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PubMed1986

Influence of ofloxacin, norfloxacin, nalidixic acid, pyromidic acid and pipemidic acid on human gamma-interferon production and blastogenesis.

Several new quinolone derivatives were investigated for their influence on human lymphocyte blastogenesis and gamma-interferon production following concanavalin A stimulation. All the antimicrobials induced inhibition of lymphocyte DNA synthesis. The gamma-interferon measurements showed that nalidixic acid and norfloxacin have a negative influence on lymphokine production and release.

Adult↗
PubMed1981

Comparative efficacy and safety of nalidixic acid versus trimethoprim/sulfamethoxazole in treatment of acute urinary tract infections in college-age women.

One hundred and thirty-five college-age women with acute urinary tract infections caused by gram-negative Enterobacteriaceae were treated by random allocation with either nalidixic acid (NA), 1 g every 6 h for 7 days, or trimethoprim/sulfamethoxazole (TMP/SMZ), 160/800 mg every 12 h for 10 days. The clinical and bacteriological cure rates were 98.0% in each group on the last day of therapy. At 1 and 4 week posttherapy, both the clinical and bacteriological cure rates for NA declined to 90.0 and 74.0% respectively; for TMP/SMZ, they declined to 93.0 and 72.0% respectively. By 4 weeks posttherapy, 96.0% of the TMP/SMZ group and 93.0% of the NA group had remained free of the initial urinary pathogens. Neither drug was associated with emergence of resistant bacterial mutants in urine. The antibody-coated bacteria tested (ACBT) localized 31.5% of the infections of the kidney and 67.7% to the bladder. Upper tract symptoms did not correlate with the presence of a positive ACBT. The response to therapy was similar for the two regimens regardless of ACBT results. After treatment, the emergence of resistant Enterobacteriaceae in fecal flora was 1.1% in the NA group and 2.3% in the TMP/SMZ group. The incidences of drug reactions were 7.0% with NA and 6.3% and TMP/SMZ.

Adult↗
PubMed1989

Efficacy of nalidixic acid in the treatment of acute bloody diarrhea.

Of sixty four children (mean age 20.1 +/- 1.2 mo) with acute bloody diarrhea and high fever, 47 had infection with non-typhoidal Salmonella (NTS) (20), Shigella (15) and enteropathogenic E. coli (EPEC) (12) and were treated with nalidixic acid (NA). The mean duration (h) of presence of macroscopic blood in the stool following institution of treatment was significantly shorter (p less than 0.05) in those with EPEC (11.5 +/- 4.9) as compared to NTS (30.4 +/- 15.4) or Shigella groups (22.9 +/- 15.6). The number of children having less than or equal to 50% reduction in stool frequency within 72 h was: NTS (17); Shigella (14); EPEC (10). Negative stool cultures on day 5 were obtained in all patients with Shigella and EPEC and 16 (80%) of those with NTS. Two patients with NTS and one with EPEC failed to respond to NA.

Acute Disease↗
PubMed2005

Adsorption of the quinolone antibiotic nalidixic acid onto anion-exchange and neutral polymers.

Pharmaceutical products are being found in surface and ground waters around the world. While the consequences to human health are unknown, it is suspected that these contaminants adversely alter aquatic ecosystems. This study presents adsorption results for one pharmaceutical product, nalidixic acid (NA), on neutral and anion-exchange polymers at three pH values. The adsorption of NA below and above its pKa of approximately 6 on polymers with different matrices, forms, and degrees of polarity were evaluated. By comparing the Freundlich constants KF and n, the results show that the neutral form of NA adsorbs to a greater extent on neutral polymers, and that the anionic form of NA adsorbs more to anion-exchange polymers. Also, results of the adsorption experiments suggest that aromatic ring interactions between NA and the surface of both neutral and anion-exchange polymers are important in the adsorption process. These results have important implications for the treatment of pharmaceutical-contaminated water, as many pharmaceutical contaminants are ionizable and have aromatic rings in their structure. This study illustrates the importance of pH and sorbate and sorbent structure in considering polymer sorption for treatment of pharmaceutical-contaminated aqueous systems.

