MIIM - Antibiotics II - Week 9 Flashcards
Name 3 nucleic acid pathways that can be targetted.
Inhibiting synthesis of precursors
Inhibiting DNA replication
Inhibiting RNA polymerase
What nucleic acid pathway do quinolones inhibit? What enzyme specifically?
Inhibits DNA replication
Affects DNA gyrase
What is the action of DNA gyrase?
Required to supercoil bacterial DNA
Are quinolones bactericidal or bacteriostatic?
Bactericidal
Name three reasons to use antibiotic combinations.
To cover a range of organisms which might reasonably be expected to be present
To achieve synergy
To cover the possibility of the presence of antibiotic resistant mutants
What is the therapeutic guideline for staph blepharitis?
Antibiotic efficacy uncertain - chloramphenicol 1% ointment 1-2x daily for 1 week
What is the therapeutic guideline for chronic blepharitis (rosacea)?
Doxycycline one daily for 8 weeks
What is the therapeutic guideline for conjunctivitis (empirical treatment) (2)?
Delayed prescription approach - chloramphenicol or framycetin
What is the therapeutic guideline for conjunctivitis (non-empirical treatment) (3)?
Gentamycin, tobramycin, or quinolone drops when indicated
What is the therapeutic guideline for conjunctivitis (chlamydia)?
Systemic therapy with azithromycin
What is the therapeutic guideline for HSV keratitis?
Acyclovir 3% 5x daily for 14 days
What should be done with bacterial keratitis?
Referral
Define minimal inhibitory concentration.
The lowest concentration of an antimicrobial agent that will inhibit the growth of an organism under test over a suitable defined time interval
Describe the tube method for determining minimal inhibitory concentration (3).
Serial dilutions of the antibiotic are made in a suitable broth and a standard number of bacteria from the patient is added.
After overnight incubation, the growth is scored.
The last dilution which inhibits growth is the minimal inhibitory concentration.
Define the term sensitive or susceptible.
An infection with that organism will respond to the usually recommended dose on an antimicrobial
Define intermediate in terms of minimal inhibitory concentration (2).
The microorganism may be inhibited by attainable concentrations of certain drugs if higher doses can be used safely, or if the infection involves a body site in which the drug is physiologically concentrated.
Define resistant in terms of minimal inhibitory concentration.
Antimicrobials that do not inhibit the test organism within the range of achievable levels.
Describe the disc diffusion method for determining minimal inhibitory concentration (3).
A standard number of bacteria from the patient is inoculated onto an agar plate.
Discs impregnated with appropriate concentrations of different antibiotics are added.
After overnight inculation, zone diameters are measured and correlated with minimal inhibitory concentration.
Name 4 mechanisms of resistance to antibiotics. Give two examples for each (6).
Drug inactivation -by hydrolysis -by covalent modification Altering the target of drug action -modify target to a less sensitive form -overproduce the target Reduce access of drug to target -reduced entry into the cell -increase efflex from the cell Failure to activate inactive precursor of drug
Consider resistance to B-lactam antibiotics involving reduced affinity for penicillin binding proteins. Does this cause problems of resistance at other sites?
Yes, but not in the eye
Name three ways resistance to B-lactams can occur.
Production of B-lactamases
Alteration of penicillin-binding proteins
Reduced entry into the cell
Briefly explain how B-lactamase acts.
It breaks the B-lactam ring, disabling the molecule
List and describe the two ways resistance to glycopeptides can occur.
Alteration of the target - mutation of the terminal amino acids into lactate
Production of excess target - peptidoglycan
Name 4 ways resistance to aminoglycosides can occur.
Efflux from the cell
Modified outer membrane leading to reduced entry
Enzymatic inactivation
Ribosomal mutation leading to reduced binding
Name two ways resistance to macrolides can occur.
Increased efflux from the cell
Modification of the target - methylation of the 23S renders 50S resistant
Describe the main way resistance to tetracyclines occurs.
Predominantly efflux from the cell
Name two ways resistance to quinolones can occur.
Increased efflux from the cell
Modification of the target - mutation in DNA gyrase reducing antibiotic binding
Name 4 ways genetic material for antibiotic resistance can be acquired by a bacteria.
Transformation
Transduction
Conjugation
Transposition
Name three intrinsic resistances to antibiotics.
Cell wall impermeability
Lack of a target
Chromosomal resistance gene
Name two acquired resistances to antibiotics.
Mutation
Horizontal gene transfer
Briefly describe transformation.
A dead bacteria with the genes for resistance releases free DNA when lysed.
The recipient bacteria take up the free DNA and incorporate it into their genome.
Briefly describe transduction.
A bacteriophage infects a bacteria with resistance.
Once it finishes killing the bacteria, the bacteriophage has a copy of the resistance gene.
It infects another bacteria, which receives the resistance gene from the bacteriophage.
Briefly describe conjugation.
The gene for resistance is found on a plasmid.
The bacteria connects to a recipient bacteria via a pilus, and sends it a copy of the plasmid.
Briefly describe transposition.
The gene for resistance is found on a plasmid with a transposon.
The plasmid is transferred to a recipient via conjugation.
The transposon transposes the plasmid into the genome.
List the 5 drug resistance mechanisms.
Prevent drug entry Drug efflux Inactivate drug Modify drug target Use an alternate pathway
How can the threat of resistance be reduced.
Controlled use of antimicrobials to reduce the natural selection of resistant strains.
