Unit 8 Antimicrobial Chemotherapy Flashcards
Antimicrobial activity is the ability to
Produce the death of the organism
Or
Prevent the development and multiplication of microorganisms
Antimicrobial
Substance with Antimicrobial activity that can be used for the treatment of infectious diseases because of its effectiveness and lack of toxicity
Categories Antimicrobial
Antibacterial
Antiviral
Antifungal
Antiparasitic
Selective toxicity
Harms the microorganisms but not the human cells
Therapeutic target
The structures we target in order to kill a microorganism like it’s fundamental structures
Characteristics we aim for Antimicrobial
Minimum toxicity for the host
Active at low concentration
Antimicrobial activity
Narrow spectrum
Selectively active on some species
Broad spectrum
Active against large number of microorganisms
Bacteriostatic
Inhibit the growth of microorganisms
The performance of the patient’s defense mechanisms in essential here
Bactericidal
Kills the microorganisms
Depends on the concentration, if it’s low it could be static
Mechanism of action
The specific biochemical interaction through which an antimicrobial produces its pharmacological effect.
Why an antibiotic might not work against a bacteria
Depends on the structure of the bacteria and the mechanism of action
Mode of action of B-lactam
Bind to the proteins PBP involved in cell wall synthesis
Efficacy of antibiotics depends on
A target for the antibiotic must exist
Antibiotic shouldn’t be inactivated or modified
Sufficient amount of antibiotic must reach the target
Two types of antibiotic resistance
Intrinsic : possessed by all the bacteria of a specie by innate genetic characters.
Acquired : by certain individuals of a specie due to chromosomal mutations, selective pressure or horizontal transmission
How is the resistance of an antibiotic passed to the whole population
-Horizontal transmission
-selective pressure
-mutation
and selection by the use of antibiotics by killing the sensitive population and leaving the mutant
Antibiotic resistance by inactivation : 3 mechanisms
Hydrolysis
Transference of a chemical group
Reduction/oxidation
Resistance by modification of the target exemples
Alteration of peptidoglycan structure
Modification of PBPs
Interference with protein synthesis
Mutation in rRNA
Interference with DNA synthesis (mutation in gyrase and topoisomerase)
Resistance by active efflux pump
Expel antibiotics outside of the cell
Different level of specificity
Can affect all classes of antibiotics
Produce a low level resistance
Reduction of permeability
Can generate resistance to what
Affects the transport through the outer membrane
Due to changes in the number, size or specificity of the porins
Can generate resistance to hydrophilic b-lactam and fluoroquinolone
Low level resistance
Mechanisms of bacterial resistance
Modification of the target
Reduced permeability to antibiotics
Active efflux pump
New metabolic pathways
Enzymatic inactivation
The mechanisms of resistance to b-lactam antibiotics are
Destruction by b-lactamase
Modification of the target PBPs, no recognition
Reduction of permeability
Efflux pumps
How do b-lactamase works
When is it the most effective
Break the b-lactam ring. More effective in gram- because Periplasmic space is bigger
Enterobacteriaceae (type of b-lactamase)
TEM 1
Extended spectrum b-lactamase
Carbapenemase
TEM 1
Resistance to penicillin only
Extended spectrum b-lactamase ESBL
Resistance to penicillin and cephalosporin of all generations
Carbapenemase
Against all b-lactam including carbapeneme
B-lactamase inhibitors
Irreversible binding to b-lactamase.
Combined with some penicillin
Exemple:
Clavulanic acid
Sulbactam
Tazobactam
Resistance to macrolides
Target modification (ribosomes)
Active efflux pumps
Enzyme inactivation
Ribosomes modification
Methylation of 23S ribosomal RNA fraction
Change in ribosomal proteins
Resistance to quinolone
Modification of targets : gyrase and topoisomerase
Pumps
Antibiogram/sensitivity test function
Determine the resistance of a bacteria to a type and a quantity of antibiotic
Two types of antibiograms
Disk plate diffusion
Dilution technique
Disk plate diffusion
Bacteria classified resistance according to the inhibition area measured in mm
Dilution techniques
In a liquid medium, specific concentration of bacteria and drug.
To determine the minimum concentration of antibiotic required to inhibit growth MIC
Agar diffusion
In a plate, band with progressive concentration of antibiotics
Types of dilution techniques
Agar diffusion
Micro broth dilution
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Classification resistance bacteria
Susceptible ( using standard dosing regimen )
Susceptible when exposure is increased/ intermediate (dosing regimen is increased )
Resistant
Dosing regimen
Frequency and dose at which a drug is administered
Exposure depends on
Dose, dosing intervals, infusion time, mode of administration, excretion of the drug
MIC
Minimum inhibitory concentration
To set the susceptibility of an antibiotic, 3 data are collected
The range ( lowest MIC- highest MIC)
MIC50 : MIC that inhibits at least half of the bacteria
MIC90 : MIC that inhibits at least 90%
Undesirable effects of antibiotics in the patient
Target also exists in the host
Toxic side effect unrelated to the mechanism of action
Hypersensitivity
Kills normal microbiota
Association of antibiotics function
Increase intensity of action
Extension of spectrum
Systemic infections
Prevent emergence of resistance ( some microorganisms have several mechanisms of resistance)
Interaction between antibiotics
Additive effect
Synergistic effect
Antagonistic effect
Disadvantages of association of antibiotics
Possible increase of toxicity
Possible antagonism
Addition
Actions are added with no increase in the sum effect
Independent
Synergy
Action of antibiotic together is better than separately
Antagonism
The association in less effective
Prophylaxis
Treatment given in advance to prevent disease
When to prescribe antibiotics
Prophylaxis
Treatment of bacterial infections
What are the criteria to consider when prescribing antibiotics
Bacteria involved
Patient
Antibiotic dosage, administration route…
What to keep in mind when prescribing antibiotics
Side effects
Respect treatment dose and duration
Associations
Antibiotics in dentistry
Oral flora in abundance
Most dental infections are polymicrobial
Involvement of anaerobes
Microorganism has several mechanism of resistance
Emergence of resistance
