Antimicrobial Therapy: Rifampin, Glycopeptides, Nitrofurans, Ionophores, Polypeptides, Mupirocin

Question 1

Rifampin

Answer 1

• Derived form rifamycin C produced by Amycolatopsis rifamycinica
• Bactericidal
• T>MIC
• Resistance is due to target mutations

Question 2

Rifampin:

Spectrum

Answer 2

Gram positve aerobes, Staphylococcus, Rhodococcus, Chlamydophila and Anaerobes

Drug of choice for Rhodococcus in foals

Question 3

Rifampin:

MOA

Answer 3

bind to RNA polymerase inhibiting RNA synthesis

Question 4

Rifampin:

Absorption

Answer 4

well absorbed in most species

Question 5

Rifampin:

Distribution

Answer 5

moderate protein binding, but highly lipophilic penetrating cellular membranes, CNS, Prostate, and Bronchiole fluid.

It has poor penetration into aqueous humor

Question 6

Rifampin:

Metabolism

Answer 6

not specifically assessed in veterinary species.

In humans, it is extensively metabolized and some metabolites are active

Question 7

Rifampin

Elimination

Answer 7

Only a small amount is eliminated inthe urine as active drug / metabolite

Is suficient in concentration to be effective for UTI

Question 8

Rifampin:

Adverse Effects

Answer 8

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

Question 9

Nitrofurantoin:

Absorption

Answer 9

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

Question 10

Nitrofurantoin:

Distribution

Answer 10

poor tissue distribution and short drug expsosure

Moderate protein binding

Question 11

Nitrofurantoin:

Metabolism

Answer 11

a small amount of metabolism

Question 12

Nitrofurantoin:

Elimination

Answer 12

high concentrations of drug in urine, small amounts in bile

Question 13

Nitrofurantoin:

MOA

Answer 13

bacteria metabolize to reactive metabolites inhibiting bacterial energy metabolism and protien, DNA, RNA, and cell wall synthesis

Question 14

Nitrofurantoin:

Spectrum

Answer 14

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

Question 15

Nitrofurantoin:

Adverse Effects

Answer 15

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)

Question 16

Nitrofurantoin:

Clinical Use

Answer 16

UTIs in nonazotemic animals when more common antimicrobials cannot be administered

Question 17

Nitrofurans in Food Animals

Answer 17

No Allowable extralable use in food animals

Including topical medication

Question 18

Ionophores:

Menosin

Answer 18

Originally isolated form streptomyces cinnamonensis and lasalocid most common

Question 19

Ionophores:

MOA

Answer 19

• 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

Question 20

Ionophore:

Adverse Effects

Answer 20

• 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

Question 21

Bambermycins

Answer 21

originally isolated for Streptomyces

Uses: feed additive to imporve feed efficiency in cattle, swine, chickens, turkeys. Also decreases shedding of E. coli, Salmonella

Question 22

Bambermycins:

MOA

Answer 22

Inhibits cell wall synthesis through inhibition of peptidoglycan glycosynthransferase

Question 23

Bambermycins:

Spectrum

Answer 23

Gram positive

Question 24

Polypeptides:

Bacitracin

Answer 24

• 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

Question 25

Polypeptides:

Bacitracin:

MOA

Answer 25

inhibits peptidoglycan formation in bacterial cell walls

Question 26

Polypeptides:

Bacitracin:

Spectrum

Answer 26

Gram positive

Question 27

Polypeptides:

Bacitracin:

Adverse Effects

Answer 27

Highly nephrotoxic, therefore only topical

Oral not absorbed form GIT = topical administration

Question 28

Mupirocin

Answer 28

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

Question 29

Mupirocin:

MOA

Answer 29

binding to an RNA synthetase

Question 30

Mupirocin:

Adverse Effects

Answer 30

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

Question 31

Silver Sulfadiazine

SSD

Answer 31

Topical use - often used in human burn patients

Poor solubility leads to little systemic silver absorption even in open wounds

Question 32

SSD

Spectrum

Answer 32

including gram positve, gram negative, some anaerobes and yeast and fungal

Question 33

SSD

mechanism

Answer 33

not well defined

Question 34

SSD:

Adverse Effects

Answer 34

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