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Treatment of bacillary dysentery: a comparison between enoxacin and nalidixic acid.

A prospective randomized study has been conducted in Rwanda to compare the efficacy of enoxacin versus nalidixic acid for the treatment of bacillary dysentery in adults. Seventeen patients received nalidixic acid and 21 received enoxacin. All isolates (37 shigella, 1 campylobacter) were sensitive in vitro to the two drugs. All patients showed a favourable clinical and bacteriological response and the results obtained with both drugs were comparable. Enoxacin seems to be a good alternative to nalidixic acid for bacillary dysentery due to multiresistant shigella.

Adult↗

Differential susceptibility of Aeromonas hydrophila and Enterobacteriaceae to nalidixic acid.

The susceptibility of 49 strains of Aeromonas hydrophila and 77 strains of Enterobacteriaceae towards nalidixic acid was compared by tube dilution and agar diffusion methods. A higher susceptibility was exhibited by Aerom. hydrophila and no overlap in MICs was found for strains of the two groups of microorganisms. Discs containing 0.25 microgram of nalidixic acid produced measurable zones of growth inhibition with Aerom. hydrophila and no zones with the Enterobacteriaceae. The use of a disc with 0.25 microgram of nalidixic acid for the primary differentiation of strains of Aerom. hydrophila from those of the Enterobacteriaceae with similar biochemical properties is suggested.

Aeromonas↗

Mechanism of action of nalidixic acid on Escherichia coli. IV. Effects on the stability of cellular constituents.

Cook, Thomas M. (Sterling-Winthrop Research Institute, Rensselaer, N.Y.), William H. Deitz, and William A. Goss. Mechanism of action of nalidixic acid on Escherichia coli. IV. Effects on the stability of cellular constituents. J. Bacteriol. 91:774-779. 1996.-Treatment of Escherichia coli 15TAU with nalidixic acid resulted in degradation of the nucleic acids of the cells, whereas protein was unaffected. Deoxyribonucleic acid (DNA) degradation appeared to be more extensive than ribonucleic acid degradation during periods of comparable bactericidal action. The onset of DNA degradation was evident prior to a measurable bactericidal effect. However, within the range of 2 to 20%, DNA degradation was accompanied by a decrease in viable cell numbers. Degradation of DNA to acid-soluble material occurred only under conditions permitting the bactericidal action of nalidixic acid. Arrest of the bactericidal action of nalidixic acid by the addition of dinitrophenol or chloramphenicol also inhibited DNA degradation. The acid-soluble products, which were excreted into the medium, have not been characterized completely, but probably were not phosphorylated.

Bacterial Proteins↗

Norfloxacin versus nalidixic acid in the treatment of urinary tract infections.

Norfloxacin (MK-0366), a new oral quinoline antimicrobial agent, was shown to have much wider spectrum than nalidixic acid which includes Pseudomonas aeruginosa and gram-positive cocci. Many studies have been undertaken to determine the clinical effectiveness of norfloxacin in patients with urinary tract infections. Seventy-two patients with urinary tract infections caused by sensitivity strains were treated with either 400 mg norfloxacin per 12 hours or nalidixic acid 500 mg every 8 hours for 7 days. Follow-up examinations showed that norfloxacin is more effective than nalidixic acid, 93% and 83%, respectively, for the eradication of bacteriuria and symptoms. Adverse reactions due to norfloxacin were fewer and minor, and the tolerability seemed to be better than that of nalidixic acid.

Adult↗

Emergence of nalidixic acid resistance in Shigella sonnei isolated from patients having acute diarrheal disease: report from eastern province of Saudi Arabia.

During the 5 years of the study period (October 1999-October 2003), 110 strains of Shigella were isolated from fecal samples of patients having acute diarrheal diseases. Shigella sonnei phase 1 was the most prevalent (88/110, 80.0%) serotype. Resistance to nalidixic acid was not encountered from 1999-2002. Nalidixic acid resistance was observed in 6/13 (46.1%) of the S. sonnei phase 1 strains isolated from April-August 2003. Minimum inhibitory concentration to nalidixic acid among these strains was 48-96 microg/ml. All the six nalidixic acid resistant strains of S. sonnei phase 1 had reduced susceptibility (MIC 0.25 microg/ml) to ciprofloxacin.

