Flashcards in Antimicrobial therapy 1 and 2 AND Antimicrobial therapy reading Deck (159):
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?
Which breed of dog can't be given sulphonamides?
What organ system is affected by erythromycin?
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?
List 3 concentration dependent bacteriocides
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
Common cause of skin infectins
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
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
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
- aminoglycosides (PN)
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)
o all organic acids, charged at physiological pH
o most are renally excreted and concentrated in urine
o wide therapeutic indices in general
What are the penicillin sub-families? 5
natural (penicillin G an V)
Spectrum of natural penicillins
narrow spectrum, beta‐lactamase
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
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
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
o limited by resistance
Water soluble TCs - pharmacokinetics?
oral bioavailability affected by food (milk) – especially the water soluble
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
How are aminoglycosides bactericidal?
cause a mis-reading of mRNA allowing nonsense proteins to be produced
What are current thoughts on the ways of increasing efficacy and lowering toxicity of aminoglycosides?
What is the spectrum of activity of aminoglycosides?
varies within the family of drugs
o noted for their G‐ve aerobic antibacterial actions
o they do have good actions against Staphylococci but generally have poor
action against other G+ve cocci
o inactive against obligate anaerobes and facultative anaerobes growing under
anaerobic conditions (need oxygen to enter cells).
What are the pharmacokinetics of aminoglycosides?
weak bases, highly hydrophilic
o do not cross cellular barriers, low volume of distribution
What sort of toxicity are aminoglycosides noted for?
noted for their nephrotoxicity and otoxicity
o skeletal neuromuscular junction blockade can occur, particularly in
What are amikacin and tobramycin?
newer aminoglycosides, licensed for human use
What is known about amikacin?
less active than gentamicin but resistant to many of the inactivating enzymes
produced by bacteria so may be effective for bacterial infections which are resistant to gentamicin
What is known about tobramycin?
more active than gentamicin vs. Pseudomonas aeruginosa
o reduced nephrotoxicity
Why are macrolides and lincosamides grouped?
These are two families of antimicrobial drugs which have similar spectra of activity and
pharmacokinetic properties. Both groups are bacteriostatic and work by inhibiting protein synthesis.
What is the spectrum of activity of macrolides /lincosamides?
narrow spectrum (G+ves mainly); effective vs. Staphylococci particularly
o active vs. anaerobes (especially Clindamycin) and Mycoplasma
Pharmacokinetics - macrolides / lincosamides?
lipophilic weak bases, distribute widely
o ion‐trapped in acidic fluids‐ milk, prostatic, intracellular
o eliminated by hepatic metabolism
Toxicity - macrolides / lincosamides?
o Erythromycin ‐ causes vomiting consistently in dogs
o Interactions with other drugs (e.g., terfenadine) well recognised in human
medicine (led to terfenadine being removed as an over‐the‐counter antihistamine)
What is spiramycin?
- a macrolide combination with metronidazole
o synergistic combination for anaerobes in mouth, produced for the
managements of gingivitis
o remarkable tissue binding capacity
What are azithromycin and clarithromycin?
- new macrolide
- similar spectrum activity to erythromycin
o more potent and longer half lives than erythromycin in people
o more work is required in veterinary medicine but these drugs may be more
convenient in terms of having to dose less frequently in the dog and cat
What sort of action do potentiated sulphonamides have?
Either drug alone is bacteriostatic but together they produce a bactericidal effect and are synergistic in their actions
Which spp can you use trimethoprim in?
Trimethoprim was developed for
human use and is not appropriate for systemic infections for many veterinary species since
its half life is very short and does not match the sulphonamide with which it is combined.
Spectrum of activity - potentiated sulphonamides
- broad spectrum antimicrobials (not difficult G‐ves or serious anaerobic
o synergism occurs even if the organisms is resistant to sulphas
Pharmacokinetics - potentiated sulphonamides
widely distributed (weak acid ‐ sulphas; weak bases ‐ diaminopyrimidines)
o ideally, would like the combination to have matched pharmacokinetics
Toxicity - potentiated sulphonamides
idiosyncratic immune‐mediated reactions (many), particularly in Dobermann
Pinschers but many breeds are affected
o Crystalluria, particularly occurs in concentrated acidic urine
How have fluoroquinolones been developed?
structural modifications made to nalidixic acid to
improve the spectrum of activity and reduce the toxicity.
How do fluoroquinolones affect bacteria?
They are bactericidal and kill by a
concentration dependent mechanism having a marked post‐antibiotic effect (PAE). They
inhibit the bacterial enzyme, DNA gyrase and so prevent super‐coiling of bacterial DNA.
