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Small Animal Final Year > AB selection for respiratory disease > Flashcards

AB selection for respiratory disease Flashcards

1
Q

What are the principles of antimicrobial therapy?

A
  1. Disease must be caused by a pathogenic infectious agent
  2. The infectious pathogen cannot be removed by the hosts defence mechanisms (e.gfoal vs healthy adult horse)
  3. The infectious organism is know (or suspected)
  4. The organisms is susceptible to the drug selected in-vivo
  • Based on experience of that drugs
    • Potentially in that group of animals
  • Based on culture and sensitivity
    • Although never totally reliable
    • Different micro-environments
    • (pH, O2, CO2 etc)
    • Kinetics of the drugs
  1. The hosts defenses will contribute to a cure
  2. Therapeutic concentrations at the site of infection can be predicted
  3. Concurrent antimicrobial administration may be synergistic, may reduce resistance, may extend spectrum of activity
  • Although rare
  • Rifampicin
  • Must not replace rational selection
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2
Q

Discuss kinetics of antimicrobials?

A

Time dependent kinetics

Effective when in contact with bacteria

Concentrations must be above MIC

  • > 50% of dosing interval (see MIC for at least 50% of dosing interval)

Concentration dependent kinetics

  • These are minority aminoglycosides and fluroquinolones
  • They have a peak effective concentration
  • Advantage giving drugs once a day rather than multiple reduces toxic effects
  • Bind to bacteria with ‘post antimicrobial effect’
  • >10 x MIC
    *
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3
Q
A
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4
Q

Discuss the beta-lactams?

A

Penicillin and cephalosporins

Inhibit cell wall synthesis

Bactericidal

  • Must penetrate the outer membrane though porins
  • Rate of penetration differs between drugs (hence spectrum of activity –cephalosporins penetrate g-ve)
  • Extended spectrum beta lactams (ESBLs)
  • Have different activity but all do same thing (bind PBPs)

Bind penicillin binding protein PBPs

  • Affinity of PBPs varies between species of bacteria
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5
Q

Discuss beta-lactam resistance?

A

Resistance

Chromosomal or plasmid mediated

  • Reduced permeability of drug into cell wall (hence most G-veare resistant)
  • Modification of PBP affinity (rare)
  • Inactivation of the drug (beta lactamases)
  • Often specific to cephalosporins or penicillins
  • Retained in periplasmicspace in G-ve bacteria

Resistance to beta-lactamases

  • Modifying beta-lactam ring (eg cloxacillin)
  • Beta-lactamase inhibitors (egClavulanic acid)
  • Resistance is relatively common but these still work for many problems especially respproblems in equid
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6
Q

What is the spectrum of activity of beta lactams?

A

Spectrum of activity

Many gram positive organisms

Some gram negative organisms

Most obligate anaerobes

  • Eg Strep equi va requi and zooepidemicus
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7
Q

What are the Pharmacokinetics of beta lactams?

A

Poor oral bioavailability in horses (10%)

  • And often induce diarrhoea
  • Do not give penicillins orally to horses as can induce fatal D+ as it kills all bacteria in hindgut

Penetration

  • Fair volume of distribution (except CNS and eye)
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8
Q

Discuss toxicity of beta lactams?

A

Rare

Hypersensitivity reaction

  • Differentiate from procaine reactions following ia/iv administration
  • Intra arterial injection with penicillin will cause severe neurological collapse so always drawback when injection penicillin

Procaine concentrations increase with heating

Procaine is a local anaesthetic has a 42 day detection time do not use in performance animal

Immune mediated heamolytic anaemia(not common)

Safest AB in pregnant animals and lactation

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9
Q

Discuss different penicillins and their efficacy?

A

Penicillin G (IV form of penicillin)

  • Most gram positive and gram negative cocci
  • Some aerobic and anaerobic bacilli
  • Not pseudomonas
  • Intravenous penicillin (Na/K)
  • Rapid peak concentration
  • Rapid decrease in concentration
  • Dose TID –QID (3-4 times to keep concetrationsabove MIC for 50% of dosing interval)

Intramuscular procaine penicillin

  • Slower absorption
  • Twice daily doses maintains concentrations
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10
Q

Discuss Benzathine penicillin G (Pen LA)?

A
  • Slow absorption
  • Fails to reach MIC
  • AVOID IT
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11
Q

Discuss dosing with penicillins?

A
  • Most licensed doses are ineffective at maintaining MIC
  • 20,000 iu/kg BID IM or TID IV
  • Do not learn doses
  • So may have to double dose and interval as seen on the data sheet in order to reach MIC
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12
Q

Discuss potentiated penicillins?

A

Potentiated pencillins

  • Widely used in small animal practice
  • No licensed IV formulation (Augmentin)
  • Occasionally used in foals
  • In human medicine this is reserved for amoxycillin resistant beta- lactamase producing ABs
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13
Q

What are penicillin take home messages?

