L17 Intro to antimicrobial chemotherapy Flashcards
Chemotherapy
the use of drugs that are selectively toxic to pathogens but innocuous to the host
What to treat syphilis
Paul Ehrlich used Salvarsan (arsphenamine)
antibacterials drugs
- aminoglycosides
- tetracyclines
- amphenicols
- penicillins
- macrolides
- cephalosporins
Antifungals drugs
- azoles
- echinocandins
- polyenes
- allylamines
Penicillins
antibiotics that got their name from the Penicillium mold
cephalosporins on bacterial cell membrane
A large group of bactericidal antimicrobials that work via their beta-lactam rings. The beta-lactam rings bind to the penicillin-binding protein and inhibit its normal activity. Unable to synthesize a cell wall, the bacteria die.
Antibacterial drugs that inhibit cell wall synthesis
Penicillins and Cephalosporins
Antibacterial drugs that inhibit protein synthesis
aminoglycosides
tetracyclines
amphenicols
macrolides
aminoglycosides
The aminoglycosides are antimicrobial drugs used alone or in combination with β-lactam antibiotics for the treatment of certain serious aerobic gram (−) infections. Broad spectrum
Inhibit protein synthesis
tetracyclines as an antibacterial
Inhibit the 30S ribosomal subunit, hindering the binding of the aminoacyl-tRNA to the acceptor site on the mRNA-ribosome complex. When this process halts, a cell can no longer maintain proper functioning and will be unable to grow or further replicate.
Inhibits protein synthesis
amphenicols
Class of antibiotics with a phenylpropanoid structure.
Inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit and affecting the activity of the peptidyltransferase enzyme
macrolides
Ability to bind the bacterial 50S ribosomal subunit causing the termination of bacterial protein synthesis.
Antifungal drugs that inhibit cell wall synthesis
Echinocandins
Antifungal drugs that alter cell membrane integrity or permeability
polyenes
allylamines
azoles
polyenes on fungal membrane
antifungal by virtue of binding to ergosterol, which is a prevalent steroid in the fungal cell wall, resulting in depolarization of the membrane leading to increased K+ and Na+ permeability and ultimately cell death.
Alter fungal membrane integritiy
allylamines
interfering with the enzymes involved in the manufacture of ergosterol, a crucial component of the fungal cell membrane.
alter fungal membrane integrity and permeability
Azoles
Work primarily by inhibiting the cytochrome P450-dependent enzyme lanosterol 14-alpha-demethylase.Enzyme is necessary for conversion of lanosterol to ergosterol, vital component of cellular membrane of fungi.
alter fungal membrane integrity and permeability
Mechanisms of action of anti-HIV drugs
entry inhibitors
* reverse transcriptase inhibitors
* integrase inhibitors
-tegravir
* protease inhibitors
-navir
Mode of action of anti-bacterial/fungal drugs
A drug can be -cidal or -static depending on the species
- -cidal - lethal to organism and kills microbes
- -static - slow down microbial growth by blocking replication
Spectrum of action of anti-bacterial/fungal drugs
- broad spectrum - drugs are effective against a wide range of species
- narrow spectrum - drugs are effective against specific species
Minimum inhibitory concentration (MIC)
The lowest concentration of a drug required to inhibit the visible growth of a microorganism
Minimum bactericidal / fungicidal concentration
The lowest concentration of a drug required to kill a microorganism
Antimicrobial resistance - a global issue
In the top ten health treats
* antimicrobial misuse and overuse (human health, agriculture)
* spread of drug-resistant microbes, e.g., poor infection prevention
* economic cost, e.g., prolonged hospital stays, disability and death
Spread of drug resistance
- person → person (by bacteria)
- bacterium → bacterium (by plasmids)
- plasmid → plasmid by transposons
many strains carry multiple resistance genes
HIV - mutations and (multi)drug resistance proteins
- reverse transcriptase
- protease
- integrase
- gp41
(AST)
Antimicrobial susceptibility testing
Antimicrobial susceptibility testing
- phenotypic or genotypic identification of microbe(s)
- susceptibility and resistance of microbe isolates towards drugs
- 2 standards and interpretation: EUCAST & CLSI
phenotypic identification I, II & III
- Disk Di ffusion
- Gradient diffusion (Indicate MIC)
- Broth microdilution (Determine MIC)
phenotypic identification (I) - disk diffusion
collect samples (e.g., body fluids) for culture→
select colonies to prepare a suspension →
inoculate onto an agar plate →
incubation
Zone of inhibition to see how its effectiveness.
genotypic identification method
PCR
Treatment and prevention of antibacterial drugs
- spectrum of action
- broad spectrum drugs affect both harmful and beneficial species in the GI tract
▪ reduce competition between species / increase levels of resistance genes / reduce diversity - preoperative prophylaxis - ↓ risks of surgical site infection
- toxicity
Prevention of antifungal drugs
- spectrum of action
- route of administration, e.g., oral / topical / intravenous
- toxicity
anti-HIV drugs
- combination therapy - single-pill, fixed-dose (e.g., Stribild)
- potential drug-drug interactions
- HIV prevention - PrEP (pre-exposure prophylaxis) / PEP (post-exposure prophylaxis)
Broad spectrum
drugs are effective against a wide range of species
Narrow spectrum
drugs are effective against specific species
Mechanism of drug action
The process by which a drug produces a biological effect
Big zone of inhibition means
More effective drug that inhibits growth of bacteria
Antifungal susceptibility testing (AFST) colour detection
If alive colour if dead no colour
32 well containing strip
another antifungal susceptibility test
