Antibiotics Flashcards
Antibiotics - define
Natural products of fungi and bacteria - soil dwellers
- natural antagonism and selective advantage - kill or inhibit the growth of other microorganisms
Antibiotics - derived from
most derived from natural products by fermentation,
then modified chemically :- ↑ pharmacological properties
↑ antimicrobial effect
Some totally synthetic - e.g. sulphonamides
Principles of Antibiotics as Therapeutic Agents - selective toxicity due to what and effect
Selective Toxicity
Due to the 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
Principles of Antibiotics as Therapeutic Agents - Therapeutic Margin = explain
active dose (MIC) versus toxic effect
narrow for toxic drugs - e.g. aminoglycosides, vancomycin
ototoxic, nephrotoxic
Microbial antagonism - purpose
Maintains flora - complex interactions
Competition between flora
Limits growth of competitors and PATHOGENS
Effect of loss of flora on bac/pathogen
Loss of flora → bacterial or pathogen overgrowth
e.g. Antibiotic Associated Colitis :
(clindamycin, broad-spectrum lactams, fluoroquinolones)
- pseudomembranous colitis
Clostridium difficile (part of normal flora of 3% of population)
Antibiotic Associated Colitis - effect on body
Ulcerations – inflammation
Severe diarrhoea
Serious hospital cross-infection risks
Pseudomembranous colitis effect on c. difficile
Pseudomembranous colitis
Clostridium difficile
overgrowth
Antibiotic + immunity =
Antibiotic + immunity → bacterial clearance
Antibiotics classified by
Classified by:-
Type of activity
Structure
Target site for activity
Bactericidal AB - effect, use
Bactericidal:
Kill bacteria
Used when the host defense mechanisms are impaired
Required in endocarditis
Bacteriostatic AB - effect, use
Bacteriostatic:
Inhibit bacteria
Used when the host defense mechanisms are intact
Used in many infectious diseases
Spectrum of Activity - describe for AB
Broad Spectrum Antibiotics:
Effective against many types
Example: Cefotaxime
Narrow Spectrum Antibiotics:
Effective against very few types
Example: Penicillin G
ABs in relation to bac enzymes
Antibiotics are often structural mimics
of natural substrates for bacterial enzymes
Protein synthesis inhibitors describe action with examples at each step
Binding fmet t-RNA
Initiation complex formation
- Aminoglycosides
e. g. streptomycin = bind to 30S ribosome
Translocation of fmet t-RNA
to P site
- e.g. genatmicin (aminoglycoside) = bind to 30S ribosome
Competition with new
Aminoacyl t-RNA
at the A site
- e.g. tetracycline (aminoglycoside) = bind to 30S ribosome
Blocks formation of
peptide bond
peptidyl transferase
- e.g. chloramphenicol (aminoglycoside) = bind to 50S ribosome
Block translocation of
peptidyl t-RNA
- e.g. erythromycin (macrolide) and fusific acid = bind to 50S ribosome
When do we use antibiotics ?
Treatment of bacterial infections
Prophylaxis - close contacts of transmissible infections
carriage rates (↑ ~80% in outbreaks)
e.g. meningitis
- prevention of infection e.g. tuberculosis
- peri-operative cover for gut surgery - people with ↑ susceptibility to infection
Describe inappropriate use of ABs
Inappropriate use - viral sore throats - patient pressure
Route of Administration of ABs for serious infection
Serious infections – hospitalisation - systemic treatment
e.g. i/v rapid delivery, high [blood]
often unable to take oral – vomiting, unconscious,
poor gut absorption due to trauma
?? i/v with perivascular collapse (e.g. septicaemia ) i/m injection - meningitis case
Route of Administration of ABs for topical infection
Topical - conjunctivitis, superficial skin infections, burns
antiseptic creams, heavy metal ointments
Dose of antibacterial
MIC depends on what
This will depend upon the age, weight, renal and liver function of the patient and the severity of infection
Depend on the susceptibility of the organism
Will also depend upon properties of the antibiotic i.e. enough to give a concentration higher than the MIC (minimum inhibitory concentration)
! at the site of infection
Antibiotic Combinations - used when and effects
BEFORE an organism identified in life-threatening infections
e.g. endocarditis, septicaemia
Polymicrobial infections e.g. abscess, G.I. perforation
anaerobes and aerobes
Less toxic doses of an individual drug possible
Synergy e.g. penicillin and gentamicin
Co-trimoxazole (sulphonamides + trimethoprim)
reduce antibiotic resistance e.g. Tuberculosis
Basic penicillins - example and active against what
Basic penicillins e.g. benzylpenicillin(PenG), penicillin V
Active against streptococci, pneumococci, meningococci, treopnemes.