A
  • Often first line in small animal medicine
  • Requirement for IM dosing makes less popular in equine use
  • Effective for most respiratory and skin diseases
  • Procaine has a >4-6 week racing prohibition
    • Only anti-infective agent that is controlled Procaine penicillin, Benzyl Penicillin (IV)
  • Skin, respiratory, GI, Urinary diseases
  • Horses get huge doses of it 40-60mls a day they soon get sick of daily injections
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14
Q

Discuss cephalosporins?

A

Cephalosporins

Effective against Staph aureus

  • Penicillinase producing

Effective against anaerobes (except bacteroides)

Second, third and fourth generation drugs

  • More gram negative effects

Penetration –fair, synovial fluid and urine

  • Ceftiofur (IM) -Equine
  • Cephalexin (SA) –oral
  • Cefquinome(IV)-OF HISTORICAL INTEREST NO LONGER AVAILABLE
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15
Q

Discuss aminoglycosides?

A

Aminoglycosides

Often combine these with a beta-lactam

Bactericidal

Spectrum of activity

  • Aerobic gram negative bacteria
  • Staphylococci (if you are dealing with methicillin resistant staph it can be controlled with aminoglycosides especially gentamycin)
  • Not effective vs anaerobes (inability to pass into cell)

Mechanims:

  • Inhibit protein synthesis
  • Post antimicrobial effect

Resistance

  • Decreased cell penetration
  • Changes in ribosomal binding
  • Aminoglycoside modifying enzymes
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16
Q

Discuss the pharmacokinetics of aminoglycosides?

A

Pharmacokinetics

  • Poor absorption (none)
  • Poor distribution across cell membranes
  • Poor concentrations in bronchial secretions (has a license for this though even though it is not very effective and has low concentration in lungs, best given by nebulisation to get high concentration in horse)
  • Consider inhalation
  • Majority need to be given IV to be effective
17
Q

Discuss toxicity of amminoglycosides?

A

Toxicity

Nephrotoxic(most is reversible)

  • Accumulation in proximal tubule leading to cell death occasionally (proteinaceous casts etc)
  • Usually resolve when you stop dose

Increases with

  • TID dosing cf SID dosing (same total dose)
  • Neomycin is more nephrotoxic than Gentamycin
  • Hypovolaemia (so use alongside fluid therapy)
  • Other drugs
  • Ototoxic???
18
Q

Discuss use of aminoglycosides in equine medicine?

A

Widely used in equine medicine

Usually used in combination

  • Gentamicin and penicillin

Available with penicillin

  • Neomycin / procaine penicillin (IM)
    • However recommended dose fails to achieve MIC for penicillin but if you raise it to MIC level for Penicillin you give too much gentamicin so use penicillin top up separately
      • Increasing dose risks nephrotoxicity
      • Usually reversible
  • Streptomycin –rarely effective
19
Q

Summarise aminoglycosides?

A
  • Used for bone and joint disease
  • Surgical colic
    • Although questionable kinetics in the latter
  • Rarely useful systemically in respiratory disease
  • Extends gram negative cover when used with penicillin
20
Q

Discuss tetracyclines?

A

Tetracyclines

Commonly used drugs in equine practice

Bacteriostatic (does not worry equine vet they are only static)

Spectrum of activity

  • Gram positive
  • Gram negative
  • Mycoplasma
  • Rickettsia and Ehrlichia (Anaplasma phagocytophila)
  • Poor/no anaerobic effects (so not a drug to use on own)
21
Q

What is the mechanism of action of tetracyclines?

A

Mechanism of action

Inhibit protein synthesis

Resistance

Reduced active transport into cell (plasmid) (one of oldest Abs have in equine medicine but surprisingly does not see much resistance)

22
Q

Discuss oxytetracycline?

A

Oxytetracycline has poor bioavailability in horses

  • Doxycylcine much improved (Not licenced in horses)
  • Do not give orally as give causes fatal D+

IM use leads to inflammation

  • IV Use only in horses

Distribution (high vol of distribution so gets into lungs well)

  • Widely distributed across membranes
  • High lipid solubility
  • Poor CSF
23
Q

Discuss toxic effects of tetracyclines?

A

Toxic effects

  • Diarrhoea–in hind gut fermenters
    • Change in GI flora allowing pathogens to grow
    • E.g Clostridial perfringens
  • Cardiac dysrrhthmias(reported) So inject slowly
    • Following rapid IV administration
      • Chelation of ionisedcalcium???
      • Or carrier (propylene glycol)
  • GI irritant
    • Oesophageal ulceration and stricture
    • Administer with water
  • Despite poor press widely used
24
Q

Summarise tetracyclines?

A

Tetracyclines

  • Good for respiratory infections
  • Great activity against all the streps
  • Strep equi varequi
  • Good lung penetration
  • Mycoplasma
  • Bordatella
  • GI disease….
  • Good for skin and bone infection
  • Good for abscesses (lipid soluble)
  • CHEAP (ISH)
  • Available IV, PO
25
Q

Discuss sulphonamides/pyrimidines?

