Showing papers on "Quinolone published in 1986"

Inhibition of Micrococcus luteus DNA gyrase by norfloxacin and 10 other quinolone carboxylic acids.

Abstract: The ability of norfloxacin, amifloxacin, cinoxacin, ciprofloxacin, flumequine, nalidixic acid, ofloxacin (OFL), oxolinic acid, perfloxacin, pipemidic acid, and rosoxacin to inhibit the in vitro supercoiling activity of Micrococcus luteus DNA gyrase was compared with the ability of each drug to inhibit the growth of the M. luteus strain from which the gyrase was purified. The potency of the quinolones as DNA gyrase inhibitors did not always correlate with antimicrobial potency. For example, OFL was a less potent inhibitor of gyrase than rosoxacin, yet the MIC of OFL was 16-fold lower than that of rosoxacin. Similarly, the MICs of norfloxacin and ciprofloxacin (the most potent of the antibiotics tested in these assays) were several hundredfold lower than the MIC of nalidixic acid (the least potent of these antibiotics), but the inhibition of purified gyrase by these two quinolones was only 8- to 16-fold lower than that of nalidixic acid. These results suggest that factors in addition to inhibition of gyrase supercoiling activity are important in determining the potency of these drugs. Further studies indicated that the uptake of norfloxacin, OFL, and amifloxacin by M. luteus cells may not account for the large differences in MICs observed for these drugs (MICs of 0.8, 2.0, and 128 micrograms/ml, respectively).

Antibacterial activity of ofloxacin and its mode of action.

Abstract: The antibacterial activity of ofloxacin against Enterobacteriaceae,Pseudomonas aeruginosa, Haemophilus influenzae, Branhamella catarrhalis, andNeisseria gonorrhoeae was comparable to norfloxacin and enoxacin, and far exceeded the activity of pipemidic acid and nalidixic acid. The activity of ofloxacin was two to eight times less than that of ciprofloxacin. Ofloxacin was more active againstStaphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Acinetobacter spp.,Legionella spp., andBacteroides fragilis, than norfloxacin, enoxacin, pipemidic acid and nalidixic acid, and the activity of ofloxacin was comparable to that of ciprofloxacin. Ofloxacin was two to seven times more effective than norfloxacin in systemic infections in mice withS. aureus, Escherichia coli, Serratia marcescens andP. aeruginosa. Ofloxacin strongly inhibited DNA supercoiling activity of DNA gyrase purified fromE. coli KL-16. There is a parallel relationship between antibacterial activity of ofloxacin and its inhibitory action against DNA gyrases from ofloxacin-susceptible and ofloxacin-resistant clinical isolates ofE. coli. These results indicate that the high bactericidal action of ofloxacin and the related new quinolone agents can be explained by their potent inhibitory activities against DNA gyrase in bacterial cells.

Elimination of plasmids from Enterobacteriaceae by 4-quinolone derivatives

Abstract: Twelve 4-quinolones (cinoxacin, ciprofloxacin, enoxacin, flumequin, nalidixic acid, norfloxacin, oxolinic acid, pefloxacin, pipemidic acid, rosoxacin, and piromidic and beta-hydroxypiromidic acids) and novobiocin, were used at subinhibitory concentrations to eliminate from Escherichia coli 11 antibiotic resistance plasmids belonging to different incompatibility groups. The 12 4-quinolones were also tested for their ability to cure virulence plasmids from five species of Enterobacteriaceae. All quinolones eliminated three antibiotic resistance plasmids (R446b, R386, S-a) and one virulence plasmid (pWR105), but at a low rate. Optimal curing of antibiotic resistance plasmids was obtained in human urine. Two virulence plasmids (pWR24 and pWR110) were eliminated only by flumequin and pefloxacin. Novobiocin eliminated three antibiotic resistance plasmids (R446b, R386, pIP24). The variable and low level of plasmid loss may be explained by the induction of the recA system. In addition, the inability to eliminate certain plasmids could be due to their presence in high numbers per cell.

Comparative in vitro activity of seven quinolones against 100 clinical isolates of Clostridium difficile.

