Antibiotics

Question 1

Beta-lactam antibiotics

Answer 1

• Agents: Penicillins, Cephalosporins, Monobactams, Carbapenems
• MOA: Irreversibly inhibit enzymes that crosslink peptidoglycan polymers in cell wall > cell bursts - inhibit Penicillin Binding Proteins (PBPs)
• Effective against: gram +organisms
• Do not penetrate normal BBB
• Toxicity: Hypersensitivity reactions, Anorexia, nausea, vomiting, diarrhea (aminopenicillins), Procaine penicillin- CNS excitation
• Emergent resistent organisms HUGE problem
• Very commonly used in small and large animals

Question 2

What does the beta-lactam ring confer?

Answer 2

• Antibacterial activity
• Hydrolytic instability
• Microbial resistance (most)

Question 3

What are the 5 subgroups of penicillins?

Answer 3

1. Natural
2. Beta-lactamase resistant
3. Aminopenicillins
4. Extended-Spectrum
5. Augmented

Question 4

Describe properties of beta-lactamase-resistant penicillins

Answer 4

Agents: dicloxacillin, methicillin, cloxacillin

• narrower spectrum than pen G
• must confirm sensitivity

Question 5

Describe cephalosporins

Answer 5

• 4 generations
• newer agents: greater gram - coverage, greater resistance to b-lactamase, and are more expensive (limits use in LA- cephapirin only)
• Toxicity: relatively non-toxic, cross-hypersensitivity w/ penicillin, GI disturbances, chronic use = overgrowth
• Cats: cephaloridine + furosemide (nephrotoxic): Discontinued

Question 6

2nd generation cephalosporins: Cefoxitin

Answer 6

Spectrum: Good Q1/Q2, better Q3 than 1st gen.

Uses: limit to cases supported by C&S

Question 7

1st Generation Cephalosporin: Cephalexin

Answer 7

• 1st gen
• approved ONLY for dogs
• Uses: 1st line in S.A.; treatment for bacterial pyoderma
• Spectrum: Good Q1/Q2 + some Q3
• good oral bioavailability (chewable)

Question 8

3rd Generation Cephalosporin: Ceftiofur

Answer 8

• 3rd gen
• Formulations approved in: cattle, horses, swine, chickens, turkeys, goats, dogs
  
  • given parenteral, IM or SC, once daily protocols for most species
  • good tissue distribution
• Spectrum: improved gram - over 2nd gen
• Uses: Most have limited use

Question 9

Imipenem

Answer 9

• beta lactam
• belongs to carbapenem class
• expensive (IV)
• Effective against Q1/2/4
• limit use to highly-resistant causes
  
  • Gram - beta-lactamase + organisms that are pen-resistant

Question 10

Cell Wall Inhibitors/Beta Lactams

Answer 10

• two major groups (penicillin, cephalosporins)
• most orally absorbed and distribute in body
• do not cross BBB
• ineffective against intracellular organisms
• Elimination: primarily renal acid secretion pump/filtration
• Penicillins are commonly used for UTIs
• Safe: little organ toxicity
• widely used in small/large animals

Question 11

Aminoglycosides: Gentamycin, Amikacin

Answer 11

• Agents:
  
  • Gentamycin: dogs & cats
  • Amikacin: dogs, horses, neonatal foals
• bactericidal agents (concentration-dependent)
• MOA: Cause irreversible inhibition of protein synthesis by binding to ribosomal subunit (30S)
• Organ Toxicities: Nephrotoxicity, ototoxicity, neuromuscular weakness, anaphylactic reactions
• Resistance: enhanced enzymatic degradation (not amikacin), decr membrane transport, altered ribosomal binding site
• Effective against: Gram - (esp. aerobic bacilli), a few Gram +
• Drug interactions: synergystic w/ beta-lactams, loop diuretics- concurrent use may incr toxicity, Cisplatin, amphotericin B, polymixin B = incr nephrotoxin

Question 12

Tetracyclines

Answer 12

• Agents:
  
  • ​Oxytetracycline: large animals ONLY
  • Doxycycline: dogs/cats, crosses BBB, hepatic, not renal elimination, DO NOT DRY PILL, erlichiosis
• bacteriostatic - (time-dependent w/ persistent effects)
• MOA: reversible inhibition of protein synthesis by binding 30S ribosomal subunit
• amphoteric compounds
• Effective against: gram +, gram - anaerobes, and Mycoplasmas
• Toxicity: GI disturbances, superinfections (cats, horses), ruminal dysfunction, pain & swelling (IM), arrhythmias (IV) shock - horses (oxytetracycline)
• Drug interactions:
  
  • Sucralfate- decr absorption
  • Antacids/Al- bind> decrabsorption
  • Warfarin: dose reduction due to decrease in prothrombin

Question 13

Macrolides

Answer 13

• Agents:
  
