Antimicrobial therapy 1 and 2 AND Antimicrobial therapy reading Flashcards
When are ABs most effective?
When they supplement the body’s natural defences rather than being used alone
What is the most important resistance code?
R plasmids (may involve genes that impart resistance to unrelated ABs)
What may impair the effectiveness of antimicrobial therapy? 3
urinary calculi, FB or need for surgical drainage
How would the mechanism of bacterial killing affect the type of drug?
Concentration versus time-dependent actions
Why are more selective drugs preferred?
less likely to disrupt the normal flora
What should be considered when choosing whether to use a bacteriostatic or bacteriocidal drug?
Bactericidal drugs are often favoured because they may be more effective when host defences are impaired. However, there may be little difference in efficacy between bactericidal and bacteriostatic drugs when treating non‐critical infections in otherwise healthy patients.
To which organ is gentamicin toxic?
nephrotoxicity
Which breed of dog can’t be given sulphonamides?
Dobermans
What organ system is affected by erythromycin?
GIT
Name 5 bacteriostatic drugs
tetracyclines, chloramphenicol, non‐potentiated sulphonamides, macrolides and lincosamides
How and when do bacteriostatic drugs work?
temporarily inhibit the growth of an organism but the effect is reversible once the drug is removed. For these drugs to be clinically effective the drug concentration at the site of the infection should be maintained above the MIC throughout the dosing interval. As a result, adherence to correct dose timing is important and clients should be instructed to administer drugs every 24, 12 or 8 hours rather than once, twice or three times daily.
List 6 bacteriocidal drugs
aminoglycosides, cephalosporins, fluoroquinolones, metronidazole, penicillins, potentiated sulphonamides
When to use bacteriocidal drugs
- depends on nature or site of infection
- reduced immunocompetence of host
How are bacteriocidal drugs further classified?
time or concentration dependent
List time-dependent bacteriocidal drugs 3
penicillins, cephalosporins, TMPS
Why shouldn’t time dependent bacteriocidal drugs be given with bacteriostatic drugs?
bacteria need to be multiplying for bacteriocidal drugs to be effective
How high a dose of bacteriocidal drugs should be given?
above MIC for 80% of 24 hours to reduce risk of resistance emerging
Is there any benefit achieivng a Cmax 2-4 times the MIC for bactericidal drugs?
no
List 3 concentration dependent bacteriocides
aminoglycosides
fluorquinolones
metronidazole
What determines antibacterial success with concentration dependent bactericides (aminoglycosides, fluoroquinolones and metronidazole)
all 3 - peak concentration
fluoroquinolones - area under the plasma concentration/time curve
Common bacterial cause of UTIs
E.coli
Common cause of skin infectins
Staphylococcus spp
Which group of bacteria are you likely to find in pyothorax and abscesses?
obligate and facultative anaerobes
Where might bacteria come from in supparative cholangiohepatitis?
GIT contents - gram negative plus anaerobes
What are the atypical bacterial spp which don’t gram stain?
rickettsia, mycoplasma, chlamydia, borrelia, bartonella, mycobacterium
What is the most practical classification of bacteria in small animal practice? 5
- gram positive aerobic (and facultative anaerobes)
- gram negative aeorobic (and facultative anaerobes)
- obligate anaerobes (gram negative and positive)
- penicillinase-producing staphylococcus
- atypical bacterial spp
Define pharmacokinetic phase
distribution to the site of infection
What affects pharmacokinetics?
if tissue has adequate blood supply, antibac concentrations in serum/plasma being equal to extracellular (interstitial) space unless highly protein bound (uncommon), diffusion to certain areas limited, poorly vascularised tissues
What are some consequences of poor AB compliance by owner?
inadequate response to treatment, risk of resistance, increased risk of recurrent infetions, abrupt discontinuation may cause side effects (some drugs), risk of toxicity (if owner tries to catch up on missed doses), increased costs, creation of doubt in clients mind about efficacy (drug/clinician), accumulation of unused meds in home.
What is perioperative infection risk influenced by?
Clinical status of patient Nature of surgery Use of implants Experience of surgeon Duration of surgery Total duration of anaesthesia Administering propofol Clipping Animals with high/low BCS Animals with concurrent endocrinopathies
How does duration of surgery affect infection risk?
1.5 hours infection rate is 8%
How does total duration of anaesthesia affect infection risk?
For every minute beyond 60 minutes, there is a 0.5% increase in risk
How does propfol affect infection risk?
Animals receving propofol 3.8 times more at risk than those that don’t
How does clipping affect infection risk?
Surgical sites clipped before anaesthetic induction are 3 times more likely to develop post-op infection. Especially in animals >8years
When is prophylactic AB treatment indicated?
- after dentals (controversial)
- leucopaenia (viral or drug induced)
- contaminatd surgery
- surgeyr where consequences are disastrous (orthopaedic)
- major tissue trauma (major thoracic and abdominal surgery)
- surgery time >90 mins
When should prophylactic ABs be given?
