antimicrobial resistance and transfer Flashcards
antibiotic
natural substance produced by a microbe that inhibits growth of another microbe
are antimicrobial agents synthetic?
semi-synthetic: antibiotics tend to undergo synthetic modification
*chemotherapeutic agents are entirely synthetic
Out of the different groups of antimicrobials, which are there most of for humans and why?
antibacterials: easier targets
antifungals, antihelminths, antivirals interact with host cell machinery, more difficult to isolate target cells to pathogens
How might selective toxicity be achieved?
- exploit phenotypic and metabolic differences between the host and pathogen e.g. cell wall structure, production of specific cell intermediates
- antimicrobial agent should target site present in pathogen but not on host; easier to find in prokaryotic vs. eukaryotic cells, very difficult for viruses
- relative: high dose or extended treatment may damage host
what is the therapeutic ratio?
highest dose tolerated without harming patient/
minimum dose required to eliminate pathogen
or: toxic dose (TD50)/effective dose (ED50 = dose required to treat half the population)
Advantage of a high therapeutic ratio?
effective dose, minimal side effects, safer
Antibiotics that have a high and lower therapeutic ratio?
high: B-lactams, macrolides, quinolones
low: aminoglycosides, vancomycin
Factors affecting therapeutic ratio?
- selective toxicity
- immune response e.g. allergic reactions like penicillin in sensitised individuals
- bioavailability of the drug: determined by solubility, metabolism, chemical modification and excretion rates
- effect on normal flora: may promote growth of opportunistic pathogens
- potential for development of resistance: especially for long term treatment
Difference between bactericidal and bacteriostatic drugs?
spectrum
bactericidal agents; usually act rapidly, kill bacteria
bacteriostatic agents; inhibit growth of bacteria, need to be taken for a longer time *bacteria may multiple if drug is discontinued
- can be dose dependent
- some drugs are bacteriostatic to certain organisms, bacteriocidal to others
Broad spectrum agents
- affect a wide range of bacteria
- often given prior to diagnosis
- will impact on normal flora e.g. amoxicillin is active against a wide range of Gram +ve and some Gram-ve organisms
e. g. ceftriaxone (4th generation cephalosporin) has extended action
narrow spectrum agents
affect a limited range of bacteria
e. g. gentamicin: Gram -ve bacteria
e. g. penicillin: Gram +ve bacteria
- administered after diagnosis of infectious agent
Reasons why treatment may be ineffective
- drug not reaching infected areas at effective concentrations: dose is too low, poor bioavailability
- depressed immune system, especially if drug is bacteriostatic
- pathogen may be resistant to drug
- pathogen may release toxins when killed e.g. endotoxin from G-ve cells may cause allergic reactions
- environmental factors may limit drug activity e.g. acid pH in urine
Types of resistance? (4)
intrinsic: some microbes inherently resistant
acquired:
- mutation
- (mobile genetic elements) spread of resistance plasmid
- (mobile genetic elements) spread of resistant gene via transposon
pathways to intrinsic resistance
impermeability, efflux (both lead to reduced drug accumulation), biofilms, enzymatic inactivation
Describe impermeability?
antimicrobial can’t bind to surface of bacterial cell;
- chromosomal mutation can change structure of drug binding site
- or chromosomal mutation leads to changes to the structure of membrane preventing antibiotic entering the cell and e.g. targeting ribosome or DNA replication