Most strains of Staphylococcus aureus are resistant.
Anti-staphylococcal penicillins - example and active against what
Anti-staphylococcal penicillins e.g. flucloxacillin
narrow spectrum, G+ves, beta-lactamase resistant, less potent that PenG
Not MRSA
benzlypenicillin - use
Pen G benzlypenicillin (G= gold standard);
not acid stable ∴ i/v or i/m good for some G-ves as well as G+ves
phenoxymethlypenicillin - use
penV phenoxymethlypenicillin
oral (more acid stable than penG)
less active v G-ves, but same activity v G+ves as PenG
Broader spectrum penicillins - example and active against what
Broader spectrum penicillins e.g. ampicillin
Spectrum of activity is similar to basic penicillins but also includes some Gram-negative organsims and also enterococci
Anti-pseudomonal penicillins - example and active against what
Anti-pseudomonal penicillins e.g. piperacillin
extended spectrum beta-lactam antibiotic
also G+ve, G-ve, anaerobes
Beta-lactam/beta-lactamase inhibitor combinations - example and active against what
eta-lactam/beta-lactamase inhibitor combinations
e.g. co-amoxiclav (Augmentin)
Spectrum like amoxicillin plus activity against some Gram-negatives and Staph aureus
cefalexin - use
cefalexin An oral agent primarily used to treat UTIs
cefuroxime - use
cefuroxime A parenteral 2nd generation agent with good activity against many Gram-positive and Gram-negative organisms
cefotaxime - use
efotaxime A parenteral 3rd generation agent with greater activity against many Gram- negative and retaining anti-Gram-positive activity
Ceftazidime - use
Ceftazidime A parenteral 3rd generation agent with a spectrum of activity extended to include Pseudomonas aeruginosa
Aminoglycosides - give examples
This group includes gentamicin, amikacin and streptomycin
Aminoglycosides - characteristics
These agents cannot be absorbed from the gut and must be given parenterally
They are active predominantly against Gram-ve bacteria including Pseudomonas aeruginosa
These agents are nephrotoxic and ototoxic and serum levels must be monitored
Macrolides - example and used for
e.g. erythromycin
Used to treat Gram-positive infections esp. in those allergic to beta-lactams
Also active against
Mycoplasma pneumoniae and
Legionella pneumophila
Glycopeptides - examples and used for
Includes vancomycin and teicoplanin
Active only against Gram-positive organisms
Parenteral only
Usually reserved for situation when other agents cannot be used e.g. against MRSA
Tetracyclines - examples and used for
Includes oxytetracycline, doxycycline
Broad spectrum
Used mainly for treating:
Chlamydia
Mycoplasma pneumoniae
Acne
Quinolones - examples and used for
Includes ciprofloxaxin, moxifloxacin
Older drugs such as ciprofloxacin active mostly against Gram-negatives
- Useful for complicated UTIs and gastrointestinal infections
Newer agents have better anti-Gram-positive activity
- Useful for some respiratory tract infections
Trimethoprim – used for
Trimethoprim – useful for UTIs. Combined with sulphamethoxazole as co-trimoxazole
Metronidazole – used for
Metronidazole – active against anaerobic bacteria (and some parasites)
Chloramphenicol – used for
Chloramphenicol – broad spectrum.
Used rarely systemically because of side-effects.
Commonly used topically for eye infections
Fusidic acid – used for
Fusidic acid – narrow spectrum, used in combination to treat Staphylococcal infections only.
Nitrofurantoin - used for
Nitrofurantoin – useful for UTIs.
Linezolid - used for
Linezolid – an oxazolidinone. The newest antibiotic reserve for multi-resistant Gram-positive infections
Daptomycin - used for
Daptomycin – lipopeptide with similar spectrum of activity to vancomycin
Tigecycline - used for
Tigecycline – glycylcycline (related to tetracyclines) – reserved for use against multiply-resistant Gram-positive and Gram-negative bacteria
