What is Levofloxacin (fluoroquinolone antibiotic)?

What is Levofloxacin?

Levofloxacin is a second-generation fluoroquinolone antibiotic—specifically the pure L-isomer of ofloxacin—with broad-spectrum activity against Gram-positive and Gram-negative bacteria, particularly effective for respiratory tract infections due to its enhanced activity against Streptococcus pneumoniae compared to other fluoroquinolones like ciprofloxacin. 1

Chemical Structure and Formulation

• Levofloxacin is chemically designated as (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid hemihydrate, appearing as a light yellowish-white to yellow-white crystalline powder 1

• Available as oral tablets in 250 mg, 500 mg, and 750 mg strengths, as well as intravenous formulation 1

Mechanism of Action

• Levofloxacin acts on bacterial DNA topoisomerase II (DNA gyrase) and topoisomerase IV, enzymes essential for bacterial DNA replication, transcription, repair, and recombination 2, 3

Antimicrobial Spectrum

• Gram-positive coverage: Enhanced activity against S. pneumoniae (including penicillin-resistant strains), superior to ciprofloxacin and ofloxacin 4, 3, 5

• Gram-negative coverage: Active against Haemophilus influenzae, Moraxella catarrhalis, and Pseudomonas aeruginosa (though less active than ciprofloxacin against P. aeruginosa) 4, 6

• Atypical pathogens: Effective against Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella pneumophila 6, 7

• Mycobacterial activity: Greater bactericidal activity than ciprofloxacin against multidrug-resistant tuberculosis 4

Pharmacokinetics

• Absorption: Rapidly and completely absorbed after oral administration with approximately 99% bioavailability, reaching peak plasma concentrations in 1-2 hours 1, 8

• Distribution: Volume of distribution ranges from 74-112 L with widespread tissue penetration; achieves concentrations in respiratory tissues approximately 2 times higher than plasma 1, 3

• Food effects: Can be taken with or without food, though food delays peak concentration by approximately 1 hour without significantly affecting overall absorption 1

• IV-to-oral equivalence: Intravenous and oral formulations are bioequivalent, allowing seamless transition between routes without dose adjustment 1, 5

Approved Clinical Indications

• Respiratory infections: Community-acquired pneumonia, nosocomial pneumonia, acute bacterial sinusitis, acute exacerbations of chronic bronchitis 9, 1, 7

• Urinary tract infections: Complicated and uncomplicated UTIs, acute pyelonephritis 1, 8

• Skin infections: Complicated and uncomplicated skin and skin structure infections 1, 7

• Other infections: Chronic bacterial prostatitis, inhalational anthrax, plague 1, 7

• Pediatric use: Approved for children ≥6 months for inhalational anthrax and plague exposure, though safety beyond 14 days is not established 1

Dosing Regimens

• Standard dose: 500 mg once daily for 7-14 days for most infections 3, 7

• High-dose short-course: 750 mg once daily for 5 days, specifically designed to overcome fluoroquinolone resistance mechanisms and approved for CAP, acute bacterial sinusitis, complicated UTI, and acute pyelonephritis 4, 8

• Severe pneumonia: 750 mg daily recommended for ICU-level pneumonia or when P. aeruginosa is suspected (in combination with antipseudomonal beta-lactam) 9

Critical Safety Warnings

• Tendon rupture: Black box warning for tendon rupture or tendinitis, particularly affecting the Achilles tendon; risk increased in patients >60 years, those taking corticosteroids, or transplant recipients 1

• Myasthenia gravis: Can cause life-threatening worsening of muscle weakness and breathing problems in patients with myasthenia gravis 1

• Central nervous system effects: May cause seizures, increased intracranial pressure, and tremors, especially when combined with NSAIDs 1

• QT prolongation: Can prolong QT interval; avoid in patients with known QT prolongation or uncorrected hypokalemia 1

• Peripheral neuropathy: May cause permanent nerve damage 1

Drug Interactions

• Chelation: Take 2 hours before or after antacids, multivitamins, or supplements containing magnesium, aluminum, iron, or zinc, as these form stable coordination compounds that reduce absorption 1

• Warfarin: May enhance anticoagulant effects, requiring INR monitoring 1

• Antidiabetic agents: Can cause dysglycemia (both hypo- and hyperglycemia) 1

Resistance Considerations

• Resistance to levofloxacin remains <1% overall in the US for S. pneumoniae, though cross-resistance exists among all fluoroquinolones 4, 7

• Previous fluoroquinolone exposure precludes empirical use of levofloxacin for community-acquired pneumonia due to resistance concerns 4, 6

• The 750 mg dose was developed specifically because treatment failures occurred with 500 mg daily dosing for pneumococcal pneumonia 4, 6

Key Clinical Advantages

• Once-daily dosing improves compliance compared to twice-daily fluoroquinolones 8, 7

• Superior respiratory tract penetration compared to ciprofloxacin makes it the preferred fluoroquinolone for pneumonia 4, 6

• Monotherapy option for CAP in appropriate patients, whereas other agents may require combination therapy 8, 10

• Well-established tolerability profile with lower rates of phototoxicity, hepatotoxicity, and cardiotoxicity compared to some newer fluoroquinolones 3, 5