Quinolones

Key Examples

• Ciprofloxacin
• Moxifloxacin
• Levofloxacin

 

Common indications

1. Urinary tract infection (UTI).
2. Severe gastrointestinal infection, e.g. with Shigella, Campylobacter.
3. Lower respiratory tract infection (LRTI) (moxifloxacin, levofloxacin).
4. Ciprofloxacin is the only oral antibiotic in common use with activity against Pseudomonas aeruginosa. Moxifloxacin and levofloxacin do not have this property.

Quinolones are generally reserved as second or third-line treatment due to the potential for rapid emergence of resistance and an association with Clostridium difficile infection.

 

 Mechanisms of action

• Quinolones kill bacteria by inhibiting DNA synthesis. 
• They are particularly active against aerobic Gram-negative bacteria, which explains their utility in treatment of urinary and gastrointestinal infections. Moxifloxacin and levofloxacin are newer quinolones with enhanced activity against Gram-positive organisms. They can therefore be used to treat LRTI, which may be caused by either Gram-positive or Gram-negative organisms.
• Bacteria rapidly develop resistance to quinolones. Some bacteria prevent intracellular accumulation of the drug by reducing permeability and/or increasing efflux. Others develop protective mutations in target enzymes. 
• Quinolone resistance genes are spread horizontally between bacteria by plasmids, accelerating acquisition of resistance.

 

Important adverse effects

• Quinolones are generally well tolerated although they can cause gastrointestinal upset (including nausea and diarrhoea) and immediate and delayed hypersensitivity reactions. 
• Class-specific adverse reactions include neurological effects (lowering of the seizure threshold and hallucinations), and inflammation and rupture of muscle tendons. 
• Quinolones (particularly moxifloxacin) prolong the QT interval and therefore increase the risk of arrhythmias. 
• They promote Clostridium difficile colitis, particularly the hypervirulent 027 strain.

 

Warnings

• Quinolones should be used with caution in people at particular risk of adverse effects including those with or at risk of seizures, who are growing (potential risk of arthropathy); and with other risk factors for QT prolongation (such as cardiac disease or electrolyte disturbance).

 

Important interactions

• Drugs containing divalent cations (e.g. calcium, antacids) reduce absorption and efficacy of quinolones. 
• Ciprofloxacin inhibits certain cytochrome P450 enzymes, increasing risk of toxicity with some drugs, notably theophylline. 
• Co-prescription of NSAIDs increases the risk of seizures, and of prednisolone increases the risk of tendon rupture. 
• Quinolones should be prescribed with caution in patients taking other drugs that prolong the QT interval or cause arrhythmias, such as amiodarone, antipsychotics, quinine, macrolide antibiotics and SSRIs.