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Comparison of the effect of nalidixic acid and thymine deprivation on excision repair in Escherichia coli.

There is a difference in the extent of inhibition of thymine dimers (TT) excision in ultravioley (UV) irradiated cells of E. coli after preirradiation depression of protein and DNA syntheses induced by a simultaneous deprivation of essential amino acids (AA-) and thymine(T-) or by deprivation of essential amino acids and addition of nalidixie acid (NAL+). This difference has been noted in both E. coli B/r Her+ and E. coli K12 SR20 uvr+ cells. Depression of DNA synthesis with the aid of malidixic acid as exogenous agent will inhibit TT excision to a lesser degree than depression of DNA synthesis by thymine starvation. The extent of TT excision has no appreciable influence on restoration of the sedimentation profile of newly synthesized DNA nor again on UV resistance of cells in conditions of dark repair. At the time when there are TT still present in DNA, the DNA molecule, having the size of the molecule of unirradiated cells, will become synthesized.

DNA Repair↗

Comparative controlled clinical trial of pivmecillinam and nalidixic acid in patients with acute simple urinary tract infections.

We performed a controlled double-blind clinical study with PMPC to investigate its therapeutic usefulness in acute simple cystitis in comparison with NA, with the results as follows: 1. In both treatment groups, PMPC proved to be remarkably more active (MIC) than NA against the bacterial isolates tested in vitro. 2. PMPC, administered in dosis (200 mg per day) one-tenth those of NA (2,000 mg per day), produced a greater improvement (therapeutic effects) than NA. 3. Side-effects were apparently less frequent with PMPC, as compared to NA. The results indicate a remarkable usefulness of PMPC in the treatment of acute simple cystitis.

Acute Disease↗

Bioequivalence study of nalidixic acid tablets: in vitro-in vivo correlation.

The USP dissolution test was used to select seven products with a wide range of dissolution characteristics for in vivo examination. The bioequivalence of seven (500 mg) products was evaluated in two crossover urinary excretion experiments. In each study three products were compared with the innovator product (Negram-Winthrop-Breon) in 12 subjects according to a 4 x 4 latin square design. Significantly different, lower bioavailability was observed in two products in relation to that of the innovator product. Linear in vitro-in vivo correlations were found between the cumulative amount excreted at 24 h and the log of the amount dissolved at 30 min and between log of the cumulative amount excreted up to 24 h and the log of the amount dissolved at 45 min.

Adult↗

Role of mutation in the gyrA and parC genes of nalidixic-acid-resistant salmonella serotypes isolated from animals in the United Kingdom.

To answer the question as to whether isolates of salmonella from animals with decreased susceptibility to quinolones possess the same mechanism of resistance as isolates from humans, the polymerase chain reaction (PCR) was used to amplify a 347 base pair fragment equivalent to codons 39-159 covering the quinolone resistance determining region (QRDR) of the gyrA gene of Salmonella typhimurium NCTC 74, and 196 veterinary isolates of 26 serotypes of salmonella (109 from turkeys, 29 from chickens, the remainder from cattle, parrots, pigs, dogs, a pigeon, an exotic bird, a duck, a partridge, a sheep, a horse and environmental samples including litter, a nest and water). All PCR products were electrophoresed for single-stranded conformational polymorphism (SSCP). The DNA sequence of all eight novel SSCP patterns was determined. Nucleotide substitutions were identified in the gyrA gene of all except two isolates; all substitutions conferred a substitution at serine 83 or aspartate 87, as has previously been shown for isolates from humans. No mutations conferring an amino acid substitution in parC (the gene encoding the secondary target for quinolones) were revealed in the 48 isolates requiring 0.5-1 mg/L ciprofloxacin for inhibition, or the isolates for which no mutation in gyrA was revealed. The accumulation of enrofloxacin and ciprofloxacin was determined for 30 representative isolates (of which five were multiply drug resistant). Five isolates accumulated one-quarter to one-half the concentration achieved by the corresponding wild-type serotype. For two of these five isolates no mutation in gyrA was revealed, and one lacked OmpF.

Animals↗

[Efficiency of inhibitors (phenylethanol, nalidixic acid, sodium azide)in the isolation of strictly anaerobic bacteria from a polymicrobial specimen].

The efficacy of inhibitors (PEA, Ac Nal, Az de Na) in the isolation of strict anaerobes in polymicrobial sample. The efficacy of three inhibitors to select strict anaerobic bacteria in the polymicrobial sample had been studied. First step: The most frequent anaerobes encountered in the infections are isolated in the agar Columbia containing the different inhibitors. This step allowed us to check the inhibition of the germ we have to isolate. Next step: polymicrobial mixtures were made. The composition of which is very similar to the samples we receive in the laboratory. The swarming Proteus is the facultative anaerobic germ which gives us difficulties when isolating strict anaerobic bacteria. Then, the different mixtures were isolated separately in the agar in which the inhibitors were added. The plates containing Azide of Na and PEA gave us the best results.

Azides↗

Activity of minocycline against Acinetobacter calcoaceticus var. anitratus (syn. Herellea vaginicola) and Serratia marcescens.

