In Vitro Susceptibility Comparisons and Recommendations for Oxolinic Acid

Klein, Dolph; Matsen, John M.

doi:10.1128/aac.9.4.649

Cited by 5 publications

(3 citation statements)

References 5 publications

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“…The use ofthe MAC as the criterion ofactivity (1,10). When tested against nalidixic acid-resistant strains, the superiority of flumequine and oxolinic acid was even more marked than with susceptible strains, the MAC of nalidixic acid being at least 16 times higher than that of flumequine and 32 times that of oxolinic acid.…”

Section: Resultsmentioning

confidence: 99%

Activity of flumequine against Escherichia coli: in vitro comparison with nalidixic and oxolinic acids

Greenwood¹

1978

Antimicrob Agents Chemother

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The in vitro activity of the new antibacterial agent, flumequine, against Escherichia coli was compared with those of oxolinic acid and nalidixic acid. As judged by turbidimetric criteria, flumequine was considerably more active than nalidixic acid and slightly less active than oxolinic acid against both nalidixic acid-susceptible and -resistant strains. Resistance to all three drugs could be easily induced in vitro. The comparative efficacy of flumequine, oxolinic acid, and nalidixic acid was also tested in an in vitro model of the treatment of bacterial cystitis. In this system, suppression of bacterial growth was obtained with markedly lower concentrations of flumequine and oxolinic acid than of nalidixic acid, but prevention of the emergence of bacterial populations that exhibited increased resistance to these compounds depended on the maintenance of adequate drug levels.Flumequine is a new antibacterial agent structurally related to nalidixic and oxolinic acids (Fig. 1). Like nalidixic acid and other members of this group, flumequine is generally more active against enterobacteria than against other organisms (14), and it is likely that its potential therapeutic usefulness will hinge on its effectiveness in the treatment of urinary tract infections. We have therefore examined the activity of the new compound against Escherichia coli, the most common urinary tract pathogen, by continuous turbidimetric monitoring of static cultures exposed to the drug and by means of a mechanical model that simulates the hydrokinetic aspects of the treatment of bacterial cystitis. The activity offlumequine in these systems was compared with those of nalidixic and oxolinic acids.MATERIALS AND MErHODS Flumequine was provided by Riker Laboratories Ltd., nalidixic acid was provided by Winthrop Laboratories, and oxolinic acid was provided by Wm. R. Warner & Co., Ltd. Solutions of the drugs were freshly prepared as they were required by dissolving weighed powder in 0.5 ml of 1 N NaOH and adjusting to the required concentration with sterile distilled water.The growth medium was a "complete" broth (pH 6.8; 325 mosmol/kg), which has previously been described (7).Turbidimetric studies were performed with a 12-channel bacterial growth-monitoring device (12). Volumes of broth (25 ml each) were inoculated with bacteria from overnight broth cultures to produce an inoculum of ca. 5 x 106 bacteria per ml. The drug was either included in the broth to which the inoculum was added or, in experiments designed to study the response of dense inocula, was added at a standard point in the logarithmic growth phase (30% of maximum opacity) equivalent to a viable count of ca. 5 x 107 bacteria per ml. The design of the in vitro "bladder" model has been described in detail elsewhere (8,13

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Section: Resultsmentioning

confidence: 99%

Activity of flumequine against Escherichia coli: in vitro comparison with nalidixic and oxolinic acids

Greenwood¹

1978

Antimicrob Agents Chemother

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“…Oxolinic acid (5-ethyl-5,8-dihydro-8-oxo-l,3 dioxolo[4,5- g ]quinoline-7-carboxylic acid, Figure 1 A) is a first generation quinolone, developed by Warner-Lambert, approved by the FDA in the 1970s for the treatment of bacterial urinary infections not associated with bacteremia in adults [ 24 ]. The spectrum of activity is rather narrow and includes some Gram-negative bacteria [ 25 , 26 , 27 ]. Still, it has not proven itself to be more effective or better tolerated than other drugs such as nalidixic acid, ampicillin or trimethoprim-sulfamethoxazole [ 24 , 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

Rare-Earth Metal Complexes of the Antibacterial Drug Oxolinic Acid: Synthesis, Characterization, DNA/Protein Binding and Cytotoxicity Studies

Măciucă

Arbănași

Mihăilă³

et al. 2020

Molecules

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“Drug repositioning” is a current trend which proved useful in the search for new applications for existing, failed, no longer in use or abandoned drugs, particularly when addressing issues such as bacterial or cancer cells resistance to current therapeutic approaches. In this context, six new complexes of the first-generation quinolone oxolinic acid with rare-earth metal cations (Y3+, La3+, Sm3+, Eu3+, Gd3+, Tb3+) have been synthesized and characterized. The experimental data suggest that the quinolone acts as a bidentate ligand, binding to the metal ion via the keto and carboxylate oxygen atoms; these findings are supported by DFT (density functional theory) calculations for the Sm3+ complex. The cytotoxic activity of the complexes, as well as the ligand, has been studied on MDA-MB 231 (human breast adenocarcinoma), LoVo (human colon adenocarcinoma) and HUVEC (normal human umbilical vein endothelial cells) cell lines. UV-Vis spectroscopy and competitive binding studies show that the complexes display binding affinities (Kb) towards double stranded DNA in the range of 9.33 × 104 − 10.72 × 105. Major and minor groove-binding most likely play a significant role in the interactions of the complexes with DNA. Moreover, the complexes bind human serum albumin more avidly than apo-transferrin.

