Antibiotics; types, sites of action, organisms they are effective against, antibiotic resistance mechanisms Flashcards
what are antibiotics?
agents produced by microorganisms that kill or inhibit the growth of other microorganisms in high-dilution.
They are molecules that work by binding a target site to a bacteria.
what are antimicrobials?
semi-synthetic derivatives of antibiotics
which type of antimicrobial ( antifungals, antibacterials, antihelminthics, antiprotozoals, antiviral agents ) is what’s thought of as antibiotics?
antibacterials
what are the 3 main target sites of antibiotics?
within the bacterium:
- cell wall (peptidoglycan) synthesis
- PBPs in cell wall
- cell membrane - nucleic acid synthesis
- DNA
- topoisomerase Iv or DNA gyrase - protein synthesis
- ribosomes
how do antibiotics inhibit cell wall synthesis?
These disrupt peptidoglycan production (for cell envelope)
They do this by binding covalently and irreversibly to the penicillin binding proteins (PBSs)
Cell wall is disrupted, lysis occurs
what are the main group of antibiotics that target cell wall synthesis?
these are the most commonly prescribed antibiotics
beta lactams
what are the subcategories of antibiotics within beta lactams?
penicillins
Carbapenems
Monobactams
Cephalosporins
list 3 penicillins
Penicillin V
Flucloxacillin
Amoxicillin
Penicillin G
Piperacillin
give an example of a Carbapenem (beta lactam, targets cell wall)
Meropenem
give examples of Cephalosporins (beta lactams, target cell wall)
Cefuroxime
Ceftriaxone
Cefotaxime
why/when are Cephalosporins used over penicillins?
Still beta lactams
But good for people with non-severe penicillin allergy
Work against some resistant bacteria too
Can get into different parts of the body eg. CNS, to treat meningitis
name the category of antibiotics that target cell wall synthesis but are not beta lactams ?
why/when are these used?
GLYCOPEPTIDES
Use for gram positives that are resistant to beta lactams eg. MRSA, enterococci and some coagulation negative staph
and for people with penicillin allergies
name 2 examples of glycopeptides
vancomycin bacitracin
teicoplanin (IV)
are antibiotics that target cell wall synthesis better suited to treating gram positive or gram negative bacteria?
Gram positive bacteria → thick cell wall therefore use beta lactams (they are the main cell wall weapons)
Gram negative bacteria → additional wall reduces antibiotic penetration/diffusion therefore don’t tend to use cell wall weapons
which antibiotic would you prescribe to treat cellulitis? (skin and soft tissue infection)
commonly caused by these bacteria : S.aureus and group A,C,G strep
these are gram positive
flucloxcalccin
which antibiotic would you prescribe to treat strep throat?
Group A,C,G strep
oral penecillin V
or
IV benzylpeneckllin
which antibiotic would you prescribe to treat pneumonia ?
caused by S.pneomniae
oral amoxilcin or IV benzylepenecillin
which antibiotic would you prescribe to treat MRSA caused cellulitis?
vancomycin bacitracin and teicoplanin (IV)
these are glycopeptides
can’t use beta lactams because MRSA in resistant
how do antibiotics that taste protein synthesis work ?
target ribosomes
prevent synthesis of subunits eg. 50S and 30S
list the types of antibiotic that target protein synthesis
macrolides
lincosamides
tetracyclines
aminoglycosides
protein synthesis inhibitors: macrolides
- give an example
- when/why used?
Eg. Clarithromycin – oral (& IV)
Use on gram positives
Eg. S. aureus, β haemolytic strep
Use if penicillin allergy
Use if severe pneumonia
why use Clarithromycin to treat sever pneumonia
why. not a cell wall weapon?
Atypical pneumonia eg, legionella
multiply inside cells,
therefore no good having a cell wall active antibiotics as can’t get to it if it’s hiding inside a cell
So use protein synthesis inhibitors instead
protein synthesis inhibitors: lincosamides
- give an example
- when/why used?
Eg. Clindamycin = oral (& IV)
Use on gram positives
Eg. S. aureus, β haemolytic strep , anaerobes
Use for cellulitis if penicillin allergy
Ues for necrotising fasciitis
Turns off toxins made by gram positive bacteria
protein synthesis inhibitors: tetracyclines
- give an example
- when/why used?
