Microbiology Antibiotics 2 Flashcards
Fluoroquinolones example
- Ciprofloxacin
- Levofloxacin
- Moxifloxacin
Aminoglycosides example
• Gentamicin
Glycopeptides example
- Vancomycin
* teicoplanin
Macrolides example
- Erythromycin
* Clarithromycin
Tetracyclines example
• Minocycline
Fluoroquinolones: Used
Mainly used in hospital to treat Gram negative infection and lower resp tract infections
Fluoroquinolones: Action
By inhibiting DNA gyrase,
Fluoroquinolones: Resistance
Increasingly common – mainly target site modification but also efflux pumps.
Fluoroquinolones:Absorption
Good oral bioavailability so po often as good as iv
Fluoroquinolones:Distribution
Wide tissue distribution (2-3 L/Kg)
Fluoroquinolones:Excretion and metabolism
Excretion y metabolism (ciprofloxacin, moxifloxacin) Renal clearance (Ciprofloxacin, moxifloxacin, levofloxacin)
Fluoroquinolones: Side effects
Generally safe: • Rashes/phototoxicity • Tendenitis and rupture • GI upset • OTC prolongation (moxifloxacin) - (more likely to have ventricular tachy arrhythmia) • Hepatotoxicity
Spectrum-ciprofloxacin: targets
- Aerobic Gram negative bacterial (coliforms, Pseudomonas, gonococci, H. influenza, atypical chest pathogens (legionella,mycoplasma, chlamydia))
- Border line activity against S.aureus and streptococci
- Not active against anaerobes
- Some activity against M. tuberculosis
Spectrum – moxifloxacin: Target
- Much improved activity versus Staphylococci and Streptococci
- Poor activity vs. P.aeruginosa, better activity against anaerobes
Spectrum – moxifloxacin:Indications
- Community acquired chest infections (moxifloxacin/levofloxacin)
- UTI/acute pyeonephitis (ciprofloxacin, levofloxacin) NB resistanct
- Intraabdominal infection (+ metronidazole)
- Bone/joint infection
- Oral therapy of P.aeruginosa (ciprofloxacin)
Aminoglycosides: Action
Inhibiting of protein synthesis at ribosoms
Aminoglycosides: Resistance by
Enzymes (aminoglycoside monitoring enzymes) but rare
Aminoglycosides: Absorption
Intravenous/Im only
Poor oral absorption
Aminoglycosides: Distribution
Modest tissue penetration – concentrated in the kidney and ears (toxicity)
Aminoglycosides:Excretion
Renal excretion – accumulation in renal failure, no metabolism
Aminoglycosides:Examples
Gentamicin
Tobramycin
Amikacin IV
Aminoglycosides: Reduced use because
Toxicity requires therapeutic drug monitoring
Aminoglycosides: Antimicrobial spectrum
Broad Gram negative activity
Coliform
P.aeruginosa
No anaerobic activity
Aminoglycosides: Indications
- In combination therapy for intra abdominal infection
- In combination therapy for infective endocarditis
- In combination therapy for neutropaenic sepsis
- In combination therapy for neonatal sepsis (pen/fluclox)
- In combination therapy for P. aeruginosa infection (Cf)
- In combination therapy for S. aureus
Aminoglycosides: Side effects
- Nephrotosicity (reversible)
8. Otototoxicity (irreversible)
Glycopeptides Example
Vancomycin
Glycopeptides Absorption
Intravenous hospital only, wide use to treat multi resistant Gram positive infection, especially MRSA
Glycopeptides Action
Inhibiting cross linking of bacterial cell wall
Glycopeptides Resistance
Rare except in Enterococci and due to altered target side (enterococci, Staphylococci) and permeability (Staphylococci)
Glycopeptides Excretion
Renal
Glycopeptides Metabolism
None
Glycopeptides Absorption note
Used for C.diff as although it has no oral bioavailabiity this doesn’t matter as it can target the gut without being absorbed.
