Quinolones

Fluoroquinolones: Overview (quick guide table)

Fluoroquinolones are a class of broad-spectrum antibiotics with excellent bioavailability, allowing for effective oral and intravenous use, and are primarily used to treat various bacterial infections, particularly those caused by Gram-negative organisms. Some fluoroquinolone also show excellent activity against certain Gram-positive, especially strep pneumonia and atypical bacteria.

Ciprofloxacin and levofloxacin have exceptional penetration into the prostate and central nervous system (CNS), making them particularly valuable in treating conditions like prostatitis and certain CNS infections. Additionally, these two are the only oral options available for treating some susceptible strains of Pseudomonas aeruginosa.

The mechanism of action of fluoroquinolones involves the inhibition of bacterial DNA gyrase and topoisomerase IV, enzymes critical for DNA replication, transcription, and repair.

However, due to increasing bacterial resistance, drug interactions, potential side effects, the use of fluoroquinolones is more restricted today.

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Common Fluoroquinolones:

• Ciprofloxacin IV/po
• Levofloxacin IV/po
• Moxifloxacin IV/po

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Spectrum:

1. Ciprofloxacin: (more of gram negative coverage)

   • Gram-positive: Limited.
   • Gram-negative: Broad coverage, including Pseudomonas, Enterobacteriaceae
   • Anaerobes: No anaerobic coverage
   • Atypical: Covers Legionella, Mycoplasma, Chlamydia

2. Levofloxacin:

   • Gram-positive: Good coverage against Strep pneumoniae, even Penicillin resistant strains
   • Gram-negative: Broad, including some Pseudomonas and Enterobacteriaceae
   • Anaerobes: No anaerobic coverage
   • Atypical: Covers Legionella, Mycoplasma, Chlamydia and even mycobacteria

3. Moxifloxacin: (more of gram positive coverage - less commonly used )

   • Gram-positive: Good coverage against Strep pneumoniae
   • Gram-negative: Broad, but NO Pseudomonas coverage
   • Anaerobes: ?Good anaerobic coverage
   • Atypical: Covers Legionella, Mycoplasma, Chlamydia and even mycobacteria

Key Uses:

1. Ciprofloxacin: 

   • Urinary tract infections (UTIs): Effective for complicated and uncomplicated UTIs.
   • Gastrointestinal infections: Used for infections caused by Salmonella, Shigella, Campylobacter.
   • Pseudomonas infections: Commonly used in hospital-acquired infections where Pseudomonas is a concern.

2. Levofloxacin:

   • Respiratory infections: Effective for community-acquired pneumonia and sinusitis. Good for pneumonia caused by Streptococcus pneumoniae and Legionella.
   • UTIs: Also used for complicated UTIs, but less than ciprofloxacin.
   • Skin infections: Occasionally used for soft tissue infections involving Gram-negative bacteria.

3. Moxifloxacin: (liver elimination: i.e. to be avoided in UTI and no need for renal dose adjustment)

   • Respiratory infections: First-line treatment for community-acquired pneumonia and bronchitis. Superior lung penetration compared to other fluoroquinolones.
   • Intra-abdominal infections: Due to its anaerobic activity, used for mixed infections in intra-abdominal cases.

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Key Notes:

• Ciprofloxacin is anti-Pseudomonal, making it useful in treating hospital-acquired infections, but it is not recommended for respiratory infections due to poor Streptococcus coverage.
• Levofloxacin offers both respiratory and UTI uses with some Pseudomonas activity. It is often considered a respiratory fluoroquinolone.
• Moxifloxacin is the only fluoroquinolone with reliable anaerobic coverage and is ideal for intra-abdominal infections. It does NOT cover Pseudomonas.
• Increasing resistance: Overuse of fluoroquinolones has led to rising resistance in Gram-negative bacteria, limiting their use in many settings.
• Black box warnings:
  • Risk of tendinitis and tendon rupture, especially in older adults or those on steroids.
  • Peripheral neuropathy and CNS effects (confusion, seizures) are potential side effects.
  • Can prolong the QT interval, leading to an increased risk of arrhythmias. Avoid with Amiodarone, Sotalol etc...
• Not first-line: Fluoroquinolones are no longer considered first-line treatment for many common infections (e.g., sinusitis, bronchitis, and uncomplicated UTIs) due to these safety concerns.

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Summary:

• Ciprofloxacin: Excellent for UTIs, GI infections, and Pseudomonas, but avoid in respiratory infections.
• Levofloxacin: Great for respiratory infections and UTIs with some Pseudomonas activity.
• Moxifloxacin: Ideal for respiratory infections and intra-abdominal infections, but lacks Pseudomonas coverage. It also has anaerobic coverage.
• Use cautiously due to the risk of tendon rupture, peripheral neuropathy, and other serious side effects. Beware of major drug interactions with anti-arrhythmics, cyclosporine, warfarin and antacids and mineral supplements.