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PubMed1989

[Selective medium with nalidixic acid for isolating antibiotic-producing Actinomyces].

The majority of actinomycetes belonging to various genera proved to be resistant to nalidixic acid concentrations having an inhibitory effect on bacteria with trailing growth i.e. B. subtilis and B. mycoides. The bacteria prevented isolation of actinomycetes as pure cultures. The use of a selective medium with nalidixic acid for isolation of soil actinomycetes resulted in 20 per cent increase in the number of the actinomycetes isolated as pure cultures. Preliminary treatment of the soil samples with calcium carbonate under moist conditions followed by the inoculation to the medium with nalidixic acid made it possible to increase isolation of actinomycetes at most 100-fold. With this complex method 495 actinomycete cultures were isolated, their antibiotic properties were studied and their taxonomic position at the genus level was determined. The complex method including the preliminary treatment of soil samples with calcium carbonate followed by inoculation to the selective medium with nalidixic acid is efficient and may be recommended for screening organisms producing new antibiotics.

Actinomyces↗
PubMed1990

[Comparison of the in vitro antibacterial activity of ofloxacin and nalidixic acid].

The in-vitro activity of ofloxacin and nalidixic acid was determined against 964 Gram-negative and 66 Gram-positive isolates from different clinical specimens. Ofloxacin showed excellent in vitro activity against Enterobacteriaceae. The compound was significantly more potent than nalidixic acid against Pseudomonas spp. Acinetobacter spp. and Staphylococcus spp. We conclude from our studies that ofloxacin could be a valuable therapeutic agent with a variety of indications.

Acinetobacter↗
PubMedDate not supplied

[Effect of nalidixic acid and mitomycin C on growth and biosynthesis of extracellular proteins by Serratia marcescens].

The effect of various concentrations of nalidixic acid and mitomycin C on the dynamics of growth of Serratia marcescens and synthesis of endonuclease and other extracellular enzymes by it was studied. The synthesis of extracellular endonuclease was induced during inhibition of the cell division under the effect of nalidixic acid and mitomycin C. The induction of the endonuclease synthesis preceded the start of the division of the resistant cells which overcame the phase of the population retarded growth. The fermentation broth of the cells exposed to nalidixic acid and mitomycin C contained increased amounts of protein and possessed higher activities of chitin phosphodiesterase and phosphatase. It was shown by PAAG-electrophoresis with sodium dodecyl sulphate that the pattern of the extracellular proteins of S. marcescens undergone quantitative and qualitative changes under the effect of nalidixic acid and mitomycin C.

Bacterial Proteins↗
PubMed1996

Synthesis and in vitro investigations of nalidixic acid amides of amino acid esters as prodrugs.

For a new DDS of nalidixic acid (1) to overcome its therapeutic drawbacks, amides of glycine ethyl ester and the methyl esters of alanine, phenylalanine, leucine, isoleucine and valine, 2(a-f), were synthesized as prodrugs. The stability of the prepared prodrugs in pH 1.2, 7.4 and 80% human plasma was investigated and showed higher stability in the buffers than in the plasma. It was noticed that the reversion of the parent drug from the synthesized prodrugs occurred through two steps, the first was hydrolysis of the ester moiety with formation of nalidixic acid amides of the amino acids as intermediates. The second step was the hydrolysis of these intermediates to 1 and the corresponding amino acid. The prodrugs showed an increase in the lipophilicity compared with 1 as indicated from the log P values. The plasma protein binding potency was studied in vitro using BSA and revealed a decrease in the percentage bound in case of glycine and alanine derivatives (of low lipophilicity) and increase in the percentage bound of phenylalanine, leucine and isoleucine derivatives (of high lipophilicity). Lower binding potency and higher lipophilicity was observed in the case of valine derivative, that was suggested to be owed to some steric hindrance with the binding sites.

Amides↗
PubMed1979

Nalidixic acid causes a transient G1 arrest in the yeast Saccharomyces cerevisiae.

