What is the coverage and dosage of Levofloxacin (Levofloxacin) for various bacterial infections?

Levofloxacin Antimicrobial Coverage and Dosing

Bacterial Coverage Spectrum

Levofloxacin provides broad-spectrum coverage against both Gram-positive and Gram-negative organisms, with particularly strong activity against respiratory pathogens including Streptococcus pneumoniae (including multi-drug resistant strains), Haemophilus influenzae, Moraxella catarrhalis, and atypical organisms such as Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella pneumophila. 1

Gram-Positive Coverage

• Streptococcus pneumoniae: Levofloxacin demonstrates excellent activity against both penicillin-susceptible and penicillin-resistant strains, including multi-drug resistant S. pneumoniae (MDRSP) defined as resistance to ≥2 of the following: penicillin (MIC ≥2 mcg/mL), 2nd generation cephalosporins, macrolides, tetracyclines, or trimethoprim/sulfamethoxazole 1
• Methicillin-susceptible Staphylococcus aureus (MSSA): Covered with MIC₉₀ of 1.0 mg/L for ciprofloxacin and 0.5 mg/L for levofloxacin 2
• Streptococcus pyogenes and Enterococcus faecalis: Covered for skin/soft tissue and urinary tract infections 1
• MRSA is NOT adequately covered by levofloxacin 3

Gram-Negative Coverage

• Haemophilus influenzae (including β-lactamase producing strains): Excellent coverage with 100% eradication rates in some studies 4, 1
• Moraxella catarrhalis: Excellent coverage 1
• Enterobacteriaceae: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae, Serratia marcescens 1
• Pseudomonas aeruginosa: Covered but MUST be combined with an antipseudomonal β-lactam due to rapid resistance development 3, 1

Atypical Pathogens

• Legionella pneumophila: Levofloxacin has the most clinical data among fluoroquinolones for Legionella, with 70% clinical success rates 2, 3, 1
• Mycoplasma pneumoniae: 96% clinical success rate 1
• Chlamydophila pneumoniae: 96% clinical success rate 2, 1

Critical Pharmacodynamic Considerations

Levofloxacin exhibits concentration-dependent killing with a prolonged post-antibiotic effect, requiring an AUC:MIC ratio ≥30 for optimal bacterial eradication against S. pneumoniae. 2

• The modal MIC of levofloxacin against S. pneumoniae is 1 μg/mL, which is one-half of the susceptibility breakpoint (2 μg/mL), providing a narrower safety margin compared to other respiratory fluoroquinolones like gatifloxacin 2
• Monte Carlo simulation demonstrates that levofloxacin 500 mg once daily achieves the target AUC:MIC ratio ≥30 with only 82% certainty, compared to 99% for gatifloxacin 2
• Peak:MIC ratios of 10:1 to 12:1 correlate with optimal bactericidal activity 2

Standard Dosing Regimens by Indication

Community-Acquired Pneumonia (CAP)

• High-dose short-course: 750 mg once daily for 5 days (for non-MDRSP strains) 5, 3, 1
• Standard regimen: 500 mg once daily for 7-14 days (for MDRSP and severe infections) 5, 3, 1
• Severe CAP requiring ICU: 750 mg IV once daily or 500 mg IV twice daily, often combined with other antibiotics 2, 5
• Clinical success rates: 90.9-95% across multiple trials 1, 6, 7

Acute Bacterial Sinusitis

• High-dose short-course: 750 mg once daily for 5 days 2, 1
• Standard regimen: 500 mg once daily for 10-14 days 2, 1
• Clinical success rates: 88.6-91.4% 1

Acute Exacerbation of Chronic Bronchitis

• Standard dose: 500 mg once daily for 7 days 5, 1
• Covers S. pneumoniae, H. influenzae, H. parainfluenzae, M. catarrhalis, and MSSA 1

Nosocomial Pneumonia

• 750 mg once daily for 7-14 days (IV followed by oral) 1
• Must add antipseudomonal β-lactam when P. aeruginosa is documented or presumptive pathogen 1

Complicated Skin and Skin Structure Infections

• 750 mg once daily for 7-14 days (IV followed by oral) 1
• Clinical success rate: 84.1% 1

