Antimicrobials Basics Flashcards
MIC minimum inhibitor concentration
Minimum plans concentration of antibiotics required to inhibit visible growth of organisms after 24 hours of incubation
Optimal dose of antibiotic
It is the dose of antibiotic that inhibits the growth of 90% of microorganisms at the site of infection
Time dependent killing
The antimicrobial effect of such antibiotics is dependent on time during which plasma concentration above MIC
No post antibiotic effect
Antibiotics with TDK with no PAR
1. β-lactam • penicillin • cephalosporins • monobactams • carbapenems 2. Vancomycin 3. Flucytosine Multiple dosing is required
Antibiotics with TDK along with prolonged post antibiotic effects
Drugs have cidal effects at very high 🔼🔼 concentration
But they have static effects both at high 🔼 and low 🔽 plasma concentrations
Examples of TDK word prolonged post antibiotic effect PAE
Protein synthesis inhibitors like: 1. Erythromycin 2. Clarithromycin 3. Clindamycin 4. Linezolid 5. Streptogramins 6. Tetracyclins 7. Azoles Effect depends on bioavailability (are under curve) 🔼 dose ➡️🔼 effect
Concentration dependent killing
Antimicrobial effect depends on plasma concentration above MIC
Examples of concentration dependent killing CHF
- Aminoglycosides
- Fluoroquinolones
- Daptomycin
- Azithromycin
- Telithromycin
- Metronidazole
- Amphotericin-B
- Rifampin (movement depends on concentration gradient)
Examples of intrinsic drug resistance
- Aminoglycosides:
Never active against anaerobes, bcz they can’t enter - Vancomycin:
Not acting against G -ve bacteria
Large size ➡️ can’t pass through porins - Cell wall synthesis inhibitors:
Not active against mycoplasma
Types of acquired resistance
1. Genetic basis • chromosomal mediated: Spontaneous mutation Hyper mutation Adaptive mutation • horizontal gene transfer 2. Bio mechanical basis
Types of chromosome mediated resistance
- Spontaneous mutation
- Hypermutation
Accelerated mutation
Eg., MDR TB Beijing type - Adaptive mutation:
E. coli was sensitive to Fluoroquinolones, but not now due to mutation of DNA gyrase
Spontaneous mutation and antibiotic resistance
Type of chromosome mediated resistance
Due to faulty DNA replication
via biomechanical changes
Eg.,
1. Rpob gene mutation: rifampin resistance
2. 🔽 porins in G -ve bacteria: Pseudomonas
3. Efflux pumps:
β lactams, Tetracyclines, fluoroquinolone
4. Drug inactivating enzymes: β lactamases
Types of horizontal gene transfer
One bacteria to another: 1. Conjugation: M/C Plasmid 2. Transduction: Bacteriophage 3. Transformation: direct Within one bacteria: Via transposons b/w DNA & plasmid and b/w 2 plasmids Gene cassettes carry information of gene resistance (integron)
Biofilm
parts
- Persisters:
Initially bacteria which later do not multiply and grow - Colony communicating via quorum sensing
- Exopolysaccharide layer
Cause of resistance in biofilms
- Biomechanical barrier to antibiotics
- 🔽 replication bcz 🔽 entry off O2 and nutrients
- Produced efflux pumps
- Drug inactivating enzymes
- Persisters (initial central bacteria) with spore like configuration