Acute Disease↗

[Effect of nalidixic acid on the activation of RNA synthesis in outgrowing spores of Bacillus subtilis].

Outgrowth of B. subtilis spores depends on the action of DNA gyrase (comp. Matsuda and Kameyama 1980). Application of nalidixic acid (100 micrograms/ml) to dormant spores of Bacillus subtilis prevents the outgrowth. Application of nalidixic acid (100 micrograms/ml) during the early outgrowth phase (after a 20 min germination period) does not prevent, but only delay spore outgrowth. Germination of spores is not influenced. Nalidixic acid is an effective inhibitor of RNA synthesis in outgrowing spores, whereas vegetative cells are more resistant. Spores can grow out inspite of a remarkably reduced intensity of RNA synthesis. Nalidixic acid particularly inhibits the synthesis of stable RNA, probably that of ribosomal RNA. We suggest that DNA gyrase-catalyzed alterations in DNA structure are involved in the regulation of the gene expressional program of outgrowing B. subtilis spores.

Bacillus subtilis↗

Selective antimicrobial modulation as prophylaxis against infection during granulocytopenia: trimethoprim-sulfamethoxazole vs. nalidixic acid.

Sixty-two profoundly granulocytopenic patients with acute leukemia undergoing induction chemotherapy were prospectively randomized to receive either trimethoprim-sulfamethoxazole plus nystatin or nalidixic acid plus nystatin for prevention of infection. Patients given trimethoprim-sulfamethoxazole plus nystatin during initial remission induction experienced an increased duration (22.6 vs. 13.6 days) of profound granulocytopenia (less than 100 granulocytes/mm3; P = 0.007). Acquisition of gram-negative bacilli was more frequent among patients treated with nalidixic acid plus nystatin while filamentous fungi were acquired more frequently by patients receiving trimethoprim-sulfamethoxazole plus nystatin (P = 0.05). The median duration of on-study time prior to documentation of first infection was longer for patients receiving trimethoprim-sulfamethoxazole plus nystatin (17 days) than for those receiving nalidixic acid plus nystatin (eight days) (P = 0.0002). Three infection-related deaths occurred among patients receiving nalidixic acid; seven occurred among patients receiving trimethoprim-sulfamethoxazole, five of which were secondary to pneumonia due to Aspergillus flavus. Both of these methods of selective antimicrobial modulation have apparent advantages, but each has disadvantages serious enough to limit their routine use.

Adolescent↗

A comparison of the efficacy of nalidixic acid and cephalexin in bacteriuric women and their effect on fecal and periurethral carriage of enterobacteriaceae.

Eighty-one women were randomly selected for treatment with nalidixic acid (1 g four times a day) or cephalexin (500 mg four times a day) as therapy for 131 episodes of bacteriuria localized using the antibody-coated bacteria (ACB) test. Bladder infections were treated for three days and renal infections for 14 days. Rates of cure were not significantly different between treatment groups in each drug regimen. However, significantly more relapses occurred in the patients with ACB-positive infections treated for 14 days with cephalexin than in those treated for 14 days with nalidixic acid. More early reinfections occurred in the cephalexin-treated group after both three and 14 days of therapy. Resistance to nalidixic acid developed in the infecting bacteria in the urine during therapy with nalidixic acid in 3% of women after three days and in 16% of women after 14 days. Simultaneous resistance appeared in the urine, periurethral area, and fecal flora of these patients.

Antibody-Coated Bacteria Test, Urinary↗

Studies on molecular interactions between nalidixic acid and liposomes.

The interaction between nalidixic acid sodium salt (NANa) and liposomes prepared from alpha-L-dipalmitoyl-phosphatidylcholine (DPPC) or from its binary mixture with dioleoyl-phosphatidylcholine (DOPC) was studied with differential scanning calorimetry (DSC) and electron paramagnetic resonance (EPR) spectroscopy. We evaluated the role of broadband ultraviolet-B (UV-B) irradiation on the molecular interactions between the lipids and the NANa, and determined the decay-kinetics of the incorporated spin labeled fatty-acid free radicals. Multilamellar and unilamellar vesicles were prepared by sonication and extrusion. The entrapment efficiencies were determined spectrophotometrically. The size-distribution of the liposomes and its change in time was checked by dynamic light scattering (DLS). Our results indicate that NANa mainly interacts with lipid head groups. However, its effect and presumably the formation of the free radicals, induced by broadband ultraviolet-B, is not localized only to the head group region of the lipid molecules. Depending on DOPC content, interaction between the NANa and the lipids modifies the phase-transition parameters of the liposome dispersions.