Eg. Doxycycline = oral
Broad but mainly use for gram positives
Eg S. aureus and streps
Use for cellulitis if penicillin allergy
Use for pneumonia
what group of antibiotics that target protein synthesis are used to treat gram negative bacteria? and why?
aminoglycosides
Gram negative bacteria → additional wall reduces antibiotic penetration/diffusion therefore don’t tend to use cell wall weapons, favour protein synthesis method
name an amminoglycoside that is used to treat gram negative bacteria
what diseases can It treat?
gentamicin - IV only
Use for UTIs
can amminoglycosides be used to treat gram positive?
mainly used for gram negatives
but can be used synergistically for streps (which are gram positive)
Use for infective endocarditis (synergistically)
list specific protein synthesis inhibitors
Examples that synthesis 505 subunits
Clarithromycin
Clindamycin
Linezolid
Chloramphenicol
Streptogramins
Examples that synthesis 305 subunits
Doxycycline
gentamicin
give examples of nucleic acid synthesis inhibitor antibiotics
DNA gyrase eg. quinolines
RNA polymerase eg. rifampin
folate synthesis inhibitors
name a quinoline and what its used for?
Eg. ciprofloxacin - oral and IV
Better for gram negative then positive
Use if penicillin allergy
Use on UTIs
Use on intra-abdominal infections
name 3 folate syyntheisis inhibitors
how do they work?
what are they used for?
these are anti-metabolites that stop folic acid synthesis
Synthesis sulfonamides
Synthesis trimethoprim
Co-trimoxazole
Mainly used for gram negative
Use for UTIs
name a membrane inhibitor antibiotic
nitrofurantoin
Used for gram negative and gram positives
Use for lower UTIs when resistant to trimethorpims
Fist in to cell wall category
can beta lactams be used to treat gram negative?
sometimes
if they have specific side chains that make their range broader
give 3 examples of beta lactams that can treat gram negative
(1 penicillin, 1 Carbapenem, 1 Cephalosporin)
these are really important and useful antibiotics with low resistance
Piperacillin-tazobactam
Meropenem
Cefuroxime
what are the 2 categories of antibacterials antibiotics?
Bacteriostatic
bactericidal
what are the main differences between Bacteriostatic and bactericidal antibiotics ?
Bactericidal antibiotics
- Kill bacteria
Bacteriostatic antibiotics
- Inhibit bacterial growth
what does MIC mean?
Minimum inhibitory concentration,
defines in vitro levels of susceptibility or resistance of specific bacterial strains to applied antibiotics.
is an antibiotic with a really low MIC always the most effective?
a lower MIC value indicates that less of the drug is required in order to inhibit growth of the organism, drugs with lower MIC scores are more effective antimicrobial agents
However this isnt always true because there are other factors to consider
what are the 2 major determinants of antibacterial effects?
Concentration at binding sites
- Drug must occupy an adequate number of binding sites, to create a sufficient concentration to have sufficient effect
Time at binding site
- Antibiotic must remain at binding site for sufficient period of time in order for the metabolic process of the bacteria to be sufficiently inhibited
how do pharmokinetics affect antibiotics?
A
absorption from site of administration into bloodstream
how do pharmokinetics affect antibiotics?
D
Distribution to site of infection -
Consider the pH of the site? Is the antibiotic lipid soluble? Can it penetrate the site (get through memebranes?) How fat is a patient?
Antibiotic must reach the site of bacterial infection
how do pharmokinetics affect antibiotics?
M + E
rate of elimination from body via metabolism (liver) or excretion (kidney)
Half life of antibiotic helps us to decide dosage
briefly, what are the 4 mechanisms of antibiotic resistance?
Change antibiotic target/ masking
Destroy antibiotic
Prevent antibiotic access
Remove antibiotic from bacteria
explain the mechanism of resistance and give examples:
- Change antibiotic target/ masking
Bacteria mask or change the molecular configuration of antibiotic binding site
eg. MRSA resistant to flucloxacillin
Enterococci resistant to vancomycin
TB resistant to rifampicin
explain the mechanism of resistance and give examples:
- Destroy antibiotic
The antibiotic is destroyed or inactivated
Examples:
Beta lactam ring of penicillins + cephalosporins hydrolysed by bacteria enzyme beta lactamase, so it is unable to bind to penicillin binding sites (PBP)
explain the mechanism of resistance
- prevent antibiotic access
Modify the bacteria membrane porin channel (size, number and selectivity)
explain the mechanism of resistance
- Remove antibiotic from bacteria
Proteins in bacterial membranes act as an export or efflux pumps
So the level of antibiotic is reduced by removing it
what does MRSA stand for and which antibiotic is it resistant to?
how has it become resistant?
