PHA 520 - L2 Antibiotics (Anti-infectives)

What are antimicrobials (anti-infective drugs)?

Agents that kill or inhibit the growth of microorganisms. They include antibacterials/antibiotics, antifungals, and antivirals.

What is an antibiotic?

An antibacterial agent that destroys or inhibits the growth of microorganisms and is used to prevent or treat infectious disease.

What is MOA (mechanism of action) in antimicrobial therapy?

The mechanism by which an antimicrobial destroys or inhibits the growth of its target. Antimicrobial MOAs target biochemical differences between bacterial (prokaryotic) and animal (eukaryotic) cells.

What is selective toxicity?

The ability to kill an invading organism without harming the host's cells by taking advantage of biochemical differences between microorganisms and animal cells. Selective toxicity is relative, so drug concentration must be controlled to kill/inhibit the organism while remaining safe for the host.

What is a bacteriostatic antibiotic?

An antibiotic that arrests bacterial replication and growth, limiting spread while the host immune system eliminates the pathogens. It requires a functional immune system.

What is a bactericidal antibiotic?

An antibiotic that kills bacteria.

Why should bacteriostatic and bactericidal antibiotics generally not be combined?

Their interaction may be antagonistic.

What is antibiotic spectrum?

The range of organisms against which an antibiotic is effective.

What is the difference between broad-spectrum and narrow-spectrum antibiotics?

Broad-spectrum antibiotics work against many organisms; narrow-spectrum antibiotics work against specific families of organisms.

Which antibiotic spectrum is preferred when possible?

Narrow-spectrum therapy is preferred when possible because it specifically targets the organism.

What is empiric therapy?

Initiating treatment before a firm diagnosis has been determined; an "educated guess" directed against the anticipated and likely cause of infection based on experience.

When may a bacterial culture be obtained before starting empiric therapy?

When the infection is particularly severe (e.g., sepsis), chronic, or has failed to respond to the first antibiotic choice.

What is combination antimicrobial therapy?

Using more than one antimicrobial at the same time.

Why is combination antimicrobial therapy used?

To treat mixed infections, prevent emerging drug resistance, minimize toxicity, achieve synergistic activity, and prevent inactivation of an antibiotic by bacterial-produced enzymes.

What is responsible antimicrobial use?

Using antimicrobials only when appropriate by obtaining an accurate diagnosis, determining whether and when antimicrobial therapy is needed, tailoring treatment to the patient, using the narrowest effective spectrum and shortest necessary duration, and considering non-antimicrobial interventions when appropriate.

Why is responsible antimicrobial use important in veterinary medicine?

It benefits the individual animal and public health while helping limit antimicrobial resistance, including the transfer of resistant bacteria from animals to humans.

What role do veterinarians have in antimicrobial stewardship?

Control and eradicate zoonoses and use antibiotics appropriately, especially in food animals, to limit transfer of antibiotic resistance to humans and emergence of resistant bacterial strains.

What are Rickettsial diseases?

A group of infectious diseases caused by rickettsia bacteria. They are very small bacteria that must invade cells to multiply and therefore behave somewhat like viruses.

How are most Rickettsial diseases transmitted?

Through bites of external parasites/arthropod vectors such as ticks, fleas, lice, and mites.

What are examples of intracellular/Rickettsial-type infections listed in this lecture?

Borrelia (Lyme disease), Ehrlichia spp., Anaplasmosis, Rocky Mountain Spotted Fever (RMSF), and Salmon Poisoning.

How is Lyme disease transmitted?

Borrelia burgdorferi is transmitted by a deer tick vector.

What are the general characteristics of fluoroquinolones?

Broad-spectrum, rapidly bactericidal antibiotics with rapid oral absorption, wide tissue distribution, long half-lives, and concentration-dependent activity that permits SID (once-daily) dosing.

What are examples of fluoroquinolones?

Enrofloxacin (Baytril), marbofloxacin (Zenequin), orbifloxacin (Primor), ciprofloxacin (Cipro), and pradofloxacin (Veraflox).

What are the major toxicities of fluoroquinolones?

CNS toxicity, chondrotoxicity, and ocular/retinal toxicity.

What CNS toxicity can fluoroquinolones cause in dogs?

Increased frequency and intensity of seizures.

What is fluoroquinolone chondrotoxicity?

Erosion/damage of articular cartilage, especially developing cartilage in rapidly growing juvenile dogs.

When should fluoroquinolones be avoided in growing dogs?

Use very judiciously in rapidly growing juveniles; avoid in small-to-medium breed dogs until about 8 months and large breeds until about 18 months.

What species-specific ocular toxicity can fluoroquinolones cause?

Cats are particularly susceptible to retinal toxicity, which can cause blindness; doses should therefore be kept low.

Can fluoroquinolones be used extra-label in food-producing animals?

No. Extra-label use in food-producing animals is prohibited.

What are the general characteristics of tetracyclines?

Bacteriostatic, broad-spectrum antibiotics that enter almost all tissues and body fluids at high levels, readily penetrate intracellularly, and cross the blood-brain barrier.

What are examples of tetracyclines?

Doxycycline and tetracycline.

What are the major toxicities/adverse effects of tetracyclines?

