5_Antibiotics Flashcards
3 possible outcomes if antibiotic is added to bacteria
-
Resistant:
- Bacteria are resistant and continue to grow.
-
Bacteriostatic:
- Bacterial growth stops but the bacteria are not killed and growth will resume after removal of the antibiotic (bacteriostatic). Killing of the bacteria depends on the immune system.
-
Bactericidal:
- Bacteria are killed (bactericidal).
minimum inhibitory concentration (MIC):
define, and which types of Abx have this?
- the lowest concentration at which bacterial growth is inhibited.
- Both bacteriostatic and bactericidal antibiotics have MICs.
minimal bactericidal concentration (MBC):
define
- the lowest concentration at which bacteria are killed.
- A bactericidal antibiotic is where the MBC and MIC are close.
what determines if an Abx is bactericidal or bacteriostatic?
dependent on drug dose and bacterial species and needs to be empirically determined.
how does the MIC (min. inhibitory conc)
Disc Diffusion Assay work? (aka Kirby-Bauer)
- Abx diffuses out of the disk at a set rate –> forming a gradient of Abx conc.
- The surface of the plate is inoculated with bacteria and the bacteria grow overnight.
- The agar will be clear at concentrations of antibiotic that inhibit bacterial growth (zone of inhibition). The more sensitive the bacteria, the larger the zone of inhibition:
- small zone = resistant
- large zone = sensitive
- The exact size of resistant zones varies depending on the Abx.
what does size of “zone of inhibition” correlate to in a disc diffusion assay?
correlates to the antibiotic concentration (differs between antibiotics).
what determines resistance?
determined by the achievable clinical dose
define:
sensitive, intermediate, and resistant
- Sensitive = inhibited by 1/2 of the achievable clinical dose or lower.
- Intermediate = inhibited by concentrations higher than 1/2 the achievable dose.
- Resistant = cannot be inhibited by an achievable dose.
natural intrinsic resistance:
define and examples
- These are properties that make the bacteria more resistant.
- Gram-negative membrane
- efflux pumps (Type I secretion)
- proteases that destroy drugs
3 main types of resistance
- natural (intrinsic)
- mutational
- acquired
mutational resistance:
define
- These arise from mutation of the chromosome.
- Spread is clonal or vertical (through spreading the resistant strain).
acquired resistance:
define
- These are acquired on mobile genetic elements from other bacteria.
- Spread can be by spread of resistant bacteria AND spread of the resistance gene
how do random chromosomal mutations occur?
what increases the frequency of such mutations?
- Chromosomal mutations occur when DNA polymerase makes errors.
- Under stress the error rate increases (can affect error prone polymerases)
combination antibiotics:
function
useful for treating bacteria w/ high mutation rates;
(e.g. Mycobacterium tuberculosis)
how do resistant clone mutants spread?
resistant clones w/ chromosomal mutations are spread by clonal (vertical) spread/ transmission
efflux pumps:
function
Type I secretion; modified version on in Gram-positive bacteria
Efflux pumps remove the drug from the bacteria.
- They can be non-specific or specific
- They can be intrinsic, acquired, or mutational (depression of pump expression)
two principles of antibiotic exclusion:
define
Size exclusion
- particularly important for Gram-negative bacteria where the antibiotic has to pass through outer membrane porins
Active transport
- through the cytoplasmic (plasma, inner membrane) of Gram negative and Gram positive bacteria
- oxidative phosphorylation
- slow growth states (SCVs) or bacteria in biofilms
what produces beta-lactamases?
and function?
- gram-negative and gram-positive bacteria produce beta-lactamase
- beta-lactamase inactivates penicillin by cleaving a beta-lactam ring
beta-lactamase inhibitors can be co-administered with penicillin;
what it the purpose of this?
- The inhibitors are harder to cleave –> the b-lactamase remains bound to the inhibitor essentially keeping it from being available to bind to and cleave the b-lactam antibiotic.
beta-lactamase resistant drugs:
what do these do?
- there are beta-lactamase resistant forms of beta-lactam antibiotics
- emerging beta-lactamases destroy resistant forms (ESBL) extended spectrum beta-lactamases
fosfomycinase:
function
antibiotic that cleaves fosfomycin
modification/and inactivation of aminoglycosides
Aminoglycosides are inactivated by modification by the bacteria. There are 3 basic modifications that will inactivate Aminoglycosides:
- N-acetylation
- O-phosphorylation
- O-adenylation
what can inactivate chloramphenicol?
Chloramphenicol can be inactivated by acetylation (acetyl transferase)
how is vancomycin resistance acquired and encoded?
what do these do?
- acquired and encoded by 7 genes.
- These genes change the D-Ala-D-Ala pentapeptide –>
- D-Ala-D-Ser or,
- D-Ala-D-Lac
- There are 3 types of Vancomycin resistance operons: VanA, VanB, VanC.
metabolic bypass:
define
- There are either modification or complete substitution of Dihydropteroic acid synthetase and Dihydrofolate reductase.
- Among these are unique bypass mechanisms such as the synthesis of drugresistant, plasmid-coded dihydrofolate reductase or dihydropteroate synthetase
