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Antimicrobial Agents and Chemotherapy Aug 1978Spontaneous mutants with various patterns of resistance to pipemidic acid (PPA), piromidic acid (PA), and nalidixic acid (NAL) were isolated from Escherichia coli K-12....
Spontaneous mutants with various patterns of resistance to pipemidic acid (PPA), piromidic acid (PA), and nalidixic acid (NAL) were isolated from Escherichia coli K-12. Most mutants were less resistant to PPA than to PA and NAL, and some mutants resistant to PA and NAL were hypersusceptible to PPA. As for the mutants tested, resistance to the drugs was conferred by mutations at nalA and new nal genes designated as nalC and nalD, both of which were located at about 82 min on the recalibrated map. Resistance to PA and NAL was due to decreased sensitivity of the bacterial DNA synthesizing system to them and insufficient drug transport, whereas resistance to PPA was only due to the former.
Topics: Chromosome Mapping; Conjugation, Genetic; DNA, Bacterial; Drug Resistance, Microbial; Escherichia coli; Mutation; Nalidixic Acid; Nicotinic Acids; Pipemidic Acid; Piromidic Acid; Transduction, Genetic
PubMed: 358918
DOI: 10.1128/AAC.14.2.240 -
FEMS Microbiology Ecology Feb 2006Inferences about which microorganisms degrade polycyclic aromatic hydrocarbons in contaminated soils have largely been obtained using culture-based techniques, despite...
Inferences about which microorganisms degrade polycyclic aromatic hydrocarbons in contaminated soils have largely been obtained using culture-based techniques, despite the low percentage of microorganisms in soil that are believed to be culturable. We used a substrate-responsive direct viable count method to identify and quantify potential polycyclic aromatic hydrocarbon-degrading bacteria in a soil containing petroleum wastes. Bacteria were extracted and their response to substrates determined in the presence of DNA gyrase inhibitors, which cause viable and active cells to elongate. When yeast extract, a widely used carbon source, was added as a growth substrate, together with nalidixic acid, piromidic acid and ciprofloxacin, a significant increase in elongated cells to 47%, 37% and 22%, respectively, was observed within 24 h. With pyrene as the main substrate, 10 mg L(-1) of nalidixic acid or piromidic acid caused 18-22% and 8-12%, respectively, of the cells to elongate within 24 h; whereas the effect of 0.5 mg L(-1) ciprofloxacin was not significant until 53 h later. Enlarged cells were identified and enumerated by fluorescent in situ hybridization, using Alpha-, Beta- and Gammaproteobacteria, and domain Bacteria-specific probes. The Bacteria-specific probe detected 35-71% of the total microorganisms detected by the DNA-binding dye 4,6-diamidino-2-phenylindole. Initially, 44%, 13% and 5% of the total bacteria in the soil extract were Alpha-, Beta- and Gammaproteobacteria, respectively. Without pyrene or a gyrase inhibitor, these subgroups decreased to 30% of the total population but were predominant with piromidic acid or unchanged with ciprofloxacin when pyrene was the main substrate. The proportion of elongated Alpha- and Betaproteobacteria (potential pyrene degraders) increased significantly (P<0.05). This approach links phylogenetic information with physiological function in situ without the conventional cultivation of bacteria and can be used to probe and enumerate degradative groups at even a finer level of discrimination.
Topics: Anti-Bacterial Agents; Bacteria; Biodegradation, Environmental; Ciprofloxacin; Colony Count, Microbial; Culture Media; DNA, Bacterial; In Situ Hybridization, Fluorescence; Indoles; Nalidixic Acid; Piromidic Acid; Pyrenes; Soil Microbiology; Staining and Labeling
PubMed: 16420636
DOI: 10.1111/j.1574-6941.2005.00035.x -
Antimicrobial Agents and Chemotherapy Apr 1976Pipemidic acid, a structural relative of piromidic and nalidixic acids, exhibited substantial therapeutic activity when it was administered orally to mice bearing either... (Comparative Study)
Comparative Study
Pipemidic acid, a structural relative of piromidic and nalidixic acids, exhibited substantial therapeutic activity when it was administered orally to mice bearing either widely disseminated or relatively localized infections with Staphylococcus aureus and a variety of gram-negative bacilli. The activity of pipemidic acid was always greater than that of piromidic and nalidixic acids; in infections with Pseudomonas aeruginosa and in bacilli resistant to the latter two drugs, pipemidic acid exhibited significant activity. In limited comparative studies, the activities of pipemidic acid were generally superior to the activities of cephalexin, ampicillin, and carbenicillin. Gentamicin, administered subcutaneously, was more active than pipemidic acid, given either orally or subcutaneously, against both systemic and localized infections with P. aeruginosa. The therapeutic accomplishments of pipemidic acid were attained with well-tolerated doses.
