Lecture 17-18 Flashcards
What color will gram positive bacteria stain?
purple
What color will gram negative bacteria stain?
pink
Name the following types of bacteria in the test tubes below and briefly describe what they mean:
- obligate aerobe
- obligate anaerobe
- facultative anaerobe - uses ATP in the presence of oxygen (aerobe) but switches to fermentation in the absence of oxygen (anaerobic)
- micraerophilic - prefers lower oxygen and increased CO2 (capnophile)
What is the most clinically significant gram -ve bacteria?
E.Coli
What types of animal are highly reliant on their GIT flora?
herbivores much more so than carnivors are
What are the three main antibacterial targets and name a drug for each mechanism?
- Inhibitors of cell wall synthesis: Beta Lactams (Penicillins, Cephalosporins)
- Inhibitors of DNA synthesis and integrity: Sulphonamides and Fluroquinolones
- Inhibitors or transcription and translation: aminoglycosides, tetracyclins, macrolides
How can you find out if a pathogen is sensitive to or resistant to antibiotics that are available?
You can grow the bacterium and then add a disc of antibiotic and observe what happens
What is an importantant consideration to consider when looking at disc diffusion tests?
In vitro doesnt always equate to in-vivo efficacy
What is a MIC and how are they conducted?
An MIC is a mininum inhibitory concentration. It is the lowest concentration that prevents growth after 24 hours of incubation. This is calculated quantitatively using serial dilution techniques
What is the MBC and what does it show?
Minimum bactericidal concentration. It its the lowest concentration where 99.9% of a culture is killed after 24 hours of incubation.
What type of antibiotic is it if MBC >>> MIC?
bacteristatic (microorganism arrestor)
What type of antibiotic would it be if MBC ~ MIC?
bactericidal (microorganism killer)
Are inhibitors of cell wall synthesis bactericidal or bacteristatic?
Inhibitors of cell wall synthesis = bactericidal
Are fluroquinolones and aminoglycosides bacteriostatic or bacteriocidal?
bactericidal
Are sulphonamides, tetracyclins and macolides bacteristatic or bactericidal?
bacteristatic
Differentiate between the terms time dependant and dose dependant killers:
Time dependant killers - duration of time (determines how many bugs are killed)
Dose dependant killers - the difference between the drug concentration and the MIC determines how many bugs are killed
What type of killer are inhibitors of cell wall sythesis?
Time dependant killers
What classes of antibiotic are dose dependant bactericidals:
Aminoglycosides and flurquinolones
What is the post-antibiotic effect and what are the theories on why this effect occurs?
Perisitant suppression of bacterial growth after removal of the antimicrobial agent. The theories on why this occurs include drug persistence and synthesising enzymes prior to replication/slow recovery from non-lethal damage
What is the spectrum of activity?
The broad groups of bacteria the antibiotic is effective against. Usually expressed relative to four quadrants.
- Gram + aerobes
- Gram + anaerobes
- Gram - aerobes
- Gram - anaerobes
What are the principle mechanisms of resistance?
- Intrinsic resistance (e.g aminoglycosides and anaerobes)
- Decreased permeability to the drug in the cytoplasmic membrane
- Increased production of a drug destroying enzyme e.g. beta-lactamase
- The target enzyme/protein is replaced by one with less affinity for the drug e.g. altered penicillin binding protein in MRSA
- Active extrusion of the drug via MDR P-glycoprotein pump
- Biofilms provide a barrier to hosts immune system and many antibiotics
Briefly explain the mechanism of action of beta-lactams:
- Penicillin transverses Gram +ve cell wall and reaches cell membrane
- Binds to penicillin binding protein (PBP)
- Disrupts cell wall synthesis
- Bacteria lyse due to impaired osmotic regulation
- Lysis of bactericidal and beta-lactams can only kill bacteria during their replication phase - time-dependant bactericidal
What are the mechanisms of resistance of beta-lactams?
- Gram -ves: cell wall/membrane is inherently less permeable to beta-lactams
- Decreased affinity of the PBPs for beta-lactams - e.g. MRSA - this is a dead end resistance mechanism. It cannot be circumvented by a higher dose or higher dose frequency
- Beta-lactamases, penicillinases and cephalosporinases - hydrolysis of beta-lactamases
What is the response of pharamcologists to beta-lactamases?
The pharmacologists response is to use a sacrificial beta-lactam. The second beta-lactam irreversibly binds to beta-lactamase and therefore spares the first (more clinically efficacious) beta-lactam (essentially acts as a suicide inhibitor)
What is an example of a beta-lactamase inhibitor?
amoxycillin-clavulanic acid as a result the amoxycillin may still be able to work despite the presence of beta-lactamase
What is the spectrum of the natural penicillin and what is an example of one?
Quite narrow spectrum: predominantly gram +ves and anaerobes (G+ & G-)
An example: benzylpenicillin
What is the spectrum of aminopenicillins?
Broader spectrum: as above but also some gram -ves e.g. E.coli and Proteus
Examples include: amoxycillan and ampicillin
What is an example of a beta-lactamase stable penicillin?
methicillan (MRSA) and cloxacillin
What is an example of an extended spectrum penicillin?
ticarcillin, piperacillin
What is an example of a third generation cephalosporin?
Ceftiofur
When are carbapenems used and what is an example of this class of drug?
One of the reserve drug classes - these are extremely efficacous - they are often used for severely ill immunocompromised people. Examples include imipenem and meropenem
How toxic are the beta-lactams?
these drugs are typically very safe: can be used in geriatrics, juveniles, pregnancy and during lactation
What species should oral-beta lactams be avoided in?
Should be avoided in any small animlals like rabbits and guinea pigs
What type of drug is cephalexin?
An example of a first generation cephalosporin and is well suited to staph pyoderma
What is the duration of action of cefovecin?
Decreased clearance rates in cats and dogs prolongs the duration of action to two weeks. Testing on other species has not shown the same duration of action.
What is the most commonly dispensed antibiotics in small animal practice?
Procaine Penicillin (predominantly gram +ve coverage and also has excellent anarobic coverage (G+ and G-)
Ceftiofur (a 3rd generation cephalosporin) has a 0wd milk WHP this is often quite misleading why?
The drug does not distribute to the udder very well at all this is why there is a zero day withholding period. Hence this is not a very good drug to give for mastitis.
