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Unit 7: Antimicrobials and Antimicrobial Resistance - Coggle Diagram
Unit 7: Antimicrobials and Antimicrobial Resistance
The History of Antimicrobial Drugs
Revolution between the first and second WW
Salvarsan - worked agains syphilis but contained arsenic
Domagk used to treat infections in animals with dyes (the first 'sulfa' drug)
Fleming - Penicillin (kills many bacterial species)
Development of new drugs
Altered versions of Pencillin
Antimicrobials: Themes and Terminology
Selective toxicity
Interfere with structures found in microbes not human cells
Toxicity is expressed as therapeutic index
Spectrum of activity
Broad spectrum and narrow spectrum
Tissue distribution, metabolism, excretion
depends on antimicrobials and their behaviour in the body
Effects of combinations
Antagonistic, synergistic, additive
Adverse affects
Toxic effect, allergic reactions, suppression of normal microbiota
minimum inhibitory concentration (MIC)
lowest concentration that prevents growth in vitro
minimum bactericidal concentration (MBC)
lowest concentration able to kill 99.9% of cells in vitro
Antimicrobial susceptibility testing
Kirby-Bauer disc diffusion test
Size of zone of inhibition is looked at on the dish
Commercial modifications
Faster results, less labor-intensive
Determine growth rate via turbidity
E test - uses strip with gradient of drug
Mechanisms of Antimicrobial Drug Action
Drug targets - cell walls
B-lactam drugs
Disrupt peptidoglycan synthesis in cell wall --> cell lysis
All have B-Lactam ring
Bacteria synthesize B-Lactamase which inactivate antibiotics
Drugs that inhibit protein synthesis
exploit differences between prokaryotic and eukaryotic ribosomes
aminoglycosides - irreversibly bind 30S ribosomal subunit --> blocks initiation of translation, misreading of mRNA
tetracyclines - reversibly bind 30S subunit --> block tRNA attachment, prevents continuation of translation
macrolides - reversibly bind 50S subunit --> prevents continuation of translation
Cell wall synthesis inhibitors
Vancomycin blocks peptidoglycan synthesis
Drugs that inhibit nucleic acid synthesis
fluotoquinolones
inhibit topoisomerases
rifamycins
block prokaryotic RNA polymerase from initiating transcription
Drugs that interfere with metabolic pathways
Sulfonamides - sulfa drugs
trimethoprim
All are folate inhibitors
Drugs that interfere with cell membrane integrity
Daptomycin
Gram-positives
Polymyxin B
Gram-negatives
Antibacterial drugs against Mycobacterium
Waxy cell prevents entry of many drugs, growth is slow
Isoniazid
Ethambuto
Antimicrobial Resistance
Mechanisms of antimicrobial resistance
Change the target so it doesn't bind the drug
Keep the drug and take the target away from each other
Destroy the drug
Stop growing or grow slowly
how antimicrobial resistance can be acquired
Intrinsic resistance
Naturally resistant
Acquired resistance
Evolutionary changes by spontaneous mutation or horizontal gene transfer
how antimicrobial resistance can be slowed
Cooperation globally
Responsibilities of healthcare workers
only prescribe suitable antibiotics, make patients know what they are taking
Responsibilities of patients
Economic factors that are slowing the development of new drugs
Medical tourism
Global travel
Farm use of antibiotics
Pros
Less infections, easier to manage
Cons
More resistant bacteria
Tracking of CRE at the PHO labs
Carbapenem resistance
Emerging antimicrobial resistance
Staphylococcus aureus
Most common in healthcare facilities, low affinity to B-lactam drugs including methicillin (MRSA)
Streptococcus pneumoniae
Susceptible to penicillin
Enterococci (VRE)
Gram-positive, cause infection in wounds, less susceptible to antibiotics --> low affinity to B-lactam drugs
Carbapenem resistant enterobacteraciae (CRE)
Gram-negative, resistant to many drugs (outer membrane prevents entry)
NDM-1
Broad spectrum zinc-containing enzyme that can destroy almost all carbenicillins
Mycobacterium tuberculosis (XDR-TB)
Can become resistant to first-line drugs via mutation