Antibiotics Flashcards
What are antibiotics
Molecules that kill bacteria or inhibit their growth-can be biological origin (produced by environmental microbes) or (semi) synthetic origin (produced by chemists)
What makes a useful antibiotic
inhibit specific cellular processess in bacterial cells exhibit toxic effects on bacteria, but not on humans-selective toxicity
What is selective toxicity
Selective toxicity – antibiotics exert their activity by inhibiting
gene products found in bacterial cells, but not in humans
Ideally, such targets are completely absent from human cells (enzymes that make peptidoglycan) or, if present in human cells, possess unique properties in bacteria that can be exploited to confer specificity (ribosomes)
-> Minimize side effects
Disinfectants
Toxic to humans and bacteria (e.g. bleach)
Nonspecific effects
Used to eliminate organisms on inanimate objects, surfaces
Antiseptics
Generally toxic to bacteria
Nonspecific effects (e.g. protein denaturation)
Too toxic for systemic use in humans (e.g. peroxides, alcohols)
OK for topical use
Antibiotics
Target specific cellular processes
Exhibit effects on bacteria but not on humans – selective toxicity
Can be administered systemically
Antibiotics can be classified as what two things
bacteriostatic
bacteriocidal
bacteriostatic
inhibit growth of bacteria (but do not kill
them) - rely on immune system to eradicate
-number of viable cells doesn’t decrease, but it doesn’t increase. it just stays constant
Bacteriocidal
: kill bacteria directly
important for immunocompromised patients, device-associated
infections, endocarditis
-graph would should number of bacteria decreasing
pharmacology/bioavailability
Not all antibiotics penetrate all tissues
equally. To be effective, an antibiotic needs to get to site of infection at
therapeutic levels
Spectrum of activity
- the collection of bacterial species that is
susceptible to a given antibiotic
-narrow spectrum
-broad spectrum
Narrow spectrum antibiotic
effective against a relatively small group of
bacteria (e.g. aerobic Gram-positive bacteria)
Broad spectrum antibiotic
effective against a wide range of bacteria (e.g.
Gram-positive and Gram-negative bacteria)
Are broad spectrum antibiotics desirable, list an advantage and a disadvantage
Advantage: Can be used when infectious agent is unknown or in emergency
Disadvantage:
Affects many members of natural microbiota, leading to
undesirable secondary effects
(diarrhea, antibiotic resistance)
What does susceptibility mean?
Bacteria are considered to be “susceptible” to an antibiotic if their growth
can be inhibited by concentrations of the antibiotic that can be readily
achieved in a patient at the site of infection
Susceptibility determinations are made with in vitro susceptibility tests – they
require pure cultures of infectious organism, obtained from the infected
patient
(i.e. need to isolate infectious agent away from normal microbiota)
Why do we need to measure susceptibility?
-Infectious bacteria must be susceptible for an antibiotic to be clinically effective
-But, all isolates of a given bacterial species are NOT susceptible to the
same antibiotics (e.g. some staphylococci are susceptible to methicillin;
some are resistant)
-So, simply identifying the bacterial cause of a disease is not enough – for
optimal therapy, must know the antibiotic susceptibility profile for that
specific isolate (antibiogram)
Relating to bacterial suseptibility, for optimal therapy what must you know
the antibiotic susceptibility profile for that specific isolate (antibiogram)
How do we measure susceptibility
- bacterial growth in liquid medium: quantitative approaches
- MIC
- MBC
- put in tubes with increasing amounts of antibiotic. the amount of antibiotic where growth stops is MIC, when bacteria die it is MBC
Minimum Inhibitory Concentration
Defines the lowest concentration of antibiotic that inhibits growth
-there should be no bacterial growth
Minimum bacterial concentration
defines the lowest concentration of antibiotic that kills a defined proportion of bacterial population after specified time (99.9% of bacteria killed after 24 hours)
To be therapeutically effective what must be true of an antibiotic
to therapeutically effective, antibiotic must achieve or exceed these concentrations at site of infection in host
Toxic side effects of drugs examples
- tetracycline
- streptomycin
- chloramphenicol
- tetracycline: discoloration
- streptomycin: auditory damage
- chloramphenicol :anemia
Hypersensitivity
Anaphylactic shock in resonse to peniciclin
Alteration of normal microflora
- antibiotic-associated diarrhea/enterocolitis
- clostridium difficile is responsible for many of the severe complications (pseudomembraneous enterocolitis)
Selection for antibiotic resistance
Heritable change in bacterial genotype that confers enhanced growth in the presence of an antibiotic-renders antibiotic useless
List 4 Unintended consequences of antibiotics
- toxic effects
- hypersensitivity
- alteration of normal microflora
- selection for antibiotic resistance
How do bacteria become antibiotic resistant?
- genotypic changes that enable growth in the presence of an antibiotic usually occur by one of these mechanisms
- horizontal gene transfer
- spontaneous mutations
Horizontal gene transfer
- Acquisition of foreign DNA encoding resistance genes, (getting DNA from someone else that has the resistance genes)
- can enable rapid emergence of multi-drug resistant strains
- (plasmids and transposons)
Spontaneous mutations
-(strong selection for growth superimposed on large populations of bacteria can lead to emergence of rare resistant mutants)
Three mechanisms by which bacteria overcome inhibition by antibiotics
- Modification (inactivation) of antibiotic molecule itself
- Modification (reprogramming) of antibiotic target
- Reduction of antibiotic concentration/prevent access to target
Modification (inactivation) of antibiotic molecules itself
- Cleavage of β-lactams by β-lactamases
- Enzymatic modification of aminoglycosides, chloramphenicol (cat)