Antibiotics Flashcards
Antibiotics are widely used and misused
Widely used and misused drugs – 20-50% questionable use
In hospitals - >10% of drug budget
25% of patients have received antibiotics within previous 24h
In ICU 50% of patients are on antibiotics
50 million prescriptions per year
80% of human use is in the community as a result of prescription of antibiotics
50% - respiratory infections
15% urinary tract infections
What are antibiotics natural products of?
What does chemical modification allow?
Natural products of fungi and bacteria - soil dwellers
- Have natural antagonism and selective advantage over other organisms in the soil
- Kills or inhibit the growth of other microorganisms
Most derived from natural products by fermentation, then modified chemically :
- Increased pharmacological properties
- Increased antimicrobial effect
so can be absorbed and survive inside bloodstream
some antibiotics synthetic e.g sulphonamides
Antibiotics have selective toxicity, what does this mean?
Due to differences in structure and metabolic pathways between host and pathogen
Harm microorganisms, not the host
Target in microbe, not host (if possible)
Difficult for viruses (intracellular), fungi and parasites
Variation between microbes
Effect on commensals – can be severe, needs to be considered when using antibiotics
Antibiotics must have therapeutic margin, what is this?
Difference between active dose that needs to be given to kill the organism, compared to the toxic dose that will cause a toxic effect in the host.
Antibiotics must have an active dose (MIC)
Active dose (MIC) vs toxic effect
Narrow for toxic drugs – e.g aminoglycosides, vancomycin, ototoxic, nephrotoxic
If you don’t get dose right it can have toxic effects
There is no safe drug, need to balance therapeutic imperative and host damage..
What antibiotics are involved in loss of flora?
Bacterial/pathogen overgrowth
E.g in colitis
Clindamycin, broad spectrum lactams, fluoroquinolones
Pseudomembranous colitis – caused if C. difficile overgrows
Overgrowth of clostridium difficile
What does overgrowth cause?
But can be part of normal flora of 3% of population
a spore forming condition which can contaminate environment, can get outbreaks
Causes:
Ulcerations – inflammation
Severe diarrhoea
Serious hospital cross infection risks
A combo of antibiotics and immunity causes bacterial clearance
What do immunosuppression patients need?
Immunosuppression patients e.g due to cancer chemotherapy, myeloma, HIV with low CD4, elderly, babies, diabetes, alcoholics
Treating these people requires different antibiotics, e.g different dosage, to ensure bacteria is cleared
Classified by:
Type of activity
Structure
Target site for activity
Antibiotics activity can be bactericidal or bacteriostatic
What is bactericidal antibiotics?
Kill bacteria
Used when the host defence mechanisms are impaired
Required in endocarditis, kidney infection
What are bacteriostatic antibiotics?
Inhibit bacteria
Used when the host defence mechanisms are intact
Used in many infectious diseases
Varies for drug, species and concentration of drug e.g normal concentration might be bactericidal but increasing its concentration might make it bacteriostatic.
Both work clinically very well.
What two spectrums can antibiotics be?
Broad spectrum antibiotics
- Effective against many types e.g cefotaxime
Narrow spectrum antibiotics
- Effective against very few types e.g Penicillin G
How has the activity of cephalosporins been refined?
First generation cephalosporins not very good at killing gram negatives but good at gram positives
Second generation even distribution
Third generation good for gram negatives but lost activity against some gram positives
What antibiotics are beta-lactams?
Penicillin’s
Basic penicillin’s e.g benzylpenicillin (PenG, penicillin V)
- Active against streptococci, pneumococci, meningococci
- Most strains of Staphylococcus aureus are resistant
- Need a different type to kill off Staph Aureus
Anti-staphylococcal penicillin’s e.g flucloxacillin
- Narrow spectrum, G+ves beta-lactamase resistant, less potent that PenG for some other organisms
- Not MRSA
What are the other types of penicillin besides basic and anti-staphlococcal penicillin?
Broader spectrum penicillin’s e.g ampicillin
- Spectrum of activity is similar to basic penicillin’s but also includes some gram negative organisms and also enterococci
Anti-pseudomonal penicillin’s e.g piperacillin
- Extended spectrum beta-lactam antibiotic
- Also G+ve, G-ve, anaerobes
Beta-lactam/beta-lactamase inhibitor combinations e.g co-amoxiclav (Augmentin)
- Spectrum like amoxicillin plus activity against some gram-negatives and S.aureus
Many antibiotics target enzymes that make cell walls
If bacteria can’t make cell wall it dies
What antibiotics target cell wall synthesis?
Cyclocserine
Vancomycin
Penicillin’s
Monobactams
Carbapenems
Beta lactam antibiotics
Cephalosporins