Study guide: Mechanisms of antibacterial & microbial resistance Flashcards
What are 3 features unique to gram-negative bacteria?
- thin peptidoglycan (PG)
- Safranin (red)
- outer lipid rich membrane + lipoproteins repel many drug: polar drugs enter through porins to access PG
Which is easier for a drug to penetrate- gram positive or negative bacteria, and why?
Gram positive, low MW enter easily across exposed PG layer, itself a key target
How does the murein (peptidoglycan) layer differ between gram positive and negative bacteria?
Gram positive: thick PG
Gram negative: thin PG
How does gram staining distinguish between gram positive and negative bacteria?
Gram _p_ositive: purple dye
Gram negative: safranin (red)
Ribosomes and cell walls are common targets for antibiotics – which is unique to bacteria, and which is slightly different from its human counterpart?
bacteria vs humans:
- cell wall (humans have no cell walls)
- 70S ribosome (humans: 80S)
- outer membrane (gram negative only)
- Different needs for substrates
What are the differences between bactericidal and bacteriostatic antibiotics, and which one requires a competent immune system to resolve the infection?
Bactericidal: kills bacteria; irreversible (penicillin)
Bacteriostatic: prevent replication; reversible (tetracycline) - the patient’s own immune system must deal with getting rid of rest of the infection
Describe 3 (there are 4 in the lecture) categories of adverse effects of antibiotics – which is specific to antibiotics?
- Direct toxicity: aminoglycosides generate free radicals that damage neurons in inner ear
- Allergic reactions: rapid, immune-mediated development of rash, hives
- Idiosyncratic reactions: hemolysis in G-6-PD-deficient patients treated with sulfonamides
- Changes in normal body flora: killing some bacteria allows other to proliferate; vaginal yeast infections (this is specific to antibiotics)
Contrast between prophylactic, pre-emptive, empiric and definitive / directed therapy.
Prophylactic: antibiotic used before an infection
Pre-emptive therapy: antibiotic used during symptoms occur to prevent anticipated infection or symptoms
Empiric therapy: selection of an antibiotic based on most likely cause of infection
Definitive/directed therapy: selection of an antibiotic based on positive identification of the causative organisms
Define the terms “sensitivity”, “MIC”, and “clinical breakpoint”
Sensitivity: the ability of a bacteria to be inhibited/killed by a particular antibiotic; drug affects the bacteria at lowest concentration is the one to which it’s most sensitive
Minimum inhibitory concentration (MIC): lowest concentration of drug that inhibits growth of organism
Clinical breakpoint: highest plasma concentration that can safely be achieved in a patient
What is the purpose of broth dilution and disk diffusion testing?
Broth dilution: bacteria in liquid are exposed to increasing concentrations of a drug - the lowest concentration that eliminates growth is MIC
Disk diffusion: bacteria are plated onto agar studded with small disks containing different antibiotics - if bacteria surrounding a disk are dead, they are susceptible to that drug
How are MIC and breakpoint concentrations used together to determine bacterial sensitivity?
Sensitive: MIC < breakpoint
Intermediate: MIC near breakpoint
Resistant: MIC > breakpoint
Contrast between the terms “broad spectrum” and “narrow spectrum” – why would a narrow spectrum drug sometimes be more appropriate?
Broad spectrum: active against many types of bacteria
Narrow spectrum: active against only one or a few types of bacteria (might be more appropriate: to kill/inhibit only unwanted bacteria; lessen resistance)
Contrast between time- and concentration-dependent antibiotic effects, and the dosing strategy required for each – give an example drug for each.
Time dependent: constant rate of killing, provided that drug concentration exceeds MIC (beta lactams)
Concentration-dependent: rate of killing increase with drug concentration above MIC (aminoglycosides)
State 3 advantages of combining antibiotic drugs - are all combinations of antibiotics equally beneficial, or can some be detrimental?
- both MOA to produce a synergistic effect (greater than sum of individual drugs), in some cases combined antibiotics can antagonize each other’s effects
- Combining antibiotics can also minimize risk of resistance development
- Lower doses of each agent can be used, minimizing side effect severity
What is the difference between intrinsic and acquired resistance?
Intrinsic: trait that confers protection against antibiotic action, shared by all members of a bacterial species, not related to antibiotic exposure
Acquired: certain gene changed become favored as a result of pressure from antibiotic exposure
What are 4 general mechanisms by which bacteria can become resistant to antibiotics, and which one of these is specific to gram negative bacteria?
- Altered receptors or targets so drugs cannot bind (vancomycin)
- Drug destruction or inactivation (beta lactams)
- New resistant pathway (sulfonamides)
- Decreased drug exposure: less uptake/more efflux (regulating outer membrane pore function, or efflux transporter expression) - this mechanism is relevant to gram negative bacteria
Can more than one resistance mechanism appear in the same strain of bacteria?
With in same species of bacteria, there may be multiple strains with varying types of resistance
A single species may have multiple acquired resistance mechanisms
What are the 3 main modes of horizontal transfer of acquired resistance, and how does each work?
- Transformation: uptake of naked DNA containing resistance genes
- Transduction: DNA transferred by infection with viruses
- Conjugation: DNA transfer between bacterial cells via plasmid exchange
Are resistance genes always acquired horizontally (from another organism)?
Bacterial proliferation and transfer between hosts (poor hygiene, hospital acquired infections)
Increased exposure of bacteria to antibiotics -> selection pressure (over prescription, wrong prescription, use in agriculture)
What is “antibiotic stewardship”?
coordinated data-driven programs that focus on reducing inappropriate antibiotic use in clinical settings and agriculture
What are two general categories of initiatives that are being supported to combat drug resistance development?
- Government
- WHO, World Bank
