Antimicrobial Chemotherapy Flashcards
(33 cards)
Use of drugs to combat infectious agents
Use of drugs to combat infectious agents
❑ Antibacterial
❑ Antifungal
❑ Antiparasitic
❑ Antiviral
Differential toxicity: based on the concept that the drug is more toxic to the infecting organism than
to the hosT
What are antibiotics?
Antibiotics: Substances produced by a microorganism that in small
amounts inhibit the growth of or kill bacteria.
❖ Majority of antibiotics are based on naturally occurring compounds
❖ May be natural or synthetic
❖ Used in the body to treat infections
Discovery of antibiotics
➢ Discovered in 1928
➢ First antibiotic was named Penicillin, from
Penicillium fungus which produced it.
➢ Underfunded research until 1942 (WW2), when it
was then produced in bigger quantities…Helped
save millions of lives
➢ Before this, primitive treatments were used such
as Silver nitrate, Arsenic - Extremely cytotoxic
Antibiotic Producing Microorganisms
Gram-positive rods:
➢ Bacillus subtilis: Bacitracin
➢ Bacillus polymyxa: Polymyxin
Fungi:
➢ Penicillium notatum: Penicillin
➢ Cephalosporium spp: Cephalothin
Antibiotic Producing Microorganisms
7
Actinomycetes:
➢ Streptomyces venezuelae: Chloramphenicol
➢ Streptomyces griseus: Streptomycin
➢ Streptomyces nodosus: Amphotericin B
➢ Micromonospora purpurea: Gentamicin
What makes an ideal antibiotic?
Have the appropriate spectrum of activity for the clinical setting
➢ No toxicity to the host, be well tolerated
➢ Low propensity for development of resistance
➢ Does not include hypersensitivities in the host
➢ Have rapid and extensive tissue distribution
➢ Have a relatively long half-life
➢ Be free of interactions with other drugs
➢ Be convenient for administration
➢ Be relatively inexpensive
Spectrum of activity
Narrow
Broad
Narrow spectrum
effective how?
Effective against a limited number of species (either G +ve or G –ve
species). Main example: penicillin, G +ve bacteria
Broad spectrum
Effective how?
Effective against a wide variety of species (e.g. both G +ve and –ve).
Main examples is TetracyclineW
What is
Minimum Inhibitory Concentration (MIC):
Minimum concentration of antibiotic required to inhibit the growth of the test
organism
What does mean?
- Minimum Bactericidal Concentration (MBC)
Minimum concentration of antibiotic required to kill the test organism
What does mean
- Prophylaxis:
Antimicrobial agents are administered to prevent infection
General structural features of
bacterial cells
Cell shape
Cell wall
Cell membrane(s)
Capsules
Pili and/or Fimbriae
Cytoplasmic inclusions
Bacterial DNA and nucleic acids
Ribosomes
Flagella
Spores
Why is the cell wall important?
It is the most appealing target for antibiotics, found
in both Gram-positive and Gram-negative bacteria
❖ Contain peptidoglycan molecules NAM (n-acetyl
muramicacid) and NAG (n-acetyl glucosamine).
❖ They are cross-linked through activity of
transglycosylase and transpeptidase enzymes (PBP)
❖ Many antibiotics inhibit the activity of these two
enzymes
Gram negative
meaning
Gram negative : two cell
membranes: inner and
outer membrane. Cell wall
is in between these two
Gram positive meaning
Gram positive: one plasma
membrane, one thick cell
wall of peptidoglycan.
Mechanisms of activity /
Mode of action
Step One
- Inhibition of cell wall synthesis:
Cell wall active agents:
Bactericidal, time
-dependent killing
-
β
-lactams:
Penicillins, cephalosporins,
cephamycin, carbapenems
Role of the INNER cell membrane?
Thin structure lying inside the cell wall and enclosing the cytoplasm of the cell.
Role:
1) Selective barrier through which materials exit and enter the cell = selective
permeability
2) Large molecules e.g. proteins cannot pass through the membrane
3) Allows entry of smaller molecules: e.g. H2O, CO2 and some other sugars
Role of the OUTER cell membrane?
Thin structure lying beyond the cell wall. Only Gram negative bacteria.
Role:
1) Selective barrier
2) Contains proteins for transport
3) Lipopolysaccharide – bacterial defence
4) Allows selective uptake and efflux
Mechanisms of activity /
Mode of action
Step Two
- Disruption of cell membrane:
❑ Bactericidal, time dependent killing
❑ Antimicrobial peptides / Polypeptide antibiotics
➢ Polymyxin B, colistin (antibacterial) or miconazole
(antifungal)
▪ Cationic (+ive charge)
▪ Affinity to Lipopolysaccharide (LPS) on cell surface (-ve
charge)
▪ Interacts and disrupts membrane
▪ Pore formation
▪ Results in loss of metabolites and/or cell lysis
What is the role of DNA/Chromosome?
Most have smaller rings of independently replicating DNA named
plasmids
Role:
▪ DNA replication, transcription.
➢ Differences between prokaryotic and eukaryotic DNA replication,
transcription and translation allows use of antibiotics to inhibit
bacterial growth without harming the host
Mechanisms of activity / Mode of action
Step Three
- Inhibition of nucleic acid synthesis
❑ Binding to DNA gyrase and topoisomerase 5, two
essential enzymes for DNA replication
❖ Class: Quinolones/ Fluoroquinolones
(ciprofloxacin, norfloxacin, levofloxacin,
moxifloxacin)
❖ Bactericidal, concentration dependent
❑ Inhibition of DNA-dependent RNA synthesis
❖ Class: Rifamycin (rifampicin, rifabutin
Role of ribosomes
Cytoplasm of a bacterial cell contains numerous 70S ribosomes
(consisting of 50S and 30S subunits). Consists of rRNA and protein.
Role:
▪ Protein synthesis
▪ Antibiotic target site: e.g. streptomycin can attach to the small
subunit and inhibit protein synthesis
Mechanisms of activity / Mode of action
Step Four
- Inhibition of protein synthesis (ribosomes are the site of protein synthesis)
❑ Many classes of antibiotics inhibit protein synthesis by binding to the
ribosome.
Classes:
Macrolides, ketolides, Tetracyclines, Aminoglycosides, Streptogramins,
Lincosamides
