Antibiotics Flashcards
What are antimicrobials
Antimicrobials are substances that kill or inhibit the growth of microorganisms
What are antibiotics
- Substances produced by living organisms with activity against bacteria
- Many of our current drugs are not true antibiotics but are either synthetic or semi-synthetic
- Chemically modified to improve pharmacological and antimicrobial properties
Briefly describe how the first antibiotic was discovered
- Alexander Flemming was growing a culture of staphylococcus aureus which was contaminated with penicillium notatum
- The penicillium produced a substance that created a zone of inhibition on the culture
What does selective toxicity mean
- Only targets specific cells due to the differences between the pathogen and the host
What does therapeutic margin mean
- The difference between the therapeutic dose and the toxic dose
- The greater the margin the safer the drug
What is the effect on normal microbiota when using antibiotics
- The use of broad-spectrum antibiotics can lead to dybiosis
- Loss of flora can lead to bacterial or pathogen overgrowth
How does antibiotics work along side immunity
- Antibiotics work alongside natural immunity to clear bacteria.
- When patients are immunosuppressed it affects the types of antibiotics used
How are antibiotics classified
- Type of activity
- Structure
- Target site for activity
What types of activities can antibiotics be
- Bactericidal
- Bacteriostatic
What is the function of bactericidal antibiotics
- Kill bacteria
- Used when the host defence mechanisms are impaired
- Required in endocarditis, kidney infection diseases
What is the function of bacteriostatic antibiotics
- Inhibit bacteria
- Used when the host defences mechanisms are intact
- Used in many infectious diseases
How are antibiotics classified on their spectrum of activity
- Broad spectrum antibiotics
- Narrow spectrum antibiotics
Describe beta-lactams as antibiotics
- Basic penicillins
- Active against streptococci, pneumococci, meningococci, treopnemes
- Most strains of Staphylococcus aureus are resistant.
Describe Anti-staphylococcal penicillins
e.g. flucloxacillin
- narrow spectrum, Gram-positive, beta-lactamase resistant, less potent than PenG
Describe broader spectrum penicillins e.g. ampicillin
Spectrum of activity is similar to basic penicillins but also includes some Gram-negative organisms and also enterococci
Describe Anti-pseudomonal penicillins e.g. piperacillin
extended spectrum beta-lactam antibiotic also gram positive and negative anaerobes
Describe Beta-lactam/beta-lactamase inhibitor combinations
e.g. co-amoxiclav (Augmentin)
Spectrum like amoxicillin plus activity against some Gram-negatives and Staph aureus
List some targets of activity for antibiotics
- Cell wall synthesis
- DNA Gyrase
- RNA elongation
- DNA-directed RNA polymerase
- Protein synthesis inhibitors 50S, 30S and tRNA
- Cytoplasmic membrane structure
- Folic acid metabolism
Briefly describe how cell wall inhibitors work
- Peptidoglycan synthesis involves enzymes called penicillin-binding proteins (PBPs)(Transpeptidases)
- When new peptidoglycan units are added to a growing cell wall, the peptide side chain on one subunit must be linked to peptide side chain on another (Transpeptidation)
- Structure of penicillins resembles the two amino acids at the end of the side chain – terminal D alanyl-D-alanine
- The transpeptidation enzyme binds penicillin instead of its true substrate due to this structural similarity, thereby blocking the transpeptidation reaction that forms the peptidoglycan cross-links
How does beta-lactams work on gram negative bacteria
- Beta-lactams travel through porins present on outer membrane and bind transpeptidases
- This stops production of the peptidoglycan layer
- Activates autolytic enzyme mechanisms
How does folic acid synthesis inhibitors work
- Sulphonamides acts as competitive inhibitors for dihydropteroate synthetase in the production of folic acid
- Trimethoprim inhibits dihydrofolate reductase
- Conditions are synergistic and bactericidal
Describe how protein synthesis inhibitors work
- Either bind to the 30S or 50S subunit and blocks formation of peptide chain
When do we use antibiotics
- Treatment for bacterial infections
- Prophylaxis - Prevent infections
- Inappropriate use - viral sore throats
What route of administrations are used
- Oral
- IV
- Injection
- Topical
Why are antibiotic combinations used
- Before an organism is identified in life-threatening infections
- Polymicrobial infections
- Less toxic doses of an individual drug possible
- Synergy between more than one antibiotic
- reduce antibiotic resistance
What is meant by MIC dose
- The minimum does required to cause inhibition
- A therapeutic dose will be higher than the MIC
What is antibiotic susceptibility testing
- Test which antibiotics work against an infection and at what concentration
