Miscellaneous antimicrobials

Question 1

Metronidazole (nitroimidazole class) formulations

Answer 1

1. Eradia oral suspension
   -for treatment of Giardia duodenalis in dogs
   -not licensed for bacterial infections in animals but used at lower dose than for giardia
2. human products: oral tablets, injectable solution, topical cream

Question 2

Mechanism of Metronidazole

Answer 2

Intracellular anaerobic metabolism of metronidazole produces reactive metabolites leading to DNA damage

Question 3

Spectrum of activity of metronidazole

Answer 3

-ANAEROBES (clostridium, Bacteroides, Brachyspira)

-Protozoa (trichomonas, Giardia)

-Maybe Campylobacter and Helicobacter (more in humans)

-Limited activity against aerobic bacteria

Question 4

MIC data for metronidazole

Answer 4

MIC is low
-very good first choice if suspect anaerobic bacteria

Question 5

Resistance for metronidazole

Answer 5

Rare
-cross-resistance between nitroimidazoles though

Question 6

Bioavailability and elimination of Metronidazole

Answer 6

Good oral bioavailability; penetrates many tissues

Elimination: hepatic metabolism; elimination in bile and urine

Question 7

Adverse Effects of metronidazole

Answer 7

1. Potential carcinogenic long term= banned in food animals because don’t want people exposed

2.Teratogenic- avoid in pregnant animals

3. Minimal GI upset
4. Neurotoxicity: ataxia, seizures, lethargy
5. Drug interactions: caution if used with hepatic enzyme substrate drugs (CYP inducers/inhibitors)

Question 8

Nitrofurans formulations

Answer 8

1. Nitrofurazone
   -topical ointments for wounds
   -intrauterine solutions in horses
2. Nitrofurantoin (humans)
   -single day gram neg UTI therapy

Question 9

Nitrofurans mechanism of action

Answer 9

Block bacterial pyruvate metabolism therefore preventing energy production

Question 10

Spectrum of activity for nitrofurans

Answer 10

Gram-negative enterics
**but cannot use for systemic infections because reaching MIC levels in plasma results in toxicity… must be used locally

Question 11

Resistance of nitrofurans

Answer 11

Possible but generally no cross resistance with other antimicrobial classes

Question 12

Pharmacokinetices of Nitrofurans

Answer 12

-good oral absorption, topical absorption unknown
-wide distribution in body
-Excreted by kidneys! High concentration in urine
*so use low oral dose and get high levels in urine= UTI treatment

Question 13

Adverse events of Nitrofurans

Answer 13

1. CArdiomyopathy (ventricular dilation)
2. Reproductive (endocrine) toxicity
3. Carcinogenicity= banned in food animals

Question 14

When is nitrofurans used?

Answer 14

1. Nitrofurazone in wound creams and solutions
   -topical or intrauterine/intravaginal use in horses
   -NOT for food animals!
2. Nitrofurantoin in e coli/ MDR UTIs in dogs and cats
   -when not many options and test for susceptibility

Question 15

Rifampin (Rifamycins) formulation and mechanism

Answer 15

Human tablets

-Inhibits the bacterial RNA polymerase and killing intracellular pathogens
**time dependent!

Question 16

Rifampin spectrum of activity

Answer 16

-Mycobacterium (TB)
-Staph isolates
-Rhodococcus equi pneumonia in foals

Question 17

Resistance in Rifampin

Answer 17

Resistance emerging rapidly so typically given with macrolide or other antibiotic
*resistance from a single aa change in bacterial RNA polymerase reducing binding ability

Question 18

Adverse effects of Rifampin

Answer 18

1. Red-tinged fluids (urine, sweat, saliva)
2. Hepatic CYP and P-gp enzyme induction = increased clearance of other drugs
3. Teratogenic
4. Blood dyscrasias (rare)= anemia and decreased platelets

Question 19

Glycopeptides (Vancomycin) formulations and mechanisms

Answer 19

Humans products (oral, injectables)

Mechanism: inhibit peptidoglycan synthesis for cell walls

Question 20

Spectrum of activity for vancomycin

Answer 20

Gram + rods and cocci
(Enterococcus and MRSA)
*but save for human med not vet med

**gram - bacteria often resistant

Question 21

Vancomycin resistance

Answer 21

Major human health concern
-Vancomycin resistant Enterococci
-MRSA with decreased susceptibility to vancomycin
-plasmid-mediated van A gene changes target binding site

Question 22

Vancomycin pharmacokinetics

Answer 22

-poor oral absorption, limited tissue distribution

-excreted via glomerular filtration AND dose changed needed for renal failure patients

Question 23

Adverse events of Vancomycin

Answer 23

1. injection irritation= give slow
2. Nephrotoxic , ototoxic, allergenic

Question 24

Polymyxin B formulations and mechanism

Answer 24

Topical (Polysporin, Surolan) and opthalmic

Disrupts bacterial cell walls
of gram neg bacteria!

Question 25

Polymyxin B adverse events

Answer 25

Wide range of toxicity with systemic administration so used topically or ophthalmic

Question 26

Bacitracin

Answer 26

Active against gram positive bacteria
-mechanism similar to beta lactams

-found in topical formulations (BNP triple ointment with Polymyxin B and neomycin) AND feed mixes in poultry and swine as a growth promotor and prevention of clostridial enteritis

Question 27

Fusidic acid

Answer 27

-inhibits bacterial protein synthesis

-Isaderm germ- used for superficial pyoderma (hot spots). Often susceptible to MRSP/staph

Question 28

Mupirocin

Answer 28

-blocks bacterial protein synthesis
-only used topically, often for staph infections OR intranasal for nasal MRSA carriers

**only human product in Canada; in USA: Muricin product

Question 29

Linazolid

Answer 29

-should not be used in vet med
-used against gram pos and anaerobes (human therapy= MRSA, VRE, C. diff)

Question 30

Colistin

Answer 30

-should not be used in vet med
-related to polymyxin B and used for gram neg enterics
-oral use in swine production in China; API use in Canada
**leads to pan-resistant enteric pathogens