Adsorption↗
PubMed1969

Specific loss of newly replicated deoxyribonucleic acid in nalidixic acid-treated Bacillus subtilis 168.

Bacillus subtilis 168 thyA, thyB cells degrade and lose from 20 to 30% of their deoxyribonucleic acid (DNA) in 3.5 hr of exposure to 20 mug of nalidixic acid per ml. Degradation appears to be initiated at the replication point and to proceed sequentially along the chromosome from the most recently synthesized DNA to "older" DNA. Both DNA strands appear to be degraded equally, and essentially all of the products of degradation are soluble in cold acid.

Bacillus subtilis↗
PubMedDate not supplied

Outbreak of dysentery due to nalidixic acid resistant S. dysenteriae 1 at Agartala, Tripura: a hospital based study.

During the epidemic of bacillary dysentery at Agartala, Tripura, a total of 62 hospitalized patients suffering from diarrhoeal diseases were studied during the later part (11-16 June, 1988) of the epidemic. Principal features of Shigellosis cases were discussed. Of these 62 cases investigated, 19(30.6%) cases had the mucoid diarrhoea. From them S.dysenteriae type 1 and S.flexneri had been recovered from 31.6% and 10.5% cases, respectively. All the strains of S.dysenteriae type 1 isolated during the period of investigation were resistant to nalidixic acid.

Disease Outbreaks↗
PubMed1976

Effects of 3'-fluorothymidine, nalidixic acid, and mitomycin C on temperature-sensitive mutants of the DNA polymerase of phage T4.

The temperature-sensitive DNA polymerase mutator mutants A58 and L98 are less inhibited by 3'-Fluorothymidine than the T4 wild type and the antimutator mutant CB121, in consequence of the assumed differences between the polymerase-associated exonuclease activities. This interpretation is confirmed by results with nalidixic acid and mitomycin C. The use of systems of different temperature-sensitive mutants of one or more genes is proposed for 1.) investigating the mode of action of drugs, 2.) studies on the mechanism of enzyme action and the functions affected in temperature-sensitive enzymes, and 3.) for enzyme-specific drug screening.

Chloramphenicol↗
PubMed1983

Researches on antibacterial and antifungal agents. I. Analogs of nalidixic acid with a pyrrole moiety.

The synthesis and antibacterial activities of 4-hydroxyquinoline-3-carboxylic acid and 1,4-dihydro-1-ethyl-4-oxoquinoline-3-carboxylic acid containing a pyrrole or 2,5-dimethylpyrrole group at 6 position are reported. Reaction of 1-(4-aminophenyl)pyrrole or 2,5-dimethyl-1-(4-aminophenyl)-pyrrole with ethoxymethylenemalonate diethyl ester (EMME) afforded the related pyrroleanilinomethylenemalonates, which were subjected to thermal cyclization to give the required quinoline derivatives. These compounds on ethylation furnished at last the quinolonecarboxylic analogs of nalidixic acid.

Anti-Bacterial Agents↗
PubMed2000

Distinct mechanisms of guanine-specific DNA photodamage induced by nalidixic acid and fluoroquinolone antibacterials.

Fluoroquinolone antibacterials, which have been used for the treatment of a variety of infectious diseases, are reported to be photocarcinogenic. We investigated the mechanisms of DNA damage by UVA radiation (365 nm) plus fluoroquinolone antibacterials using 32P-labeled DNA fragments obtained from the human c-Ha-ras-1 proto-oncogene and the p53 tumor suppressor gene. Photocarcinogenic nalidixic acid (NA), which is an old member of synthetic quinolone antibacterials, caused DNA damage specifically at 5'-GG-3' sequences, whereas lomefloxacin (LFLX) did not exhibit the site preference for consecutive guanines. LFLX-induced DNA photodamage was inhibited by sodium azide and enhanced in D2O, suggesting that singlet oxygen plays the key role in the DNA damage. LFLX plus UVA induced the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) depending on LFLX concentrations, and 8-oxodG formation was enhanced in single-stranded DNA. In contrast, NA induced larger amounts of 8-oxodG in double-stranded DNA. ESR spin destruction method revealed that NA induced DNA photodamage through electron transfer but LFLX did not. These findings indicate that DNA damage induced by photoactivated LFLX and NA plays an important role in expression of their photocarcinogenicity.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1987

Regulatory role of recF in the SOS response of Escherichia coli: impaired induction of SOS genes by UV irradiation and nalidixic acid in a recF mutant.

