Antimicrobials microbio

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  • Created by: Amh
  • Created on: 22-03-16 10:39
Who founded chemotherapy
Paul Ehrlich, Trypan red and arsenic v syphilis
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Who first observed Penicillin
Fleming in 1929
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Who first purified Penicillin?
Florey and Chain in 1940, used clinically in 1944
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What is an antbiotic
a A natural antimicrobial substance produced by a micro-organism
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Give an example of antibiotics we use today and their natural source?
Fungi Penicillium spp - penicillin, and Cephalosorium - cephalosporin, Bacteria - Actinomycetes - streptomyces spp - gave us streptomycin
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What are antimicrobials
Antibiotics and synthetic substances
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Give an example of a synthetic antimicrobial
Sulphonamides, and Quinolones
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What are some bacterial targets
Cell wall synthesiis, bacterial protein synthesis, Folic acid synthesis, Nucleic acid metabolism, bacterial cell membrane
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How do Beta-lactams work
inhibit cell wall synthesis, bind to transpeptidases involved in cross linking NAG and NAM residues in cell wall - the unsupported cell wall ruptures and cell bursts
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Where do Beta lactams get their name
they all have a beta lactam ring
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What does the activity (effectiveness) depend on
The affinity for transpeptidases (Penicillin binding proteins) on target organsim
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Give some examples of Beta lactams
Penicillin, Flucloxacillin Amoxicillin, Cephalosporins, Carbapenems
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What is penicillin effective against
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What is Flucloaxacillin effective against
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What is amoxicillin effective against
Gram negatives, streptococci, and eneterococci
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What is Cephlosporins affective against
– 1 st Generation < +ve Gram -ve < 4th Generation
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What are Carbapenems affective against
Multidrug resistant gram negatives
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How do Glycopeptides work
Act on cell wall synthesis in Gram-positive bacteria, bind D-Ala-D-ala precursors of the cell wall syntheiss preventinf access of transpeptidases PBP)
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What is some examples of Glycopeptidases?
Vancomycin, Teicoplanin
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Do Glycopeptidases work against gram negative bacteria
No they are too big to penetrat gram neg membrane
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how are Glycopeptidases given
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When are the used
For patients with allergies or MRSA
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What drugs target protein synthesis
Aminoglycosides, tetracylines, macrolides and lincosamides
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Which of thes drugs targets the 30s subunit
Aminoglycosides and tetracyclines target the 30S
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Which of thes drugs targets the 50s subunit
macrolides and lincosamides
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How do aminoglycosides work
bind to 30s subunit on ribosome and disrupts the structure preventing initiation of protein synthesis
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Give examples of aminoglycosides
Gentamicin, tobramycin, amikacin, streptomycin
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What are Gentamicin, tobramycin, amikacin effective against
Gram-positive and Gram-negative bacteria
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What is Streptomycin effective against?
Mycobacterium tuberculosis
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How are Aminoglycosides given
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what are some side effects of Aminoglycosides
Cause hearing loss and renal impairment at high dose (e.g. treating meningitis) – Requires therapeutic monitoring of serum levels
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How do Tetracyclines work
Bind to the 30S subunit and prevent incorporation of amino acids resulting in Incomplete non-functional proteins
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Give an example of tetracylcines
doxycycline / minocyclinev
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How do Macrolides work
Bind to 50S subunit and prevent translocation of polypeptide chain along ribosome
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Give an example of macrolides
erythromycin / clarithromycin / clindamycin
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What in clindamycin (macrolide) effective against?
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Why are Macrolides and tetracyline similar
They are both bacteriostatic, achieve high intracellular conc in host (good against intracelluar pathogens) both interup protein syntheis
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Which 2 classes of antibiotics inhibit nucleic synthesis
Quinolones, and Rifampicin
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Give an example of Quinolones
Ciprofloxacin, and Levofloaxacin
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How do quinolones work
Inhibit DNA synthesis by binding to • DNA gyrase (GyrA, GyrB) • DNA Topoisomerase (ParC, ParE)
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Do they work against gram negatives?
Yes they work against gram negs and pos
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How does Rifampicin work?
Inhibits RNA polymerase
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How is Rifampicin used?
Ass an adjunctive to other antibiotics (antibiotics that work close to DNA are morelikley to gain resistance)
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Why is folate acid synthesis a target in bacteria
Humans do not synthesize their own folic acid - they obtain it form diet, whereas bacteria do, and folic acid is essential for bacteria
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Which 2 drugs interfer with folic acid synthesis
Sulfonamides, and trimethoprim
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Where do sulfonamides act
They inhibit PABA to DHF conversion by inhibiting dihydropterate synthase
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How does Trimethoprim work?
It stops the conversion of DHF to THF by inhibitinf DHFR
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What are membrane distrupting agents
Catinionic peptides such as polymyxinn B and some disinfectants
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Why aren't Cationic peptides used
Toxic because of lack of selectivity
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Why do we do sensitivity testing?
To see whether the therapy will be effective, to reduce sideeffects, to obtain data on prevalence of resistance, and to enable antimicrobial policies to be formed
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What guidlines are there for susceptibility testing?
guidelines such as CLSI (US) or BSAC (UK) are used
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What is MIC
Minimal inhibitory concentration of antibiotic required to inhibit growth
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What are some methods of susceptibility testing?
Disc diffusion (BSAC), Agar dilution, broth microdilution, Gradient Etest, automated VITEK system, molecular detection of resistance mechanisms
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What is the US reference method
Broth Microtitre Dilutions
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How do Broth Microtitre Dilutions work
microtitre plates are filled with broth bacteria are added and varying conc of antibiotics are added, there are incubated at 35'c and then checked for turbidity MIC = 1st dilution with no visible signs of growth
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What is the UK reference method
Agar dilutions
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How do agar dilutions work
Uses Isosensitest agar supplemented with increasing concentrations of antimicrobial MIC = dilution of 1st plate on which no colony recovered
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What is the disc diffusion test
Organisms is grown on media then discs of antibiotics are added, the plate is incubated overnight and zones of inhibition are measuread and compared either to a sensitive control or ‘zone diameter breakpoints’
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What is the Etest method
Organsim is grown on plate then strip js added, strip has varying conc of antibacteria agent, allows you to see the exact conc required, you caan use multiple stripts on plate to determine the most effective antimicrobial
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What are some automated methods of antisuscptibillity methods?
– MicroScan WalkAway – Vitek – Phenoix, all use microdiultion cards and high resolution optical scanning for microbial growth
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What is the MIC50 and the MIC90
MIC50 = Concentration required to inhibit 50 % of the population • MIC90 = Concentration required to inhibit 90 % of the population
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What is the geometric mean of MIC
a measure of level of susceptibility of the species as a whole
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How can you do Molecular Detection of Resistance Genes
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What are some methods for carrying out this PCR
Dallene ultiplex, Voets multiplex,
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How else can you determine resistance genes
DNA microarrays, Fluorescent in-situ hybridization (DNA probes with fluorescent tags)
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Why are bactericidals important
They activley kill bacteria - needed for severe infections, and immunocomprimised
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Is MIC a measure of bacterialcidials or bacterostatics
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**not finished ad pharmaco ****
and definitions
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Who first observed Penicillin


Fleming in 1929

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Who first purified Penicillin?


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Card 4


What is an antbiotic


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Card 5


Give an example of antibiotics we use today and their natural source?


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