A

Sulphonamides/ Pyrimidines

  • Bacteriostatic alone, bactericidal together
  • Widespread resistance following long term use
  • Mechanism of action
    • Inhibit DNA synthesis (purines)
    • Reduce bacterial folic acid availability (do not give to pregnant mares)
    • Pyrimidines also have anti-protozoal effects
      • Pyrimethamine
  • Spectrum of activity
    • Gram positive, gram negative
    • Not anaerobes ( so not useful for horses with dental disease)
  • Resistance fairly uncommon
26
Q

Discuss potentiated sulphonamides resistance and pharmokinetics?

A

Resistance

  • Increased bacterial production of PABA
  • Overcomes inability to synthesisefolic acid
  • NOTE: Necrotic tissue, abscesses contain excessive amounts of PABA –thereby blocking the effects

Enzymes that destroy antibiotic

  • Dihydrofolate reductase

Pharmacokinetics

  • Well absorbed –improved with empty stomach
  • Much better fed on empty stomach squirted in horses mouth
  • Good distribution –including CSF
27
Q

Discuss potentiated sulphonamides (TMP-S) toxicity?

A

Horse:

  • CARDIOVASCULAR COLLPASE AND DEATH Following IV use in the sedated horse (alpha 2)
  • Presumably due to solvents not drugs
  • So do not give together/ specific contradindication
  • Can give sulphonamides and then sedate but do not sedate then give

Nephrotoxicity

Haemolyticanaemia

Aplastic anaemia–rare

NEONATAL LOSS –AVOID IN LAST TRIMESTER

Dogs

Immune mediated polyarthropathy (Doberman)

Acute renal failure (crystalluria)

28
Q

Summarise TMP-S?

A

Uses

  • Respiratory disease (with exception of strangles not efficacious in pus filled environment)
  • Skin disease
  • Liver disease
  • Note –rarely used in small animal practice except on basis of cost
  • Available IV and PO
29
Q

Discuss quinolones?

A

QUINOLONES (non licensed in equines)

Broad spectrum

  • But mainly gram negative effects
  • Including pseudomonas
  • Poor gram positive
  • Not effective against streptococci so unlikely to effect the GI system or Resp system
  • No anaerobic

Mechanism of action

  • DNA inhibition (DNA gyrase)

Side effects

  • Damage to cartilage
  • When used in skeletally immature animals
30
Q

Discuss quinolones further, kinetics and use?

A

Kinetics

  • Good oral bioavailability (IV and oral formulation available)
  • Large volume of distribution
  • Liver, lung, urinary system
  • Tissue concentrations exceed plasma (inc intracellular)

USE

  • Respiratory, skin, urinary
  • Gram negative disease
  • Exotics

Enrofloxacin (EQ –no VPL)

Marbofloxacin(SA)

31
Q

Discuss macrolides and equids?

A

Macrolides AND ADULT HORSES DO NOT GO TOGETHER AS IT DESTROYS HINDGUT

  • Only used in a foal infection of rhodococcus
  • Erythromycin
  • Azithromycin: Longer duration of action

Mechanism of action

  • Inhibit bacterial protein synthesis

Kinetics

  • Lipid soluble
  • Good absorption and volume of distribution
  • Very high tissue concentrations cf plasma
  • Intracellular penetration
32
Q

Summarise macrolides?

A

Uses

  • Treatment of Rhodococcus equi infections in foals
  • AVOID IN ADULT HORSES as get D+, if the mare licks foals face she will get D+, if its in environment horse will get D+
  • NO VPL in veterinary species

Side effects

  • Severe diarrhoea
  • Effects on bacterial flora
  • Increased intestinal motility (Motilin receptors) Can be used below MIC doses which increase gut motility
33
Q

Discuss Rifampins?

A

Rifampin

  • Often combine macrolides with this
  • Excellent penetration
  • Effective against intracellular infections (which is where rhodococcusattack)
    • Concentrated in phagocytic cells
  • Spectrum of activity
    • Gram positive and negative infections
  • Used in combination with macrolides for the treatment of R equi
    • Must be used in combination
    • Avoid resistance –single mutation in RNA polymerase –reducing binding to rifampin
34
Q

Discuss metronidazole?

A
  • Effective against anaerobes
  • Bacteroides (the only anaerobe specifically give metronidazole for as penicillin’s target other anaerobes), Clostridium spp
  • Used for mixed infections where anaerobes expected
  • GI disease (Helicobacter), wounds, dental

Kinetics

  • Good oral bioavailability (also can be given rectally with lower availability)
  • Good distribution except into uterus

Side effects

  • Nausea, anorexia (2%) Because it tastes awful?
  • Can be given per rectum to reduce some of awful taste but they still become nauseous
35
Q

Discuss metronidazole further?

A

Metronidazole

  • NO VPL in any species
  • Cannot be given to horses entering human food chain
  • Therefore any horse receiving metronidazole must be permanently declared as not being suitable for human consumption
  • Clients responsibility to do this
  • You responsibility to inform them
36
Q

Discuss D+ in horses?

A

Diarrhoeain horses

Any antibiotic may affect GI flora

  • Also in rabbits

Inducing bacterial overgrowth of pathogens

  • Salmonella spp
  • Clostridia spp

These complications can be fatal

  • Penicillin, oxytetracylcine, cephalosporins
37
Q
A

Small Animal Final Year (317 decks)

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