What are the four categories of antibiotics?
- Inhibitors of cell wall synthesis
- Inhibitors of cell membranes
- Inhibitors of protein synthesis
- Inhibitors of nucleic acid synthesis
Name three classes of drugs that are cell wall inhibitors.
- B-lactams
- Glycopeptides
- Bacitracin
What are the four categories of drugs under B-lactams?
- Penicillins
- Cephalosporins
- Carbapenems and monobactams
- B-lactamase inhibitors
What is the MOA of Penicillins?
B-lactam ring binds to an enzyme (DD-transpeptidase) that would normally catalyze the cross links between peptidoglycan layers. DD-transpeptidase is also known as Penicillin binding protein.
What is another name for DD-transpeptidase?
Penicillin binding protein
What do Penicillins do?
They can kill Gram +, some Gram - and anaerobes.
They are bactericidal and time-dependant.
What is the resistance of Penicillins?
Bacteria that do not have cell walls lack Penicillin binding protein, therefore they have poor permeability (Gram -) and are not actively dividing. All of these have intrinsic resistance. Acquired resistance is through chromosomal or plasmid mediated secretion of B-lactamases.
T/F: Formulation of Penicillin affects its absorption rate.
True
T/F: Penicillins are weak acids that tend to ionize and stay in the ECF.
True.
High concentration in kidneys, synovial fluid, lungs, skin, and soft tissue. Poor penetration into the eye, prostate, and CNS.
How are Penicillins excreted from the kidney?
Unchanged!
Some have biliary excretion (amoxicillin and ampicillin.)
Renal excretion of Penicillins can be blocked by ______ and other _____ _____ (same for all B-lactams.)
Renal excretion can be blocked by probenecid and other weak acids.
What are some types of Penicillin?
Penicillin G, Amoxicillin, Ampicillin, Cloxacillin, Ticarcillin, Amoxicillin-Clavulanic Acid.
What are some adverse effects of Penicillins? (5)
- Generally a wide safety margin
- Can have hypersensitivity reactions, especially in horses, and cross-hypersensitivity is possible.
- Can have alterations in GI microflora, leading to dysbiosis, GI stasis, and endotoxemia.
- Hyperkalemia/arrhythmia
- CNS excitement/convulsions.
Name three features of Penicillin G.
- Kill Gram + and anaerobic bacteria (narrow spectrum.)
- Susceptible to B-lactamases
- Used more often in large animals.
Name three features of Ampicillin and Amoxicillin.
- Kill more Gram - bacteria but do kill slightly less Gram +.
- Susceptible to B-lactamases
- Used in small animals, equines and cattle mastitis.
Name two features of Cloxacillin.
- B-lactamase resistant!
2. Used to treat bovine mastitis.
Name three features of Ticarcillin.
- “Anti-pseudomonas” drug
- Not frequently used
- Used as a topical for ear infections.
What are B-lactamase Inhibitors?
They are a type of drug that can be combined with B-lactams because they combat B-lactamase.
These drugs are not antibiotics themselves but are combined with a B-lactam (usually Penicillin) and allow them to do their job more effectively.
Name three B-lactamase Inhibitors.
- ** Clavulanic acid **
- Sulbactam
- Tazobactam
How many generations of drugs are Cephalosporins?
Four
What does a first generation cephalosporin do?
- Effective against Gram + bacteria.
- It is less susceptible to B-lactamases than Penicillins.
- It is not effective against Gram - bacteria.
What do second generation cephalosporins do?
They are similar to first generation but have greater efficacy against Gram - bacteria (more broad spectrum.)
What are third generation cephalosporins used for?
- They are more effective against Gram - and anaerobic bacteria.
- They have less Gram + activity (except for Ceftiofur.)
What are fourth generation cephalosporins used for?
- Broad spectrum drug with activity against Gram + cocci, Gram - bacilli, and pseudomonas.
