antibiotic resistance Flashcards
Antibiotic innactivation or modification
bacteria develop enzymes that destroy antimicrobials
- → e.g. beta lactamase
Alteration of target or binding site
Antibiotic can’t bind anywhere on bacteria
e.g. MRSA (staphylococus aureus) modifies penicillin binding locations
Bypassing metabolic inhibition
→ Antibiotics like sulfonamides disturb metabolic pathway for synthesis of folic acid
→ but, some bacteria find folic acid from environment, bypassing action of sulfonamides
Preventing antibiotic accumulation
create efflux pumps: pump antibiotic out of bacteria
- Both dec. intracellular antibiotic concentrations
- For new antibiotic, pathogen relies on:
variation → selection pressure → mutation → thrive w antibiotic t
what does Exposure to antibiotics in the environment encourage
resistance as small numbers of ‘resistant mutants’ will survive whilst susceptible organisms die off
Likely to happen in gut of someone taking antibiotics or in bacteria in hospital
Natural Resistance
- target is not present (missing cell wall)
- target is not accessible (gram -ve outer membrane blocks some drugs)
- developmental structure
- metabolism
Biofilm:
- Microbial community→ more resistant to antimicrobial agents and host defences
Spatial heterogeneity:
range of diff species, each w own functions and properties
Tolerant, metabollicaly inert:
- unaffected by antibiotics (survive and proliferate)
- Spores increase
Acquisition of resistant (new) enzyme
Penicilin alterered
- Methicillin Resistant S. aureus MRSA
- Flucloxacillin replaced Methicillin
- MRSA means resistance to Flucloxacillin
Replacement of sensitive pathway
Evolution
Changes not present naturally, acquired directly or by HGT
HGT:
complex multi-species communities in GI tract
Cross resistance:
Single mechanism, closely related antibiotics
Multiple resistance:
Multiple mechanism, unrelated antibiotics
what may bacteria possess
genes which code for enzymes that chemically degrade or inactivate the antibiotic
β -lactamases and cephalosporinases:
disrupt the β-lactam ring of the antibiotics
ESBLs
enzymes that inactive almost all penicillins and cephalosporins
- Produced by some Gram-negative baczteria
what do efflux pumps do
actively export antibiotics out of the bacterial cell
Genetic change =
inc rate of efflux - antibiotic pumped out of the cell before it has time to act
Penicillinase
Include clavulanic acid sensitive & insensitive
Cephalosporinase
Include clavulanic acid sensitive & insensitive
b-lactamases inhibitors
- Clavulanic acid
- Co-amoxyclav
- Amoxicillin & Clavulanic acid
- Oral and IV
- Tazobactum
- Piperacillin&Taxobactam
- IV
- Ceftolozane & Tazobactam
- Resistant urinary tract infections
Metalloenzyme
resistant to all beta-lactames inc carbapenems