1,2-Dipalmitoylphosphatidylcholine↗

Comparison of cinoxacin and nalidixic acid in patients with cystitis.

A single-blind comparative study was undertaken in 95 patients with cystitis. Each patient received either cinoxacin. 250 mg. qid or nalidixic acid, 1 Gm. qid for seven to fourteen days. Fifty-five patients fulfilled all the criteria for efficacy evaluations; in the cinoxacin-treated group, 26 patients (93 per cent) had a satisfactory symptomatic response, and in the nalidixic acid group there were 25 patients (93 per cent) with a satisfactory symptomatic response. The bacteriologic response was also similar in both groups. One patient in each group became reinfected with a new pathogen and in 1 patient, who received conoxacin, the causative pathogen was not eliminated. four female patients in the cinoxacin group had seven adverse drug reactions, compared with 9 patients in the nalidixic acid group who had 18 adverse reactions. It is concluded that cinoxacin has advantages over nalidixic acid for the treatment of patients with cystitis due to susceptible organisms.

Adult↗

[Effect of puromycin, nalidixic acid and cycloheximide on neuromuscular transmission].

The action of puromycin, nalidixic acid and cycloheximid on neuromuscular transmission has been assayed using diaphragm-phrenic nerve preparation from rat. The results demonstrate that all antibiotics used, reversibly blodk neuromuscular transmission. Cycloheximid seems to act presynaptically by inhibiting acetylcholine release from nerve terminal. Puromycin and nalidixic acid act as curare-like agents. They seem to compete with acetylcholine for fixation at the cholinergic receptor.

Animals↗

Survival of recombination-deficient mutants of Escherichia coli during incubation with nalidixic acid.

The ability of several Escherichia coli strains deficient in recombination (rec) to survive in the presence of nalidixic acid was determined. Genetic blocks of the RecBC or the RecF pathways resulted in increased sensitivity to nalidixic acid when compared with the wild-type strain. Mutants lacking functional recA, recL, or recB recC recF genes showed the most rapid decrease in colony-forming ability when incubated with nalidixic acid. However, the uvrB gene also plays a role in maintaining cell viability.

DNA Repair↗

Cross-resistance of nalidixic acid resistant Enterobacteriaceae to new quinolones and other antimicrobials.

One hundred urine isolates Enterobacteriaceae screened for resistance to 30 micrograms nalidixic acid by disc diffusion test were examined by MIC determination for in vitro susceptibility to nalidixic acid, ciprofloxacin, enoxacin, gentamicin, nitrofurantoin, trimethoprim, cephalexin and ceftazidime. Those resistant to nalidixic acid and also gentamicin or a cephalosporin were further examined to determine the mechanism of resistance. Compared to the total urine isolates of Enterobacteriaceae from the same time period, this population as a whole was less susceptible to all antimicrobials tested except gentamicin. Strains that exhibited multiple resistance had the conventional mechanisms of resistance to those antimicrobials. No multiply resistant strains had a permeability barrier due to outer membrane protein alterations causing cross-resistance to chemically unrelated classes of antimicrobials.

Anti-Bacterial Agents↗

Studies on the action of nalidixic acid in the yeast Saccharomyces cerevisiae.

The effect of the antibiotic nalidixic acid on macromolecular metabolism in the yeast Saccharomyces cerevisiae has been studied. It was found that, upon the addition of nalidixic acid to a logarithmically growing culture, there is a transient inhibition of total cell ribonucleic acid, deoxyribonucleic acid, and protein synthesis, after which the cells show an almost complete recovery. In addition, there is no preferential inhibition of yeast mitochondrial deoxyribonucleic acid synthesis.

Centrifugation, Density Gradient↗

Novobiocin, nalidixic acid, etoposide, and 4'-(9-acridinylamino)methanesulfon-m-anisidide effects on G2 and mitotic Chinese hamster ovary cell progression.