- They are resistant to B-lactamases from Gram -.
- They are the “big-gun” cephalosporin.
Which generation of cephalosporins is considered the “big-gun” to use?
Fourth generation
Name three first generation cephalosporins.
- Cephalexin
- Cefazolin
- Cephapirin
What is an example of a second generation cephalosporin?
Cefoxitin
Ceftiofur, Cefpodoxime, and Cefovecin are examples of what generation of cephalosporin?
Third Generation
Name one drug that is a fourth generation cephalosporin.
Cefepime
What is the MOA of Cephalosporins?
Same as Penicillins.
B-lactam ring binds to an enzyme (DD-transpeptidase) that would normally catalyze the cross links between peptidoglycan layers. DD-transpeptidase is also known as Penicillin binding protein.
What are Cephalosporins used for?
- Great against Gram +
- Better than Penicillins against Gram -
- Variable against anaerobes
- Slightly more broad spectrum than Penicillins
T/F: Cephalosporins are bactericidal and time-dependent.
True
T/F: Cephalosporins have lower resistance than Penicillins.
False. They have the same amount of resistance.
Cephalosporins are less susceptible than Penicillins to B-lactamases. The B-lactamases that impact them are referred to as what?
Cephalosporinases
Are cephalosporins polar and lipid soluble?
They are polar and the are poorly lipid soluble.
T/F: Cephalosporins have great protein binding ability and are poor at metabolization and renal excretion.
False.
Cephalosporins have variable protein binding ability and variable metabolism and renal excretion.
What are the adverse effects of Cephalosporins? (5)
- Hypersensitivity reactions
- Acute anaphylaxis or local allergic reactions.
- Possible IMHA
- Alterations in intestinal microflora lead to clostridial overgrowth in guinea pigs, hamsters, and rabbits. Can also cause dysbiosis, GI stasis and endotoxemia.
- Cross hypersensitivity is variable.
This class of drugs leads to clostridial overgrowth in the GI tact of small rodents (rabbits, hamsters, and guinea pigs.)
Cephalosporins
What drug is commonly used in small animals as first-line oral antibiotics and is a first generation cephalosporin?
Cephalexin/Cefadroxil
What is Cefazolin used for?
First generation cephalosporin that is used prophylactically during surgery for small animals and horses. It should only be given parenterally.
Which cephalosporin is used to treat mastitis in cattle (intramammary infusion)?
Cephapirin
What is Cefoxitin and what is is used for?
Cephoxitin is a second generation cephalosporin that is given IV to treat serious infections.
What is the main use for Ceftiofur?
Used in large animals for foot rot, respiratory disease and mastitis.
What are some uses for Cefovecin?
Cefovecin is commonly used in small animals. It is injectable and highly protein bound - unusually long duration of activity (dosed q7-14 days.) It is labeled for pyoderma due to Staph and Strep in dogs and Pasteurella in cats.
What are some uses for Cefpodoxime?
Cefpodoxime is used in small animals for Gram - infections. It comes as a pro-drug ester that is converted to an active antibiotic after GI absorption.
Name two Carbapenem and Monobactam drugs.
Imipenem and Meropenem
What are the uses for Carbapenem and Monobactam drugs?
They are able to kill Gram - and Gram + (not MRStaph). They are resistant to most B-lactamases.
T/F: Imipenem and Meropenem are used as “Big Guns” for some extended spectrum B-lactamase (ESBL) producing E. coli.
True
T/F: Carbapenems and Monobactams are bactericidal and time-dependent.
True
What are the adverse effects of Imipenem (Carbapenem)?
- CNS effects - tremors and seizures!
- Hypersensitivity reactions
- Vomiting, anorexia, diarrhea
- Local reactions (hair loss at injection site and thrombophlebitis.)
How do Carbapenems acquire resistance?
Through chromosomal mediated or plasmid mediated secretion of B-lactamases.
