Indications
Levofloxacin, available in oral and intravenous formulations, is indicated for the treatment of various infections in adults caused by susceptible bacteria. These infections include those affecting·he upper and lower respiratory tracts, skin and skin structures, urinary tract, and prostate. Additionally, the oral formulation is approved for both adults and children aged six months and older for post-exposure management of inhalational anthrax caused by Bacillus anthracis, as well as for the treatment and/or prophylaxis of plague due to Yersinia pestis. In its ophthalmic formulation, levofloxacin is prescribed for bacterial conjunctivitis caused by susceptible organisms. In Canada, an inhalational solution is available for managing·hronic pulmonary Pseudomonas aeruginosa infections in cystic fibrosis patients aged 18 years or older.
Pharmacodynamics
Levofloxacin is a bactericidal antibiotic that functions by inhibiting·has a relatively long·her antibiotics, which allows for once or twice-daily dosing·however, it is associated with QTc interval prolong·hould be administered with caution in patients who have risk factors for prolong·h as hypokalemia or concomitant medications. The drug exhibits in vitro activity against various aerobic gram-positive and gram-negative bacteria and shows some activity against certain anaerobic bacteria and pathogens like Chlamydia and Legionella. Resistance to levofloxacin can develop, often due to mutations in DNA gyrase or topoisomerase IV or through alterations in drug efflux. While cross-resistance may occur between levofloxacin and other fluoroquinolones, it is unlikely to develop with other antibiotic classes due to differences in chemical structure and mechanisms of action. Local antibiograms should be referenced to ensure effective coverage of pathogens in specific geographic areas.
Absorption
Levofloxacin is rapidly and almost completely absorbed following·h an oral bioavailability of approximately 99%. This high bioavailability means that the intravenous and oral formulations are generally interchang·he time to peak concentration (Tmax) is typically reached 1 to 2 hours post-administration, and the maximum concentration (Cmax) is proportional to the dose administered; a 500mg intravenous dose infused over 60 minutes results in a Cmax of 6.2 ± 1.0 µg/mL, while a 750mg dose over 90 minutes yields a Cmax of 11.5 ± 4.0 µg/mL. Although food intake marginally delays Tmax by about an hour and slightly reduces Cmax, these chang·halation leads to approximately 50% lower systemic absorption compared to oral administration.
Metabolism
Levofloxacin undergoes minimal metabolism in humans, with two metabolites, desmethyl-levofloxacin and levofloxacin-N-oxide, being·her metabolite is believed to have significant pharmacological activity. After oral administration, less than 5% of the dose is recovered in the urine as these metabolites, signifying·he drug. The specific enzymes responsible for the demethylation and oxidation of levofloxacin have not yet been identified.
Mechanism of Action
Levofloxacin, a member of the fluoroquinolone antibiotic class, functions by inhibiting two critical bacterial enzymes: DNA gyrase and topoisomerase IV. Both are type II topoisomerases that play distinct roles within bacterial cells. DNA gyrase, exclusive to bacteria, introduces negative supercoils into DNA during replication to alleviate torsional strain from positive supercoils and is crucial for chromosome condensation and transcription initiation. This enzyme consists of two A subunits and two B subunits, with the A subunits being the target of fluoroquinolone antibiotics. Topoisomerase IV, on the other hand, assists in the relaxation of positive supercoils and is pivotal at the final stages of DNA replication, where it "unlinks" newly replicated chromosomes, facilitating cell division completion. Levofloxacin's inhibition of these enzymes likely occurs through complexation with the topoisomerase enzymes, ultimately blocking DNA replication, thereby halting cell division and leading to bacterial cell death.
