Antimicrobial Therapy: Rifampin, Glycopeptides, Nitrofurans, Ionophores, Polypeptides, Mupirocin Flashcards
Rifampin
- Derived form rifamycin C produced by Amycolatopsis rifamycinica
- Bactericidal
- T>MIC
- Resistance is due to target mutations
Rifampin:
Spectrum
Gram positve aerobes, Staphylococcus, Rhodococcus, Chlamydophila and Anaerobes
Drug of choice for Rhodococcus in foals
Rifampin:
MOA
bind to RNA polymerase inhibiting RNA synthesis
Rifampin:
Absorption
well absorbed in most species
Rifampin:
Distribution
moderate protein binding, but highly lipophilic penetrating cellular membranes, CNS, Prostate, and Bronchiole fluid.
It has poor penetration into aqueous humor
Rifampin:
Metabolism
not specifically assessed in veterinary species.
In humans, it is extensively metabolized and some metabolites are active
Rifampin
Elimination
Only a small amount is eliminated inthe urine as active drug / metabolite
Is suficient in concentration to be effective for UTI
Rifampin:
Adverse Effects
Vomiting, Anorexia, Diarrhea
Hepatic (up to and including tru toxicity) - Need to monitor chemistry profile
CYP induction: enhances metabolism of other drugs metabolized by CYT3A)
cyclosporin, digoxin, cisapride, diazepam, chloramphenicol
Discoloration of body fluids (tears, saliva) and urine to an orange/red color
Bad tasting
Nitrofurantoin:
Absorption
well absorbed after oral administration
Microcrystalline formulations rapidly absorbed, more likely to cuase nausea and vomiting
Macrocrystalline formulations slowly absorbed, less GI upset
Feeding does not affect absorption
Nitrofurantoin:
Distribution
poor tissue distribution and short drug expsosure
Moderate protein binding
Nitrofurantoin:
Metabolism
a small amount of metabolism
Nitrofurantoin:
Elimination
high concentrations of drug in urine, small amounts in bile
Nitrofurantoin:
MOA
bacteria metabolize to reactive metabolites inhibiting bacterial energy metabolism and protien, DNA, RNA, and cell wall synthesis
Nitrofurantoin:
Spectrum
Gram postive, and gram negative urinary pathogens including:
Enterococcus
Proteus and Pseudomonas are intrinsically resistant
Time dependent (T>MIC)
Bacteriostatic to bactericidal depending on concentration and MIC
Activity is limited ot UTI
Nitrofurantoin:
Adverse Effects
Nausea, vomiting, brown colored urine
Neuropathy has been reported in humans treated ling term and may occur in dogs with long term admin,
Do NOT use in azotemic patients (increase adverse effects, decreases efficacy)
Nitrofurantoin:
Clinical Use
UTIs in nonazotemic animals when more common antimicrobials cannot be administered
Nitrofurans in Food Animals
No Allowable extralable use in food animals
Including topical medication
Ionophores:
Menosin
Originally isolated form streptomyces cinnamonensis and lasalocid most common
Ionophores:
MOA
- Act on cell wall causing ion fluxes resulting in changes of intracellular pH and subsequent bacterial death
- Gram positive bacteria, coccidia
- Alters rumen flora shifting volatile fatty acid production form lactic acid to propionic acid resulting in better glucose metabolism and feed conversion
- Alters metabolism of lactic acid decreasing formations of 3-methylindole which is pneumotoxin resulting in severe respiratory distress “fog fever”
- Fog fever typically happens when cattle move to a more lush pasture in the fall
- A 1-6 day lead time feeding ionophores is needed to prevent
Ionophore:
Adverse Effects
- In general, well tolerated
- Toxicity is due to cell membrane disruption in cardiac and skeletal muscle
- Horse and cattle: cardiac > skeletal
- Sheep: skeletal > cardiac
- Horses are very sensitive to monensin toxicity
- Toxicity in ruminants is typically due to improper feed formulation of mixing
- Remember to account for ionophores in cases of polypharmacy
Bambermycins
originally isolated for Streptomyces
Uses: feed additive to imporve feed efficiency in cattle, swine, chickens, turkeys. Also decreases shedding of E. coli, Salmonella
Bambermycins:
MOA
Inhibits cell wall synthesis through inhibition of peptidoglycan glycosynthransferase
Bambermycins:
Spectrum
Gram positive
Polypeptides:
Bacitracin
- Originally isolated for Bacillus subtilis
- commonly used in topical formulations
- Approved for use in feed additive beef cattle, swine, chickens, turkeys, quail, pheasant
- No ELDU for feed additive
Polypeptides:
Bacitracin:
MOA
inhibits peptidoglycan formation in bacterial cell walls
Polypeptides:
Bacitracin:
Spectrum
Gram positive
Polypeptides:
Bacitracin:
Adverse Effects
Highly nephrotoxic, therefore only topical
Oral not absorbed form GIT = topical administration
Mupirocin
Originally isolated from Pseudomonas fluorescens
Topical use primarily for dermatologic infections caused by gram positive including methicillin resistant Staphylococcus
There is minor acitivy agianst gram negative and anaerobes
Mupirocin:
MOA
binding to an RNA synthetase
Mupirocin:
Adverse Effects
since this is a topical it is well tolerated, potential for some skin irritation,
Do NOT infuse into deep wounds as systemic absorption can occur
Silver Sulfadiazine
SSD
Topical use - often used in human burn patients
Poor solubility leads to little systemic silver absorption even in open wounds
SSD
Spectrum
including gram positve, gram negative, some anaerobes and yeast and fungal
SSD
mechanism
not well defined
SSD:
Adverse Effects
sulfadiazine effects as well as silver effects may contribute to overall efficacy
Silver may:
Bind to DNA base pairs blocking transcription
BInd to cell surface interfering with respiration
Prevent phosphate uptake