Exponentially growing Chinese hamster ovary cells, exposed to inhibitors of topoisomerase II (novobiocin, nalidixic acid, etoposide, and 4'-(9-acridinylamino)methanesulfon-m-anisidide were blocked in progression through G2. The manner of recovery from the novobiocin-induced block, following drug removal, indicated that the blockade was at and before a specific point in G2 (a transition point). The transition point for novobiocin and putative transition points for nalidixic acid and 4'-(9-acridinylamino)methanesulfon-m-anisidide were about 30 min before metaphase. The transition point for nalidixic acid varied with concentration from about 70 min before metaphase, at 1 microgram/ml, to 24 min before metaphase at 15 micrograms/ml and above. The novobiocin- and nalidixic acid-induced G2 block could not be accounted for by cytotoxicity or DNA damage (detected by neutral elution). The novobiocin-induced G2 block could not be attributed to gross RNA synthesis inhibition. Progress beyond metaphase was blocked by novobiocin but not by nalidixic acid, when cells were exposed to drug concentrations which inhibited G2 cell progression. It is suggested that the progression of Chinese hamster ovary cells into but not through mitosis may require topoisomerase II.

Amsacrine↗

Pharmacokinetics of nalidixic acid associated with sodium citrate.

A pharmacokinetic study of sachets containing nalidixic acid (0.66 g) associated with sodium citrate (3.75 g)--NSC--was carried out in 10 healthy volunteers in order to determine the influence of the urine alcalinization due to sodium citrate on the elimination of nalidixic acid (NA) and its 7-hydroxy (HNA) and 7-carboxy (CNA) derivatives. Urine alcalinization enhanced markedly the urinary excretion of HNA, but not of NA and CNA. The urinary concentrations of bacteriologically active compounds--NA + HNA--remained above five times their minimum inhibitory concentration for 10 h following each dose. After a 3-day treatment using NSC three times daily there was no significant accumulation of NA and derivatives in the plasma and no significant change in their kinetics. Finally, from a pharmacokinetic viewpoint, the daily administration of 3 sachets of NSC each containing 0.66 g of NA seems valuable in the treatment of urinary tract infections.

Adult↗

Nalidixic acid and pivmecillinam for treatment of acute lower urinary tract infections.

Women, 15-45 years of age, with symptoms of lower urinary tract infection (UTI) were randomly treated with nalidixic acid (1 g X 3) or pivmecillinam (200-400 mg X 3) for three or seven days, respectively. Therapeutic failure, relapse, or reinfection occurred among 18% of 82 women, even though the isolated strains of gram-negative rods in these patients were susceptible in vitro to the antibiotics used. Therapeutic failure, i.e. no effect or at best only a minor effect on the symptoms, was registered in 10 of 13 cases of UTI caused by Staphylococcus saprophyticus and treated with nalidixic acid, which was consistent with the high minimum inhibitory concentrations (MIC) (128-512 micrograms/ml) of this antibiotic. S. saprophyticus was isolated in 9 of 12 patients during treatment with nalidixic acid. On the other hand, pivmecillinam therapy was clinically effective in 16 of 18 patients with UTI caused by S. saprophyticus, even though the MIC of mecillinam to these strains was considerably higher (8-64 micrograms/ml) than that vis-à-vis gram-negative rods. Thus the clinical effect of pivmecillinam was significantly better than that of nalidixic acid in cases of UTI caused by S. saprophyticus. The organism was not isolated from 14 patients receiving pivmecillinam therapy.

Adolescent↗

Determination of nalidixic acid by fluorometry with sodium borohydride and hydrogen peroxide.

A simple and sensitive fluorometric method for the determination of nalidixic acid was established by using 0.75M sodium borohydride and 7.5% hydrogen peroxide solution as fluorogenic reagents. Analyte concentrations of 0.0232-11.6 pg/mL could be determined with high precision and accuracy by the method. A relative standard deviation of 1.75% was obtained for a nalidixic acid concentration of 0.232 pg/mL. The method was satisfactorily applied to the determination of nalidixic acid in human serum, fish muscle, and chicken muscle, and the calibration curves were linear from 0.23 to 58.00 pg/mL, from 9.28 to 32.48 mg/kg, and from 4.64 to 23.20 mg/kg, respectively. The specificity of the reaction is also discussed.

Animals↗