The addition of nalidixic acid to growing cells of the yeast Saccharomyces cerevisiae resulted in a transient depression in the rate of ribosomal precursor RNA production and a transient arrest of cells in G1. Protein synthesis rates were less affected. Lower concentrations of nalidixic acid also affected RNA synthesis and progression through G1 but had no effect on protein synthesis rates. We suggest that nalidixic acid has a primary effect on RNA synthesis leading to a G1 arrest.

Cell Cycle↗
PubMed1987

Plasmid-mediated resistance to nalidixic acid in Shigella dysenteriae type 1.

In an epidemic of shigellosis in southern Bangladesh the causal organism, Shigella dysenteriae type 1, was resistant to nalidixic acid as well as to co-trimoxazole (trimethoprimsulphamethoxazole) and ampicillin. The genes coding for resistance to nalidixic acid, but not those coding for resistance to co-trimoxazole or ampicillin, are located on a conjugative 20 megadalton plasmid. This epidemic is of particular importance because of the resistance to nalidixic acid, an antibiotic to which shigellae are seldom resistant, and because plasmids were previously thought not to mediate resistance to nalidixic acid.

Ampicillin↗
PubMed1994

Double-blind comparison of oral gentamicin and nalidixic acid in the treatment of acute shigellosis in children.

To compare the efficacy of oral gentamicin with nalidixic acid in the treatment of acute shigellosis, we studied, in a double blind-trial, 79 comparable children with bloody diarrhoea of less than 72 h duration. Of them Shigella spp. were isolated in 71 patients. Patients were randomly assigned to receive either gentamicin 30 mg/kg/day or nalidixic acid 60 mg/kg/day, both given orally in four equal doses for 5 days. Stool frequency differed significantly between the groups from day two until completion of the study. Treatment failure was observed in 14 (42 per cent) patients receiving oral gentamicin compared to none of those with nalidixic acid-sensitive strains of Shigella spp. (P = 0.0002). Although all the shigella isolates were sensitive to gentamicin in vitro, 19 (58 per cent) patients on gentamicin therapy failed to eliminate shigella organisms from stool, compared to none in the nalidixic acid treated group infected with nalidixic acid-sensitive Shigella spp. (P < 0.001). One patient in each group had a bacteriological relapse. We conclude that gentamicin given orally was therapeutically ineffective in the treatment of acute shigellosis.

Acute Disease↗
PubMed1997

Transient DNA relaxation in Escherichia coli induced by nalidixic acid.

We report here the transient relaxation of plasmid DNA by inhibitors of DNA gyrase in Escherichia coli. Relaxation of plasmid DNA in the presence of nalidixic acid, an inhibitor of the A subunit of DNA gyrase, lasted less than 60 min. The effect of nalidixic acid was not observed in a nalA26 mutant, a strain resistant to nalidixic acid due to a mutation in the gyrA gene. Novobiocin, whose target is the B subunit of DNA gyrase, also caused transient DNA relaxation. Resupercoiling of relaxed DNA in the presence of nalidixic acid was inhibited by pretreatment of the cells with chloramphenicol. As mutations of both the rpoH and recA genes did not affect the resupercoiling reaction, this step seems to require protein synthesis that is independent of both heat shock and SOS responses.

Bacterial Proteins↗
PubMed2002

Nalidixic acid susceptibility test to screen ciprofloxacin resistance in Salmonella typhi.