We isolated a new recF mutant of Escherichia coli K-12 by insertion of transposon Tn5 into the recF gene. This recF400::Tn5 allele displayed the same phenotypic characteristics as the classic recF143 mutation. By using Mu d(Ap lac) fusions, the induction of nine SOS genes, including recA, umuC, dinA, dinB, dinD, dinF, recN, and sulA, by UV irradiation and nalidixic acid was examined. Induction of eight genes by the two agents was impaired by recF400::Tn5 to different extents. The ninth fused SOS gene, dinF, was no longer inducible by UV when combined with recF400::Tn5. The generally impaired SOS response in recF strains did not result from weak induction of recA protein synthesis, since a recA operator-constitutive mutation did not alleviate the inhibitory effect of the recF mutation. The results suggest that recF plays a regulatory role in the SOS response. It is proposed that this role is to optimize the signal usage by recA protein to become a protease.

Bacterial Proteins↗
PubMed1983

[Nalidixic acid: urinary levels during short-term therapy with reduced doses].

The acute inflammation of the lower afferent urinary tract is a superficial mucosal infection so long as structural and functional anomalies are excluded. A single or brief administration of antibacterially active substances with high urine concentrations can shorten uncomplicated attacks of infection and diminish the symptoms. The investigation of the urinary concentration of biologically active metabolites after administration of a daily dose of 2 g nalidixic acid revealed values which ensure that the minimum inhibitory concentrations in the afferent urinary tract are exceeded. The different responsiveness of the fluorimetric and microbiological methods applied for determination of the biologically active substances in urine led to results which were well correlated.

Adult↗
PubMed1971

Some effects of nalidixic acid on conjugation in Escherichia coli K-12.

The role of deoxyribonucleic acid (DNA) synthesis in the Escherichia coli conjugation system has been studied using nalidixic acid (NAL) to specifically inhibit DNA synthesis in matings between reciprocal combinations of male (Hfr) and female (F(-)) mutants resistant and sensitive to NAL; the physiological action of NAL on the strains utilized was also studied. Matings between combinations of mutants resistant (Nal(r)) and sensitive (Nal(s)) to NAL allow various parental functions to be established: pair formation studies show that the female cells are responsible for the slight decrease in pair formation when NAL is present in Hfr(Nal(s)) x F(-) (Nal(s)) matings. Preformed mating pairs are stable in the presence of NAL. In matings between Hfr(Nal(s)) and F(-)(Nal(r)), the transfer gradient constant increases linearly with low NAL concentration (0.1 to 0.6 mug of NAL per ml). Higher concentrations of NAL (5 mug/ml) act on Nal(s) males to rapidly stop chromosome transfer; under these conditions, however, DNA degradation is unmeasurable as determined from single-strand nicking in the male cells. This result is consistent with a model for chromosome transfer which requires DNA synthesis in the male cell. Inhibition of DNA synthesis (by 85%) in the female has no effect on conjugal chromosome transfer. High concentrations of NAL (>20 mug/ml) produce slight inhibition in chromosome transfer for the Hfr(Nal(r)) x F(-)(Nal(r)) mating tested; this effect is probably caused by action of NAL on the male. The inhibition of chromosomal transfer by NAL appears to be irreversible in the normal sense. A pulse of NAL, applied during transfer, immediately stops the transfer which is in progress. On removal of the NAL block, the temporal appearance of recombinants is consistent with the idea that a new round of transfer has commenced from the sex factor location on the male chromosome.