  • Azithromycin: less GI effects, long T1/2 with good Fpo, effective against Toxoplasma & resistant-type R. Equi in foals
  • Clindamycin
  • Tylosin
• all contain a lactone ring (basic)
• MOA: Reversible inhibition of ribosomal protein synthesis (50S)
• bacteriostatic (can be -cidal at high doses); time-dependent w/ pesistent effects
• Uses: resp infections
• Effective against: gram +, few gram -, and intracellular organisms (Rickettsia and Mycoplasma spp)
• Does not cross BBB
• Toxicity: major effects within GI system
  
  • EXTREME CAUTION in adult horses - colitis/diarrhea
  • guinea pigs and rabbits - Clostridial colitis
  • Tylosin causes rectal swelling in sheep
• Drug interactions: Bind directly to many drugs, prolongs effect of warfarin, elevated digoxin levels (dogs), major cross-resistance within group

Question 14

Phenicols

Answer 14

• Agents:
  
  • Chloramphenicol: NOT APPROVED IN FOOD ANIMALS
  • Florfenicol: derivative of chloramphenicol that is approved for use in FOOD ANIMALS
• MOA: reversible inhibitor of ribosomal protein synthesis (50S)
• Bacteriostatic
• All are organic bases
• Crosses BBB
• Toxicity: - GI disturbances esp. cats, reduced liver metabolism, decr clearance, b.m. suppression
• Drug Interactions: Aspirin - decr hepatic metabolism, may prolong ketamine/midazolam effects, may delay hepatic metabolism of lidocaine

Question 15

Potentiated Sulfonamides

Answer 15

• Agents: Sulfamethoxazole/Trimethopri, trimethoprim/sulfadiazine
• Bacteriocidal combo of two drugs > dual block of folic acid synthetic pathway
• MOA: interfere w/ folic acid synthesis necessary for pyramidine synthesis (DNA precursors)
• Effective against: gram + and gram - (not Pseudomonas or B. Fragilis)
• Toxicity: local tissue irritation, irreversible KCS, renal crystallization, idiosyncratic immune reactions, hypersensitivity, IMHA (rare)
• Drug Interactions: -Disrupt protein binding/renal tubular secretion of acidic drugs (e.g. Penicillins, barbiturates, phenylbutazone), antagonized by procaine (PABA), oral antacids reduce absorption

Question 16

Fluoroquinolones

Answer 16

• Agents:
  
  • Enrofloxacin
  • Marbofloxacin: > AUC than Enro
• MOA: inhibit bacterial DNA gyrase (aka Topisomerase II) > blocks bacterial DNA transcription, accumulate within phagocytes
• Bacteriostatic (concentration-dependent kill)
• Effective against: gram - and aerobes
• Toxicity: relatively safe, high dose = nephrotoxic, local tissue irritation (birds), mild GI upset
• Drug Interactions: Antacids/food/sucralfate reduce GI absorption, avoid w/ NSAIDs (seizures), cyclosporine- metabolism may decr/incr nephrotoxicity, flunixin-may incr its 1/2 life, theophylline: blood levels may be incr, sucralfate- may decrease enro’s absorption

Question 17

Area under the inhibitory Concentration Curve (AUICC)

Answer 17

Area under the plasma concentration time curve that is ABOVE THE MIC

• indicates overall “intensity of exposure” to an antibiotic
• >125 indicate incr successs/decr resistance

Question 18

Metronidazole

Answer 18

• concentration dependent bactericidal
• MOA: unknown; generates reactive O2 species that disrupt DNA and kill organism
• Effective against: most anaerobes and protozoal organisms
• Crosses BBB
• Adverse effects: anorexia, vomiting, diarrhea, neutrophilia, hepatotoxicity, neurotoxicity
• Drug interactions: competes for same CYP450 family as Cimetidine/Cyclosporine, Phenobarbital decr levels, Met incr levels of 5-Fluorouracil/may incr toxicity
• Approved in: dogs, cats, rabbits, rodents, small mammals, and horses
• Prohibited for use in FOOD ANIMALS

Question 19

Lincosamides

Answer 19

• Agent: Clindamycin, Lincomycin
• Bacteriostatic (time-persistent w/ persistent effects)
• MOA: binds to 50S and prevents protein synthesis by bacteria
• Effective against: most anaerobes, Strep, and Staph spp.
• Uses: dogs/cats to treat oropharyngeal infections, resp infections, sepsis, and bone infections

Question 20

What antibiotics cross the BBB?

Answer 20

Chloramphenicol, Doxycycline, Metronidazole, Penicillins/cephalosporins (incr in face of meningitis)

Question 21

What are some polypeptide agents used?

Answer 21

Vancomycin

Bacitracin

Polymixin:

MOA: causes cell membrane leakage, bacteriocidal