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

quinolone antibiotic Quinolone antibiotics constitute 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 wel ...

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 Chloroquine is an antiparasitic medication that treats malaria. It works by increasing the levels of heme in the blood, a substance toxic to the malarial parasite. This kills the parasite and stops the infection from spreading. Certain types ...

manufacture in the 1960s; nalidixic acid itself was used clinically, starting in 1967. Nalidixic acid is effective primarily against

Gram-negative bacteria Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the Crystal violet, crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelo ...

, with minor anti-

Gram-positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. The Gram stain is ...

activity. In lower concentrations, it acts in a

bacteriostatic A bacteriostatic agent or bacteriostat, abbreviated Bstatic, is a biological or chemical agent that stops bacteria from reproducing, while not necessarily killing them otherwise. Depending on their application, bacteriostatic antibiotics, disinfec ...

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 A urinary tract infection (UTI) is an infection that affects a part of the urinary tract. Lower urinary tract infections may involve the bladder (cystitis) or urethra ( urethritis) while upper urinary tract infections affect the kidney (pye ...

, caused, for example, by ''

Escherichia coli ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Escherichia'' that is commonly fo ...

'', ''

Proteus In Greek mythology, Proteus ( ; ) 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''). Some who ascribe a specific domain to Prote ...

'', ''

Shigella ''Shigella'' is a genus of bacteria that is Gram negative, facultatively anaerobic, non–spore-forming, nonmotile, rod shaped, and is genetically nested within ''Escherichia''. The genus is named after Kiyoshi Shiga, who discovered it in 1 ...

'', ''

Enterobacter ''Enterobacter'' is a genus of common Gram-negative, Facultative anaerobic organism, facultatively anaerobic, bacillus (shape), rod-shaped, non-spore-forming bacteria of the family Enterobacteriaceae. Cultures are found in soil, water, sewage, ...

'', and ''

Klebsiella ''Klebsiella'' is a genus of Gram-negative, oxidase-negative, rod-shaped bacteria with a prominent polysaccharide-based capsule. ''Klebsiella'' is named after German-Swiss microbiologist Edwin Klebs (1834–1913). Carl Friedlander described ' ...

''. It is no longer clinically used for this indication in the US 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 within the class of topoisomerase and is a subclass of Type II topoisomerases that reduces topological strain in an ATP dependent manner while double-stranded DNA is being unwound by elongating RNA-po ...

and

topoisomerase IV Topoisomerase IV is one of two Type II topoisomerases in bacteria, the other being DNA gyrase. Like gyrase, topoisomerase IV is able to pass one double-strand of DNA through another double-strand of DNA, thereby changing the linking number of DNA ...

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 (Greek: 'up' + 'guarding') is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of the use of emergency medication on site. It typicall ...

. 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 often used as a synony ...

s and

hyperglycemia Hyperglycemia is a condition where unusually high amount of glucose is present in blood. It is defined as blood glucose level exceeding 6.9 mmol/L (125 mg/dL) after fasting for 8 hours or 10 mmol/L (180 mg/dL) 2 hours after eating. Blood gluc ...

, photosensitivity reactions, and sometimes hemolytic anemia, thrombocytopenia or leukopenia. Particularly in

infants In common terminology, a baby is the very young offspring of adult human beings, while infant (from the Latin word ''infans'', meaning 'baby' or 'child') is a formal or specialised synonym. The terms may also be used to refer to juveniles of ...

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 mmHg for a supine adu ...

Overdose

In case of overdose the patient experiences

headache A headache, also known as cephalalgia, 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 (mood), depression in those with severe ...

, visual disturbances, balance disorders,

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

, metabolic acidosis and

seizures A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

Spectrum of bacterial susceptibility and resistance

Aeromonas hydrophila ''Aeromonas hydrophila'' is a heterotrophic, Gram-negative, rod-shaped bacterium mainly found in areas with a warm climate. This bacterium can be found in fresh or brackish water. It can survive in aerobic and anaerobic environments, and can ...

'', ''

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

'' 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 ''Lactobacillus'' is a genus of gram-positive, aerotolerant anaerobes or microaerophilic, rod-shaped, non-spore-forming bacteria. Until 2020, the genus ''Lactobacillus'' comprised over 260 phylogenetically, ecologically, and metabolically div ...

'', ''

Pseudomonas ''Pseudomonas'' is a genus of Gram-negative bacteria belonging to the family Pseudomonadaceae in the class Gammaproteobacteria. The 348 members of the genus demonstrate a great deal of metabolic diversity and consequently are able to colonize a ...

'' and ''

Staphylococcus ''Staphylococcus'', from Ancient Greek σταφυλή (''staphulḗ''), meaning "bunch of grapes", and (''kókkos''), meaning "kernel" or " Kermes", is a genus of Gram-positive bacteria in the family Staphylococcaceae from the order Bacillale ...

'' 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