Carbon Isotopes↗
PubMed1998

Isolation of nalidixic acid resistant Campylobacters from cases of paediatric diarrhoea in Chennai.

A short term investigation on the Campylobacter enteritis among children under 10 years of age was carried out in Chennai. The study revealed an isolation rate of 11 per cent in 100 patients suffering from acute diarrhoea comprising C. jejuni (8%) and C. coli. (3%). Among the two culture methods used, the candle jar method was found to be superior to plastic bag incubation system in recovering campylobacters on charcoal cefeperazone deoxycholate agar. While all the isolates were sensitive to ciprofloxacin, all of them exhibited resistance to nalidixic acid.

Anti-Infective Agents↗
PubMed2006

Predictive efficacy of nalidixic acid resistance as a marker of fluoroquinolone resistance in Salmonella enterica var Typhi.

BACKGROUND AND OBJECTIVES: Resistance in Salmonella enterica var Typhi (S. Typhi) to chloramphenicol, amoxicillin and co-trimoxazole has posed a challenge to treatment of typhoid fever. Ciprofloxacin has been the empirical therapy of choice, but the recent increase in minimum inhibitory concentration (MIC) to ciprofloxacin in S. Typhi, not detectable by disc diffusion (DD) tests, may result in delayed response and serious complications. Nalidixic acid (NA) resistance has been used as an indirect evidence of increased ciprofloxacin MIC in S. Typhi. We evaluated the predictive value of NA resistance for fluoroquinolone resistance in clinical isolates of S. Typhi. METHODS: A total of 70 clinical isolates of S. Typhi were tested for antimicrobial susceptibility according to the National Committee for Clinical Laboratory Standards (NCCLS) method. MIC to fluoroquinolones was carried out by the agar dilution method. RESULTS: Thirteen (18.6 %) isolates were resistant to amoxicillin, chloramphenicol and cotrimoxazole; all were sensitive to ciprofloxacin and cefotaxime. Fifty (71.4%) were resistant to NA. Nineteen (27.1 %) isolates were resistant to ciprofloxacin by MIC tests. The MIC for ciprofloxacin was 0.03-4 microg/ml for NA(S) and 0.25-4 microg/ml for NA(R) isolates. NA susceptibility showed a predictive value of 95 per cent for ciprofloxacin susceptibility while NA resistance had a predictive value of 36 per cent for ciprofloxacin resistance. Thirty isolates studied were sensitive to gatifloxacin; MIC values were 0.03-0.5 microg/ml for NA(S) and 0.25-0.5 microg/ml for NA(R) isolates. INTERPRETATION AND CONCLUSION: NA susceptibility was a good marker for fluoroquinolone susceptibility but NA resistance had a poor predictive value for ciprofloxacin resistance. NA resistant isolates should be tested for ciprofloxacin MIC before deciding a change in therapeutic regimen. Higher MIC for gatifloxacin was also noticed in NA resistant isolates.

Biomarkers↗
PubMedDate not supplied

Assessment of the effects of ciprofloxacin and nalidixic acid on cerebral blood flow and metabolism in healthy subjects by positron emission tomography.

STUDY OBJECTIVES: The mechanism by which the fluorinated quinolones produce central nervous system effects is unknown. Using positron emission tomography (PET), we evaluated the effects of two quinolones on brain blood flow as well as on oxygen and glucose metabolism. These determinations were done in conjunction with ophthalmologic and neuro-ophthalmologic testing. DESIGN: Randomized, double-blind, placebo-controlled, 7-day course of ciprofloxacin 750 mg (C750) or 500 mg (C500) every 12 hours, or nalidixic acid (NA) 1 g every 6 hours. POPULATION: Twenty-four healthy male volunteers, six in each treatment arm. RESULTS: [table: see text] CONCLUSIONS: Compared with baseline values, NA significantly reduced brain glucose uptake, whereas C500, C750, and placebo produced no detectable effect. No compound significantly altered brain blood flow or oxygen metabolism compared with baseline or other treatments. No significant effect on electroretinographic, electro-oculographic, or other neuro-ophthalmologic tests was observed.

Adolescent↗