Nalidixic acid (tradenames Nevigramon, NegGram, Wintomylon and WIN 18,320) is the first of the synthetic

quinolone antibiotic A quinolone antibiotic is a member of a large group of broad-spectrum bacteriocidals that share a bicyclic core structure related to the substance 4-quinolone. They are used in human and veterinary medicine to treat bacterial infections, as we ...

s. In a technical sense, it is a naphthyridone, not a quinolone: its ring structure is a

1,8-naphthyridine 1,8-Naphthyridine is an organic compound with the formula C8H6N2. It is the most well-studied of the six isomeric naphthyridines, a subset of diazanaphthalenes with nitrogen in the separate rings. Enoxacin, nalidixic acid, and trovafloxacin are ...

nucleus that contains two nitrogen atoms, unlike quinoline, which has a single nitrogen atom. Synthetic quinolone antibiotics were discovered by George Lesher and coworkers as a byproduct of chloroquine manufacture in the 1960s; nalidixic acid itself was used clinically, starting in 1967. Nalidixic acid is effective primarily against Gram-negative bacteria, with minor anti- Gram-positive activity. In lower concentrations, it acts in a bacteriostatic manner; that is, it inhibits growth and reproduction. In higher concentrations, it is bactericidal, meaning that it kills bacteria instead of merely inhibiting their growth. It has historically been used for treating urinary tract infections, caused, for example, by ''

Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...

'', ''

Proteus In Greek mythology, Proteus (; Ancient Greek: Πρωτεύς, ''Prōteus'') is an early prophetic sea-god or god of rivers and oceanic bodies of water, one of several deities whom Homer calls the "Old Man of the Sea" ''(hálios gérôn)''. ...

'', ''

Shigella ''Shigella'' is a genus of bacteria that is Gram-negative, facultative anaerobic, non-spore-forming, nonmotile, rod-shaped, and genetically closely related to ''E. coli''. The genus is named after Kiyoshi Shiga, who first discovered it in 1897. ...

'', ''

Enterobacter ''Enterobacter'' is a genus of common Gram-negative, facultatively anaerobic, rod-shaped, non-spore-forming bacteria of the family Enterobacteriaceae. It is the type genus of the order Enterobacterales. Several strains of these bacteria are pat ...

'', and ''

Klebsiella ''Klebsiella'' is a genus of Gram-negative, oxidase-negative, rod-shaped bacteria with a prominent polysaccharide-based capsule. ''Klebsiella'' species are found everywhere in nature. This is thought to be due to distinct sublineages developin ...

''. It is no longer clinically used for this indication in the USA as less toxic and more effective agents are available. The marketing authorization for nalidixic acid has been suspended throughout the EU. It is also a tool in studies as a regulation of bacterial division. It selectively and reversibly blocks DNA replication in susceptible bacteria. Nalidixic acid and related antibiotics inhibit a subunit of

DNA gyrase DNA gyrase, or simply gyrase, is an enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrat ...

and topoisomerase IV and induce formation of cleavage complexes. It also inhibits the nicking-closing activity on the subunit of DNA gyrase that releases the positive binding stress on the supercoiled DNA.

Adverse effects

Hives, rash, intense itching, or fainting soon after a dose may be a sign of

anaphylaxis Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the follow ...

. Common adverse effects include rash, itchy skin, blurred or double vision, halos around lights, changes in color vision, nausea, vomiting, and diarrhea. Nalidixic acid may also cause

convulsion A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term ''convulsion'' is sometimes used as a s ...

s and

hyperglycemia Hyperglycemia is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a blood sugar level higher than 11.1 mmol/L (200 mg/dL), but symptoms may not start to become noticeable until even ...

, photosensitivity reactions, and sometimes haemolytic anaemia, thrombocytopenia or leukopenia. Particularly in

infants An infant or baby is the very young offspring of human beings. ''Infant'' (from the Latin word ''infans'', meaning 'unable to speak' or 'speechless') is a formal or specialised synonym for the common term ''baby''. The terms may also be used to ...

and young children, has been reported occasionally increased

intracranial pressure Intracranial pressure (ICP) is the pressure exerted by fluids such as cerebrospinal fluid (CSF) inside the skull and on the brain tissue. ICP is measured in millimeters of mercury (mmHg) and at rest, is normally 7–15 Millimeter of mercury, mmHg ...

Overdose

In case of overdose the patient experiences

headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...

, visual disturbances, balance disorders,

mental confusion In medicine, confusion is the quality or state of being bewildered or unclear. The term "acute mental confusion"

, metabolic acidosis and

seizures An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or neural oscillation, synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much o ...

Spectrum of bacterial susceptibility and resistance

'' Aeromonas hydrophila'', ''

Clostridium ''Clostridium'' is a genus of anaerobic, Gram-positive bacteria. Species of ''Clostridium'' inhabit soils and the intestinal tract of animals, including humans. This genus includes several significant human pathogens, including the causative ag ...

'' and ''

Haemophilus ''Haemophilus'' is a genus of Gram-negative, pleomorphic, coccobacilli bacteria belonging to the family Pasteurellaceae. While ''Haemophilus'' bacteria are typically small coccobacilli, they are categorized as pleomorphic bacteria because of ...

'' are generally susceptible to nalidixic acid, while other bacteria such as ''

Bifidobacteria ''Bifidobacterium'' is a genus of gram-positive, nonmotile, often branched anaerobic bacteria. They are ubiquitous inhabitants of the gastrointestinal tract though strains have been isolated from the vagina and mouth ('' B. dentium'') of mamma ...

'', '' Lactobacillus'', '' Pseudomonas'' and ''

Staphylococcus ''Staphylococcus'' is a genus of Gram-positive bacteria in the family Staphylococcaceae from the order Bacillales. Under the microscope, they appear spherical (cocci), and form in grape-like clusters. ''Staphylococcus'' species are facultative ...

'' are resistant. ''Salmonella enterica'' serovar Typhimurium strain ATCC14028 acquires nalidixic acid resistance when ''gyrB'' gene is mutated (strain IR715).

References

External links

* * {{Authority control Quinolone antibiotics Naphthyridines WIN compounds Carboxylic acids Topoisomerase inhibitors

Adverse effects

Overdose

Spectrum of bacterial susceptibility and resistance

See also

References

External links