MRSA = Methicillin Resistant Staphylococcus Aureus
resistant version of staph A
MRSA resistant to flucloxacillin or methicillin →
antibiotics are no longer able to bind to PBP of staphylococci
acquired resistance
explain how enterococci has become resistant to vancomycin
Enterococci resistant to vancomycin →
enterococci have changed their wall components which has reduced vancomycin binding
explain how TB has become resistant to rifampicin
TB resistant to rifampicin →
multi drug resistant TB (MDR-TB) changes its RNA polymerase which reduces rifampicin activity
what are the 2 types of antibiotics resistance
(development)
intrinsic
acquired
describe intrinsic resistance
do all populations of a species have equal resistance?
when a bacterial species is naturally resistant to a certain antibiotic or family of antibiotics, without the need for mutation or gain of further genes
All subpopulations of a species will be equally resistant
describe acquired resistance
do all populations of a species have equal resistance?
A bacterium which was previously susceptible obtains the ability to resist the activity of a particular antibiotic
Only certain strains or subpopulations of a species will be resistant
give 2 examples of antibiotics that certain bacteria are resistant to?
aerobic bacteria is resistant to Metronidazole
gram negative bacteria is resistant to Vancomycin
explain Metronidazole resistance
Metronidazole can treat anaerobic bacteria - by become its active, toxic form
but Metronidazole cannot treat aerobic bacteria.
Because it doesn’t get reduced by bacteria to form its active, toxic, bacteria killing form
explain how gram negative bacteria is resistant to Vancomycin
Vancomycin cannot penetrate outer membrane of gram negative bacteria
what are the 2 mechanisms of acquired resistance?
Spontaneous gene mutation
Horizontal gene transfer
how does spontaneous gene mutation lead to acquired resistance to antibiotics?
There is spontaneously a new nucleotide base pair
This changes the amino acid sequence
This changes to enzyme of the cell structure
This can cause reduced affinity of activity of the antibiotic to this bacterium
name the 3 ways Horizontal gene transfer leads to acquired resistance to antibiotics?
- conjugation
- transduction
- transformation
how does Horizontal gene transfer via conjugation lead to acquired resistance to antibiotics?
give example
bacterial sex,
where plasmids are shared between bacteria.
Plasmids contain extrachromosomal DNA
eg. new delhi meallo-beta-lactamase
how does Horizontal gene transfer via transduction lead to acquired resistance to antibiotics?
give example
TRANSDUCTION - when bacteriophages (viruses that infect bacteria) mediate transfer of DNA between bacteria (by packaging donor bacterium in a virus particle and transferring into a recipient bacterium during infection)
eg. mecA genes for MRSA
how does Horizontal gene transfer via transformation lead to acquired resistance to antibiotics?
give example
TRANSFORMATION - when naked DNA is picked up
eg. when foregin DNA from S.mitis is picked up by S.pneumonia it becomes penicillin resiistnat
Examples of gram-positive bacteria that have acquired resistance:
MRSA
VRE
MRSA:
- through which type of acquired resistance does MRSA form from?
- name gene involved
- what is MRSA resistant to?
Transduction occurs,
insertion of staphylococcal cassette chromosome mec (SCCmec)
This contains the resistant gene mecA
It encodes PBP2a
Confers resistance to all beta-lactam antibiotics eg. flucloxacillin
VRE:
- through which type of acquired resistance does VRE form from?
- what is VRE resistant to?
VRE = Vancomycin Resistant Enterococci
Conjugation occurs,
acquired a gene encoding altered AA on peptide chain that prevents vancomycin binding
what are ESBLs?
what type of resistance is this an example of?
ESBL = Extended Spectrum Beta Lactamase
enzymes that allow for resistance to most beta-lactam antibiotics
example of gram negative acquired resistance
how do ESBLs form?
Mutation at active site causes extended range of antimicrobial resistance to form ESBL
how do ESBLs cause antibiotic resistance?
ESBL hydrolyse oxyimino side chains of cephalosporins, cefotaxime, ceftriaxone, and ceftazidime and monobactams: aztreonam
what antibiotics are capable of treating ESBLs?
Can pair together antibiotics to enhance effect eg.
Amoxicillin + Clavulanate = Co-Amoxiclav
Pipericillin + Tazobactam = ‘Tazocin’
Carbapenems (eg. Meropenem) were the last resort to treat infections due to ESBL. It remained highly resistant to beta lactamase. however why this no longer the case?
recently Carbapenem resistant enterobacteriaceae (CRE) formed. It produces carbapenemases which breaks down the antibiotics, so this treatment no longer works.
where is CRE common?
hospitals