What is the MOA for Glycopeptides (Vancomycin)?
Vancomycin binds to the peptidoglycan ‘ends’ thus preventing both formation of the long peptidoglycan polymers needed to form the cell wall and impairing cross-linking of the polymers that do form. Leads to structural instability and susceptibility to osmotic pressure.
Which drug class is Vancomycin in?
Glycopeptides
Which drug is the ‘Big Gun’ for treating MRSA infections (Gram +)?
Vancomycin
T/F: Vancomycin is a bacteriostatic and time-dependant drug.
False.
Vancomycin is bactericidal and time dependent!
What kind of resistance does Vancomycin have?
- Intrinsic lack of susceptibility in Gram -
2. Acquired resistance possible through various chromosomal and plasmid mediated resistance genes.
How should Vancomycin be administered and does it have toxic effects?
Vancomycin should be administered as a slow IV infusion and it has the potential for nephrotoxicity.
This drug is banned in food producing animals and is a member of the Glycopeptide class.
Vancomycin
What is the MOA for Bacitracin?
Binds to the protein that allows the glycopeptide building-blocks to be transported to the cell wall, thus impairing building of the peptidoglycan polymers.
Bacitracin is specifically used to kill Gram __.
Gram +
How do you administer Bacitracin?
Only use it topically. It has poor oral absorption.
Is Bacitracin bacteriostatic or bactericidal?
It may be bacteriostatic or bactericidal depending on the bacterial strain and the concentration of the drug.
Is resistance a major problem with Bacitracin?
No.
Does Bacitracin have any toxic potential?
Yes. It has potential for nephrotoxicity if used systemically (only use it topically!)
What is the MOA of Polymyxins?
It is an inhibitor of cell membranes. It acts as cationic detergents that interact with the phospholipid cell membrane and break it down. Cytoplasm leads out causing rapid cell death (active division is not required.)
What are two types of Polymyxins?
- Polymyxin B
2. Polymyxin E (Colistin)
What type of bacteria do Polymyxins kill?
Gram -, including pseudomonas.
How are Polymyxins administered?
Only administer topically!
T/F: Polymyxin is bacteriostatic.
False. It is bactericidal.
Do Polymyxins have acquired resistance?
Not usually. Resistance is rare.
Do Polymyxins have any toxic effects?
Yes. They are nephrotoxic and neurotoxic.
T/F: Polymyxins are available in double/triple antibiotics.
True
What 5 classes of drugs are inhibitors of protein synthesis?
- Tetracyclines
- Amphenicols
- Macrolides/Lincosamides
- Aminoglycosides
- Others
What is the MOA of Tetracyclines?
Inhibits transfer-RNA from binding to the 30s ribosomal subunit mRNA complex which inhibits peptide elongation.
What 5 drugs are classified as Tetracyclines?
- Oxytetracycline
- Chlortetracycline
- Doxycycline
- Minocycline
- Tetracycline
What do Tetracyclines kill?
Relatively broad spectrum. They are effective against a variety of both Gram + and Gram - bacteria, as well as other organisms (ex: rickettsiae, spirochetes, etc.) They have a moderate effect against anaerobes and the inhibit Matrix Metalloproteinases (MMP), anti-inflammatory.
What kind of resistance do tetracyclines have?
Acquired resistance is plasmid or transposon mediated (altered permeability/uptake, inactivating enzymes, and altered targets.) Cross resistance is seen within the class.
How are tetracyclines administered?
Parenterally but there are other formulations for other routes of administration (ex: oral.)
Which tetracycline is NEVER used IV in horses?
Doxycycline
What are some other ‘fun facts’ about tetracyclines?
- They have a wide distribution once absorbed.
- Plasma protein binding is variable.
- Renal excretion is variable.
- Some GI excretion and inactivation.
What kind of GI effects do tetracyclines have?
- Biliary and non-biliary routes
- Some enterohepatic circulation
- Doxy is mostly eliminated in the feces.