Spectrum of activity - fluoroquinolones
broad spectrum (includes Mycoplasma, Rickettsiae) but not anaerobes,
Streptococci or enterococci.
o minimum inhibitory concentration is very close to the minimum bactericidal
Pharmacokinetics - fluoroquinolones
- widely distributed, orally active
o crosses BBB, penetrate into cells (highly concentrated within cells)
Toxicity - fluoroquinolones - 4
- use with care in epileptics
o erosion of articular cartilage in growing dogs
o can alter the kinetics of other drugs (e.g., methylxanthines; digoxin)
o retinal blindness in cats if flexible dosing regimens adopted
Use of fluoroquinolones
- probably shouldn't use as first line antibacterial drugs
• reserve for difficult G‐ve infections which are resistant to first line drugs
• use in septicaemic patients with an appropriate beta‐lactam
• use for recurrent UTI and chronic bacterial prostatitis
Spectrum of activity - chloramphenicol
- broad spectrum, including anaerobes, G+ve and G‐ve
bacteria (not Pseudomonas spp), chlamydia, rickettsiae (but plasmid mediated resistance occurs)
Pharmacokinetics - chloramphenicol
excellent tissue penetration (small uncharged lipophilic molecule)
Toxicity - chloramphenicol - 2
o bone marrow toxicity (particularly cats ‐ reversible)
o hepatic enzyme inhibition (irreversible; particularly affects barbiturate metabolism)
What are florfenicol and thiamphenicol?
structural analogues of chloramphenicol which have been marketed for veterinary use in Europe.
Why were florfenicol and thiamphenicol produced?
to try and overcome problems of aplastic anaemia in man but not currently licensed for small animals (developed for calves)
How do ABs lead to resistance?
their use preferentially selects resistant populations of bacteria.
When to use antimicrobials? 4
- definitive diagnosis
- likely diagnosis
- likely to progress without medical therapy
- would cause critical illness
What is empirical therapy?
making an educated guess as to the cause of the illness and therefore which AB to prescribe
When is culture and sensitivity recommended?
if therapy fails or immediately recurs once therapy has ceased.
What clues would suggest that bacterial infection may cause critical illness?
- heat, redness and/or swelling
Is vomiting without diarrhoea likely to have a bacterial cause?
No - the only bacteria causing upper GIT disease is Helicobacter and this is very rare (extensive therapy required in these cases)
Is haematuria in cats <10 years old likely to be caused by bacteria?
No (in dogs yes the most common cause of UTI is bacterial). In cats, their urine is highly concentrated and bactericidal so unlikely. Approx 2 % cats presenting with signs of UTI have bacterial infection. Feline idiopathic cystitis (probably stress is a driver) most likely - these cases are often put on antimicrobials (5-7d) after which they get better but this is nothing to do with the drugs!
Is blood in faeces likely to have a bacterial aetiology?
No - only give ABs if systemic signs present.
What should you consider when deciding whether to give ABs? 7
- predict likely bacteria involved?
- predict likely susceptibility?
- culture needed/feasible?
- pharmacokinetic factors?
- potential side effects and increased risk for your patient?
- any client compliance issues?
- cost consdierations?
5 factors affecting success of AB therapy
- what bugs live where?
- bacterial susceptibility
- pharmacokinetic phase
- pharmacodynamic phase
- client compliance
Where do infections come from?
ENVIRONMENT - myocbacteria, tetanus, contaminated food (Campylobacter and E. coli)
OTHER ANIMALS - Bordatella
FROM WITHING - GIT, skin
Generally what does it mean if a bacteria is not susceptible to a drug in vitro? How can this be overcome?
they will be resistant in vivo - resistance may be overcome by high concentrations in urine or topical application.
What does it mean if a pathogen is sensitive to a drug in vitro?
The drug MAY be effective in vivo (depends on variety of pharmacological, host and bacterial factors).
minimum inhibitory concentration - lowest concentration of drug that will inhibit bacterial growth.
What is MIC90?
usual measure to determine therapeutic dose - concentration that will inhibit 90% isolates of a bacterial species.
What AM classes inhibit cell wall synthesis? 3
penicillins, cephalosporins and bacitracin
Which AM classes inhibit cell membrane function? 4
polymixins, amphotericin B, imidazoles, nystatin
Which AM classes inhibit protein synthesis? 5
chloramphenicol, macrolides/lincosamides, tetracyclines and aminoglycosides
Give an example of macrolides
What is clindamycin?
What are gentamicin and neomycin?
aminoglycosides (neomycin used especially in farm animal practice)
Which AM classes inhibit nucleic acid synthesis? 5
sulphonamides, trimethoprim, quinolones, metronidazole and rifampin
How are AMs classified as bacteriostatic or bacteriocidal?
Classification only really applies under strict lab conditions, inconsistent against all bacteria, becomes more arbitrary in clinical cases, more important to consider method of bacterial killing.
Describe the features of bacteriostatic action
Temporarily inhibit the growth of organisms, effect reversible once the drug is removed, to be clinically effective the drug concentration at the site of infection should be maintained above the MIC throughout the dosing interval (adherence to correct dosing schedule important).
True/False - many bacteriostatic drugs can be bactericidal if drug exposure is sufficiently high or prolonged.
list 5 bacteriostatic AB classes
- non potentiated sulphonamides
List 6 bactericidal AB classes
- aminoglycosdies - fluoroquinolones
- potentiated sulphonamides (TMPS)
What 2 indications suggest use of bactericidal is better than bacteristatic?
when there is concern about site of infection or host defences
Which bactericidal drugs is dosing regime very important for? 3
penicillins, cephalosporins and TMPS. DON'T give thesewith bacteriostatic drugs.
