Fluoroquinolones

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Mechanism of Action - DNA Gyre Unwinders

  • Inhibit key bacterial enzymes required for DNA synthesis: DNA Gyrase (Topoisomerase II) and Topoisomerase IV.
  • This inhibition prevents the relaxation of supercoiled DNA and separation of replicated daughter DNA strands.
  • Leads to strand breakage, disrupting DNA replication and repair, resulting in a rapid bactericidal effect.

⭐ The primary target differs by organism: DNA gyrase is the main target in Gram-negative bacteria, while topoisomerase IV is the primary target in most Gram-positive bacteria.

Fluoroquinolone inhibiting bacterial DNA gyrase

Spectrum & Generations - The Fluoro Fleet

Broad-spectrum bactericidal activity that expands with each generation. Primarily used for gram-negative and atypical infections.

  • 2nd Gen (Ciprofloxacin, Ofloxacin): Excellent gram-negative coverage, including Pseudomonas aeruginosa. Good for UTIs, prostatitis, and infectious diarrhea. Limited gram-positive activity.

  • Respiratory Quinolones (3rd & 4th Gen): Enhanced gram-positive coverage, especially for Streptococcus pneumoniae.

    • Levofloxacin (3rd): Broad-spectrum workhorse. Covers gram-positives, gram-negatives (including Pseudomonas), and atypicals. Used for community-acquired pneumonia (CAP).
    • Moxifloxacin (4th): Best gram-positive, atypical, and anaerobic coverage. Poor Pseudomonas activity.

⭐ Moxifloxacin is hepatically metabolized and does not concentrate in urine, making it ineffective for UTIs.

Pharmacokinetics - Getting Around Town

  • Absorption: Excellent oral bioavailability; however, absorption is significantly ↓ by polyvalent cations (Ca²⁺, Fe²⁺, antacids). 📌 Avoid dairy, iron supplements, or antacids within 2 hours of a dose.
  • Distribution: Wide distribution into most tissues, including bone, prostate, and lungs. Achieves high intracellular concentrations.
  • Metabolism & Excretion: Primarily renal excretion (requires dose adjustment in renal failure), except for Moxifloxacin (hepatic).

⭐ Ciprofloxacin is a notable inhibitor of the CYP1A2 enzyme, which can ↑ levels of drugs like Theophylline and Caffeine, leading to potential toxicity.

Clinical Uses - When to Call the Quins

  • GU Infections: Complicated UTIs, pyelonephritis, and prostatitis (excellent prostate penetration).
  • GI & Intra-abdominal: Potent against bacterial gastroenteritis (e.g., Shigella, Salmonella, E. coli, Campylobacter).
  • Respiratory Tract: "Respiratory fluoroquinolones" (Levofloxacin, Moxifloxacin) for community-acquired pneumonia (CAP) and atypical pneumonias (Legionella).
  • Bone, Joint, & Soft Tissue: Gram-negative osteomyelitis, diabetic foot infections.
  • Anthrax: Ciprofloxacin is the drug of choice for post-exposure prophylaxis and treatment.

⭐ Fluoroquinolones have excellent activity against Pseudomonas aeruginosa (especially Ciprofloxacin and Levofloxacin), making them crucial for hospital-acquired infections and treating infections in burn patients.

Adverse Effects - The Achilles' Heel

  • Musculoskeletal:
    • ⚠️ Black Box Warning: Increased risk of tendonitis & Achilles tendon rupture, especially in the elderly, patients with renal failure, or those on steroid therapy. 📌 FluoroquinoLONES hurt attachments to your BONES.
    • Arthropathy and cartilage damage, limiting use in pregnancy and children <18 years old.
  • Cardiovascular:
    • QT prolongation (risk of Torsades de Pointes).
  • CNS:
    • Headache, dizziness, confusion, and seizures (related to GABA antagonism).
  • Other Key Effects:
    • Phototoxicity (severe sunburn reactions).
    • Dysglycemia (hyper- or hypoglycemia).

⭐ Fluoroquinolones are notorious for disrupting gut flora, significantly increasing the risk of Clostridioides difficile infection.

Fluoroquinolone-associated tendonitis and rupture data

  • Fluoroquinolones inhibit bacterial DNA gyrase (topoisomerase II) and topoisomerase IV.
  • Black Box Warnings include tendonitis/tendon rupture, peripheral neuropathy, and CNS effects.
  • Associated with QT interval prolongation, increasing the risk for Torsades de Pointes.
  • Contraindicated in pregnancy and children due to potential for cartilage damage.
  • Absorption is impaired by divalent and trivalent cations (e.g., calcium, iron, antacids).
  • Effective against atypical pneumonias and Pseudomonas.

Practice Questions: Fluoroquinolones

Test your understanding with these related questions

A 64-year-old woman with a past medical history of poorly managed diabetes presents to the emergency department with nausea and vomiting. Her symptoms started yesterday and have been progressively worsening. She is unable to eat given her symptoms. Her temperature is 102°F (38.9°C), blood pressure is 115/68 mmHg, pulse is 120/min, respirations are 17/min, and oxygen saturation is 98% on room air. Physical exam is notable for left-sided costovertebral angle tenderness, and urinalysis demonstrates bacteriuria and pyuria. The patient is admitted to the hospital and started on IV ceftriaxone. On day 3 of her hospital stay she is afebrile, able to eat and drink, and feels better. Which of the following antibiotic regimens should be started or continued as an outpatient upon discharge?

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Flashcards: Fluoroquinolones

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Fluoroquinolones are _____ synthesis inhibitors

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Fluoroquinolones are _____ synthesis inhibitors

nucleic acid

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