- Minocycline is mostly metabolized by the liver.
Which tetracycline is mostly metabolized by the liver?
Minocycline
Which tetracycline is mostly eliminated in the feces?
Doxycycline
What toxicities are associated with tetracyclines? (4)
- Discoloration of the teeth in growing animals.
- GI disturbances (vomiting, anorexia, etc.)
- Alterations of GI microflora
- Bitter taste can cause hyper salivation in cats.
What is Oxytetracycline used for?
Broad spectrum used in food animal medicine and is also labeled for bees.
Chlortetracycline is used in what animals?
Food animals
What is the most commonly used tetracycline in small animals?
Doxycycline
What are some things to know about Doxycycline?
- Most commonly used tetracycline in small animals.
- Generally used PO (no IV in horses because it causes arrhythmias, collapse, and death.)
- Chase with water in felines to avoid esophageal stricture!!!
- Commonly used to treat rickettsia, Lyme, and to eliminate Wolbachia in heartworm dz.
When you give Doxycycline to a cat, why do you chase it with water?
Without water, Doxy will cause esophageal stricture in the cat!
What is the alternative drug that is used when there are shortages of Doxycycline?
Minocycline
T/F: Doxycycline has a higher bioavailability in horses than Minocycline.
False! Minocycline has a higher bioavailability in horses than Doxy.
What is the MOA for the Amphenicol drug class?
Irreversibly binds to and inhibits peptidyltransferase associated with the 50s subunit of the ribosome, which inhibits peptide bond formation between amino acids.
What are two drugs that fall in the Amphenicol drug class?
Chloramphenicol and Florenicol
What can Amphenicols kill?
They are relatively broad spectrum. They are effective against a variety of Gram +, Gram -, and anaerobes.
T/F: Amphenicols are bacteriostatic and time-dependant.
True
What kind of resistance do amphenicols have?
Acquired resistance tends to be plasmid mediated.
- Various acetyltransferases and nitroreductases. - Decreased permeability - Decreases sensitivity of ribosomes. - Enterobacter tend to be resistant.
Where are amphenicols metabolized?
In the liver
Chloramphenicol inhibits what?
Cytochrome P450
How are amphenicols excreted?
Variable amounts of parent drug are excreted in the urine.
What are the adverse effects of amphenicols?
- **Bone marrow suppression (non regenerative anemia, thrombocytopenia, leukemia) **
- Vomiting, diarrhea, anorexia
- Imbalances of normal flora.
- Numerous drug interactions with Chloramphenicol.
- Minimal side effects with Florfenicol.
- Dehydration and reduced fluid intake.
What are some ‘fun facts’ about Chloramphenicol?
- Illegal to use in food producing animals.
- Used in small animals for MRSA/MRSP
- Highly metabolized in the liver by glucuronidation (increased toxicity in cats when used long term.)
What are some ‘fun facts’ about Florfenicol?
- Used in large animals (including food animals.)
- Injectable only!
- Minimal side effects
- May work against bacteria resistant to Chloramphenicol (less affected by acetyltransferase.)
What is the MOA for Macrolides/Lincosamides?
Bind to the 50s ribosomal subunit and inhibit peptide chain elongation by inhibition translocation and movement along the mRNA.
What are 5 Macrolide drugs?
- Erythromycin
- Tylosin
- Tilmicosin
- Tulathromycin
- Azithromycin
What are 3 Lincosamide drugs?
- Lincomycin
- Pirlimycin
- Clindamycin
What is an example of a Pleuromutilin drug?
Tiamulin
What are examples of Streptogramins?
Streptogramin A and B
What are Macrolides and Lincosamides used to kill?
They are effective against Gram+ and some Gram -, as well as bactericides, mycoplasma, and rickettsia. Lincosamides have more anaerobic activity.
Are Macrolides/Lincosamides bacteriostatic?