They chelate calcium in teeth and bones, causing dental enamel abnormalities/discoloration during development; may delay or impair fracture healing; and oral dosing can disrupt normal GI microflora.

Why should tetracyclines be avoided in pregnant animals?

They chelate calcium during fetal tooth and bone formation, potentially causing hypoplastic dental enamel and yellow-brown tooth discoloration.

What GI flora problems can oral tetracyclines cause in animals?

They may disrupt rumen microflora in ruminants and colonic flora in horses.

What important toxicity is specifically associated with doxycycline in cats?

Esophageal stricture.

How can the risk of doxycycline-induced esophageal stricture in cats be reduced?

Use a liquid formulation or chase the dose with water.

What are the general characteristics of chloramphenicol?

A bacteriostatic, broad-spectrum antibiotic with rapid and wide distribution to tissues, including the CNS and eye, and extensive hepatic metabolism.

Which animals are at increased risk of chloramphenicol toxicity?

Cats, young animals, and patients with liver disease because they may lack adequate microsomal enzyme activity for metabolism.

What are the major hematologic toxicities of chloramphenicol?

Dose-related bone marrow suppression and non-dose-related aplastic anemia.

What precaution should owners take when administering chloramphenicol to pets?

Wear latex gloves because of the risk of human exposure and aplastic anemia.

Can chloramphenicol be used in food animals?

No. Chloramphenicol is banned from use in food animals in the United States.

What are the general characteristics of sulfonamides ("sulfas")?

Bacteriostatic antibiotics; most current formulations are potentiated sulfonamides combined with trimethoprim or ormetoprim to produce synergistic action. They are orally absorbed and extensively distributed throughout tissues and fluids.

What are examples of sulfonamides?

Sulfamethoxazole-trimethoprim (SMZ-TMP/Bactrim), sulfadimethoxine-ormetoprim, and sulfadimethoxine.

What major eye toxicity can sulfonamides cause in dogs?

Keratoconjunctivitis sicca (KCS/"dry eye"), especially with prolonged use greater than 10–14 days; it may not be reversible.

Which dogs are at greatest risk for sulfonamide-associated KCS?

Small dogs.

What immune-mediated adverse effects can sulfonamides cause?

Polyarthritis, vasculitis, anemia/thrombocytopenia, urticaria, and glomerulonephritis.

Which dogs are particularly susceptible to sulfonamide immune-mediated reactions and hepatotoxicity?

Large-breed dogs, especially Doberman Pinschers; hepatotoxicity is also more common in Dobermans and Rottweilers.

What other toxicities/adverse effects are associated with sulfonamides?

Interference with thyroid hormone synthesis, hepatotoxicity, folic acid deficiency in cats with prolonged use, and renal crystalluria especially with inadequate water intake.

What are the general characteristics of aminoglycosides?

Primarily gram-negative antibiotics that are poorly absorbed from the GI tract and therefore generally require parenteral administration. Examples include amikacin and gentamicin; neomycin and tobramycin are commonly used topically.

What are the two major toxicities of aminoglycosides?

Ototoxicity/vestibular toxicity and nephrotoxicity.

Is aminoglycoside ototoxicity reversible?

Generally no; ototoxicity is considered irreversible and may include vestibular impairment.

Is aminoglycoside nephrotoxicity reversible?

Generally yes, but recovery may be prolonged.

What factors increase the risk of aminoglycoside nephrotoxicity?

Young or old age, compromised renal function, dehydration, concurrent loop diuretics such as furosemide, sepsis, and increased total dose or treatment duration.

How can aminoglycoside toxicity be reduced?

SID (once-daily) dosing reduces toxicity.

Why are aminoglycosides generally not recommended for food animals?

They can leave prolonged tissue residues for 6–18 months.

What are the general characteristics of metronidazole (Flagyl)?

It has antibacterial and antiprotozoal activity, particularly against obligate anaerobes; is rapidly absorbed IV or PO; distributes widely; crosses the blood-brain barrier; and can reach therapeutic concentrations in pus.

What is the major toxicity of metronidazole?

Neurotoxicity with high or prolonged doses.

What are signs of metronidazole neurotoxicity?

Tremors, ataxia, muscle spasms, and convulsions/seizures.

How long can metronidazole neurotoxicity take to resolve?

Days to months; some dogs may develop uncontrollable seizures.

What adverse effects can metronidazole cause in cats?

GI upset, including anorexia and profuse salivation.

Why should metronidazole be avoided during pregnancy?

It is considered carcinogenic/mutagenic in the lecture and should be avoided in pregnant animals, especially during the first trimester.

Which antibiotic classes in this lecture are concentration-dependent and bactericidal?

Fluoroquinolones and aminoglycosides.

What is the key dosing principle for concentration-dependent antibiotics?

Achieve a high peak concentration above the MIC; they can often be given less frequently at higher doses, but toxicity must be considered.

What is MIC (Minimum Inhibitory Concentration)?

The lowest concentration of an antimicrobial that inhibits visible bacterial growth during the incubation period.

What is the most frequently used antibiotic susceptibility test mentioned in the lecture?

Kirby-Bauer disk diffusion method.