What is penicillins MOA?
Mechanism of action: interfere/block bacterial enzymes essential for assembly of bacterial cell wall peptidoglycan (only effective against actively dividing bacterial colony)
Why is penicillin effective against gram +ves but not gram -ves?
gram +ves have more peptidoglycan that penicilin disrupts -> osmotic lysis of bacteria
while gram -ves have far less
describe penicillins spectrum of activity. Eg’s…
Normal - narrow spectrum: (penicillin-G) target mainly gram +ves & anaerobes
Broad-spectrum: (amoxicillin, ampicillin) same as ‘normal’ but also some gram -ves, E.coli, proteus
Others - Extended-spectrum (ticarcillin); Beta-lactamase stable penicillins eg. methicillin
Species considerations of penicillin…?
Amoxycillin-clavulanic acid 'clavulox' (smallies) NOT for small herbivores Procaine penicillin (horses, cattle, dogs, cats)
Resistance status of beta-lactams?
gram -ves - cell wall is less permeable
beta-lactamases & penicillinases - both of which Staphylococcus aureus have
What is MRSA?
Methicillin Resistant S. aureus - a common nosocomial infection
Approaches to combating β-lactamase positive bacteria?
beta-lactamase inhibitors such as clav -> irreversibly binds to beta-lactamase thus sparing the first active beta-lactam “suicide inhibitor”
combined as amoxyclav
toxicity and residue concerns of β-lactams…?
very safe for oldies, juvies, during preg. and lactation
SE via dysbiosis: GIT signs, diarrhoea, vomiting
small herbivores
Define dysbiosis…
microbial imbalance inside body (digestive tract) from killing ‘good’ bacteria
The most commonly dispensed AB in humans & small animals?
Amoxyclav
Describe Staphylococcus aureus (“Golden Staph”) historical resistance to Penicillin G
1940- 100% susceptible1944- 1st beta-lactamase strains appear1967- 1st methicillian resistant S.aureus (MRSA)1993- MRSA widely distributed
do beta-lactams have a high toxicity?why or why not.
no.very safe can be sued in geriatrics, juveniles, pregnancy and during lactation.because side effects usually come about through dysbiosis- killing good bacteria, toxins, GIT signs (diarrhoea and vomiting most common)
One of the most commonly dispensed ABs in largie practice?
procaine penicillin
For gentamicin (aminoglycoside), describe the mechanism and spectrum of activity, species application, route and frequency of administration, indications/contraindications for use and potential side-effects
- Mechanism of action: inhibits bacterial ribosomes & prevents normal amino acid synthesis
- Spectrum of activity: highly effective against aerobic bacteria; ineffective against anaerobic bacteria
- Species application: equine med
- Route & freq. of admin: mostly parenterally (injected); some are orally administered & need to stay in intestinal tract. Once daily dose (q24h)
- Indications: highly effective against aerobic bacteria
- contraindications/side effects: neonates, food animals, animals with hypomotility, animals with intestinal disease as increased time in the gut; nephrotoxic & ototoxic (ear)
Which largie is gentamycin most commonly used in?
horse
Chemistry, pharmacokinetics and effects on clinical use of aminoglycosides?
- hydrophillic at most physiological pH levels thus -> administered parenterally (via injection) as absorption across GI tract limited after oral admin -> stays in GIT longer
- well absorbed thru abraded (damaged) skin also stays in uterus & bladder if treating infections there
- remains mostly in extracellular fluid thus >in neonates & young
- hydrophillic glycosides don’t cros BBB thus -> high in bronchial secretions used to treat pneumonia
- accumulate in kidneys & inner ear -> toxicity
- most excreted via kidney (kidney disease = increase t1/2 = [plasma drug] = toxicity; IV fluid therapy = decreased t1/2)
2 common classes of aminoglycosides and indications?
used in equine…gentamycin (most common) & amikacin (less resistance) streptomycin (banned in Aus)
For enrofloxacin (quinolone), describe the mechanism and spectrum of activity, species application, route and frequency of administration, indications/contraindications for use and potential side-effects
- Mechanism of action: interfere with DNA gyrase -> preventing bacterial DNA supercoiling (DNA storage form) -> disrupting DNA function
- Spectrum of activity: common gram -ve & gram +ve bacteria in skin, resp, urinary infections; beta-lactamase bacteria (Pseudomonas, staph, E.coli, Salmonella spp.); inconsistent against Streptococcus spp.; ineffective against anaerobic bacteria
- Species application: dogs & cats & any species really! bacterial DNA gyrase different from human gyrase thus safe for use in humans
- Route & freq. of admin: oral or injectable q24h
- Indications: common gram -ve & gram +ve bacteria in skin, resp, urinary infections; beta-lactamase bacteria (Pseudomonas, staph, E.coli, Salmonella spp.)
- contraindications/side effects: small & medium sized dogs aged 2 & 8 months; young horses; oral admin. with antacids; bubbles in joint cartilage/degeneration (growing young animals); seizures; blindness (cats)
What bacteria are fluoroquinolones not effective against?
Streptococcus spp.
Which animals should fluoroquinolones not be used in? why?
livestock animals for eating because development of resistance to quinolones in human bacteria and impact of drug residues in human food
describe approaches to combating beta-lactamase positive bacteria
1.Beta-lactamase inhibitors- use of 2nd beta-lactam that will irreversibly bind to the 2.beta-lactamase- used as a beta-lactamse inhibitor
Info about macrolide tylosin?
bacteriostatic AB for bovine pneumonia; targets + ve bacteria & mycoplasma Pasteurella spp. & moderate efficacy against anaerobes
can be bacteriocidal at [high]
MOA: inhibit protein synthesis via tRNA & also bind to P site of subunit 50s ribosome
Admin. route: IM or SC and in-feed
list the there classes of beta-lactam penicillin antibiotics and some examples
- Natural penicillins - narrow spectrum; predominantly gram positives and anaerobes (e.g. staphylococcus)- Penicillin G, benzylpenicillin2. Aminopenicillins- broader spectrum, as above plus some gram negatives; E-coli and proteus - amoxycillin, ampicillin3. Others- beta-lactamase stable penicillins, e.g. methicillin, cloxacillin, extended spectrum.
list penicillin toxicity and residual concerns
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