BACKGROUND & OBJECTIVES: Clinical non response to ciprofloxacin therapy in enteric fever is increasingly being encountered in endemic areas possibly due to the increase in the levels of resistance to ciprofloxacin in Salmonella typhi. The antimicrobial susceptibility tests for S. typhi performed by the disc diffusion method using NCCLS breakpoints fail to detect the increasing MIC of ciprofloxacin, leading to the inappropriate treatment of enteric fever with ciprofloxacin. We explored the possibility of testing S. typhi strains for their susceptibility to nalidixic acid by disc diffusion method as a marker for high MIC to ciprofloxacin. METHODS: Isolates (94) of S. typhi were tested for in vitro susceptibility to nalidixic acid (30 micrograms) and ciprofloxacin (5 micrograms) by disc diffusion method using NCCLS guidelines. The MIC of these strains to ciprofloxacin was also determined by E-test. RESULTS: Of the 94 strains tested, 56 were NARST (nalidixic acid resistant S. typhi) and 34 were NASST (nalidixic acid sensitive S. typhi). MIC of ciprofloxacin in the NASST strains varied from 0.002-0.125 microgram/ml while that for NARST strains varied from 0.023-0.38 microgram/ml, which is about 10-folds higher than that of NASST strains. INTERPRETATION & CONCLUSION: Our study shows that resistance to nalidixic acid is associated with a high MIC to ciprofloxacin in S. typhi. These strains would have been interpreted as ciprofloxacin sensitive by routine antimicrobial susceptibility testing by disc diffusion method. Hence screening of S. typhi isolates by the nalidixic acid susceptibility test may be incorporated in a clinical bacteriology laboratory to alert the treating physicians of the possibility of the failure to ciprofloxacin therapy in patients with enteric fever.

Anti-Infective Agents↗
PubMed1988

Nalidixic acid plus sodium citrate twice daily in the treatment of acute urinary tract infection. Swedish Collaborative Study Group.

Negram-Citrat (0.66 g nalidixic acid plus 4 g sodium citrate, NAC) twice daily for five days was evaluated in 257 women with symptoms of acute lower urinary tract infection and nalidixic acid sensitive bacteriuria. At two days post-treatment 85% of the patients were abacteriuric while nalidixic acid resistant Escherichia coli bacteriuria was present in five %. Side effects of NAC were usually mild and transient and resulted in interruption of medication in three % of the patients and visual disturbances were volunteered by 1.6%. At follow-up one month after treatment bacteriuria had recurred in 18% of the patients immediately cured, thus resulting in an overall success rate of 70%. Of the 35 recurring strains three (1 E. coli, 2 Staphylococcus epidermidis) were nalidixic acid resistant.

4-Quinolones↗
PubMed1980

Non-mutagenic genotoxicants: novobiocin and nalidixic acid, 2 inhibitors of DNA gyrase.

The antimicrobial agents nalidixic acid and novobiocin, both inhibitors of DNA gyrase, preferentially inhibit the growth of DNA repair-deficient Escherichia coli, Salmonella typhimurium and Bacillus subtilis. On the other hand, these agents exhibit no demonstrable mutagenicity for S. typhimurium and E. coli even when tested under conditions designed to take the metabolic properties of these agents into consideration. Novobiocin and nalidixic acid are widely used in animal and human medicine and further studies to assess their genetic and carcinogenic potentials appear to be in order.

Bacillus subtilis↗
PubMed1975

Nalidixic acid and macromolecular metabolism in Tetrahymena pyriformis: effects on protein synthesis.

A study on the effect of nalidixic acid on macromolecular metabolism, particularly of protein, in Tetrahymena pyriformis was performed. It was shown that the compound is a potent inhibitor of deoxyribonucleic acid, ribonucleic acid, and protein synthesis for this organism. A conspicuous breakdown of polysomes, accompanied by the accumulation of 80S ribosomes, occurred in cells incubated for 10 min with the drug; polysome formation was prevented. The accumulating 80S particles were shown to be run-off ribosomal units. The incorporation of amino acids by a cell-free system is not affected by nalidixic acid. In nonproliferating cells the incorporation was also not prevented, unless the cells were previously incubated with the drug. These results are discussed in terms of the possible mechanism of action of nalidixic acid in T. pyriformis.

Animals↗
PubMedDate not supplied

Nalidixic acid in children: retrospective matched controlled study for cartilage toxicity.

