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Enoxacin was evaluated in in-vitro tests and in studies of effectiveness and blood concentrations in the mouse. Enoxacin was active against both susceptible and multiresistant hospital isolates of Enterobacteriaceae, Pseudomonas aeruginosa, Haemophilus influenzae, Neisseria gonorrhoeae and staphylococci. Less susceptible were streptococci and anaerobes. Of nine quinolones tested, only norfloxacin was equivalent in vitro. The MBCs of enoxacin were one- to twofold greater than the MICs, and enoxacin was rapidly bactericidal. No single-step resistant mutants could be detected at 10 mg/l against large inocula and six to 11 steps were required for selection of resistant clones. In systemic mouse infections, enoxacin was effective in a single oral or subcutaneous dose against one strain each of Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Providencia rettgeri and Ps. aeruginosa, and two Staphylococcus aureus strains. Single oral and subcutaneous enoxacin doses (50 mg/kg) gave peak mouse blood levels of 4.9 and 9.5 mg/l and an elimination half-life of 1.8 h.
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Three novel copper(II) complexes with the second-generation quinolone antibacterial agents norfloxacin (nfH) and ofloxacin (ofloH) have been synthesized resulting in the complexes [Cu(nfH)(phen)Cl]Cl·5H(2)O (1·5H(2)O), [Cu(nfH)(2)]Cl(2)·6H(2)O (2·6H(2)O) and [Cu(II)(ofloH)(2)][(Cu(I)Cl(2))(2)] (3), respectively. The crystal structures of the complexes have been determined by X-ray crystallography revealing that the quinolones act as bidentate ligands coordinated to Cu(II) atom through the pyridone oxygen and a carboxylato oxygen. UV study of the interaction of the quinolones and the complexes with calf-thymus DNA (CT DNA) has shown that they can bind to CT DNA with [Cu(II)(ofloxacin)(2)][(Cu(I)Cl(2))(2)] exhibiting the highest binding constant to CT DNA. The cyclic voltammograms of the complexes in the presence of CT DNA solution have shown that the interaction of the complexes with CT DNA is mainly through electrostatic binding. DNA solution viscosity measurements have shown that the interaction of the compounds with CT DNA by classical intercalation may be ruled out. Competitive studies with ethidium bromide (EB) indicate that the complexes can partially displace the DNA-bound EB suggesting low to moderate competition with EB. Norfloxacin, ofloxacin and their copper complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values.
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Norfloxacin is superior to placebo in relieving symptoms of SIBO-associated IBS.
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S-25930 and S-25932, two new 4-quinolones, were compared to ciprofloxacin, enoxacin, ofloxacin, norfloxacin, cefotaxime, gentamicin, trimethoprim, and ampicillin. S-25930 and S-25932 inhibited 90% of Enterobacteriaceae at less than or equal to 1 mg/l, usually differing only two-fold. The MIC90 for Pseudomonas aeruginosa was 8 mg/l for S-25930 and 16 mg/l for S-25932, compared to MICs of 1 to 8 for the other four quinolones. Both drugs inhibited Enterobacter cloacae, Serratia marcescens and Citrobacter freundii resistant to cefotaxime and Klebsiella species resistant to gentamicin and trimethoprim. The MICs90 were 0.125 and 0.25 mg/l against staphylococci, including methicillin-resistant Staphylococcus aureus and were superior to the MICs of other quinolones; activity against haemolytic streptococci at 1-2 mg/l was also superior. S-25930 and S-25932 showed rapid bactericidal activity at the MBC concentration and both agents showed post-antibiotic suppression of growth of bacteria. The agents were active in acid medium, but activity was reduced by magnesium at 9 mM. A stepwise increase in resistance was produced by serial passage in increasing concentrations of drug.
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A total of 250 urinary isolates (188 Escherichia coli and 62 Klebsiella pneumoniae) were studied for ESBL production by double disc approximation test and disc diffusion confirmatory test (NCCLS). ESBL production was found to be 56% in E. coli and 52% in K. pneumoniae. The double disc approximation test showed false ESBL production in five (2.6%) isolates of E. coli and one (1.6%) K. pneumoniae. The susceptibility of ESBL producers to imipenem, amikacin, nitrofurantion was found to be 100%, 86% and 84% respectively. A high degree of co-resistance to co- trimaxazole and norfloxacin was found in strains of ESBL producers. Seventy five per cent of ESBL producers detected were from hospitalized patients admitted in ICU or undergoing surgery.