Topics: Ampicillin; Animals; Anti-Infective Agents; Bacterial Infections; Carbenicillin; Cephalexin; Female; Gentamicins; Kidney Diseases; Lung Diseases; Mice; Nalidixic Acid; Nicotinic Acids; Piperazines; Skin Diseases, Infectious; Urinary Bladder Diseases; Urinary Tract Infections
PubMed: 1267435
DOI: 10.1128/AAC.9.4.569 -
Antimicrobial Agents and Chemotherapy Aug 1975Pipemidic acid, 8-ethyl-5,8-dihydro-5-oxo-2-(1-piperazinyl)-pyrido [2,3-d]pyrimidine-6-carboxylic acid, is a new derivative of piromidic acid. It is active against...
Pipemidic acid, 8-ethyl-5,8-dihydro-5-oxo-2-(1-piperazinyl)-pyrido [2,3-d]pyrimidine-6-carboxylic acid, is a new derivative of piromidic acid. It is active against gram-negative bacteria including Pseudomonas aeruginosa as well as some gram-positive bacteria. Its potency is generally greater than that of piromidic acid and nalidixic acid. Cross-resistance is not observed between pipemidic acid and various antibiotics, and most of bacteria resistant to piromidic acid and nalidixic acid are moderately susceptible to pipemidic acid. The activity of pipemidic acid is scarcely affected by the addition of serum, sodium cholate, or change of medium pH, but is subject to the influence of inoculum size. Its action is bactericidal above minimal inhibitory concentrations.
Topics: Bacteria; Drug Resistance, Microbial; Microbial Sensitivity Tests; Nicotinic Acids; Piperazines; Pseudomonas aeruginosa
PubMed: 810076
DOI: 10.1128/AAC.8.2.132 -
Spectrochimica Acta. Part A, Molecular... Feb 2020The self-association of fluoroquinolones (FQ) in water would play a relevant role in their translocations across lipid membranes. Triplet excited states of these drugs...
The self-association of fluoroquinolones (FQ) in water would play a relevant role in their translocations across lipid membranes. Triplet excited states of these drugs have been shown as reporters of FQ self-association using laser flash photolysis technique. A study using low-temperature phosphorescence technique was performed with quinolone derivatives such as enoxacin (ENX), norfloxacin (NFX), pefloxacin (PFX), ciprofloxacin (CPX, ofloxacin (OFX), nalidixic acid (NLA), pipemidic acid (PPA) and piromidic acid (PRA) to explore emission changes associated with self-associations and to shed some light on the triplet excited state energy (E) discrepancies described in the literature for most of these drugs. The emissions obtained at 77 K in buffered aqueous medium revealed that the amphoteric nature of the quinolones CPX, NFX, PFX, ENX, OFX and PPA must generate their self-associations because a redshift of their phosphorescence maxima is produced by FQ concentrations increases. Hence, this effect was not observed for NLA and PRA or when all quinolones were analysed using ethanol or ethylene glycol aqueous mixtures as glassed solvents. Interestingly, the presence of these organic mixtures produced a blue-shift in the phosphorescence emission maximum of each FQ. Additionally, laser flash photolysis experiments with PRA and the amphoteric quinolone PPA, compounds with the same skeleton but different peripheral substituent, confirm the expected correlations between the amphoteric nature of compounds and their self-associations in aqueous media because the excimer generation was only detected for PPA. Now, the discrepancies described in the literature for the E of FQs can be understood considering that changes of medium polarity or proticity as well as the temperature can considerably modify their E values. Thereby, low-temperature phosphorescence technique, is an effective way to detect molecular self-associations and surrounding changes in quinolones that opens the possibility to evaluate these effects in other drug families.
