- Nalidixic acid is a first-generation quinolone antibiotic with a molecular formula of C12H12N2O3 and a molecular mass of 232.24 g/mol. Its structure features a naphthyridine core with a carboxylic acid group at the 3-position and a nitrogen-containing ring at the 7-position, which are essential for its antibacterial activity. This structural configuration classifies it as the prototypical member of the quinolone family and serves as the foundation for later fluoroquinolones.
- The antibiotic exerts its bactericidal action by inhibiting bacterial DNA synthesis. It specifically targets bacterial DNA gyrase (topoisomerase II), an enzyme essential for DNA replication and transcription. By binding to DNA gyrase, nalidixic acid induces double-stranded DNA breaks, leading to rapid bacterial cell death. This mechanism is particularly effective against gram-negative bacteria.
- Nalidixic acid demonstrates activity primarily against gram-negative bacteria, including Enterobacteriaceae such as Escherichia coli, Klebsiella species, and Proteus species. It is particularly effective in treating urinary tract infections caused by these organisms. However, its spectrum of activity is limited compared to later-generation quinolones and fluoroquinolones, as it lacks significant activity against gram-positive bacteria, Pseudomonas aeruginosa, and anaerobic organisms.
- The pharmacokinetic profile of nalidixic acid includes moderate oral bioavailability, rapid absorption, and widespread distribution in tissues, particularly in the urinary tract. It achieves high concentrations in the urine, making it effective for treating uncomplicated lower urinary tract infections. Nalidixic acid undergoes hepatic metabolism to active and inactive metabolites, with excretion occurring primarily through the kidneys. Its half-life ranges from 1.5 to 2 hours, necessitating frequent dosing (typically every 6 hours).
- Despite its efficacy, nalidixic acid is associated with potential adverse effects, including gastrointestinal disturbances (e.g., nausea, vomiting), central nervous system effects (e.g., headache, dizziness, and, rarely, seizures), and photosensitivity. Its use is also limited by the rapid development of bacterial resistance, particularly among gram-negative organisms.
