antimicrobial chemotherapy mechanisms of action and resistance Flashcards
bactericidal
An antimicrobial that kills bacteria (e.g. the penicillins).
Bacteriostatic
An antimicrobial that inhibits growth of bacteria
e.g. erythromycin
Sensitive
An organism is considered sensitive if it is inhibited or killed
by levels of the antimicrobial that are available at the site of
infection.
Resistant
An organism is considered resistant if it is not killed or inhibited
by levels of the antimicrobial that are available at the site of
infection.
MIC
Minimal inhibitory concentration is defined as the minimum
concentration of antimicrobial needed to inhibit visible growth
of a given organism.
MBC
Minimal bactericidal concentration is defined as the minimum
concentration of the antimicrobial needed to kill a given organism.
routes of administration of antimicrobial agents
topical
systemic
parenteral
Topical
Applied to a surface, usually skin or to mucous membranes e.g.
conjunctiva.
Systemic
Taken internally, either orally or parenterally
Parenteral
Administered either intra-venously (iv) or intra-muscularly (im),
occassionally subcutaneously
sites of antibiotic action
- inhibition of cell wall synthesis
- inhibition of protein synthesis
- inhibition of nucleic acid synthesis
drug groups that inhibit cell wall synthesis
- β-lactams
2. glycopeptides
β-lactams examples
- penicillins and cephalosporins
- benzyl penicillin
action of penicillins and cephalosporins
inhibit the synthesis of cell wall by binding to penicillin binding proteins, this inhibits the enzymes that produce cross bridges between carbohydrate.
benzyl penicillin
original form of penicillin isolated, less useful than derivatives
β-lactamases
enzymes produced by bacteria resistant to β-lactams, they breakdown the functional group, turning them from a toxin to a food.
glycopeptides examples
- vancomycin
- teicoplanin
vancomycin and teicoplanin action
inhibit the assembly of peptidoglycan precursor
vancomycin toxicity
toxicity is very common with vancomycin as small therapeutic range
drugs types that inhibit protein synthesis
- aminoglycosides
- macrolides and tetracyclines
- oxazolidinones
- cyclic lipoprotein
aminoglycosides use
eg, gentamicin used to treat gram negative infections
gentamicin toxicity
it is toxic to requires a careful dosing regime and monitoring of levels
examples of macrolides
erythromycin. clarythromycin
macrolides and tetracyclines use
used as an alternative to penicillin and used against gram positive bacteria
Trimethoprim and sulphamethoxazole action
inhibit different steps in purine
synthesis, and are used in a combined form in the drug co-trimoxazole
Oxazolidinones example
Linezolid
Linezolid use
used to treat MRSA infections
cyclic lipopeptide example
Daptomycin
Daptomycin use
used against MRSA and gram positives in general
drugs that inhibit nucleic acid synthesis
- Trimethoprim and sulphamethoxazole
- Fluoroquinolones
fluoroquinolone example
ciprofloxacin
levofloxacin
fluoroquinolones action
act directly on nucleic act synthesis, binding to dna-protein complex.
bacteria ciprofloxacin
gram negative
bacteria levofloxacin acts on
gram negative but also some pneumonia causing gram positives
what is the selection pressure for the selection of bacteria resistant to antibiotics
the wide spread (sometimes uncontrolled) use of antibiotics
ways in which bacteria can be resistant to β-lactams
- they can produce β-lactamase
- they can alter there penicillin binding protein target site
which genus of bacteria are always resistant to aminoglycosides?
streptococci
what type of bacteria are always resistant to vancomycin?
gram negative organsims
what is inherent/ intrinsic resistance
all strains of a given species are naturally resistant to an antibiotic
how does acquired resistance come about?
- spontaneous mutation
2. spread of resistance eg. using plasmids or transposons
transposons
packets of DNA which insert themselves into the chromosome
ways to combat β-lactamase production
- introduce a second component to the antibiotic
(β-lactamase inhibitor) protecting the antibiotic
from enzymatic degradation eg. co-amoxiclav - modify the antibiotic side chain producing new antibiotic resistant to the actions of β-lactamase eg. flucloxacillin
extended spectrum β-lactamase producing organisms
gram negative organisms resistant to all β-lactams.
Carbapenemase Producing Enterobacteriaceae (CPE) and
Carbapenem Resistant Enterobacteriaciae (CRE)
gram negative organisms resistant to the carbapenems
how vancomycin resistant enterococci are resistant
they have an altered peptidoglycan precursor
