Antimicrobial Chemotherapy 1 Flashcards
<p>What are antibiotics only active against?</p>
<p>Bacteria</p>
<p>What are bactericidal?</p>
<p>Antimicrobial that kills bacteria (penicillins)</p>
<p>What does sensitive mean?</p>
<p>An organism is sensitive if it is inhibited or killed by the antimicrobial available at the site of infection</p>
<p>What is minimal bactericidal concentration (MBC)?</p>
<p>Minimum concentration of antimicrobial needed to kill a given organism</p>
<p>What is bacteriostatic?</p>
<p>Antimicrobial that inhibits the growth of bacteria</p>
<p>What does resistant mean?</p>
<p>Organism is resistant if it is not killed or inhibited by the antimicrobial available at the site of infection</p>
<p>What is minimal inhibitory concentration (MIC)?</p>
<p>Minimum concentration of antimicrobial needed to inhibit the growth of a given organism</p>
<p>What are the routes of antimicrobial administration?</p>
<p>Topical (applied to a surface such as the skin)</p>
<p>Systematic (taken internally, such as orally or parentally)</p>
<p>Parenteral (administered intravenously or intramuscularly)</p>
<p>What is parenteral administeration?</p>
<p>Administered intravenously or intramuscularly</p>
<p>What can antibiotics do to bacteria?</p>
<p>Kill or inhibit it</p>
<p>What are the 3 areas of bacterial metabolic activity that antibiotics can act on?</p>
<p>Inhibition of cell wall synthesis</p>
<p>Inhibition of nucleic acid synthesis</p>
<p>Inhibition of protein synthesis</p>
<p>Why are humans not harmed by antibiotics that inhibit cell wall synthesis?</p>
<p>Human cells do not have cell walls</p>
<p>What bacteria inhibit cell wall synthesis?</p>
<p>B-lactams:</p>
<p>Penicillins<br></br>Cephalosporins</p>
<p>How do B-lactams stop cell wall synthesis?</p>
<p>Disrupting peptidoglycans synthesis by inhibiting enzymes (penillin-binding proteins, PBPs) responsible for cross linking the chains</p>
<p>What proteins do B-lactams target?</p>
<p>Penicillin binding proteins (PBPs)</p>
<p>What do glycopeptides act on?</p>
<p>Gram positive bacteria, they are unable to penetrate the wall of gram negative</p>
<p>What are examples of glycopeptides?</p>
<p>Vancomycin</p>
<p>Teicoplanin</p>
<p>How are glycopeptides given and why?</p>
<p>Paternally because they are not absorbed from the GI tract</p>
<p>How do glycopeptides work?</p>
<p>Inhibit cell wall synthesis at a stage earlier than B-lactams, inhibiting the seemble of a peptidoglycan precurser</p>
<p>What do glycopeptides inhibit?</p>
<p>Peptidoglycan precurser</p>
<p>What allows selective action on bacteria protein synthesis?</p>
<p>Differences between bacterial and mammalian ribosomes</p>
<p>What are different classes of drugs used to inhibit protein synthesis?</p>
<p>Aminoglycans</p>
<p>Macrolides</p>
<p>Tetraclyclines</p>
<p>Oxazolidinones</p>
<p>Cyclic lippeptide</p>
<p>What do aminoglycans act on?</p>
<p>Gram negative bacteria</p>
<p>How do aminoglycans work?</p>
<p>Insert a different amino acid into the protein</p>
What do macrolides act on?
Gram positive bacteria
What are macrolides an alternative to?
Penicillins for people who are allergic
How do tetracyclines work?
Masks the codon on mRNA so the tRNA cannot bind
What is an example of a oxazolidinone?
Linezolid
How do oxazolidinones work?
Prevents the starting codon on the mRNA to be recognised by tRNA
What is an example of cyclic lippeptide and what does it work against?
Daptomycin which works against gram positive bacteria, MRSA in particular
How does cyclic lippeptide work?
Creates pores on the cell membrane causing leakage of ions and change of membrane potential, change prevents protein, DNA and RNA synthesis
How can antibiotics inhibit DNA synthesis?
Directly
Indirectly (acting on precursors for DNA synthesis)
What are some inhibitors of nucleic acid synthesis?
Co-trimoazole
Flouroquinolones
What is co-trimoazole a combination of?
Trimethoprim and sulphamethoxazole
What does co-trimoxazole inhibit?
Steps in purine synthesis (2 of the 4 bases)
What is co-trimoxazole commonly used to treat?
Urinary tract infections
Chest infections
How does flouroquinolones work?
Inhibit DNA synthesis directly by preventing the wrapping of DNA
Who can flouroquinolone not be used in and why?
Children as it interferes with cartilage growth
What are flouroquinolones effective against?
Gram negative bacteria
How are flouroquinolones administered?
Orally
Parenterally
How can antibiotic sensitivity of an organism be measured?
In the lab
Why would we want to measure antibiotic sensitivity of an organism?
Predict if an infection will respond to treatment with that antibiotic
How is resistance acquired by bacteria?
Genetically
What are the 2 types of resistance?
Inherent resistance
Acquired resistance
What is inherent resistant?
All strains of a given species are naturally resistant to antibiotics
What is an example of inherent resistance?
Streptococci always resistant to aminoglycans
Gram negative always resistant to vancomycin
What is acquired resistance?
May be present in some strains but not others
What are the 2 ways that acquired resistance can be obtained?
Spontaneous mutation (change in structure or function which no longer allows the antibiotic to act)
Spread of resistance (genes that code for resistance can spreads from organism to organism or from species to species, being carried on plasmids or transposons)
What is resistance spread using?
Plasmids or transposons
What are plasmids?
Extra chromosomal packages of DNA
What are transporons?
Packets of DNA which insert themselves into the chromosome
What causes selective pressure and encourages new resistant organisms to outgrow sensitive strains?
Widespread use of antibiotics
What are some current issues in antibiotic resistance?
B-lactamase production
Extended spectrum B-lactamases (ESBLs)
Carbapenemase producing enterobacteriaceae (CPE) or carbapenum resistance enterobacteriaciae (CRE)
Alterations of penicillin binding protein (PBP) target site
Glycopeptide resistance
What is B-lactamase?
An enzyme that cleave the B-lactam ring of the antibiotic thus render it inactive
What produces B-lactamases?
Most hospital stains of staphyloccocuc
Common in gram negative bacteria
What produces extended spectrum B-lactamases (ESBLs)?
Some gram negative bacteria
What are carbapenemase producing enterobacteriaceae (CPE) and carbapenum resistant enterobacteriaiae (CRE)?
Extremely resistant gram negative organisms to the carbapenems
What is alteration of penicillin binding protein (PBP) active site?
Develop resistance by changing the structure of their PBP (enzymes involved in peptidoglycan synthesis)
What alters their penicillin binding proteins?
Staph.Aureus known as methicillin resistant Staph.Aureus or MRSA
What can glycopeptides usually be relied on to treat?
Gram positive bacteria
What is an example of glycopeptide resistance?
Some enterococci is vancomycin resistant
What are the 2 ways to combat B-lactamases?
Introduce a second component to the antibiotic (B-lactamase inhibitor) protecting the antibiotic from enzyme degradation
Modify the antibiotic side chain producing new antibiotic resistant to the actions of B-lactamase
What is an example of an antibiotic using a B-lactamase inhibitor?
Amoxicillin plus the inhibitor clavulanic acid
What is an example of an antibiotic with a modified side chain to be resistant to the actions of B-lactamase?
Flucloxacillin