The activity of minocycline and tetracycline against 23 isolates of Acinetobacter calcoaceticus var. anitratus (syn. Herellea vaginicola) and 178 strains of Serratia marcescens was determined by disk and microdilution methods. The results indicate that minocycline is highly active against this species of Acinetobacter, all but one strain being inhibited by 0.007 mug of the antibiotic per ml. Tetracycline was also active, though to a lesser degree, against A. calcoaceticus. Of the 178 strains of S. marcescens tested, only seven (3.9%) had a minimum inhibitory concentration of 2 mug or less of minocycline per ml. Tetracycline was less active than minocycline against S. marcescens; with 2 mug of tetracycline per ml, only 2 of 152 (1.3%) strains were inhibited. At concentrations of 8 and 16 mug of minocycline per ml, which can be achieved in the urine with the usual doses, 44.9 and 63.5% of S. marcescens strains were inhibited, which implies its possible usefulness for the therapy of urinary tract infection due to this organism.

Acinetobacter↗

Effect of antimicrobial (nalidixic acid) therapy in shigellosis and predictive values of outcome variables in patients susceptible or resistant to it.

We observed the clinical features and results of simple laboratory tests on stools of 33 children with bacteriologically proven shigellosis to identify features that could be used to assess the effectiveness of antimicrobial therapy. Persistence of fever (rectal temperature > 37.8 degrees C), abdominal pain/tenderness and anorexia on days 3 and 5 were significantly more common (P < 0.001) among children who received an antimicrobial to which the infecting Shigella was resistant. Similarly, a significantly higher number of children treated with an ineffective antimicrobial had faecal leucocytes of > 50/high power microscopic field (HPF), erythrocytes of > 50/HPF and macrophages of > 5/HPF on study day 5. The best predictors of ineffective antimicrobial therapy on days 3 and 5 of treatment were fever, presence of blood by naked eye examination of stool, and minimum change in stool frequencies. These observations suggest that by careful follow-up of clinical features and simple laboratory tests, such as stool microscopic examinations, it is possible to identify patients unlikely to respond to initial therapy by 72 hours permitting the start of alternative antimicrobial treatment. This may be of great help where stool culture and sensitivity facilities for Shigella spp. are not available.

Abdominal Pain↗

Clinical efficacy of ofloxacin in the treatment of otorhinolaryngological infections.

A multi-centered clinical study was carried out to evaluate the efficacy of ofloxacin in otorhinolaryngological infections in Japan. Ofloxacin was used at a dosage of 300 mg to 800 mg daily for three to 20 days in 206 cases of various infectious diseases in the otorhinolaryngological field such as otitis media, external otitis, paranasal sinusitis, tonsillitis and pharyngolaryngitis. Its efficacy rate was 79.9%. Minor side effects were seen in three cases (1.5%), gastro-intestinal disorders in two and headache in one. The antibacterial activity of ofloxacin was compared with the activity of pipemidic acid, nalidixic acid and norfloxacin against clinically isolated microorganisms. Ofloxacin was highly superior to pipemidic acid and nalidixic acid, and slightly more active than or equivalent to norfloxacin.

Anti-Infective Agents↗

Comparative in vitro activity of norfloxacin and four other chemotherapeutics against urinary gram-negative isolates.

Three hundred seventy-five Gram-negative bacterial strains were isolated from urine specimens of as many patients affected by symptomatic or asymptomatic urinary tract infections. Susceptibility of bacteria to five chemotherapeutics (norfloxacin, oxolinic acid, pipemidic acid, nalidixic acid and nitrofurantoin) was studied determining minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of each compound by a miniaturized dilution broth method. Norfloxacin, a quinoline carboxylic acid compound structurally related to nalidixic acid, showed a much higher antibacterial activity against all bacterial strains under examination including Pseudomonas sp. The best activity of norfloxacin was expressed either by lower MICs and lower MBCs with respect to those of the other compounds, or by a low MBC/MIC ratio, which represents an important advantage in clinical practice.

Anti-Infective Agents, Urinary↗

Comparative in vitro activity of ciprofloxacin and five other quinoline derivatives against gram-negative isolates.

A total of 375 Gram-negative bacterial strains were isolated from midstream urine specimens of the same number of patients affected by urinary tract infections. All bacteria were identified by standard bacteriological methods and their susceptibility to six quinoline derivatives (ciprofloxacin, cinoxacin, norfloxacin, oxolinic acid, pipemidic acid, nalidixic acid) was studied by determining the MICs and MBCs for each compound using a miniaturized dilution broth method in microtitre plates and twofold dilutions of each drug from 256 to 0.12 mcg/ml. Ciprofloxacin, a new quinoline carboxylic acid compound structurally related to nalidixic acid, showed a much higher antibacterial activity against all bacterial strains under examination, including Pseudomonas, than the other compounds, except for norfloxacin. The MIC90 and MBC90 of ciprofloxacin never exceeded 1 mcg/ml with any of the bacterial species; and MBC/MIC ratios were very low, which represents an important clinical advantage. Only norfloxacin showed comparable effectiveness. No bacterial strain showed resistance to the drug and the MIC90 and MBC90 never exceeded 8 mcg/ml.

Bacteriuria↗

New hemolysin (gamma) produced by Escherichia coli.

A new hemolysin (gamma) of Escherichia coli, active in the absence of viable bacteria, has been recognized in mutants resistant to nalidixic acid. Nalidixic acid affects either the production or release of the hemolysin.

Animals↗