The new fluoroquinolones allow effective oral therapy of infections due to Pseudomonas aeruginosa. Studies on efficacy and safety of these promising agents are not recommended in childhood because of cartilage toxicity which has been observed in growing animals. However, the first quinolone antimicrobial, nalidixic acid, showed identical arthropathic effects in young animals and is licensed for paediatric use. A review of the hospital charts revealed 11 patients who had received nalidixic acid over nine to 600 days and were available for control examination three to 12 years later. For each nalidixic acid case a carefully selected matched pair, who had never received nalidixic acid, was identically analyzed. Three patients from the nalidixic acid and three from the control group reported arthralgia, which was judged to have no relation to drug therapy. Growth curve and both functional and radiological joint findings were completely normal in all cases. These results suggest that quinolone-associated arthropathy does not occur in children, even after long-term therapy.

Cartilage Diseases↗
PubMed2006

Nalidixic acid resistance in Salmonella strains with decreased susceptibility to ciprofloxacin isolated from humans in Turkey.

The aim of this study was to evaluate the value of nalidixic acid resistance as an indicator of decreased susceptibility to ciprofloxacin (MIC = 0.125 - 1 mg/L) in Salmonella isolates from humans (n = 620) in Turkey. One isolate was found to be resistant, and the remaining isolates were susceptible to ciprofloxacin with the Clinical and Laboratory Standards Institute breakpoints; however, 75 isolates (12.1%) had decreased susceptibility. Resistance to nalidixic acid was observed in 76 (12.3%) isolates in the disk diffusion test. Seventy-four of these isolates had decreased susceptibility, one was fully resistant, and one isolate was susceptible to ciprofloxacin. One isolate with decreased susceptibility to ciprofloxacin was intermediate to nalidixic acid. Screening with 30-microg nalidixic acid disks had a sensitivity of 98.6% and a specificity of 99.8% for determination of decreased susceptibility to ciprofloxacin.

Anti-Bacterial Agents↗
PubMed1975

Action of Nalidixic Acid on Chloroplast Replication in Euglena gracilis.

The role of light in nalidixic acid bleaching of Euglena gracilis var. bacillaris was investigated. The kinetics of loss of the chloroplast-associated DNA and the sensitivity of chloroplast replication to ultraviolet light was followed during treatment with nalidixic acid. By using the mutant P(4)ZUL, and 3-(3,4-dichlorophenyl)-, 1-dimethylurea, it was demonstrated that the requirement for light was a functioning photosynthetic electron transport system. Ultracentifugal analysis showed a substantial decrease in chloroplast-associated DNA after 6 hours of treatment with nalidixic acid. Ultraviolet target analysis revealed that the number of chloroplast genomes per cell had been reduced. The possible role of light and implications of the reduction in chloroplast genomes for chloroplast replication are discussed.

Journal Article↗
PubMed1998

[Growing incidence of nalidixic acid resistance and sensitivity to quinolones in Salmonella typhimurium strains isolated from man or animal].

To determine the prevalence of quinolone resistance in Salmonella typhimurium strains from humans or animals (cattle, poultry, swine), the S. typhimurium strains isolated at a teaching hospital and at the central veterinary laboratory of the same district between January 1, 1995, and December 31, 1996 were studied. Susceptibility to nalidixic acid was determined using the disk diffusion method. Strains with decreased susceptibility to nalidixic acid were subjected to minimal inhibitory concentration (MIC) determination for pefloxacin, ofloxacin, ciprofloxacin, norfloxacin, levofloxacin, and grepafloxacin. Decreased susceptibility to nalidixic acid was demonstrated for 41 of the 309 strains studied and increased from 8.5% in 1995 to 18.6% in 1996. MIC90 values of fluoroquinolones for strains with decreased susceptibility to nalidixic acid were lower than 1 mg/L, which is the cutoff above which a strain is classified as susceptible, but were higher than for strains that were susceptible to nalidixic acid. These low levels of resistance may be the first step in selection of mutant strains with high levels of resistance to fluoroquinolones. This warrants continued monitoring of resistance of Salmonella to fluoroquinolones.

Animals↗