Uncomplicated Skin Infections

• 500 mg once daily for 7-10 days (oral) 1

Complicated Urinary Tract Infections/Acute Pyelonephritis

• High-dose short-course: 750 mg once daily for 5 days 1
• Standard regimen: 500 mg once daily for 10 days 1

Uncomplicated Urinary Tract Infections

• 250 mg once daily for 3 days 1

Chronic Bacterial Prostatitis

• 500 mg once daily for 28 days 1
• Microbiologic eradication rate: 75% 1

Renal Dose Adjustments

Levofloxacin is 80% renally cleared and requires dose reduction when creatinine clearance falls below 50 mL/min. 5

• CrCl 20-49 mL/min:
  • For 750 mg dose: Give 750 mg initial dose, then 750 mg every 48 hours
  • For 500 mg dose: Give 500 mg initial dose, then 250 mg every 24 hours 5
• CrCl 10-19 mL/min:
  • For 750 mg dose: Give 750 mg initial dose, then 500 mg every 48 hours
  • For 500 mg dose: Give 500 mg initial dose, then 250 mg every 48 hours 5
• Hemodialysis/CAPD: No supplemental doses needed after dialysis as levofloxacin is not effectively removed 5

Hepatic Considerations

• No dose adjustment required for hepatic impairment, as levofloxacin levels are unaffected by liver dysfunction 5

Pediatric Dosing

Levofloxacin is generally NOT recommended for routine pediatric use due to concerns about effects on bone and cartilage growth, but may be considered when benefits outweigh risks (e.g., MDR-TB, resistant infections). 5

• Children ≥5 years: 10 mg/kg once daily (maximum 750 mg) 5
• Children 6 months to <5 years: 10 mg/kg divided every 12 hours (maximum 750 mg/day) due to faster drug clearance 5
• Adolescents with skeletal maturity: 500 mg once daily for atypical pneumonia 3

Critical Contraindications and Warnings

Absolute Contraindications

• Pregnancy: Avoid due to teratogenic effects (class effect of fluoroquinolones) 5
• Recent fluoroquinolone use: Do NOT use if patient received fluoroquinolones within past 90 days due to high risk of resistant organisms 3

Important Drug Interactions

• Do NOT administer within 2 hours of antacids or medications containing divalent cations (calcium, magnesium, aluminum, iron) as these markedly decrease fluoroquinolone absorption 5

Special Monitoring Requirements

• QT prolongation risk: Obtain baseline ECG in elderly patients and those on QT-prolonging medications; monitor at 2 weeks and after adding any QT-prolonging drugs 5
• Tendon rupture risk: Increased with concomitant corticosteroid use, particularly in elderly patients 5
• Hypoglycemia risk: Monitor blood glucose in diabetic patients, especially when combined with hypoglycemic drugs 5

Treatment Duration Guidelines

Treatment should generally not exceed 8 days in responding patients. 2, 5, 3

• Response should be monitored using clinical criteria including body temperature, respiratory parameters, and hemodynamic stability 5
• The 750 mg high-dose regimen allows for 5-day treatment courses in CAP, ABS, and complicated UTI/pyelonephritis 3, 1

Common Pitfalls to Avoid

• Do NOT use levofloxacin as monotherapy for P. aeruginosa infections - always combine with antipseudomonal β-lactam 3, 1
• Do NOT assume MRSA coverage - levofloxacin is inadequate for MRSA 3
• Do NOT use in patients with suspected or confirmed tuberculosis without appropriate TB treatment, as levofloxacin may delay TB diagnosis and increase fluoroquinolone resistance 3
• Do NOT use as first-line therapy for acute otitis media in children - reserve for treatment failures only 4
• Ciprofloxacin does NOT reliably cover S. pneumoniae due to MICs above PK/PD breakpoints 2

Comparative Efficacy Considerations

• Levofloxacin has superior activity against S. pneumoniae compared to ciprofloxacin or ofloxacin, but slightly less activity than newer fluoroquinolones like gatifloxacin or moxifloxacin 2, 6
• For acute bacterial rhinosinusitis, predicted clinical efficacy is 90-92% (similar to respiratory quinolones, ceftriaxone, and high-dose amoxicillin/clavulanate) 2
• Resistance rates to levofloxacin among S. pneumoniae remain <1% overall in the US 7