Describe the spectrum of tetracyclines.
"Broad-spectrum" 4-quadrant coverage (gram + and - anaerobes and facultative/ aerobes)
What is the MOA of tetracyclines?
bind to 30S ribosome and interfere with tRNA binding, preventing peptide chain elongation
Tetracyclines are ___________; the pharmacodynamic MOA is....
bacteriostatic; time spent over MIC (the longer the conc is above MIC, the better)
Describe the pharmacokinetic properties of tetracyclines.
- Orally bioavailable- recommended to give on an empty stomach except doxy
- Lipid soluble (high Vd), crosses BBB, penetrates cell membranes, VERY GOOD for resp
How are tetracyclines eliminated?
hepatic and renal
What drugs are important members of the tetracycline drug class? (5)
What are general tetracycline toxicities an adverse effects? (3)
- Nephrotoxic (esp if concurrent dehydration, other nephrotoxic drugs concurrently, myoglobinemia)
- outdated inventory- risk for fanconi-like tubular disease
What are species-specific tetracycline toxicities? (3)
- Cats: fever, depression
- Horses: enterocoloitis d/t loss of colonization resistance to pathogens (b/c the drugs have such potent anaerobic spectrum)
- Dogs and cats: esophageal stricture; make sure to rinse down pills
What is the risk of rapid IV administration of tetracyclines? (3)
collapse, depletion of serum Ca++, cardiac depression
Why do tetracyclines cause yellowing of teeth?
- chelation of Ca++ (less severe with lipophilic agents, Doxy and Mino)
- More likely in young immature animals
What pathogens have resistance to tetracyclines, and what type of resistance does each have?
- Enterobacteriacea: acquired
- Pseudomonas: intrinsic
- Staphylococcus: acquired
- Acquired via plasmids and transposons
How is resistance to tetrcyclines acquired in Enterobacteria and Staph? (2)
- encoded in plasmids and transposons
- Efflux pumps- membrane proteins actively pump out drug
- Ribosomal protection proteins- inhibit binding of TCNs to the 30S subunit
What are some non-antimicrobial properties of tetracyclines? (4)
- anti-inflammatory: inhibit neutrophil chemotaxis; Ca++ chelation perturbs microtubule formation
- anti-granuloma formation: inhibition of protein kinase C
- immune-suppressive: inhibition of protein kinase C
- inhibition of matrix-metalloproteases: lipases and collagenases (ie. for used in foals with tendon contracture at VERY high doses- risk for renal damage beware)
How is susceptibility to tetracycline reported on a C&S report?
- tetracycline is often the only included drug and serves as a class representative
- if the bug is susceptible to tetracycline, it is susceptible to all of them
- EXCEPTION: gram positive organisms, usually Staph; even if resistant to tetracycline, may be susceptible to doxy or mino
What are bacterial differentials for cats with UR signs?
- Chlamydophila felis (intracellular)
- Mycoplasma (intracellular)
- Pseudomonas aeruignosa
- [usually brought on by a virus and then secondary bacterial infection]
What is empirical topical therapy for feline respiratory virals with conjunctivitis?
- Oxytet ointment
- Good alternatives: Chloramphenicol, Erythromycin
- [NOT TRIPLE ANTIBIOTIC- this doesn't get intracellular; Chlamydia and Myco are both intracellular]
What is empirical systemic therapies for cats with upper respiratory infection?
- URI is VIRAL- supportive care most indicated, +/- antivirals
- Many (perhaps unnecissarily) add a systemic antibiotic to cover for secondary bacterial infection- Doxy PO
What systemic antibiotics should not be used with feline URI with secondary bacterial infection and why not?
- Amoxicillin-Clavulanate, Amoxicillin, Cefadroxil
- These drugs do not get intracellular bacteria (remember we are going after Chlamydia and Myco, which are both intracellular)
Describe infectious bovine keratoconjunctivitis (IBK). What are the implicated microbes? (3)
- multi-factorial- faceflies/ tall grass, UV from sun, feed from overhead bunks/ dust---> then microbes come in
- BHV-1 may play a role
- Moraxella bovis, Moraxella boviculi, Branhamelia ovis [Moraxella is gram -]
How is IBK diagnosed?
- clinical- classic target-shaped ulcer on the eye
- if you want an etiologic diagnosis, plate the sample the day of sampling
What is the therapy for IBK? (2)
- Oxytet subQ (labelled)
- Also, subconjunctival PenG
What is the spectrum of chloramphenicol/ florfenicol?
"broad-spectrum" 4-quadrant coverage AND intracellular coverage
What are the pharmacodynamics of cloramphenicol/ florfenicol?
- time over MIC (the more time spent above MIC, the better)
What microbes have resistance to chloramphenicol? What kind of resistance does each have? (2)
- Pseudomonas has intrinsic resistance
- Enterobaceria- acquired resistance
Describe the pharmacokinetics of chloramphenicol? (4)
- orally bioavailable
- highly lipid soluble- high Vd, crosses BBB, enters CSF, milk, and crosses placenta
- poor protein-binding
- pH does not influence distribution
What are toxicities associated with chloramphenicol?
- idiosyncratic aplastic anemia (humans only)--> fatal pancytopenia, irreversible
- dose-related- inhibition of mitochondrial protein translation--> reversible [common in cats, no one uses this drug in cats for this reason]
- [d/t reactive intermediate that is toxic to erythroid stem cells]
What are the implications of using chloramphenicol and possible risks? (3)
- contact risk for DVM and client- carcinogenic
- banned from use in food animals
- should never be a first choice drug
What are side effects of chloramphenicol? (5)
- hindlimb weakness
- drug interactions (inhibits P450 elimination of other drugs)
- antimicrobial antagonism (inhibits bactericidal drugs, esp fluoroquinolones)
- anaphlyactic shock
How is chloramphenicol metabolized/ eliminated?
hepatic- glucuronide conjugation and eliminated in bile
When are chloramphenicols indicated?
- Dogs: last resort with MSRS, respiratory, ophthalmic (topical), prostatitis, +/- UTI
- Horses: misc soft-tissue infections, deep abscesses
- [DO NOT USE EMPIRICALLY- must have susceptibility information to support its use]
Why don't we use chloramphenicol in cats?
impaired metabolism (b/c cats don't glucuronidate well) [likely d/t obligate carnivore diet- they don't need plant detoxification system]
What is unique about florfenicol? (versus chloramphenicol)
- labelled for use in non-lactating cattle and swine (used off-label for foot rot)
- does not cause aplastic anemia (can have dose-dependent bone marrow suppression- clinically insignificant)
What are side effects of florfenicol?
transient diarrhea (ie. we DO NOT use this in horses)
What bugs have intrinsic resistance to chloramphenicol/ florfenicol? (4)
Mucobacteria, Nocardia, Rhodococcus, Pseudomonas aeruginosa
What are acquired resistance mechanisms in chloramphenicol/ florfenicol? (3)
- acetyl transferase enzymes produced by bacteria--> carried on plasmids in both Gram + and Gram -
- RNA mutations- drug targets
- multidrug efflux pumps
What is appropriate empirical therapy for a surgical site infection?
- [primary differential is staph pseudintermedius]
- doxycycline is appropriate first choice drug
If osteomyelitis is present, __________ drugs are indicated.
What are major differentials for wounds and draining tracts in dogs? (8)
- Staphylococcus (coag +: pseudintermedius, aureus, schleiferi ssp coagulans)
- Pseudomonas aeruginosa
- Streptococcus canis