12: Protein Inhibiting Abx

Aminoglycoside mechanism of action

Inhibits 30S ribosomal subunit

Examples of aminoglycosides

Gentamicin and amikacin

Route of administration for aminoglycosides

Parenterally (poor oral absorption)

Aminoglycoside spectrum of activity

• G-

• Staphs

• Pseudomonas

Type of bacteria that aminoglycosides have NO activity against

Anaerobes; aminoglycosides enter cells via O₂ dependent mech

Indications for use of gentamicin v amikacin

Gentamicin more common in adult horses because it is cheaper, amikacin used in foals because it is more efficacious

Why do we commonly combine an aminoglycoside with a penicillin

• Covers G-, streps, G+, and staphs

• Mitigates development of resistance

Adaptive resistance

Reversible refractiveness/resistance to bactericidal action

How does adaptive resistance help determine our dosing regimen

We want the dosing interval to be long enough that the bacteria revert to a susceptible state

Consequences of aminoglycosides being weak bases

• Don’t get into host cells (no activity against intracellular bacteria)

• Poor activity in acidic environments

• Doesn’t penetrate barriers well

How can we get away with giving aminoglycosides once a day

They have long post-antibiotic effects

Adverse affects of aminoglycosides

Nephrotoxicity (and ototoxicity and neuromuscular blockade)

When do we more commonly see the neuromuscular blockade as an adverse affect of aminoglycosides

When co-administered with anesthetics

How do we decrease nephrotoxicity associated with aminoglycosides

Keep the trough concentrations low (longer dosing intervals!)

Tetracyclines mechanism of action

Inhibits the 30S ribosomal subunit

Examples of tetracyclines

• Tetracycline

• Oxytetracycline

• Doxycycline

Tetracyclines spectrum of activity

Broad, but not everything

• G+, but not staph

• G-, but lots of exceptions

• Anaerobes, but not all

Type of bacteria that tetracyclines are known for treating

Intracellular

Primary indication for oxytetracycline

Large animal use

Why is doxycycline more popular in small animal than tetracycline

Doxy is more lipophilic → larger volume of distribution → longer dosing intervals

Compartment that tetracyclines do not get into well and why

CNS; tetracyclines are a substrate for the p-glycoprotein pumps at the BBB

Bonus effects of tetracyclines

• Anti-inflammatory

• Mild immune suppression

• Chelates Ca⁺⁺

Side effects associated with tetracyclines

• Self-limiting GIT signs

• Discoloration of teeth (oxy/tet > doxy)

Side effects specifically associated with doxycyline

• FATAL cardiovascular collapse in horses if IV

• Esophageal stricture in cats

Chloramphenicols mechanism of action

Inhibits 50S ribosomal subunit

Examples of chloramphenicols

Chloramphenicol and florfenicol

Chloramphenicols spectrum of activity

G+, G-, anaerobes, and intracellular

Bacteria that florfenicol is good for, but not chloramphenicol

E. coli and friends

Which type of chloramphenicol has less resistance and why

Florfenicol; the drug has only one site to acetylate and be inactivated by, while chloramphenicol has two acetylation sites

How does chloramphenicol slow its own metabolism

It is eliminated by the liver, and it is also a cytochrome P450 inhibitor

Why are chloramphenicols good for abscesses and most barrier restricted compartments

It is lipophilic enough to get into cells and across barriers, but isn’t totally stuck to plasma proteins

Which chloramphenicol is prohibited for use in food animals

Chloramphenicol

Side effects associated with chloramphenicols

GIT signs

MAJOR limiting factor of using chloramphenicol

Causes aplastic anemia in humans

T/F: florfenicol causes aplastic anemia in humans

NO, that’s chloramphenicol

Macrolide mechanims of action

Inhibits the 50S ribosomal subunit

Examples of macrolides

• Azithromycin

• Erythromycin

• Clarithromycin

• Tylosin

• Tilmicosin

• Tildipirosin

• Tulathromycin

• Gamithromycin

Macrolide spectrum of activity

• Broad: G+ and G-

• Anaerobes

• Intracellular

Macrolide specifically labeled for Mycoplasma

Tylosin

Why do we really like macrolides for respiratory infections

Accumulates in the lung and pulmonary macrophages

Side effects associated with macrolides

• GIT upset, especially in ruminants and hindgut fermenters

• Anhidrosis in foals

Why should macrolides be used with caution in horses

Prokinetic effects can be dramatic

Specific side effect associated with tilmicosin

Cardiotoxicity; can be fatal in humans

Macrolide that is commonly used in combination for Rhodococcus equi

Clarithromycin/azithromycin (with rifampin)

Lincosamides mechanism of action

Inhibits 50S ribosomal subunit

Exampls of lincosamides

Clindamycin

Lincosamide spectrum of activity

G+, anaerobes, and intracellular

Major indications for clindamycin

Dental or bone infections in small animals

Side effects associated with clindamycin

• GI upset

• Esophageal stricture

• Fatal colitis in ruminants and hindgut fermenters