Nalidixic Acid and Other Quinolones
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
Nalidixic acid has been used successfully for the treatment of uncomplicated urinary tract infections in childhood and for prolonged treatment of children with urinary infections associated with renal tract abnormalities (Kneebone, 1965). The absence of reported cases of arthropathy and tendonitis makes it a more attractive option than other quinolones. Since resistance to nalidixic acid can emerge during treatment of complicated urinary sepsis, it is best avoided in favor of agents that attain effective blood and tissue levels. In a recent French study of 110 children seen in hospital practice and aged between 11 days and 12 years, E. coli was the predominant isolate (78%), and 9% of total isolates were resistant to nalidixic acid (Garaffo et al., 2014).
High-Performance Liquid Chromatography
Adorjan Aszalos in Modern Analysis of Antibiotics, 2020
Nalidixic acid is used intravenously to treat systemic infections, especially those of the urinary tract. To determine nalidixic acid and its active metabolite, hydroxynalidixic acid, in plasma, an octadecylsilane column was used with a mobile phase of water-methanol-cetrimonium bromide (cetrimide) (50:50:0.12) flowing at 1.5 ml/min into a detector set to 313 nm [455]. The limit of detection of 1 μg/ml is well below the therapeutic range of 20—50 μg/ml. Recoveries are approximately 90%. Contents in plasma and urine were assayed using an amino-cyano column and a mobile phase of methanol-0.1 M citrate buffer, pH 3 (95:15 [sic]), flowing at 1.6 ml/min. Detection at 254 nm gave limits of detection of 0.08 μg/ml plasma and 0.42 μg/ml urine [456].
Antibiotics: The Need for Innovation
Nathan Keighley in Miraculous Medicines and the Chemistry of Drug Design, 2020
Other antibiotics target bacterial protein synthesis by acting on nucleic acid transcription and replication. Examples of the structures of this class of antibiotics are given in Figure 3 of the Supporting Material∗. Quinolone compounds, such as nalidixic acid, are particularly useful for the short-term treatment of urinary tract infections. Resistance soon develops to these compounds; consequently new analogues had to be developed. Modifications to the structure of nalidixic acid were found to increase he spectrum of activity against both gram-negative and gram-positive bacteria.
Molecular detection and Frequency of Fluoroquinolone-Resistant Escherichia coli by Multiplex Allele Specific Polymerase Chain Reaction (MAS-PCR)
Published in Egyptian Journal of Basic and Applied Sciences, 2020
Noha Tharwat Abou El-Khier, Maysaa El Sayed Zaki
Our study revealed significantly higher resistance to fluoroquinolones including ciprofloxacin and levofloxacin among E. coli isolated from HAIs compared to that of CAIs. Resistance to fluoroquinolone is an arising health problem both in HAIs and in CAIs and it is reported to range from 32% to 89% [8]. However, nalidixic acid had significant resistance among isolates of CAIs compared to HAIs. This can be explained by the nature of samples from which E. coli was isolated from CAIs as it was mainly from urine samples. Nalidixic acid is widely prescribed for short-term management of urinary tract infections, and this may lead to the presence of this high resistance [17]. On the other hand, significant higher resistance to amikacin and cefoxitin was observed in HAIs, and this may be credited to the usage of these antibiotics as empirical antibiotics in HAIs leading to the emergence of resistance. Several studies revealed a higher prevalence rate of resistance to the commonly prescribed antibiotic agents [17,18].
DFT based QSAR study on quinolone-triazole derivatives as antibacterial agents
Published in Journal of Receptors and Signal Transduction, 2022
Niloofar Ghasedi, Shahin Ahmadi, Sepideh Ketabi, Ali Almasirad
The accidental discovery of Nalidixic acid led to the development of a class of antibacterial drugs called fluoroquinolones. Today, quinolones are among the most important synthetic antibacterial agents, widely used in treating various infections. The clinical success of quinolones is due to features such as good bioavailability in oral administration, good tissue permeability, and relatively low toxicity. However, this widely used antibiotic class has been prone to resistance too. So there is the need to search for new representatives of this class, which have a potent antibacterial activity and the potential to overcome the bacterial resistance [2,3]. Hybrid molecules are chemical structures containing two or more structural domains with different biological functions and dual activities. Such hybrid molecules can overcome cross-drug resistance, create a broader range of effects, reduce toxicity, improve efficacy, and present new candidates with high potency against drug-resistant and drug-sensitive bacteria [1].
Bacterial death from treatment with fluoroquinolones and other lethal stressors
Published in Expert Review of Anti-infective Therapy, 2021
Karl Drlica, Xilin Zhao
Surprisingly, a catalase deficiency fails to eliminate paradoxical survival [35], even though the deficiency behaves as expected for moderate levels of nalidixic acid: it raises ROS concentrations, increases nalidixic acid-mediated killing, and eliminates the ability of chloramphenicol to block killing [35]. These data suggest a role for additional factors in the quinolone paradox, one of which may be the Lon protease. A deficiency in the protease eliminates high-concentration survival by nalidixic acid with little effect at the maximal bactericidal concentration [99]. The Lon deficiency also allows quinolone-mediated chromosome fragmentation and killing by very high quinolone concentrations, unlike wild-type Lon [99]. One speculation is that quinolone-mediated lesions formed at high concentration are preferentially repaired by Lon. Indeed, quinolone-dependent, peroxide-sensitive lesions are present at high, non-lethal concentrations of nalidixic acid [35]. Whether those lesions differ structurally from lesions formed at moderate, lethal concentrations is unknown.
Related Knowledge Centers
- Bacteriostatic Agent
- Chloroquine
- Enterobacter
- Escherichia Coli
- Shigella
- Urinary Tract Infection
- Proteus
- Quinolone Antibiotic
- Gram-Negative Bacteria
- Gram-Positive Bacteria