Before procedure so adequate levels are in blood at time of surgery to achieve max. effect.
When is prophylactic AB advantages lost?
if commenced any later than 3-5 hours after contamination. IV administration 20-30 mins prior to surgery is recommended
For how long post-op is therapy usually given?
not usually continued longer than 24 hours post-op
What are the most frequent veterinary nosocomial infections? 4
Klebsiella spp
E. coli
Proteus
Pseudomonas
Which ABs have the greatest potential to suppress endogenous flora that normally keep pathogenic enteric bacteria in check? Give 3 examples of each.
- If they have extensive activity against obligate anaerobes (penicillins, chlorampnehicol, lincosamides)
- if they undergo extensive entero-hepatic recycling (TCs, chloramphenicol, lincosamides)
Which ABs don’t tend to suppress endogenous flora? 4
- Cephalosporins
- aminoglycosides (PN)
- TMPS
- sulphonamides
What are the ‘points’ of the therapeutic triangle?
host, drug, bacterium
Having established there is a bacterial infection, what questions should be asked? 4
- which drugs have a suitable spectrum of activity?
- i sthe mode of action suitable for the status of the patient?
- will the drug reach the site of infection t adequate concentrations?
- will the drug harm the patient?
Name the 2 beta-lactam ABs
penicillins and cephalosporins
How do beta-lactam ABs kill?
inhibition of cross-linking of peptidoglycan molecule in cell wall. time-dependent. activation of autolysins is though to lead ot breakdown of peptidoglycans
Describe spectrum, pharmacokinetics and toxicity of penicillins and cephalosporins
Spectrum of activity
o highly variable between sub‐families
o can vary within a family (good vs. anaerobes)
• Pharmacokinetics
o all organic acids, charged at physiological pH
o most are renally excreted and concentrated in urine
• Toxicity
o wide therapeutic indices in general
What are the penicillin sub-families? 5
natural (penicillin G an V) isoxazoylpenicillins aminopenicillins carboxypenicillins ureidopenicillins
Spectrum of natural penicillins
narrow spectrum, beta‐lactamase
susceptible
Spectrum of isoxazoylpenicillins
narrow spectrum, resistant to
beta‐lactamase of staphylococci
Spectrum of aminopenicillins
broad spectrum but susceptible to beta‐lactamase unless coformulated
with clavulanic acid
Spectrum of carboxypenicillins
effective vs. difficult G‐ve organisms such as
P.aeruginosa (but susceptible to beta‐lactamases)
Spectrum of ureidopenicllins
broader spectrum than the carboxypenicillins ‐
effective vs. Klebsiella and Bacteroides fragilis
When should you use clavulanate potentiated ticarcillin?
reserved for difficult life‐threatening G‐ve infections
Which generation of cephalosporin has broadest spectrum?
second generation cephalosporins generally have broadest spectrum of activity,
retaining good G+ve activity (including vs. Staphylococci), good anaerobic activity and
reasonable G‐ve activity. These drugs are used in human medicine for surgical prophylaxis
What do third generation cephalosporins target?
developed particularly to extend the spectrum of these drugs to include Pseudomonas and Klebsiella.
They have lost some activity against the G+ve organisms and should be reserved for difficult
G‐ve infections.
What is cefovecin?
A new cephalosporin – cefovecin – was launched in 2007 for small animal use. It is classed as
a third generation drug but its spectrum does not include Pseudomonas and Klebsiella spp. Its
unique characteristics are that it has a very prolong duration of action with a single dose
providing 10 to 14 days of antibiotic cover due to a prolonged plasma clearance.
Which ribosomes do TCs work against?
both pro- and eukaryotic ribosomes
How are TCs selectively toxic?
ability of bacteria and other micro‐organisms to
concentrate these drugs within their cells, a property which mammalian cells lack. Equally,
this means that resistance to tetracyclines is achieved by loss of the transport protein from
the micro‐organism.
How are TCs divided?
water soluble and lipid soluble types
Water soluble = chlor- and oxy-
Lipid soluble = mino- and doxy-
Water soluble TCs - spectrum of activity?
Spectrum of activity
o broad spectrum antimicrobial drugs, including Chlamydiae, Rickettsiae and
Mycoplasma
o limited by resistance
Water soluble TCs - pharmacokinetics?
oral bioavailability affected by food (milk) – especially the water soluble
compounds
o distribute widely; especially lipid soluble drugs
o renal and biliary excretion (re‐circulates)
Water soluble TCs - toxicity?
avoid in renal failure as renally excreted, mildly nephrotoxic (degradation
product of drug), more likely to cause liver damage if given to animals with
renal failure at standard doses. In addition, the anti‐anabolic effects of these
drugs may worsen the azotaemia
o intravenous administration can cause circulatory collapses because chelate calcium
What are the features of lipid soluble TCs?
more lipid soluble than other tetracyclines
o penetrate the prostrate gland
o penetrate the blood bronchus barrier
• doxycycline eliminated in faeces so safer in renal failure
• doxycycline is marketed for respiratory infections
