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Following oral administration, NegGram is rapidly absorbed from the gastrointestinal tract, partially metabolized in the liver, and rapidly excreted through the kidneys. Unchanged nalidixic acid appears in the urine along with an active metabolite, hydroxynalidixic acid, which has antibacterial activity similar to that of nalidixic acid. Other metabolites include glucuronic acid conjugates of nalidixic acid and hydroxy nalidixic acid, and the dicarboxylic acid derivative. The hydroxy metabolite represents 30 percent of the biologically active drug in the blood and 85 percent in the urine. Peak serum levels of active drug average approximately 20 mcg to 40 mcg per mL (90 percent protein bound), one to two hours after administration of a 1 g dose to a fasting normal individual, with a half-life of about 90 minutes. Peak urine levels of active drug average approximately 150 mcg to 200 mcg per mL, three to four hours after administration, with a half-life of about six hours. Approximately four percent of NegGram is excreted in the feces. Traces of nalidixic acid were found in blood and urine of an infant whose mother had received the drug during the last trimester of pregnancy. (See PRECAUTIONS - DRUG INTERACTIONS.)


NegGram has marked antibacterial activity against gram-negative bacteria including Enterobacter species, Escherichia coli, Morganella Morganii; Proteus Mirabilis, Proteus vulgaris, and Providencia rettgeri. Pseudomonas species are generally resistant to the drug. NegGram is bactericidal and is effective over the entire urinary pH range. Conventional chromosomal resistance to NegGram taken in full dosage has been reported to emerge in approximately 2 to 14 percent of patients during treatment; however, bacterial resistance to NegGram has not been shown to be transferable via R factor.

Susceptibility Test

Diffusion Techniques

Quantitative methods that require measurement of zone diameters give the most precise estimates of antibacterial susceptibility. One such procedure recommended for use with a disc containing 30 mcg of nalidixic acid is the National Committee for Clinical Laboratory Standards (NCCLS) approved procedure. Only organisms from urinary tract infections should be tested. Results of laboratory tests using 30 mcg nalidixic acid discs should be interpreted using the following criteria:

Zone Diameter (mm) Interpretation
≥ 19 (S) Susceptible
14-18 (I) Intermediate
≤ 13 (R) Resistant

Dilution Techniques: Broth and agar dilution methods, such as those recommended by the NCCLS, may be used to determine the minimum inhibitory concentration (MIC) of nalidixic acid. MIC test results should be interpreted according to the following criteria:

MIC (mcg/mL) Interpretation
≤16 (S) Susceptible
≥32 (R) Resistant

For any susceptibility test, a report of “susceptible” indicates that the pathogen is likely to respond to nalidixic acid therapy. A report of “resistant” indicates that the pathogen is not likely to respond. A report of “intermediate” generally indicates that the test result is equivocal.

The Quality Control strains should have the following assigned daily ranges for nalidixic acid:

QC Strains

E. Coli

(ATCC 25922)

Disc Zone Diameter


MIC (mcg/mL)



NegGram (nalidixic acid) and related drugs have been shown to cause arthropathy in juvenile animals of most species tested. (See WARNINGS.)

Long-term administration of nalidixic acid to rats resulted in retinal degeneration and cataracts.

Hydroxynalidixic acid, the principal metabolite of NegGram, did not produce any oculotoxic effects at any dosage level in seven species of animals including three primate species. However, oral administration of this metabolite in high doses has been shown to have oculotoxic potential, namely in dogs and cats where it produced retinal degeneration upon prolonged administration leading, in some cases, to blindness.

In experiments with NegGram itself, little if any such activity could be elicited in either dogs or cats. Sensitivity to CNS side effects in these species limited the doses of NegGram that could be used; this factor, together with a low conversion rate to the hydroxy metabolite in these species, may explain the absence of these effects.

Last reviewed on RxList: 6/10/2011
This monograph has been modified to include the generic and brand name in many instances.

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