Tissue Concentration of Nalidixic Acid in Chronic Pyelonephritis

Jameson, R. M.

doi:10.1136/bmj.2.5462.621

Cited by 26 publications

(8 citation statements)

References 4 publications

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Section: Discussionmentioning

confidence: 99%

“…However, it fails to react with Hg 2+ leading to similar ring-closing reactions along with desulfurization as HgS. The chemistry of thiosemicarbazones has been studied for a considerable period of time because of their medicinal values for the treatment of tuberculosis, leprosy, smallpox, 35 and several cancer types. 36 Again, despite being extremely important biological molecule HSNO has seldom been proved to exist in aqueous solution or characterized under physiological conditions; 16 however, it has been examined computationally 37,38 and spectroscopically in an argon matrix at 12 K. 39 A recent report on the spectrometric detection of HSNO at physiological pH has attracted considerable attention of the biological community, as it could be an intermediate in the reaction of sulfide with RSNOs and a precursor for NO, nitrosonium (NO + ) equivalents, and nitroxyl (HNO).…”

Section: ■ Conclusionmentioning

confidence: 99%

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A Smart Molecule for Selective Sensing of Nitric Oxide: Conversion of NO to HSNO; Relevance of Biological HSNO Formation

et al. 2017

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A smart molecule, QT490, containing thiosemicarbazide moiety acts as a highly selective turn-on in vitro NO sensor through the unprecedented NO-induced transformation of thiosemicarbazide moiety to 1,3,4-oxadiazole heterocycle with the concomitant release of HSNO, thereby eliminating any interference from various endogenous biomolecules including dehydroascorbic acid, ascorbic acid, etc. The kinetic studies of the reactions between QT490 and NO provide a mechanistic insight into formation of HSNO/RSNO from the reaction between H2S/RSH and NO in the biological system. This novel probe is non-cytotoxic, cell permeable, water-soluble, and appropriate for intracellular cytoplasmic NO sensing with the possibilities of in vivo applications.

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Section: Discussionmentioning

confidence: 99%

Section: ■ Conclusionmentioning

confidence: 99%

A Smart Molecule for Selective Sensing of Nitric Oxide: Conversion of NO to HSNO; Relevance of Biological HSNO Formation

et al. 2017

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“…Antibiotic concentrations were doubled each day over the course of six days (0.625, 1.25, 2.5, 5, 10, 20 mg/l of each individual antibiotic), where inhibition of the ancestral strain was achieved on day 5 a protocol often used in resistance evolution experiments, 3,100–102 . The concentrations reflect physiological concentrations achieved during treatment with rifampicin maximum serum concentration 5-18 mg/l, 103 and nalidixic acid maximum plasma concentration 1.8-30 mg/l, 41 . We note that nalidixic acid itself is mutagenic approximately two-fold increase at 10 mg/l 104 , but the effect is minor relative to Δ mutS deletion.…”

Section: Methodsmentioning

confidence: 64%

“…Direct evidence for the efficacy of combinations against mutators is mixed [32][33][34] . We imposed selection for resistance by increasing the concentrations of antibiotics over a physiologically-relevant concentration gradient 35,36 . Concentrations can vary over time and space, both in clinical settings (e.g.…”

Section: Introductionmentioning

confidence: 99%

“…Using a combination of experimental evolution and stochastic modelling, we challenged populations of Escherichia coli with evolving antibiotic resistance to rifampicin and nalidixic acid, either used singly or in combination. We imposed selection for resistance using a 'ramping selection' design over physiologically-relevant concentrations of antibiotics with a delay in reaching inhibition 41,42 . This enables us to mimic environmental variation akin to what occurs in clinical (e.g.…”

Section: Introductionmentioning

confidence: 99%

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Mutators drive evolution of multi-resistance to antibiotics

Gifford¹,

Berríos-Caro

Joerres³

et al. 2019

Preprint

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Combination therapy aims to prevent growth of organisms not resistant to all component drugs, making it an obvious strategy for countering the global rise of multi-drug resistance. However, success relies on preventing resistance from arising to all component drugs before full inhibition is reached during treatment. Here, we investigated whether bacterial populations can overcome combination therapy by evolving 'multi-resistance', i.e. independent resistance mutations to multiple drugs, during single-drug and combination antibiotic treatment. Using both experimental evolution and in silico stochastic simulations, we studied resistance evolution in a common laboratory strain of bacteria (Escherichia coli K-12 BW25113). Populations were exposed to either single-drug or combination treatments involving rifampicin and nalidixic acid, with concentrations increasing through time. For wild-type populations, multi-resistance was not detected in any of the experimental populations, and simulations predict its evolution should be rare.However, populations comprising mixtures of wild-type and 'mutator' strains were readily capable of evolving multi-resistance. Increasing the initial frequency of mutators resulted in a higher proportion of populations evolving multi-resistance. Experiments and simulations produced the same qualitative-and in many cases, quantitative-insights about the association between resistance, mutators and antibiotic treatment. In particular, both approaches demonstrated that multi-resistance can arise through sequential acquisition of independent resistance mutations, without a need to invoke multi-drug resistance mechanisms. Crucially, we found multi-resistance evolved even when not directly favoured by natural selection, i.e. under single-drug treatments. Simulations revealed this resulted from elevated mutation supply caused by genetic hitch-hiking of the mutator allele on single-drug resistant backgrounds. Our results suggest that combination therapy does not necessarily prevent sequential acquisition of multiple drug resistances via spontaneous mutation when mutators are present. Indeed both combination and single-drug treatments actively promoted multi-resistance, meaning that combination therapy will not be a panacea for the antibiotic resistance crisis. inference, stochastic simulations, individual-based model, Markov chains W , K. B., 2016 Pairwise interactions and the battle against combinatorics in multidrug therapies.

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Pharmacokinetics of Nalidixic Acid in Old and Young Volunteers

Barbeau

Bélanger

1982

The Journal of Clinical Pharma

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Plasma levels of active naphthyridine were measured in healthy old (mean age 77.3 years) and young (mean age 25.4 years) subjects following oral administration of 1 Gm nalidixic acid. The plasma levels of active naphthyridine, i.e., nalidixic acid and its metabolite 7-hydroxynalidixic acid, were generally higher in the old group, particularly in the elimination phase. Significant variations in the pharmacokinetic parameters were obtained between the two groups of volunteers. The plasma half-life of active naphthyridine averaged 11.5 hours in old subjects and 2.7 hours in the younger group. Diminished renal function in the geriatric group may explain the slower elimination of the drug in the old subjects. The mean values of the other parameters calculated were: apparent volume of distribution, 0.55 (old) and 0.47 (young) liter/kg body weight; area under the curve, 327.7 (old) and 156.3 (young) micrograms/ml x hr; total body clearance 2.9 (old) and 8.3 (young) liters/hr; absorption rate constant, 0.29 (old) and 0.52 (young) hr. -1

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Tissue Concentration of Nalidixic Acid in Chronic Pyelonephritis

Cited by 26 publications

References 4 publications

A Smart Molecule for Selective Sensing of Nitric Oxide: Conversion of NO to HSNO; Relevance of Biological HSNO Formation

A Smart Molecule for Selective Sensing of Nitric Oxide: Conversion of NO to HSNO; Relevance of Biological HSNO Formation

Mutators drive evolution of multi-resistance to antibiotics

Pharmacokinetics of Nalidixic Acid in Old and Young Volunteers

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