Treatment and prevention of bacteria Flashcards
all antibiotics are
ANTIMICROBILAS BUT NOT ALL ANTIMICROBIALS ARE ANTIBIOTICS
what is an antibiotic
- A natural antimicrobial substance produced by a microorganism that is effective against bacteria
what are some examples of antibiotics
fungi
actinomycetes
name some examples of fungi
- Penicillium spp – penicllin
- Cephalopsorium – cephalosporins
name some examples to actinomycetes
- Streptomyces spp – streptomycin
What is an antimicrobial
- Any substance of natural, semi-synthetic (chemically modified natural substances) or synthetic origin that kills or inhibits the group of microorganisms
name some examples of antimicrobials
- Sulphonamides – from the dye prontosil in 1935 – synthetic
- Ampicillin – semi synthetic
- Quinolones – synthetic
what are the characteristics of the ideal antimicrobial
• Selective toxicity: drug that kills or inhibits growth of the pathogen without harming the host
• Broad spectrum -menas that it is effective against a wide range of organsims
• Long half-life (maintain therapeutic concentrations)
• Easy to administer
• Good tissue distribution
• Does not interfere with other drugs and non-allergenic
• Resistance by microorganisms not easily acquired
• Reasonable cost
This doesn’t exsit
How do you classify bacteria
- by spectrum broad spectrum or narrow spectrum
- by mode of action - bactericidal or bacteriostatic
what is broad spectrum
wide range of coverage; used when susceptibility of pathogen to drug is not known
what is narrow spectrum
small range of coverage – used when susceptibility to drug is known
what is bactericidal
- Action; irreversible damages and kills bacteria
What is bacteriostatic
- Action; inhibits bactieral growth and multiplication
What is the drugs of bactericidal
Very Finely Proficient At Cell Murder
- Vacomysin – gycopeptide
- Fluroquinoles
- Pencillins
- Aminoglycosides
- Cephalosporins
- Monobactoms
what are the drugs of bacteriostatic
- Tertacycline
- Trimethoprim
- Macrolides
- Clindamycin
- Chloramphenicol
most drugs are described as
Most antibactieral are described as being potentially both bacteriostatic and bactericidal depending on the
- Dose
- Duration of exposure
- The state of invading bacteria
what is a time kill assay
• Broth Microdilution method
– Range of antimicrobial concentations (1/4 to 2 x MIC)
– Tested alone and in combination with defined inoculum (1 x 105 cfu/ml)
– Aliquots removed at defined time points and plated for viable bacteria
– Synergy defined as > 2 log reduction
• Tests bactericidal concentrations
• Very labour intensive……
what are examples of narrow spectrum bacteria
Aerobes examples – gram positive and gram negative
- Glycopeptides, Bacitracin, Penicillin - gram positive
- Polymyxins- gram negative
- Aminoglycosides, Sulfonamides, Actinomycin – both gram positive and gram negative
anaerobes
- Nitroimidazoles – both gram positive and gram negative
What are examples of broad spectrum antibiotics
- These effects both aerobes and anaerobes
- Tetracyclines
- Phenicol’s
- Fluoroquinolones,
- Third-generation cephalosporins
- Fourth-generation cephalosporins
what is selectivity toxicity
- This is the effectiveness against a pathogen with minimal toxicity against the host (effective against the microbial organism but not toxic to humans)
how do you work out the therapeutic index
T1 = TD50/ED50
what does a low Therapeutic Index mean
- A low TI means that there is a small safety margin between beneficial and toxic dose
how does antibiotic selective toxicity work
- Exploits the differences in structure and biosynthetic pathways between bacteria and human cells
what is the difference between bacteria and humans
- Biochemistry is different – for example bacteria synthesise essential vitamins
- Bacterial cell wall, animal cells do not have a bacteria cell wall
- Bacteria have a 70s ribosome whereas eukaryotes have an 80s ribosome
- Mitochondria have 70s ribosomes
- DNA directed RNA polymerases are different
