Antibiotics symposium 1: principles of antibiotics Flashcards
what is an antibiotic?
an agent produced by microorganisms that kill or inhibit the growth of other microorganisms
What is the definition of a target site of an antibiotic?
points of biochemical reaction crucial to the survival of the bacterium
which gram staining of bacteria has more peptidoglycan?
G+
what is the name of the protein that penicillin works on?
penicillin binding protein
what drug classes come under beta lactams?
penicillins, cephalosporins and carbapenems
Which class is also active against penicillin binding proteins but is not a beta lactams?
glycopeptides
which antibiotics interfere with nucleic acid synthesis and function?
metronidazole
rifampicin
what type of bacteria can metronidazole kill?
anaerobes
which class of antibiotics works on inhibiting DNA gyrase?
fluoroquinilones
which antibiotic classes work on inhibition of ribosomal activity?
aminoglycosides tetracyclines lincosamides macrolides chloramphenicol
which drug classes inhibit folate synthesis?
sulphonamides
trimethoprim
what does bacteriostatic mean?
inhibitory to growth
in what ways can antibiotics inhibit growth?
inhibit protein synthesis
inhibit DNA replication
interfere with metabolism
in what additional way do bacteriostatic antibiotics work?
they reduce production of toxins
what is the main mechanism of bactericidal antibiotics?
inhibition of cell wall synthesis
when are bactericidal drugs particularly useful?
when there is poor tissue penetration by blood vessels
difficult to treat infections
need to eradicate infection quickly
what are the two major determinants of antibacterial effects?
concentration
time
which drugs have concentration dependent killing?
aminoglycosides
quinolones
which drugs have time dependent killing?
beta lactams
clindamycin
macrolides
oxazolidinones
which type of bacteria is flucloxacillin mainly for?
staphylococcus
which antibiotic is used for MRSA?
vancomycin
how does the half life/ elimination of the drug affect treatment?
affects the dosage intervals and duration of treatment
what are the pt considerations before prescribing antibiotics?
allergy or intolerance side effects age liver and kidney function pregnancy/breastfeeding drug interactions C. diff
what are the 4 key ways that antibiotics confer resistance?
change the antibiotic target
destroy the antibiotic
prevent antibiotic access
remove antibiotic from bacteria
describe how bacteria can change the antibiotic target
mutation in the gene for a protein to which the antibiotic binds causes the antibiotic to be unable to bind, or a gene mutates so that it produces a protein that binds to and blocks the antibiotic binding site
give examples of antibiotics that are not sensitive due to change in antibiotic target
flucloxacillin no longer able to bind PBP of staph (MRSA)
wall components change in enterococci so reduce vancomycin binding
rifampicin activity reduced by RNA polymerase in myco. TB
how do bacteria destroy an antibiotic
bacterial enzyme produced
give examples of bacteria that can destroy antibiotics
- beta lactamases hydrolyse beta lactam ring of penicillins and cephalosporins
- staphylococci produce penicillinase so penicillin but not but not flucloxacillin is inactivated
- G- bacteria phosphorylate aminoglycosides (gentamycin)
How do bacteria prevent antibiotic access?
modify the porin channel size, numbers and selectivity
give examples of bacteria that can prevent antibiotic access
pseudomonas aerguinosa against imipenem
G- bacteria against aminoglycosides
how do bacteria remove antibiotic?
develop export or efflux proteins
Give examples of bacteria that remove antibiotic
S. aureus or S. pneumoniae develop resistanance to fluoroquinolones
enterobacteriaceae get resistant to tetracyclins
what are the methods of development of bacterial resistance?
intrinsic
acquired - conjugation, transduction, transformation
give examples of intrinsic resistance (ie naturally resistant)
aerobic bacteria cant reduce metronidazole to its active form
vancomycin cannot penetrate the outer membrane of G- bacteria
what is the definition of acquired resistance?
a bacterium that was previously susceptible obtains the ability to resist the activity of a particular antibiotic
what is conjugation?
sex pilus forms through which a plasmid is transferred ‘bacterial sex’
what is transduction?
bacteriophages that have donor bacterial DNA in them infect an bacterium and transfer the DNA to the recipient bacterium
what is transformation?
bacteria can take up free DNA from the environment and incorporate it into their genome
what are the important resistant G+ organisms?
MRSA
VRE - vancomycin resistant enterococci
what does mecA do?
changes the binding site of penicillins as it encodes for a low affinity penicillin binding protein - resistance to all beta lactams
which antibiotic class promotes VRE?
cephalosporins
by what means do VRE gain their resistance?
aqcuisition of a plasmid - gene prevents vancomycin binding
how are gram - bacteria resistant to antibiotics?
they can produce beta-lactamases eg E. col, H. influenzae, N. gonorrhoea, Klebsiella pneumoniae
ESBL - more extended beta lactam inhibition
ampC beta-lactamase resistance - broad spectrum penicillin, cephalosporin, monobactam resistance, beta lactamase inhibitor resistant with inducible expression
what type of antibiotics were developed to combat G- resistance?
carbapenems
give examples of carbapenems
ertapenem, imipenem, meropenem, doripenem
what is the advantage of carbapenems over other beta lactams?
highly resistant to degradation by beta lactamases or cephalosporinases
is there resistance to carbapenems?
Yes - carbapenemases
