Lecture 17 - Miscellaneous antibiotics

What is the mechanism of action of bacitracin?

Inhibits peptidoglycan synthesis

What are the characteristics of bacitracin?

-Bactericidal

-Time dependent

What is the spectrum of action of bacitracin?

Gram (+) bacteria (usually combined with gram (-) antibiotics)

How is bacitracin absorbed?

-Not absorbed orally

-Systemic usage causes nephrotoxicity and pain

-Topical use

-Preparations made for oral use in poultry and livestock

What are the characteristics of vancomycin?

-Bactericidal

-Time dependent

What is the mechanism of action of vancomycin?

Inhibits peptidoglycan synthesis in bacterial cell wall (different site than B-lactams)

What is the spectrum of action of vancomycin?

Gram (+) bacteria only

How is vancomycin absorbed?

-No oral absorption

-Systemic administration

What are the possible toxicities associated with vancomycin?

-Painful IM and SQ injection

-Rapid IV administration causes histamine release

-Possible nephrotoxicity and ototoxicity

What are the therapeutic uses of vancomycin? What is important with ELDU?

-Last resort treatment for MRSA in humans (limited use in vet med)

-ELDU in food animals is prohibited

What are the characteristics of Polymyxin B?

-Bactericidal

-Concentration dependent

What is the mechanism of action for polymyxin B?

Interfere with bacterial cell membrane phospholipids (disrupt structure)

What is the spectrum of action of Polymyxin B?

Gram (-) aerobic bacteria (all other bacteria are resistant)

What are the pharmacokinetics of polymixin B?

-Absorption: not absorbed orally, good parenteral absorption

-Distribution: rapid to heart, lungs, liver, kidney and skeletal muscle

-Metabolism/excretion: urine

What are the therapeutic uses for Polymyxin b?

-Bowel sterilization prior to abdominal surgeries

-Flush abdomen

-Topical use

What are the toxicities associated with polymyxin B?

-Nephrotoxicity

-Respiratory paralysis

-CNS dysfunction (anorexia, pyrexia, depression)

What is the spectrum of action of rifampin?

-Gram (+) bacteria, some use in gram (-) bacteria

-Antifungal and antiviral

What is the mechanisms of action of rifampin?

Inhibits DNA dependent RNA polymerase (DdRp)

What are the characteristics of rifampin?

-Bactericidal

-PAE

-Time dependent

Why should you always combine rifampin with another antibiotic?

-High resistance rate if used alone

-Very toxic to liver

What are the pharmacokinetics of rifampin?

-Absorption: rapid oral absorption

-Distribution: Intracellular and extracellular

-Metabolism/elimination: metabolized in liver (INDUCES p450) and excreted in bile

What are the toxicities associated with rifampin?

-Red-orange color in urine, feces, saliva, and tears (Non-toxic)

-Hepatotoxicity

-Accelerates metabolism of heart medications

-Teratogenic (not for use in pregnant animals)

What are the therapeutic uses of rifampin?

-Rhodococcus equi with a macrolide

-Proliferative enteropathy in foals

-Tuberculosis (in humans)

What is important with nitrofurans in food producing animals?

Banned due to carcinogenic effects

What is the mechanism of action of nitrofurans?

Inhibits bacterial carbohydrate synthesis

What are the characteristics of nitrofurans?

-Bacteriostatic

-Time dependent

What is the spectrum of action of nitrofurans?

-Broad spectrum

-Highly effective against gram (-) bacteria and some gram (+)

-Antiprotozoal

What are the pharmacokinetics of nitrofurans?

-Administration: oral and topical, not good systemically

-Distribution: poor since it’s rapidly eliminated

-Metabolism/excretion: urinary tract

What are the toxicities associated with nitrofurans?

-Mild GI upset

-Rarely neurologic, pulmonary, hepatic, and allergic reactions

-Cannot be used in pregnant animals

-Carcinogenic concerns

What are the therapeutic uses of nitrofurans?

-Lower urinary tract infections

-Infections in eyes, ears, MM, and skin

What are the characteristics of nitroimidazoles (metronidazole and ronidazole)?

-Bactericidal

-Time dependent

What is the spectrum of action of metronidazole?

-Protozoa causing intestinal disease

-Obligate anaerobes

What is the pharmacokinetics of metronidazole?

-Administration: good orally

-Distribution: Wide distribution, can penetrate CNS

-Metabolized/eliminated: metabolized in liver, eliminated in urine and feces

What are the toxicities associated with metronidazole?

-Avoid in pregnant and nursing animals

-CNS toxicity (high doses)

-Anorexia, neutropenia, vomiting, reddish brown urine

-Immunosuppressive

What is important with metronidazole in food producing animals?

Prohibited

Why is it important that rifampin induces p450?

Most other antibiotics inhibit p450 so there are a lot of drug-drug interactions