Antimicrobial Therapy Flashcards
What are the four categories of antimicrobials?
1) antibacterials
2) antivirals
3) antifungals
4) antiparasitics
What are the three main methods of non-selective killing of microbes?
1) sterilization
2) disinfection
3) antisepsis
What is sterilization?
The complete destruction of all microbes and spores
What is disinfection?
The destruction of most all microbes
What is antisepsis?
The use of disinfectants on the skin
What are some methods for sterilization?
1) autoclave
2) ethylene oxide gas
3) pressured steam
What are some disinfectant agents?
1) phenolics
2) iodophors
What is the central tenet to the clinical application of antimicrobials?
selective toxicity
What were some of the first antibacterials?
1) sulphonamide
2) pencillin
3) streptomycin
What is an “antibiotic”?
A secretion from a microbe that kills another bacteria
What is MIC? MBC?
MIC - minimum inhibitory concentration. the minimum concentration of drug needed to prevent growth
MBC - minimum bactericidal concentration. the minimum concentration of drug that kills 99.9% of the microbial population
What is the name of an antimicrobial which leads to the “stationary growth” of a bacterial population?
bacteriostatic
What is one way in which to get an MIC?
- serial dilutions
- E-test for abx sensitivity
What is the difference between MIC/MBC and resistance/sensitivity?
MIC and MBC are quantitative values. Resistance and sensitivity are clinical values.
What is the Kirby-Bauer method?
Disk diffusion assay in petri dish/agar culture. Disks impregnated with abx are then placed with the microbial culture
What is the difference between narrow and broad spectrum antibiotics?
Narrow-spectrum antibiotics usually only work against Gram-positive bacteria, while broad-spectrum antibiotics will work against both Gram-positive and Gram-negative
What are three contributing factors to antibiotic susceptibility?
1) targeting the access of the abx to the bacterium
2) targeting the affinity of the abx to whatever its target is
3) susceptibility to its own inactivation
What are the five major mechanistic classes of antibiotics?
1) cell wall biosynthesis inhibitors
2) protein biosynthesis inhibitors
3) nucleid acid biosynthesis inhibitors
4) metabolic inhibitors
5) membrane disrupting agents
How do abx target cell wall biosynthesis?
The synthesis of the peptidoglycan layer has several steps that occur throughout the cell and different abx can inhibit the different steps of this process
What is the peptidoglycan layer also called?
murein layer
What are examples of some abx which affect cell wall biosynthesis?
1) penicillin
2) vancomycin
3) bacitracin
4) carbapenems
What is a beta-lactam abx?
Beta-lactam antibiotics are abx that have a cyclic amide group. This mimics a peptide bond.
How are cell wall synthesis inhibitors selective?
There are no cell walls in mammals and thus they cannot be targeted
What are some side chain modifications of penicillin and what do they do?
Penicillin G is the original penicillin, but could not be given orally. Pencillin V can be taken orally. Ampicillin and piperacillin are more effective against Gram negatives
What do the different generations in cephalosporins indicate generally?
side chain modifications
What do all beta-lactams have in common in their mechanism of action?
They all prevent the final cross-linkage in the cell wall
What do bacteria use to overcome beta-lactam abx?
beta-lactamase inactivates these abx
What do we use to overcome beta-lactamase?
Beta-lactamase inhibitors
What are some beta-lactamase inhibitors?
Clavulanic acid and sulbactam
What is Augmentin?
Augmentin is amoxicillin with a beta-lactamase inhibitor, clavulanic acid.
What do beta-lactams do in addition to inhibiting penicillin-binding protein?
activate cell wall degradation enzymes
How does the bacterium die when it is treated with penicillin?
bacteria will expand, as cell wall is weakened, it will balloon out in response to osmotic forces and then rupture.
Isoniazid and ethambutol are cell wall inhibitors of which bacteria?
Mycobacteria, because they have different cell wall structures
What are some protein biosynthesis inhibitors?
aminoglycosides, tetracyclines, macrolides
How are protein biosynthesis inhibitors selective?
Bacterial ribosomes are different in composition than mammalian ribosomes
What are some side effects of protein biosynthesis inhibitors?
They may inhibit mitochondrial ribosomes due to their similarity to prokaryotic ribosomes
What are some nucleic acid biosynthesis inhibitors?
rifamycins, quinolones, and metronidazole
How do rifamycins work?
inhibition of RNA synthesis
How do quinolones work?
inhibition of topoisomerases which supercoil DNA
How does metronidazole work?
clipping DNA in anaerobic bacteria
What are some metabolic inhibitors?
sulfonamides and trimethoprim
How do sulfonamides work?
Sulfonamide is an analog of PABA, a precursor of folic acid
How is inhibiting the production of folic acid selective?
Folic acid enzymes are unique to microbes. Structural differences in enzymes between species.
How do membrane disrupting agents work?
They bind membrane and create pores which lead to bacterial rupture
What are some examples of membrane disrupting agents?
colistin and daptomycin
What is an example of host-drug interactions governing abx use?
Furantoin is excreted quickly and through the urinary system which makes it great for UTIs
How does antimicrobial resistance work?
natural selection leads to preferential selection of genes that would resist antibiotics
What is the resistome?
The catalog of abx resistance genes in the microbial environment
What are three biochemical mechanisms of abx resistance?
1) altered permeability of abx in bacteria
2) modified targets
3) drug modification
