Fluoroquinolones

Fluoroquinolones: Introduction

Fluoroquinolones are a class of broad-spectrum synthetic antibiotics that are highly effective against both Gram-negative and Gram-positive bacteria. They are widely used to treat a variety of infections, particularly urinary tract infections, respiratory infections, and gastrointestinal infections.

History

• The first quinolone, nalidixic acid, was discovered in 1962 as a byproduct of chloroquine synthesis.

• Later, the addition of a fluorine atom led to fluoroquinolones, which have improved potency, broader spectrum, and better tissue penetration.

Mechanism of Action

• Fluoroquinolones inhibit bacterial DNA synthesis by targeting two key enzymes:

  1. DNA gyrase (topoisomerase II): Essential for supercoiling and replication of bacterial DNA.

  2. Topoisomerase IV: Involved in separation of replicated DNA into daughter cells.

• Inhibition of these enzymes leads to DNA damage and bacterial death, making fluoroquinolones bactericidal.

Spectrum of Activity

• Gram-negative bacteria: Escherichia coli, Klebsiella, Pseudomonas, Salmonella, Shigella

• Gram-positive bacteria: Some activity against Staphylococcus aureus and Streptococcus pneumoniae

• Atypical pathogens: Mycoplasma, Chlamydia, Legionella

• Other uses: Certain fluoroquinolones can target Mycobacterium tuberculosis and Plasmodium falciparum in some contexts

Common Uses

• Urinary tract infections (UTIs): Especially complicated or resistant infections

• Respiratory tract infections: Pneumonia, bronchitis

• Gastrointestinal infections: Salmonella, Shigella, traveler's diarrhea

• Bone and joint infections

• Anthrax exposure (ciprofloxacin is FDA-approved for this)

Advantages

• Broad-spectrum coverage, including many Gram-negative pathogens

• High oral bioavailability and good tissue penetration

• Convenient dosing with some agents having once-daily administration

• Useful for infections caused by bacteria resistant to other antibiotics

Risks and Concerns

• Tendinopathy and tendon rupture: Especially in older adults or with concurrent corticosteroid use

• QT interval prolongation: Can lead to arrhythmias

• Peripheral neuropathy: Rare but potentially serious

• Gastrointestinal disturbances: Nausea, diarrhea

• Central nervous system effects: Headache, dizziness, confusion in some cases

• Resistance: Increasing resistance among E. coli, Pseudomonas, and S. pneumoniae

Examples of Fluoroquinolones

• Ciprofloxacin – mainly Gram-negative coverage, widely used for UTIs

• Levofloxacin – broad coverage, including respiratory pathogens

• Moxifloxacin – better Gram-positive coverage, used for respiratory infections

• Ofloxacin – less commonly used today but still effective for UTIs and other infections

• Norfloxacin – mainly urinary tract infections