Glycopeptides Side effects
Nephrotoxicity (around 10%) increased by use of other
Nephrotoxicity agents (gentamicin, frusemide)
Otoxicity very rare
Red man syndrome 9vancomycin) – histamine release mean the does is given too quickly
Thrombocytopenia (teicoplanin in big doses)
Glycopeptides Requires
Therapeutic drug monitoring
Glycopeptides Spectrum
Broad Spectrum: Active against nearly all gram positive bacteria, expecially multi resistant strains.
Not activie against Gram negative bacteria
Glycopeptides Indications
- MRSA infection
- Clostridium difficle associated diarrhoea (CDAD) as 2st line treatment
- Multiresistant Gram positive infection i.e. coagulase negative Staphylococci, Cornebacteria, Enterococci
- Prosthetic infection (Line, joint tc
- Penicillin allergy
Macrolides: Examples
Erythromycin/clarithromycin
Macrolides: Absorption
- IV and po agents widely used in hospital and community to treat lower respiratory tract infection and in penicillin allergy.
- Reasonable bioavailability
- Good oral absorption
Macrolides: Action
Inhibition of protein synthesis at ribosome
Macrolides: Resistance
Common, due to target modification
Macrolides: Distribution
Good tissue penetration
Macrolides: Excretion
Biliary and renal
Macrolides: Side effects
Nausea and GI upset, especially erythromycin (pharmacological effect on stomach motility)
Macrolides: Spectrum
- Active against gram positive organism i.e. s. aureus ( not MRSA), Streptococci, resistance 10-20%
- Active against atypical respiratory pathogens legionella, Mycoplasma, chlamydia
- No activity against Gram negatives except for campylobacter
Macrolides: Indications
- Skin/soft tissue infection if penicillin allergic
- Community acquired pneumonia
- Campylobacter infection
- H. Pylori
- (Staph and strep)
Tetracycines: Examples
Minocycline
Doxycycline
Tetracycines: Used in
Primary Care to treata acne
In hospital as oral therapy for MRSA
Tetracycines: Action
Inhibits synthesis at ribosome
Tetracycines: Resistance
Relatively common due to efflux pumps and target site modification
Tetracycines: Contraindicated in children as
Concentrated in bones/teeth, bind to calcium
Tetracycines: Absorption
Only orally
Metronidazole: Absorption
Good bioavailability
Available as iv/po
Metronidazole: Widely used to
Treat anaerobic infection
Metronidazole: Action
Disrupts DNA
Metronidazole: Distribution
Wide tissue distribution
Metronidazole: Resistance
Very rare in anaerobes
Metronidazole: Safety concerns
Early pregnancy
Disulphuram-like reaction with alcohol, rare peripheral neuropathy on long therapy (Augments hangover)
Trimethoprim: Absorption
Po/Iv only with sulphamethoxazole (co-trimoxazole) to treat PCP
Trimethoprim: Used to treat
Uncomplicated UTI
Trimethoprim: Action
Inhibits Folate metabolism by inhibition of dihydrofolate reductase
Trimethoprim: Resistance
By over production or modification target enzyme enzyme (20% E.coli)
Renal excretion
Linezolid Which forms is available for clinical use
Oxazolidinase
Linezolid Active against
A wide range of gram positive bacteria including multi-resistant strains (MRSA, VRE)
Linezolid Absorption
Good bioavailability
Linezolid Penetration
Moderate/good tissue distribution
Linezolid Excretion/metabolism
None enzymatic degradation
Breakdown products renally excreted
Daptomycin: Absorption
Only lipopeptide antibiotic available. Iv only.
Daptomycin: Active against
A wide range of gram positive bacteria including multi resistant strains (MRSA, VRE)
Daptomycin: Absorption
Poor oral absorption
IV only
Daptomycin: Exrection
Renal
Daptomycin: Penetration
Poor lung penetration
Daptomycin: Toxicity
Muscle toxicity
Daptomycin: Second line for
Gram positive infection
Daptomycin: Not suitable for
Use in lung infection