Nalidixic Acid in Urinary Infections

Abstract

Nalidixic acid (" negram ") is one of a new series of 1,8-naphthyridine derivatives with antibacterial properties which have been synthesized by Lesher et al. (1962). Chemically it is 1-ethyl-7-methyl-1,8-naphthyridine-4-one-3-carboxylic mg./kg. throughout pregnancy and for one week afterwards. On these dose levels there were no adverse effects on the course of pregnancy or on the growth and survival capacities of the offspring. At the highest dose level of 300 mg./kg., which is that approaching the limit of rat tolerance, there was maternal mortality and interference with the course of pregnancy of the survivors. At the end of the study there was no evidence of gross disease among survivors at all dose levels. Doses of 200 mg. /kg./day were given to three pregnant monkeys. One animal was medicated for two months and others for one month prior to delivery. The drug was given to all animals during the first two weeks post partum. No untoward reactions were noted. Each mother delivered one normal offspring, and mothers and offspring were observed for three months after stopping medication and appeared normal during this time. The body weight of the mothers was normal throughout the study. The Somers test has been repeated using pregnant rabbits; no teratogenic changes or other congenital malformations were observed. Human VolunteersThe drug was given to 13 men and 9 women four times a day for up to 180 successive days. The maximum sustained dose was 8 g./day for 56 days. An initial single 4-g. dose was well tolerated by most volunteers. Clinical TrialMid-stream specimens of urine were collected in both sexes except when a specimen was taken at the time of cystoscopy. The urines were refrigerated and cultured within an hour of arrival in the laboratory.

The Response of <i>Escherichia col</i><i>i</i> to Nalidixic Acid

“…It is well known from early work on the compound [5][6][7] that the activity of nalidix-ic acid in vitro is affected by the density of the bacterial inoculum and by the ready emergence of bacterial resistance, and clini cal trials [5,[7][8][9][10][11][12][13][14] have confirmed that re sistance can also emerge during nalidixic acid therapy. However, the frequency with which such resistance is encountered in clin ical practice has been the subject of con troversy [15] and little is known of the con ditions which favour or oppose the emer gence of resistance.…”

Nalidixic Acid: Microbiological and Clinical Studies on Urinary Infections in Children

“…High urinary levels were obtained in human volunteers following moderate oral dosage. There was little ill-effect and the drug was used successfully in a series of clinical trials (Lishman and Swinney, 1963;Barlow, 1963;Ward-McQuaid, Jichlinski, and Macis, 1963). It has come to be regarded as an effective antibacterial agent for urinary infections.…”

Tissue Concentration of Nalidixic Acid in Chronic Pyelonephritis

“…Nalidixic acid (Negram) has been used to treat urinary-tract infections (Lishman and Swinney, 1963;Barlow, 1963;Jameson and Swinney, 1963;Ward-McQuaid et al, 1963;Swinney, 1964). The results obtained were encouraging and led to the study of the tissue concentration of nalidix acid in the pyelonephritie kidney.…”