Fluoroquinolone antibacterials: SAR, mechanism of action, resistance, and clinical aspects

Gootz, Thomas D.; Brighty, Katherine E.

doi:10.1002/(sici)1098-1128(199609)16:5<433::aid-med3>3.0.co;2-w

Cited by 161 publications

(108 citation statements)

References 45 publications

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“…Fluoroquinolones interact with DNA gyrase and topoisomerase IV, the two bacterial type II topoisomerases. DNA gyrase is involved in maintaining appropriate DNA supercoiling during DNA synthesis and transcription, while topoisomerase IV is involved in decatenation of chromosomal DNA and chromosome segregation (10,14). Besides inhibiting the catalytic activities of the enzymes, quinolones form a stable enzyme-DNA-quinolone cleavable complex.…”

Section: Resultsmentioning

confidence: 99%

“…Irreversible, lethal single-and double-stranded breaks are released when the complex dissociates. The interaction of fluoroquinolones with the enzyme-DNA complex also interferes with chromosome replication and chromosome segregation (10,13,14,40). ABT-492 was a potent inhibitor of the topoisomerases of both E. coli and S. aureus, as measured by the formation of cleavable complexes (Table 5).…”

Section: Resultsmentioning

confidence: 99%

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In Vitro Antibacterial Potency and Spectrum of ABT-492, a New Fluoroquinolone

Nilius

Shen

Hensey-Rudloff

et al. 2003

Antimicrob Agents Chemother

100

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ABT-492 demonstrated potent antibacterial activity against most quinolone-susceptible pathogens. The rank order of potency was ABT-492 > trovafloxacin > levofloxacin > ciprofloxacin against quinolone-susceptible staphylococci, streptococci, and enterococci. ABT-492 had activity comparable to those of trovafloxacin, levofloxacin, and ciprofloxacin against seven species of quinolone-susceptible members of the family Enterobacteriaceae, although it was less active than the comparators against Citrobacter freundii and Serratia marcescens. The activity of ABT-492 was greater than those of the comparators against fastidious gram-negative species, including Haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, and Legionella spp. and against Pseudomonas aeruginosa and Helicobacter pylori. ABT-492 was as active as trovafloxacin against Chlamydia trachomatis, indicating good intracellular penetration and antibacterial activity. In particular, ABT-492 was more active than trovafloxacin and levofloxacin against multidrug-resistant Streptococcus pneumoniae, including strains resistant to penicillin and macrolides, and H. influenzae, including ␤-lactam-resistant strains. It retained greater in vitro activity than the comparators against S. pneumoniae and H. influenzae strains resistant to other quinolones due to amino acid alterations in the quinolone resistance-determining regions of the target topoisomerases. ABT-492 was a potent inhibitor of bacterial topoisomerases, and unlike the comparators, DNA gyrase and topoisomerase IV from either Staphylococcus aureus or Escherichia coli were almost equally sensitive to ABT-492. The profile of ABT-492 suggested that it may be a useful agent for the treatment of community-acquired respiratory tract infections, as well as infections of the urinary tract, bloodstream, and skin and skin structure and nosocomial lung infections.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

In Vitro Antibacterial Potency and Spectrum of ABT-492, a New Fluoroquinolone

Nilius

Shen

Hensey-Rudloff

et al. 2003

Antimicrob Agents Chemother

100

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“…Structure activity relationship, mechanism of action, resistance and clinical aspects of some fluoroquinolones antibacterial have been screened (Goots and Brighty, 1996). A series of benzoquinolizine-2-carboxylic acid arginine salt of nadifloxacin have been synthesized and found out the excellent activity against hospital infections of multi-drug-resistance vancomycin-resistant Staphylococcus aureus (de Souza et al, 2005).…”

mentioning

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Synthesis of some NH-Derivatives of ciprofloxacin as antibacterial and antifungal agents

Rabbani

Islam

Ahmad

et al. 2011

Bangladesh J Pharmacol

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“…Since the discovery of the original DNA gyrase inhibitor nalidixic acid, numerous structural modifications have been carried out to the quinolone nucleus to increase antimicrobial activity and improve pharmacokinetic performance (12,22,29,46).…”

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confidence: 99%

Ofloxacin-Loaded Liposomes: In Vitro Activity and Drug Accumulation in Bacteria

Furneri¹,

Fresta

Puglisi

et al. 2000

Antimicrob Agents Chemother

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Different ofloxacin-loaded unilamellar vesicles were prepared by the extrusion technique, and their antimicrobial activities were determined in comparison to those of the free drug by means of MIC determinations with both American Type Culture Collection standards and wild-type bacterial strains (six strains of Enterococcus faecalis, seven strains of Escherichia coli, six strains of Staphylococcus aureus, and six strains of Pseudomonas aeruginosa). The accumulation of ofloxacin and liposome-ofloxacin was measured by determining the amount of the drug inside the bacteria as a function of time. Encapsulated fluoroquinolone yielded MICs which were at least twofold lower than those obtained with the free drug. In particular, liposomes made up of dimyristoylphosphatidylcholine-cholesterol-dipalmitoylphosphatidylserine and dimyristoylphosphatidylcholine-cholesterol-dihexadecylphosphate (4:3:4 molar ratio) provided the best improvement in antimicrobial activity against the various bacterial strains investigated. The liposome formulation produced higher intracellular fluoroquinolone concentrations than those achieved simultaneously with the free drug in both E. coli and P. aeruginosa.Since the discovery of the original DNA gyrase inhibitor nalidixic acid, numerous structural modifications have been carried out to the quinolone nucleus to increase antimicrobial activity and improve pharmacokinetic performance (12,22,29,46).The efficacy of fluoroquinolone antibiotics has led to their proposed use for the treatment and prophylaxis of different bacterial diseases: therapy for the respiratory tract, skin structure, and bone and gastrointestinal infections, as well as urinary tract infections (20,21,23,36,41). However, many studies were developed to improve the potency and spectrum, to achieve sustained blood levels, and to reduce as much as possible drug interactions with various metabolic pathways and physiological processes. Particularly, the use of antibiotic "carrier/delivery systems" would result in enhanced concentrations of the antimicrobial agent at the site of infection. In fact, delivery systems can contribute to (i) targeting of the drug to the infected tissues, (ii) increasing intracellular antibiotic concentrations, and (iii) reducing toxicity of potentially toxic drugs resulting from the targeting to the infectious organisms.Liposomes are possible carriers for controlled drug delivery and targeting by the intravenous route. As with most drug carriers, liposomes have been extensively used in an attempt to improve the selective delivery and the therapeutic index of antimicrobial agents (3, 47). Liposomes, artificial phospholipid membranes, are usually produced from naturally occurring, biodegradable, and nontoxic lipids, such as lecithin, cholesterol, and phosphatidylserine.The aim of the study described here was to investigate the antimicrobial activity against and accumulation in bacteria of ofloxacin-loaded liposomes (of different lipid compositions) in comparison to those of free drugs. Our preliminary experi...

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Fluoroquinolone antibacterials: SAR, mechanism of action, resistance, and clinical aspects

Cited by 161 publications

References 45 publications

In Vitro Antibacterial Potency and Spectrum of ABT-492, a New Fluoroquinolone

In Vitro Antibacterial Potency and Spectrum of ABT-492, a New Fluoroquinolone

Synthesis of some NH-Derivatives of ciprofloxacin as antibacterial and antifungal agents

Ofloxacin-Loaded Liposomes: In Vitro Activity and Drug Accumulation in Bacteria

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