-
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)
- Tetracycline
- Chlortetracycline
- Oxytetracycline
- Doxycycline
- Minocycline
-
What are general tetracycline toxicities an adverse effects? (3)
- hepatotoxic
- 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- outdated inventory- risk for fanconi-like tubular disease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
- Staph
- [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?
- bacteriostatic
- 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)
- inappetence
- 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.
bactericidal
-
What are major differentials for wounds and draining tracts in dogs? (8)
- Staphylococcus (coag +: pseudintermedius, aureus, schleiferi ssp coagulans)
- Pseudomonas aeruginosa
- Actinomyces
- Nocardia
- Enterica
- Streptococcus canis
- Anaerobes
- Mycobacteria
|
|