what are the antibiotics that target cell wall synthesis
- Beta lactams - – penicillins, cephalosporins, carbapenems, monobactams, vancomycin, bacitracin
- Cell membrane – polymyxins
what are the antibiotics that target protein synthesis
- 30s subunit – tetracyclines and aminoglycosidases
- 50s – streptogramnis, chloramphenicol, linezolid, clindamycin, macrolides
what are the antibiotics that target nucleic acid synthesis
- Folate synthesis – sulhanomides and trimethoprim
- DNA gyrase – quinolones
- RNA – polymerase rifampin
what are the selective bacteria targets for antibiotics
- cell wall synthesis
- protein synthesis
- nucleic acid synthesis
how does the peptidolygcan synthesis of the cell wall work
- Lattice structure of sugar residues that are formed of chains alternating NAM and NAG residues
- Each NAM contains 4-5 AA chains (Lalanine, D-glutamine, L-lysine (m-DAP), D-alanine,)
- Pentaglycine cross linking requires D-alanine-D-alanine, but the cross link itself is formed between D-alanine and L-lysine (m-DAP) catalysed by transpeptidase
- Terminal alanine is lost
what is the structure of beta lactams
- Made out of thiazolidine ring and B-lactam ring
what are the types of beta lactams
- Pencillins (Penicillin G, Amoxicillin, Ampicillin) – contains a peptide bond similar to transpeptidase dipeptide substrante
- Cephalosporins
- 1st Gen – Cephaphrin, Cephalexin
- 2nd Gen – Cefuroxime, Cefamandole, Cefotetan
- 3rd Gen – Ceftriaxone, Ceftazidime, Ceftizoxome
- 4th Gen – Cefepime
- Carbapenems (Imipenem)
- Monobactams (Azotreonam)
is beta lactam bacteriostatic or bacteriocidal
bactericidal
what do beta-lactams target
what is the action of beta lactams
what type of bacteria does betalactams target
is it bactericidal or bacteriostatic
- Target – transpeptidase (pencillin-biding protein) is inhibited
- Action; competitive inhibitor of transpeptidase, covalently activates serine in the active site of the enzyme
- What does it target – gram negative, gram positive
- bactericidal
what does transpeptidase catalyse
- Formation of crosslinks between D-amino acids
- Hydrolysis of peptide bonds
- Hydrolyses peptide bond in penicillin
what are some examples of glycopeptides
- Vancomycin
- Teicoplanin
what do glycopeptides target
what is the action of glycopeptides
what type of bacteria does glycopeptides target
is it bactericidal or bacteriostatic
- Target – D-Ala-D-Ala peptide
- Action – forms hydrogen bonds with D-Ala-D-Ala peptide thus preventing the transpeptidation of peptidoglycan layers, they bind to the things that should be cross-linked.
- What does it target – gram positive
- bactericidal
what is the clinical significance of glycopeptides and what is its uses
What is the clincia significance - IV administration (Not absorbed orally) Used to treat • Septicaemia • Lower Respiratory Tract Infections • Skin Infections • Bone Infections
why are glycopeptides not effective in gram negative bacteria
- They are twoo large so it cannot fit through porins
- Affective in gram positive but resistance is on the rise
- Only used as a last result
what is an example of polymyxins
- Polymyxin B
* Polymyxin E (Colistin)
what do polymyxin target
what is the action of polymyxin
what type of bacteria does polymyxin target
is it bactericidal or bacteriostatic
Targets; LPS and phospholipids
Action
1. Binds to LPS or negatively charged phospholipids, displacing cations such as calcium and magnesium
2. Destabilises the outer plasma membrane of bacteria.
3. ↑ Permeability of membrane → leakage of ions.
Targets – gram negative bacteria
- bactericidal
what does chloramphenicol target
protein synthesis
what do chloramphenicol target
what is the action of chloramphenicol
what type of bacteria does chloramphenicol target
is it bactericidal or bacteriostatic
- Targets; 50S ribsome subunit
- Action; inhibits the formation of peptide bonds in the growing polypeptide chains
- Bacteira that it effects include gram positive, gram negative,
- bacteriostatic