Yes. They are bacteriostatic and they may be bactericidal in some situations. They are also time dependent.
What kind of resistance do Macrolides and Lincosamides have?
Chromosomal mutation or plasmid mediated resistance. There can also be cross resistance between groups.
What are some ‘fun facts’ about Macrolides and Lincosamides?
- They have various routes of administration.
- They are generally widely distributed (higher conc. in the lungs, bones, prostate, and milk.)
- **Some macrolides accumulate in phagocytes, which can prolong clinical effect. **
- Extensively metabolized in the liver; Macrolides undergo enterohepatic circulation, while Lincosamides are excreted as active and inactive metabolites in bile.
What are the adverse effects of Macrolides/Lincosamides?
- Local reactions at the injection site.
- GI disturbances
- Cardiotoxicity with Tilmicosin
- Numerous drug interactions
What Macrolide causes cardiotoxicity?
Tilmicosin
How is Erythromycin administered?
- IM use in cattle for bovine respiratory disease.
- Poor oral absorption but good distribution once absorbed.
Does Erythromycin cross the BBB?
No!
What are some adverse effects of Erythromycin?
- Vomiting can occur with oral use.
- Use extreme caution in horses that are >4 months of age!
Is Erythromycin okay to use in small herbivores (like rabbits)?
No
What are the main uses for Erythromycin?
It is used in combination with Rifampin for Rhodococcus equip in foals and it is used to treat bovine respiratory diseases.
What is Tylosin used for and who is it contradicted to use in?
Tylosin is used in cattle and swine for antibiotic responsive diarrhea. It is contraindicated in horses and small herbivores.
Is Tilmicosin used in large animals or small animals?
Large animals
What toxic effect does Tilmicosin have?
It is cardiotoxic. Accidental self-injection can be fatal in HUMANS!!!
Tulathromycin is approved for use in who?
Beef, non-lactating dairy cattle, and swine.
What is Tulathromycin used for?
Is has good efficacy against Gram - bacteria and it is less effected by efflux.
What are some uses to Azithromycin?
- Used sometimes in small animals for Mycoplasma, Chlamydophil, etc.
- May be used in foals (PO) for Rhodococcus equi.
What is Lincomycin used for? Who is it contraindicated against?
Lincomycin is used in swine and chickens. It has complete cross-resistance with Clindamycin and partial with Erythromycin.
Do not use this drug in horses, ruminants, and lagomorphs.
What is the main use for Pirlimycin?
It is used as an intramammary infusion to treat mastitis in dairy cattle.
What are some ‘fun facts’ about Clindamycin?
- Commonly used in small animals for anaerobes and Toxoplasma.
- Doesn’t have great CNS penetration.
- More anaerobic activity than other Lincosamides.
- Contraindicated in horses, rodents, ruminants, and lagomorphs.
T/F: Streptogramins A and B are bacteriostatic individually but bactericidal when combined.
True
What are Streptogramins used to kill?
Mainly Gram + (aerobes (pseudomonas) and anaerobes (including MRSA.))
Can be affective against some Gram -.
What is the MOA of Aminoglycosides?
Bind to the 30s subunit and prevents tRNA attachment. Blocks normal initiation, distorts the codon arm, and alters normal proofreading functions (leading to errors.)
What are some drugs that are in the Aminoglycoside class?
Gentamicin, Amikacin, Neomycin, Spectinomycin, Tobramycin.
What are Aminoglycosides used to kill?
They are excellent against Gram -, including pseudomonas. They are not great to use against Gram + and obligate anaerobes.
T/F: Aminoglycosides are bactericidal and time-dependent.
False! The are bactericidal and concentration dependent! They are usually dosed only one time per day.
What kind of resistance do Aminoglycosides have?
- They are ineffective in anaerobic environments because there is oxygen-dependent transport into the bacterial cell.
- They have acquired resistance and cross-resistance between other Aminoglycosides.
