principles of antibiotics Flashcards
what is an antibiotic
agents produced by micro organisms that kill or inhibit the growth of other micro organisms in high dilution
how do antibiotics re
by binding a target site on a bacteria
how to define the class of an antibiotic
the location where the antibiotic binds to the target site on the bacteria will tell you the class
what are antimicrobial
semi synthetic derivatives of antibiotics
examples of antimicrobial
anti fungal
anti bacterial
antihelminthic
antiprotozoal
antiviral agents
what do beta lactam antibiotics do
disrupt peptidoglycan production
by binding covalently and irreversibly to the penicillin binding proteins
cell wall is disrupted and lysis occurs
results in a hypo osmotic or iso osmotic environment
what are beta lactam antibiotics active against
active only against rapidly multiplying organisms
in order to bind to the penicillin binding proteins what must the beta lactam antibiotics do first
diffuse through the bacterial cell wall
what do gram negative organisms have that decreases antibiotic penetration
an additional lipopolysaccharide layer
which bacteria are more suspectible to B lactam
gram positive are more susceptible than gram negative
what causes differences in the spectrum and activity of b LACTAM antibiotic
due to their relative affinity for diff penicillin binding sites
why are beta lactams ineffective in the treatment of intracellular pathogens
because the penicillins poorly penetrate mammalian cells
what are we trying to achieve with antibiotics
they give time and support for the immune system to deal with an infection
describe the bacterial agenda
- attack and enter
- local spread
- multiply
- evade host defences
- shed from body
consequences of bacteria
direct - destroy phagocytes or cells in which bacteria replicate
toxins - exotoxin (protein production), endotoxin (gram negative)
indirect - inflammation, immune pathology
diarrhoea
describe bactericidial antibiotics
the agent kills the bacteria
they are antibiotics that inhibit cell wall synthesis
when are bactericidal antibiotics useful
- if poor penetration (endocarditis)
- difficult to treat infections
- need to eradicate infection quickly (meningitis)
describe bacteriostatic antibiotics
prevent growth of bacteria - inhibitory to growth
antibiotics that inhibit protein synthesis, dna replication or metabolism
reduce toxin production and endotoxin surge less likely
what is MBC/MIC
a ratio of minimum bactericidal concentration to minimum inhibitory concentration
what must the antibiotic do to work effectively
it should remain at the binding site for a suffficient period of time in order for the metabolic processes of the bacteria to be sufficiently inhibited
what is related to concentration within the microorganisms
the drug must not only attach to its binding target but also must occupy an adequate number of binding sites
what are the 2 major determinants of anti bacterial effects
the concentration
and the time
that the antibiotic remains on these binding sites
what is time dependent killing
key parameter isn’t he time that serum concentrations remain above the MIC during the dosing interval
what is concentration dependent killing
key parameter is how high the concentration is above MIC
what is the antibiotic dependent on
pharmacokinetics - the movement of a drug from its administration site to the place of its pharmacologic activity and then its elimination from the body
process of pharmacokinetics
- its release from the dosage form
- its absorption from the site of administration into the bloodstream
- its distribution to various parts of the body, including the site of action
- its rate of elimination from the body via metabolism or excretion of unchanged drug
how do bacteria resist antibiotics
- change antibiotic target
- destroy antibiotic
- prevent antibiotic access
- remove antibiotic from bacteria
resist antibiotics - describe change antibiotic target
bacteria change the molecular configuration of antibiotic binding site or masks it
resist antibiotics - describe destroy antibiotic
the antibiotic is destroyed or inactivated
resist antibiotics - describe prevent antibiotic access
modify the bacterial membrane porin channel size, numbers and selectivity
resist antibiotics - describe remove antibiotic from bacteria
proteins in bacterial membranes act as an export or efflux pumps - so level of antibiotic is reduced
why do bacteria develop resistant?
intrinsic - naturally resistant
acquired - spontaneous gene mutation
- horizontal gene transfer - conjugation
- transduction
- transformation
intrinsic resistance
all subpopulations of a species will be equally resistant
acquired resistance
a bacterium which was previously susceptible obtains the ability to resist the activity of a particular antibiotic
only certain strains or subpopulatuons fi a species will be resistant
2 important resistances in gram positive bacteria
MRSA
VR
describe MRSA
methicillin resistant staphylococcus aureus bacteriophage mediated acquisition of staphylococcal cassette chromosome menc
contains resistance gene mecA encodes penicillin binding protein 2a confers resistance to all b lactam antibiotics in addition to methicillin
describe VRE
vancomycin resistant enterococci
plasmid mediated acquisition of gene encoding altered amino acid on peptide chain preventing vancomycin binding
promoted by cephalosporin use
name an important resistance in gram negative bacteria
ESBL
describe ESBL
extended spectrum beta lactamase (ESBL) inhibition
these hydrolyse oxylimino side chains of cephalosporins: cefotaxime, ceftriaxone and ceftaidime and monobactams: aztreonam
