Levofloxacin
Levofloxacin
Generic Name
Levofloxacin
Mechanism
Levofloxacin is a potent member of the *fluoroquinolone* class.
• Inhibits bacterial DNA gyrase (DNA‑topoisomerase II) and topoisomerase IV, enzymes essential for DNA replication, transcription, and repair.
• Leads to double‑strand DNA breaks, ultimately causing bacterial cell death.
• Exhibits a broad spectrum that covers Gram‑positive cocci (e.g., *Streptococcus pneumoniae*, *Staphylococcus aureus*), Gram‑negative bacilli (e.g., *Escherichia coli*, *Pseudomonas aeruginosa*), and atypical organisms (e.g., *Mycoplasma pneumoniae*, *Legionella pneumophila*).
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Pharmacokinetics
- Absorption: Excellent oral bioavailability (~99%) irrespective of food. ~70 % plasma protein binding.
- Distribution: Widely distributed; crosses into most tissues, including lungs, sinuses, and bone. Penetration into CSF is limited unless inflamed.
- Metabolism: Minimal hepatic metabolism; primarily excreted unchanged.
- Elimination: Renal clearance dominates; 80–90 % excreted renally within 24 h.
- Half‑life: ~4–6 h (oral); ~8–9 h (IV) in healthy adults. Extends in renal impairment.
- Volume of distribution: ~0.8 L/kg (oral) and ~0.6 L/kg (IV).
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Indications
| Infection | Typical Dose | Formulation |
| Community‑acquired pneumonia | 500 mg PO or IV once daily | Oral / IV |
| Atypical pneumonia | 500 mg PO or IV daily | Oral / IV |
| Acute bacterial sinusitis | 500 mg PO daily | Oral |
| Acute exacerbation of COPD (with bacterial infection) | 500 mg PO or IV daily | Oral / IV |
| Urinary tract infection (cystitis) | 250 mg PO daily | Oral |
| Complicated UTI / pyelonephritis | 500 mg PO/IV daily | Oral / IV |
| Skin/soft tissue infections (SSTI) | 500 mg PO/IV daily | Oral / IV |
| Bone and joint infections (chronic *S. aureus*) | 500 mg IV 2 × daily, then 500 mg PO | IV / Oral |
| Infections due to *Pseudomonas* (nosocomial) | 500 mg IV 2 × daily | IV |
| Prevention of *Pseudomonas* infection in cystic fibrosis | 500 mg PO twice daily | Oral |
*Adjust dosing for maternal‑fetal or renal impairment per dose‑adjustment tables.*
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Contraindications
Contraindications
• Known hypersensitivity to quinolones or any component.
• Pregnancy (category C) – avoid due to risk of cartilage damage.
Warnings
• Tendonitis/Tendon rupture – increased in patients >60 yr, concurrent steroids, renal or cardiac failure, or taking *Amiodarone*.
• Central nervous system – risk of seizures, altered mental status (especially in renal failure).
• QT prolongation – monitor ECG in patients with pre‑existing long QT or on QT‑extending drugs.
• Gastric irritation – may cause dyspepsia or esophagitis; advise to take with water and remain upright for 30 min.
• Clostridioides difficile – risk heightened by broad‑spectrum activity; monitor for antibiotic‑associated diarrhea.
• Hemorrhagic complications – rare but possible.
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Dosing
| Patient 50 mL/min (IV) | Oral Dosing |
| 500 mg IV once daily (pneumonia, sinuses, UTI, SSTI) | 500 mg PO daily |
| 500 mg IV twice daily (Pseudomonas, severe tissue infections, CF prophylaxis) | 250 mg PO daily (cystitis) |
| Renal impairment (CrCl 30–49 mL/min) | CrCl <30 mL/min (IV) | CrCl <30 mL/min (PO) |
| 500 mg IV/PO once daily | 500 mg IV every 48 h | 250 mg PO every 48 h |
• Administration: Take with water; avoid calcium‑, iron‑ or magnesium‑containing products 2 h before or after dosing.
• IV infusion rate: 1 mg/kg/hr (50 mg/kg over 3 h maximum) to minimize infusion reactions.
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Adverse Effects
Common (≤10 % incidence)
• Gastrointestinal: nausea, vomiting, diarrhea.
• Central nervous system: headache, dizziness.
• Peripheral neuropathy: transient paresthesias, muscle weakness.
• Photosensitivity: rash, sunburn.
Serious (≤1 % incidence)
• Tendon rupture (especially Achilles).
• Severe CNS events (seizures, psychosis, delirium).
• Severe cardiac: QT prolongation, torsades de pointes.
• Hypersensitivity: anaphylaxis, urticaria, angioedema.
• Clostridioides difficile colitis.
• Ocular: optic neuritis, retinal detachment.
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Monitoring
| Parameter | Frequency | Rationale |
| Renal function (CrCl) | Baseline; every 3–5 days in >60 yr or renal impairment | Adjust dose & avoid accumulation |
| Serum electrolytes (K⁺, Mg²⁺) | Baseline; repeat if symptoms | Low Mg/K may exacerbate CNS toxicity |
| ECG | Baseline in patients >60 yr or on QT‑extending drugs | Detect QT prolongation |
| Signs of tendon irritation | Patient counseling; prompt reporting | Early detection prevents rupture |
| Blood glucose | In diabetics | Levofloxacin can induce hypoglycemia |
| Clinical response | 48–72 h | Ensure efficacy, switch if inadequate |
| Adverse event reporting | Continuous | Capture rare but serious effects |
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Clinical Pearls
- Use sparingly for uncomplicated cystitis – high cure rates with amoxicillin/trimethoprim; reserve levofloxacin for refractory or drug‑resistant cases.
- For *Pseudomonas* coverage, consider combination therapy (e.g., ceftazidime + levofloxacin) rather than monotherapy to prevent resistance.
- Avoid in pregnancy and lactation; if exposure unavoidable, counsel about potential cartilage toxicity.
- Take with a full glass of water and remain upright to reduce GI irritation and esophageal ulceration.
- Discontinue promptly if tendon pain appears; secondary antibiotics may be more appropriate until healing.
- Use with caution in patients with a history of seizures, bipolar disorder, or on valproate – prophylactic dose adjustment and close neurologic monitoring are advised.
- Levofloxacin extends half‑life in renal impairment; dose delay may be preferable over dose reduction to maintain peak plasma levels.
- Beta‑chloramphenicol or fluoroquinolone alternation – avoid overlapping therapy due to potential additive CNS toxicity.
- Do not mix levofloxacin with calcium‑rich dairy products – solid absorption inhibition can reduce efficacy.
> *Levofloxacin remains a frontline agent for a broad array of bacterial infections, yet its safety profile demands vigilant dosing, monitoring, and patient education.*