanisms of antibacterial resistance

Intrinsic and extrinsic

Intrinsic antibacterial resistance

Certain antibacterials were never going to work on types of bacteria because of specific, innate, and normal bacterial mechanisms

Extrinsic antibacterial resistance

Certain antibacterials that used to work no longer work because of acquired genomic changes

Where do most bacteria acquire their β-lactamase superpowers

Klebsiella

Type of bacteria that is GREAT at acquiring AB resistance

Pseudomonas

General mechanisms of intrinsic resistance

• Biofilm

• Electrical charge

• Efflux pumps

• Slow generation rate

Survival event that encourages acquired AB resistance

Selection pressure due to AB use

Three mechanisms that allow bacteria to acquire genetics

• Transduction via bacteriophages

• Conjugation via plasmids

• Transformation via transposons

Four mechanisms of acquired resistance

• Inhibits uptake

• Rapid efflux pumps

• Modification of AB structure

• Mutated bacterial target

How does medicated milk replacer contribute to AB resistance

They are too low of a dose to fight the diseases of interest but high enough of a dose to impose a selection pressure on bacterial populations

T/F: mastitis usually needs ABs

FALSE; most mastitis is environmental

Why is judicious use of ABs with BRD so difficult

Alternative strategies and diagnostics cost money, and ABs are easy

Where do we see most AB overuse in horses

Upper respiratory infections