Topics: Buffers; Dimerization; Fluoroquinolones; Luminescent Measurements; Models, Molecular; Photolysis; Water
PubMed: 31670049
DOI: 10.1016/j.saa.2019.117569 -
Journal of Bacteriology Nov 1981In Escherichia coli K-12 mutants which had a new nalidixic acid resistance mutation at about 82 min on the chromosome map, cell growth was resistant to or...
In Escherichia coli K-12 mutants which had a new nalidixic acid resistance mutation at about 82 min on the chromosome map, cell growth was resistant to or hypersusceptible to nalidixic acid, oxolinic acid, piromidic acid, pipemidic acid, and novobiocin. Deoxyribonucleic acid gyrase activity as tested by supercoiling of lambda phage deoxyribonucleic acid inside the mutants was similarly resistant or hypersusceptible to the compounds. The drug concentrations required for gyrase inhibition were much higher than those for cell growth inhibition but similar to those for inhibition of lambda phage multiplication. Transduction analysis with lambda phages carrying the chromosomal fragment of the tnaA-gyrB region suggested that one of the mutations, nal-31, was located on the gyrB gene.
Topics: Bacteriophage lambda; DNA Topoisomerases, Type II; Drug Resistance, Microbial; Escherichia coli; Genes, Bacterial; Mutation; Nalidixic Acid; Transduction, Genetic
PubMed: 6271730
DOI: 10.1128/jb.148.2.450-458.1981 -
Hinyokika Kiyo. Acta Urologica Japonica Oct 1983The relationship between the concentrations of various antimicrobial agents in the genital organs of male rats, serum, liver and kidney after oral administration,... (Comparative Study)
Comparative Study
The relationship between the concentrations of various antimicrobial agents in the genital organs of male rats, serum, liver and kidney after oral administration, intramuscular infusion and i.v. infusion were systematically compared and studied. The concentration of Ampicillin in human prostatic tissues after intramuscular infusion was also measured. The drug concentration in the prostatic tissues after oral administration of nalidixic acid (20 mg/kg) was highest 21.5 micrograms/g (2-hour value) which was about 4 times the serum level, followed by chloramphenicol, Cefalexin, Ampicillin, piromidic acid and erythromycin. The concentration of Ampicillin and Cefaloridine in the prostatic tissues after intramuscular infusion was high, but the concentration of Cefazolin, was low after both intramuscular infusion and i.v. infusion. The drug concentration in the prostatic tissues after i.v. infusion of Cefaloridine, Erythromycin, and Ampicillin was high. The concentration of Erythromycin was high only after i.v. infusion. The concentration of both Chloramphenicol and Gentamicin in the blood, and in the prostatic tissues were low. Of the drugs tested, the concentration of Ampicillin in human prostatic tissues was the highest being about 8 micrograms/g at 60 minutes after intramuscular infusion, which was about 40% of its concentration in the blood. The concentrations of antimicrobial agents in the epididymis and testis of the rats were low. Even the relatively high values were only about 10% of the concentration in the blood. The concentration of nalidixic acid in the prostatic tissues was 4 times as high as that of Piromidic acid. In summary, the antimicrobial agents showing high concentrations in the prostatic tissues were nalidixic acid by oral administration, Ampicillin and Cefaloridine by intramuscular infusion, and i.v. infusion, which showed relatively high concentrations in the blood. Irrespective of the route of administration, the concentrations of Chloramphenicol and Gentamicin in the male genitals were low. The drug concentration in the testis was very low irrespective of the chemotherapeutic and administration form. This seems to signify the presence of the so-called blood-testis barrier to protect the important function of spermatogenesis.
Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Epididymis; Humans; Injections, Intramuscular; Injections, Intravenous; Kidney; Liver; Male; Prostate; Rats; Rats, Inbred Strains; Testis
PubMed: 6681499
DOI: No ID Found -
The Journal of Toxicological Sciences Nov 1978Pipemidic acid (PPA) orally given in a dose of 100 mg/kg/day or more was found to cause lame gait in immature beagle dogs of about 3 months old. Their diarthrodial...
