nalidixic

Nalidixic acid is a synthetic quinolone antibiotic and the earliest member of its class. Introduced in the mid-20th century, it served as a prototype for later, more potent fluoroquinolones and is now largely of historical and niche use. It is primarily active against certain Gram-negative enteric bacteria and has been used to treat uncomplicated urinary tract infections caused by susceptible organisms.

Mechanism of action is via inhibition of bacterial DNA gyrase (topoisomerase II) and, to a lesser extent, topoisomerase IV. This interference with DNA replication typically results in a bactericidal effect against susceptible strains, though activity can vary among species. The drug exhibits a relatively narrow spectrum, with good activity against many Enterobacteriaceae such as Escherichia coli, Proteus, Klebsiella, and some Salmonella and Shigella species, but limited activity against Gram-positive organisms and poor activity against Pseudomonas aeruginosa.

Pharmacokinetically, nalidixic acid is administered orally and has a moderate bioavailability with peak plasma levels occurring within a few hours. It is excreted primarily by renal pathways, with renal function influencing systemic exposure. Absorption can be influenced by food intake, and dosing reflects this variability.

Clinical use has diminished in many regions due to safety concerns and the rise of fluoroquinolones, which offer broader coverage and more favorable pharmacodynamics. Nalidixic acid remains of historical interest and may be encountered in certain settings or regions where older agents are still in use. Resistance to nalidixic acid can arise rapidly through mutations in target enzymes and, increasingly, through broader quinolone resistance mechanisms, limiting its effectiveness.

Adverse effects are generally nonspecific and may include gastrointestinal upset, skin rashes, and photosensitivity; rarer but more serious reactions and resistance development have contributed to its reduced role in modern therapy.