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“…Since the discovery of nalidixic and oxolinic acids (10,13), many modifications have been introduced in the chemical structure of the quinolonic ring, yielding new drugs with improved antibacterial efficacy against gram-positive and anaerobic bacteria and with enhanced bioavailability, such as norfloxacin (11), ofloxacin (21), ciprofloxacin (25), and tosufloxacin (23). In a recent review, Domagala (4) established a model in which every junction of a substituent has a specific property in addition to that of the substituent itself.…”

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confidence: 99%

Antibacterial Activities and Pharmacokinetics of E-4767 and E-5065, Two New 8-Chlorofluoroquinolones with a 7-Azetidin Ring Substituent

Gargallo-Viola

Ferrer

Tudela

et al. 2001

Antimicrob Agents Chemother

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E-4767 {(؊)-7-[3-(R)-amino-2-(S)-methyl-1-azetidinyl]-8-chloro-1-cyclopropyl-1,4-dihydro-6-fluoro-4-oxo-3-quinolinecarboxylic acid} and E-5065 [(؊)-7-(3-amino-1-azetidinyl)-8-chloro-1-cyclopropyl-1,4-dihydro-6-fluoro-4-oxo-3-quinolinecarboxylic acid] are two new chlorofluoroquinolones with an azetidine moiety at position 7. Their in vitro activities were evaluated in comparison with those of ciprofloxacin, ofloxacin, fleroxacin, and tosufloxacin, while ciprofloxacin was used as a reference for in vivo studies. Against gram-positive organisms, E-4767 and E-5065 were, in general, eight-and fourfold more active than tosufloxacin, which is the most potent of the reference compounds. E-4767 and E-5065 were also more potent than the reference compounds against all species of enteric bacteria tested. The MICs of E-4767 and E-5065 at which 90% of the isolates tested were inhibited (MIC 90 s) were 0.007 to 0.5 g/ml and 0.03 to 2 g/ml, respectively, for gram-positive organisms and <0.003 to 0.06 g/ml and 0.007 to 0.12 g/ml, respectively, for members of the family Enterobacteriaceae except Serratia marcescens and Providencia spp. (MIC 90 s of E-4767 and E-5065 for these species were <0.5 g/ml and <2 g/ml, respectively). For Pseudomonas aeruginosa both compounds had a MIC 90 of 0.5 g/ml. E-4767 and E-5065 were 356-and 32-fold more potent than ciprofloxacin against Bacteroides spp., and their MIC 90 s for Clostridium spp. were 0.25 and 0.5 g/ml, respectively. Both products showed a remarkable reduction of activity when the pH was below 4.8 and, in general, were less active in the presence of 5 or 10 mM Mg 2؉ . The presence of horse serum or human urine (pH 7.2) decreased the activity of E-4767 and E-5065 only two-to fourfold more than the activity observed in broth. After an oral dose of 50 mg/kg of body weight, the maximum levels in serum (the maximum concentration of drug in serum was reached 30 min postadministration) of E-4767 and E-5065 were approximately threefold higher than that of ciprofloxacin. The area under the concentration-time curve from 0 to 4 h for ciprofloxacin was about two-and fourfold lower than that for E-4767 and E-5065, respectively. These two new chlorofluoroquinolones were as effective as or more effective than ciprofloxacin against all experimental infections evaluated, not only against gram-negative bacteria, such as Escherichia coli or P. aeruginosa, but also against gram-positive pathogens, such as Staphylococcus aureus or Streptococcus pneumoniae. E-4767 was the most effective compound, with a 50% effective dose (ED 50 ) of <17 mg/kg for all strains tested except ciprofloxacin-resistant S. aureus strains. The ED 50 of E-4767 for these strains was <47.5 mg/kg. Against gram-positive experimental infections, the ED 50 values of E-4767 were 3-to 14-fold lower than those of E-5065 and up to 25 times lower than those of ciprofloxacin.Since the discovery of nalidixic and oxolinic acids (10, 13), many modifications have been introduced in the chemical structure of the quinolonic ring, yielding new drug...

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In Vitro Susceptibility Comparisons and Recommendations for Oxolinic Acid

Cited by 5 publications

References 5 publications

Activity of flumequine against Escherichia coli: in vitro comparison with nalidixic and oxolinic acids

Activity of flumequine against Escherichia coli: in vitro comparison with nalidixic and oxolinic acids

Rare-Earth Metal Complexes of the Antibacterial Drug Oxolinic Acid: Synthesis, Characterization, DNA/Protein Binding and Cytotoxicity Studies

Antibacterial Activities and Pharmacokinetics of E-4767 and E-5065, Two New 8-Chlorofluoroquinolones with a 7-Azetidin Ring Substituent

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