antimicrobials and resistance Flashcards
What is the difference between endotoxins and exotoxins?
Endotoxins - Inflammatory response to bacterial products
Exotoxins - Response to bacterial secretions
what is a bacterial endotoxin
-released when organism dies
-triggers immune system
-heat stable, intrinsically poorly antigenic
-overactivates complement cascade to generate effects
what are the effects of bacterial endotoxin activating the complement cascade
-high fever
-severe fluid from blood system–> vascular collapse
-IV coagulation then organ haemorrhaging
-septicaemia/endotoxic shock–> death
what are the factors facilitating entry/invasion/survival of bacterial exotoxins
-mucinase, collagenase, urease, leukocidins etc
what are antimicrobial agents
-inhibit/kill microorganisms
-99% unsuitable for treatment of infectious diseases- e.g. disinfectants, antiseptics
-<1% suitable for treatment= chemotherapeutic agents
what is the mark of a successful CTA
-its selective toxicity i.e. toxicity to prokaryotes»>toxicity to eukaryotes
what is a therapeutic dose
-level of CTA needed for clinical treatment of an infection in a specific host
what is a toxic dose
level of same CTA which is too toxic for use in that host
therapeutic index=
toxic dose/therapeutic dose
High- selectively toxic, useful
Low - toxic to host, side effects
what do bacteriostatic CTAs do
-inhibit bacterial growth/multiplication but then reply on the hosts immune system to remove the bugs
-it is therefore essential to give full course of such agents to allow sufficient time for immune system to complete its job whilst preventing regrowth of the bacterial population
what are bactericidal CTAs
rapidly lethal to the bacteria in their own right
depending on bug and conditions, some agents may be…
bactericidal and bacteriostatic e.g. chloramphenicol kills H.influenzae but only inhibits E.coli
what are the mechanisms of action of antibiotics
- Inhibition of cell wall synthesis
- inhibition of protein synthesis
- Inhibition of nucleic acid
- impair membrane functions
- metabolic antagonism
what are the antibiotics that inhibit cell wall synthesis
cycloserine
glycopeptides- bacitracin
beta-lactams e.g. penicillins and cephalosporins
what are the antibiotics involved in inhibition of protein synthesis
aminoglycosides
tetracyclines
chloramphenicol
what are the antibiotics involved in inhibiting nucleic acid synthesis
quinolones
rifampin
what is metabolic antagonism
-CTAs are structural but not functional analogues of bacterial growth factors
-not functional when bacteria tries to put it into macromolecules its making
-bactericidal
-selectively toxic
What are the mechanisms of bacterial resistance
- production of enzymes- attack CTA, prevent activity or degrade CTA
- modify CTAs target- as produced or after production. must be a sublethal change
- alter CTA uptake/retention- no entry to cell. upregulate removal»>uptake
- upregulate target production- dilute out effect of CTA
- modify metabolic pathways
- cross resistance
what do bacteria release to digest CTA
-beta lactamase inactivates beta-lactam agents
-acetyltransferase inactivates chlroamphenicol
What CTA targets can mutate to increase resistance?
-23S protein of the 50S ribosomal subunit
-30S ribosomal subunit
-DNA-dependent RNA-polymerase
-DNA gyrase
-dihydropteroate synthetase
How can bacterium alter the uptake of CTAs
-enhance existing permeability barrier
-alter/remove specific transport system
-develop specific antagonism
What are cross-reactive agents
-ESBLs- extended spectrum beta lactamases
-metallo beta lactamases
what are the methods of development of resistance
-spontaneous mutation
-recombination
how does spontaneous mutation lead to CTA resistance under normal conditions
CTA resistance lost by back mutation or overgrowth by S bacteria
how does spontaneous mutation lead to CTA resistance during treatment
resistant clone selected