For which ABs does peak concentration achieved or AUC predict therapeutic success? 3
aminoglycosides, fluoroquinolones, metronidazole (i.e. concentration dependent)
What is a red AB?
no useful activity against vast majority of bacteria in a qudrant
What is a green AB?
excellent activity against most bacterial spp in this quadrant
What is a blue AB?
good activity against many bacterial spp in this quadrant but some important spp are resistant
What is a brown AB?
has moderate activity against bacterial spp in a quadrant - some spp will be susceptible, others will be resistant
Name two AB classes that don't work against obligate anaerobes (gram negative and positive)
- fluoroquinolones (except pradofloxacin)
Name 3 AB classes that don't work against penicillinase producing staph
- Penicillin G
In what kind of environment does Metronidazole work?
Name 3 AB classes that don't work against gram negative aerobes
- Penicillin G
- Lincosamides/ macrolides
Name 2 AB classes that don't work against gram positive aerobes
Name ABs that work against obligate anaerobes (gram negative and gram positive) - 6
- Penicillin G
Name AB classes that work against penicillinase producing staph - 6
- 1st and 2nd generation cephalosporins (and cefovicin)
- clindamycin (blue, all above are green)
Name AB classes that work against gram negative aerobes - 5
- 2nd and 3rd generation cephalosporins (not cefovicin)
- amoxy-clav (blue, all above are green)
Name AB classes that work against gram positive aerobes - 7
- Penicillin G
- lincosamides/ macrolides
- fluoroquinolones (blue, all above are green)
What is a brown antibacterial?
If it doesn't appear in a quadrant as either red, green or blue, it means it has activity in that quadrant but there are a significant number of resistant bacterial species as well.
What are the brown drugs?
- 1st generation cephalosporins, cefovicin and amoxycillin (WITHOUT clavulanic acid) against gram negative aerobes and obligate anaerobes
- lincosamides other than clindamycin against anaerobes
- TMPS in all quadrants
- tetracyclines in all quadrants except gram positive aerobes (but excellent activity against atypical bacteria)
Define distribution that is perfusion limited
Free drug concentration achieved in plasma are directly related to or equal to the concentration in the interstitial space
Define permeability limited
The level of drug distribution to some tissues. It means the lipid membrane is very tight and so forms a barrier to drug diffusion.
True/False - most antibacterial drugs reach therapeutically adequate concentrations in bone and synovial fluid
List sites in the body that are difficult to access for drugs - 7
- prostate (dogs)
- poorly vascularised tissues (bone fragments or heart valves)
- mammary gland (not in itself a problem but the blood-milk barrier is)
List 6 intracellular bacteria
- Staphylococcus - facultative
List 5 ABs that penetrate POORLY into cells (i.e. water soluble therefore difficult to cross into tissues)
- beta lactamase inhibitors
List 5 ABs that penetrate WELL into cells
List 5 ABs that penetrate EXCELLENTLY into cells (i.e. lipid soluble)
- lipophilic tetracyclines (minocycline and doxycycline)
What environmental conditions may hinder ABs from working?
- abscess formation
- necrotic debris
- oedema fluid
- foreign material
Why do foreign material affect AB?
Phagocytes degranulate to try to destroy the foreign material --> depleted intracellular bacterial substances --> relatively inefficient in killing bacterial pathogens.
The foreign material can also protect bacteria from antibacterial drugs and prophylazis. Bacteria can form a biofilm (glycocalyx) at the site of infection
How does pus affect TMPS?
Pus inactivates TMPS
How does the presence of haemoglobin affect penicillin activity?
Penicillin activity is reduced
Low pH causes a marked loss of activity in which 3 AB drugs?
Name 4 factors affecting the post-op infection risk
- degree of contamination
- organism virulence
- patient health
- local tissue health
When to use PERI-operative ABs?
Justification based on:
- wound classification
- disease process
- patient health
- presence of implants
At how much greater risk are animals that receive propofol of infection?
ABs can NOT compensate for what? 4
- gross contamination
- local tissue trauma
- compromised patient health
- poor aseptic technique
What is the most useless drug to use for surgical prophylaxis in most small animal cases?
Amoxicillin because not effective against the most common infections in small animals. An even worse drug is a long acting version of this (e.g. farm animal formulation of amoxicillin takes 12 hours to reach therapeutic concentrations)
What type of AB drug would you use for surgical prophylaxis?
For routine surgery, the AB doesn't need to be green in all 4 quadrants
What are the best drugs for surgical prophylaxis? How to administer?
Influenced by type of surgery but common recommendations are:
- 2nd generation cephalosporin (e.g. cefuroxamie)
- 1st generation cephalosporin
Give I/V at time of induction if possible. Or SC or IM at least 1-2 hours prior to surgery.