what about Quinolones?
- member of broad-spectrum bacteriocidals
- bicyclic core structure related to the substance 4-quinolone
- Nearly all quinolones in use are fluoroquinolones (contain a fluorine)
name Fluoroquinolones
- Moxifloxacin
- Levofloxacin
- Ofloxacin
- Norfloxacin
1stG Fluoroquinolone
Norfloxacin
does NOT achieve adequate plasma levels for use in most systemic infections
Norfloxacin spectrum?
the common pathogens that cause urinary tract infections
2ndG Fluoroquinolone?
Ciprofloxacin and ofloxacin
Ciprofloxacin and ofloxacin spectrum?
- G-‘s
- gonococcus
- G-‘s cocci
- mycobacteria
- Mycoplasma pneumoniae
- Chlamydophila pneumoniae
3rdG fluoroquinolones?
- levo.floxacin
- moxi.floxacin
Levofloxacin & Moxifloxacin spectrum?
- some activity against G-‘s
- more activity against G+’ cocci:
1. S.pneumoniae
2. Enterococci
3. MRSA
broadest spectrum fluoroquinolones?
moxifloxacin
- with enhanced activity against anaerobes
- Use of moxifloxacin in urinary tract infections is not recommended
fluoroquinolones pharmacoKinetix?
- oral bioavailability: good
- distribution: penetrate most body tissues
- Elimination: kidneys (active tubular secretion)
- moxifloxacin: eliminated partly by hepatic and biliary excretion*
- Half-live: 3–8h
fluoroquinolones MOA?
- bactericidal
- in G-‘s: inhibit inhibiting topoisomerase II –> interfere with bacterial DNA synthesis
- in G+’s: inhibits topoisomerase IV –> interfere with bacterial DNA synthesis
- exhibit postantibiotic effects
what is PostAntibiotic effect?
bacterial growth continues to be inhibited even after the plasma concentration of the drug has fallen below the min inhibitory concentration of the bacterium
Resistance against fluoroquinolones?
- Efflux pumps or changing porin structure –> decreased intracellular accumulation of the drug
- Point mutations in the ABx binding regions –> Changes in the sensitivity of the target enzymes
Fluoroquinolones Clinical use?
- mainly in urogenital and GITIs by G-‘s:
(gonococci, E coli, P aeruginosa, Salmonella, shigella) - meningococcal carrier state
- tuberculosis
Ofloxacin clinical use?
- eradicates Chlamydia trachomatis
- 7d of treatment is required
Levofloxacin clinical use?
- community-acquired pneumonia
- against:
1. Chlamydiae
2. Mycoplasma
3. Legionella
Oxifloxacin clinical use?
- widest spectrum of activity
- G-‘s & G+’s
- atypical pneumonia agents
- some anaerobic bacteria
fluoroquinolones Toxicity?
- Gastrointestinal distress
- not recommended for children or pregnant women because they may damage growing cartilage and cause arthropathy
- enchance theophylline and other methylxanthines Toxicity ( increase their plasma lvl)
- prolong the QT interval