Pipemidic acid (PPA) orally given in a dose of 100 mg/kg/day or more was found to cause lame gait in immature beagle dogs of about 3 months old. Their diarthrodial joints were abnormal with increased synovial fluid and blister formation under the outer layer of the articular cartilage. However, such an abnormality was not found in dogs younger than 2 weeks or older than 12 months. The blisters were formed at the joint areas bearing the body weight at a time when PPA was considered to be present there. Nalidixic and piromidic acids, structural analogues of PPA, also caused abnormality similar to PPA. The severity of the arthropathy was slight with piromidic acid as compared with PPA and nalidixic acid. The gait abnormality was almost disappeared spontaneously even if medication was continued. The incidence of the arthropathy was not or rarely observed in any young rats, rabbits and monkeys.
Topics: Aging; Animals; Dogs; Female; Gait; Haplorhini; Joint Diseases; Macaca; Macaca mulatta; Male; Nalidixic Acid; Nicotinic Acids; Physical Exertion; Pipemidic Acid; Piromidic Acid; Rabbits; Rats; Species Specificity
PubMed: 105148
DOI: 10.2131/jts.3.357 -
Applied and Environmental Microbiology Sep 1997The direct viable count method first described by Kogure et al. (Can. J. Microbiol. 25:415-420, 1979) was improved by using an antibiotic cocktail instead of nalidixic...
The direct viable count method first described by Kogure et al. (Can. J. Microbiol. 25:415-420, 1979) was improved by using an antibiotic cocktail instead of nalidixic acid alone. We screened 100 marine isolates from two coastal areas for their sensitivities to five replication-inhibiting antibiotics, including four quinolones (nalidixic, piromidic, and pipemidic acids and ciprofloxacin) and one (beta)-lactam (cephalexin). It was shown that growth inhibition of all isolates cannot be readily achieved by using a single antibiotic. Inhibition was much more efficient when all the antibiotics were combined, making it possible to use this method with natural communities. In combination, the concentration of each antibiotic could be lowered and the incubation time could be increased without any growth. Under such conditions, it was shown that the fraction of substrate-responsive cells within natural marine communities is much greater (1 to 2 orders of magnitude) than those reported by traditional procedures. Furthermore, the new procedure made substrate-responsive cells more clearly distinguishable. These improvements resulted in an increased incubation time and were related to metabolic expression of slow-growing cells and/or to the recovery of starved cells. The increased fraction of viable cells within marine communities has ecological implications on the metabolic role of nonculturable cells.
PubMed: 16535694
DOI: 10.1128/aem.63.9.3643-3647.1997 -
Antimicrobial Agents and Chemotherapy Aug 2003The in vitro activities of 25 quinolones and fluoroquinolones against erythrocytic stages of Plasmodium falciparum and against liver stages of Plasmodium yoelii yoelii... (Comparative Study)
Comparative Study
The in vitro activities of 25 quinolones and fluoroquinolones against erythrocytic stages of Plasmodium falciparum and against liver stages of Plasmodium yoelii yoelii and P. falciparum were studied. All compounds were inhibitory for chloroquine-sensitive and chloroquine-resistant P. falciparum grown in red blood cells. This inhibitory effect increased with prolonged incubation and according to the logarithm of the drug concentration. Grepafloxacin, trovafloxacin, and ciprofloxacin were the most effective drugs, with 50% inhibitory concentrations of <10 micro g/ml against both strains. Only grepafloxacin, piromidic acid, and trovafloxacin had an inhibitory effect against hepatic stages of P. falciparum and P. yoelii yoelii; this effect combined reductions of the numbers and the sizes of schizonts in treated cultures. Thus, quinolones have a potential for treatment or prevention of malaria through their unique antiparasitic effect against erythrocytic and hepatic stages of Plasmodium.
Topics: 4-Quinolones; Animals; Anti-Infective Agents; Cells, Cultured; Erythrocytes; Fluoroquinolones; Liver; Mice; Plasmodium; Plasmodium falciparum; Plasmodium yoelii
PubMed: 12878530
DOI: 10.1128/AAC.47.8.2636-2639.2003