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A three day oral antibiotic course was given to 71 elderly bacteriuric subjects with no or only moderate mobility problems. Seven of 17 men (41%) and 34 of 54 women (63%) had strongly positive antibody coated bacteria (ACB) in the urine. Following sensitivity tests and randomization one of the following agents was given: cefadroxil 1 g tid (13 subjects): co-trimoxazole 160/800 mg bd (23 subjects); or norfloxacin 400 mg bd (35 subjects). One week after therapy urines were negative in 13 men (76.5%) and 37 women (68.5%). Patients who were fully mobile and/or were ACB(-) responded better than those with moderate mobility problems or who were ACB(+). At six months, urines were negative in six (40%) of 15 men and 15 (33.3%) of 45 women. Two men and six women of these 21 subjects had a positive urine at one month. Of the three agents tested cefadroxil was less effective in women. The study indicates that a three day course will clear bacteriuria in about 70% of patients at one week, but only about 25% will remain free of infection at six months; these are usually patients with adequate mobility and normal renal function.
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The behavior and fate of three fluoroquinolones (norfloxacin, ofloxacin, and ciprofloxacin), one sulfonamide (sulfamethoxazole), and trimethoprim were investigated at a sewage treatment plant in Umeå, Sweden, in 2004. This plant uses conventional mechanical, chemical, and activated sludge methods to treat the sewage water and digest the sludge; the dewatered digested sludge is pelleted (dry weight > 90% of total weight). Raw sewage water and particles as well as effluents and sludge from specific treatment areas within the plant were sampled. In addition to quantifying the antibiotics within the plant, we characterized the sample matrixes to facilitate evaluation of the results. Of the five substances examined, only norfloxacin, ciprofloxacin, and trimethoprim were present in concentrations higher than their limits of quantification. Norfloxacin and ciprofloxacin sorbed to sludge in a manner that was independent of changes in pH during sewage treatment, and more than 70% of the total amount of these compounds passing through the plant was ultimately found in the digested sludge. The results suggest that fluoroquinolones undergo thermal degradation during pelleting, but more studies are needed to confirm this. Trimethoprim was found in the final effluent at approximately the same concentration and mass flow as in the raw sewage, and could not be quantified in any solid sample. Predicted environmental concentrations, based on consumption data for Umeå municipality, correlated well with the results obtained, especially when the predicted concentrations were corrected to account for the amount of each active substance excreted in urine. The results obtained were compared to those of previous studies of these three substances' behavior and fate and were found to be similar, although some of the other plants studied employed the various treatment steps in different orders.
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Ofloxacin, a new pyridone-carboxylic acid derivative, was evaluated in descending nephritis and subcutaneous abscess models with Staphylococcus aureus in mice in comparison with norfloxacin. Descending nephritis was produced by intravenous injection of S. aureus 39 (MIC 0.78 microgram/ml for ofloxacin and 3.13 micrograms/ml for norfloxacin). Subcutaneous abscess was established by subcutaneous injection of soft agar containing S. aureus 56230 (MIC 0.39 microgram/ml for ofloxacin and 1.56 micrograms/ml for norfloxacin). Three days after infection, the lesions of both models were characterized by purulent inflammation accompanied with massive infiltration of neutrophils and bacterial multiplication. The animals were treated twice a day orally with each compound for 4 consecutive days, and subjected to bacteriological examination 18 h later. In the renal model, the 50% effective doses calculated on the basis of clearance of bacteria from kidneys were 38.4 mg/kg for ofloxacin and greater than 100 mg/kg for norfloxacin. In the subcutaneous model, the 50% effective doses based upon 90% reduction of viable bacteria as compared with untreated controls were 25.2 mg/kg for ofloxacin and greater than 100 mg/kg for norfloxacin. The excellent efficacies of ofloxacin in both infection models are attributed to its high oral absorbability and tissue distribution.
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Fifty-four clinical isolates of "Acinetobacter anitratus" separated cleanly into gentamicin-susceptible (16 strains) and gentamicin-resistant (38 strains) subpopulations. When tested with a 10(4)-CFU inoculum, gentamicin resistance was associated with a greater than fourfold increase in the MICs of norfloxacin, ciprofloxacin, A-56620, tobramycin, and amikacin for 50% of the strains. Antimicrobial agents with MICs for 90% of gentamicin-resistant strains in the susceptible range were ciprofloxacin, A-56619, A-56620, imipenem, SCH-34343, ceftazidime, aztreonam, carbenicillin, ticarcillin, and piperacillin. These agents may be useful alternative drugs for treating infections caused by aminoglycoside-susceptible and -resistant "A. anitratus."
The in vitro activity of S-25930 and S-25932 was compared with that of ciprofloxacin, norfloxacin and nalidixic acid against 740 clinical isolates. The data indicate that S-25930 was more active against Enterobacteriaceae than S-25932 and the latter was more active against gram-positive species. A study of clinical isolates resistant to chemically non-related classes of antibiotics revealed no cross-resistance. Nalidixic acid resistant Enterobacteriaceae showed an eight-fold decrease in susceptibility to the new agents. The killing kinetics of both compounds were good, S-25932 having an optimal bactericidal effect at a concentration of 0.5 mg/l. The data suggests that both agents are effective broad spectrum antibiotics.