Antibacterials: Quinolones

Question 1

Nalidixic Acid

Answer 1

• family: quinolone
• mechanism: bactericidal: selectively/reversibly blocks DNA replication in bacteria; inhibits the subunit of DNA gyrase, DNA topoisomerase 2
• kinetics: oral
• clinical: effective against gram +/-; UTI by E.coli, Proteus, Shigella, Enterobacter, Kleibsella, not used as much clinically because is excreted quickly, use others (especially cipro first)
• toxicity/interactions: Seizures, hallucinations, confusion; visual disturbances; metabolic acidosis; intracranial hypertension.
• misc: not used clinically anymore due to fast excretion

Question 2

Norfloxacin

Answer 2

• family: quinolone
• mechanism: Mechanism identical to that of ciprofloxacin; bactericidal, Resistance via changes in target enzymes (eg DNA gyrase) and possibly formation of inactivating enzymes
• kinetics: Oral and IV forms of levofloxacin and moxifloxacin; mostly renal clearance (not moxifloxacin—hepatic), Long half-lives of gemifloxacin and moxifloxacin permit once-daily dosing
• clinical: mainly for urinary tract infections; and atypicals (chlamydia, mycoplasma)
• toxicity/interactions: Like ciprofloxacin, GI upsets, CNS effects (dizziness, headache); tendinitis due to effects on cartilage (try to avoid in young children and pregnancy); Caution with use of class 1A and III antiarrhythmics
• misc: common side effect is bone/tendon pain, contraindicated for pregnant women/kids due to potential cartilage damage

Question 3

Ciprofloxacin

Answer 3

• family: quinolone
• mechanism: Inhibits DNA replication via binding to DNA gyrase (gram-negative organisms) and topoisomerase IV (gram-positive organisms); bactericidal Resistance: see below
• kinetics: Oral, IV; mostly renal clearance, half-life 4 h, Oral absorption impaired by cations
• clinical: Effective in urogenital, GI tracts, and some respiratory infections; activity versus gonococci rapidly declining; limited use in tuberculosis
• toxicity/interactions: GI upsets, CNS effects (dizziness, headache); tendinitis due to effects on cartilage (try to avoid in young children and pregnancy)
• misc: common side effect is bone/tendon pain, contraindicated for pregnant women/kids due to potential cartilage damage