Introduction
Levofloxacin is a synthetic broad-spectrum fluoroquinolone antibiotic that represents the L-isomer of ofloxacin. As a third-generation fluoroquinolone, it exhibits enhanced activity against Gram-positive organisms while maintaining excellent coverage against Gram-negative pathogens. First approved by the FDA in 1996, levofloxacin has become a widely used antimicrobial agent for various bacterial infections due to its favorable pharmacokinetic profile and broad spectrum of activity.
Mechanism of Action
Levofloxacin exerts its bactericidal effect through inhibition of bacterial DNA gyrase (topoisomerase II) and topoisomerase IV. DNA gyrase is essential for DNA replication, transcription, and repair, while topoisomerase IV is crucial for chromosome partitioning during cell division. By binding to these enzymes, levofloxacin creates stable drug-enzyme-DNA complexes that ultimately lead to double-stranded DNA breaks and bacterial cell death. The drug demonstrates concentration-dependent killing activity, with the area under the concentration-time curve (AUC)/MIC ratio being the primary pharmacodynamic parameter predicting efficacy.
Indications
FDA-approved indications include:
- Community-acquired pneumonia (due to S. pneumoniae, S. aureus, H. influenzae, H. parainfluenzae, K. pneumoniae, M. catarrhalis, M. pneumoniae, C. pneumoniae, or L. pneumophila)
- Hospital-acquired pneumonia
- Acute bacterial exacerbation of chronic bronchitis
- Acute bacterial sinusitis
- Complicated and uncomplicated urinary tract infections
- Acute pyelonephritis
- Complicated skin and skin structure infections
- Chronic bacterial prostatitis
- Inhalational anthrax (post-exposure)
Dosage and Administration
Standard dosing:- Community-acquired pneumonia: 500-750 mg IV or orally every 24 hours for 7-14 days
- Complicated UTI or acute pyelonephritis: 750 mg IV or orally every 24 hours for 5 days
- Uncomplicated UTI: 250 mg orally every 24 hours for 3 days
- Skin and skin structure infections: 750 mg IV or orally every 24 hours for 7-14 days
- Renal impairment: Dose adjustment required based on creatinine clearance
- CrCl 20-49 mL/min: 250-500 mg every 48 hours - CrCl 10-19 mL/min: 250-500 mg every 48 hours initially, then adjust - Hemodialysis: 250-500 mg every 48 hours after dialysis
- Hepatic impairment: No dosage adjustment required
- Elderly: Consider renal function for dosing
- Pediatrics: Generally avoided due to arthropathy risk; reserved for specific indications
Pharmacokinetics
Absorption: Rapid and complete oral bioavailability (~99%), not significantly affected by food Distribution: Wide tissue distribution, volume of distribution ~1.1 L/kg. Penetrates well into lungs, prostate, skin, and other tissues Metabolism: Minimally metabolized (<5%) in the liver; the sulfur-containing moiety undergoes oxidation Elimination: Primarily renal excretion (≥87% unchanged drug), elimination half-life 6-8 hours Protein binding: 24-38%Contraindications
- History of hypersensitivity to levofloxacin or other quinolones
- Known tendon disorders associated with previous quinolone use
- Concurrent administration with tizanidine
Warnings and Precautions
Boxed Warning:- Tendinitis and tendon rupture (especially Achilles tendon)
- Exacerbation of myasthenia gravis
- Peripheral neuropathy (may be irreversible)
- CNS effects: seizures, dizziness, confusion
- QT prolongation and arrhythmias
- Hypersensitivity reactions (including anaphylaxis)
- Clostridium difficile-associated diarrhea
- Photosensitivity reactions
- Hepatotoxicity
- Blood glucose disturbances (both hypoglycemia and hyperglycemia)
- Avoid in patients with known QTc prolongation, uncorrected hypokalemia, or taking other QT-prolonging drugs
Drug Interactions
Significant interactions:- Antacids containing aluminum, magnesium, calcium, iron, or zinc: Decreased absorption (separate administration by至少 2 hours)
- Sucralfate: Decreased absorption (separate by至少 2 hours)
- QT-prolonging drugs (antiarrhythmics, antipsychotics, antidepressants): Additive QT prolongation
- Corticosteroids: Increased risk of tendon rupture
- Warfarin: Enhanced anticoagulant effect (monitor INR)
- Theophylline: Increased theophylline concentrations
- Nonsteroidal anti-inflammatory drugs: Increased CNS stimulation risk
- Insulin and oral hypoglycemics: Altered glucose control
Adverse Effects
Common (≥1%):- Nausea (7%)
- Diarrhea (5%)
- Headache (6%)
- Constipation (3%)
- Dizziness (3%)
- Insomnia (4%)
- Tendon rupture (0.1%)
- Peripheral neuropathy
- QT prolongation and torsades de pointes
- Hepatotoxicity
- Clostridium difficile-associated diarrhea
- Severe hypersensitivity reactions
- Seizures
- Psychiatric disturbances (anxiety, depression, psychosis)
- Blood dyscrasias
Monitoring Parameters
- Clinical response to therapy
- Renal function (baseline and during prolonged therapy)
- Liver function tests (in patients with pre-existing liver disease)
- Blood glucose in diabetic patients
- Signs of tendon pain, inflammation, or rupture
- Neurological symptoms (tingling, numbness, pain)
- ECG monitoring in patients at risk for QT prolongation
- INR in patients on warfarin
- Signs of C. difficile infection (diarrhea, abdominal pain)
Patient Education
- Complete the entire course of therapy unless otherwise directed
- Take at same time each day, with or without food
- Maintain adequate hydration
- Avoid antacids, vitamins/mineral supplements, or dairy products within 2 hours of dose
- Immediately report any tendon pain, swelling, or inflammation
- Report any tingling, numbness, burning pain, or weakness
- Be aware of potential dizziness or lightheadedness
- Use sun protection due to photosensitivity risk
- Diabetic patients should monitor blood glucose closely
- Contact healthcare provider if severe diarrhea develops
- Do not take with tizanidine
- Inform all healthcare providers of levofloxacin use
References
1. FDA Prescribing Information: Levofloxacin (2023) 2. Gilbert DN, et al. The Sanford Guide to Antimicrobial Therapy. 52nd ed. 2022 3. Mandell LA, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44 Suppl 2:S27-72 4. Owens RC Jr, Ambrose PG. Antimicrobial safety: focus on fluoroquinolones. Clin Infect Dis. 2005;41 Suppl 2:S144-57 5. Rubinstein E, et al. Safety profile of parenteral and oral levofloxacin in adult patients. Expert Opin Drug Saf. 2005;4(5):889-901 6. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing. 33rd ed. 2023 7. Carbon C. Comparison of side effects of levofloxacin versus other fluoroquinolones. Chemotherapy. 2001;47 Suppl 3:9-14 8. Lode H. Evidence-based efficacy and safety of levofloxacin in uncomplicated skin and skin structure infections. Int J Antimicrob Agents. 2001;18(2):109-18
Note: This monograph provides general information and should not replace clinical judgment. Always consult current prescribing information and clinical guidelines for specific patient scenarios.