Abstract: The in vitro activity of seven quinolone derivatives against 100 clinical isolates of Clostridium difficile was determined. CI934 was the most active, inhibiting 90% of the strains at 4 micrograms/ml and 100% at 8 micrograms/ml. Ofloxacin and ciprofloxacin had moderate activity (16 and 32 micrograms/ml) whereas enoxacin, pefloxacin, norfloxacin, and nalidixic acid had poor activity (128 micrograms/ml).

Quinolones and colonization resistance in human volunteers.

Abstract: The suppression of alimentary canal flora by the three quinolones nalidixic acid, ciprofloxacin and pefloxacin was investigated in fifteen volunteers. They received the three quinolone compounds in tablet form both uncoated and colon-coated.Escherichia coli suppression was poor under nalidixic acid, but complete under ciprofloxacin and pefloxacin for both administration forms. The indigenous anaerobic flora contributing to the control of aerobicStreptococcus faecalis andCandida albicans in the intestines ('colonization resistance') was not affected by nalidixic acid and pefloxacin, and only slightly by ciprofloxacin. Out of the three quinolone compounds, only colon-coated pefloxacin was associated with a considerable absorption rate at colonie level. Using these criteria of successfulEscherichia coli clearing from the intestinal canal - left the indigenous flora more or less intact (in a 'selective' way) - and a good absorption rate, pefloxacin is found to be superior to ciprofloxacin and nalidixic acid. These results suggest that a colon-coated tablet with a low dose of pefloxacin is a promising administration form in the therapy of recurrent urinary tract infections and diarrhoeal diseases and in the prevention of gut colonization in immunocompromised hosts.

Chiral DNA gyrase inhibitors. 1. Synthesis and antimicrobial activity of the enantiomers of 6-fluoro-7-(1-piperazinyl)-1-(2-trans-phenylcyclopropyl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid

Abstract: New quinolone antimicrobial agents (racemic, (1'S,2'R)- and (1'R,2'S)-6-fluoro-7-(1-piperazinyl)-1-(2'-trans-phenyl-1'-cyclopropyl)- 1, 4-dihydro-4-oxoquinoline-3-carboxylic acids) were synthesized, and their in vitro antimicrobial potencies and spectra were determined. As compared to their conceptual parents, these agents retained a considerable amount of the antimicrobial potency and spectra of ciprofloxacin and of 6-fluoro-1-phenyl-7-(1-piperazinyl)-1,4-dihydro-4-oxoquinoline-3-carboxy lic acid against Gram-positives. Gram-negatives were considerably less sensitive. The (-)-(1'S,2'R) analogue was the more potent of the enantiomers, but the degree of chiral discrimination by most bacteria was only 4-fold. The 4-fold chiral discrimination was observed also using purified DNA gyrase obtained from Micrococcus luteus, whereas the two enantiomers were essentially equiactive against the enzyme derived from Escherichia coli. These results confirm that there is a substantial degree of bulk tolerance available at N-1 of quinolone antimicrobial agents and suggest that electronic factors controlled by substitution at that site are of considerable importance. On the other hand, chiral recognition brought about by attachment of optically active groups to the N-1 position in these derivatives is relatively small.

In vitro activities of U-63366, a spectinomycin analog; roxithromycin (RU 28965), a new macrolide antibiotic; and five quinolone derivatives against Haemophilus ducreyi.

Abstract: Theinvitro activities ofthenew spectinomycin analog U-63366, thenew macrolide roxithromycin (RU 28965), andfive new quinolone derivatives (pefloxacin, rosoxacin, norfloxacin, ofloxacin, andciprofloxacin) were studied against 23multiresistant strains ofHaemophilus ducreyi (beta-lactamase producers) isolated in Paris andwere comparedwiththeactivities oftetracycline, minocycline, chloramphenicol, streptomycin, kanamycin, gentamicin, spectinomycin, erythromycin, andnalidixic acid. Allstrains were uniformly susceptible tothesevennew antibiotics tested. Ciprofloxacin hadthegreatest inhibitory effect invitro (theMIC for 90% ofthestrains tested [MIC90] was 0.016,ug/ml), andU-63366 was themostactive aminoglycoside

Chapter 14. Quinolone Antibacterial Agents

Abstract: Publisher Summary The renewed interest in quinolone antibacterials that began 5 years ago with the first descriptions of norfloxacin (NOR), pefloxacin (PEF), and enoxacin (ENO) has continued unabated. After two decades of only modest improvements in the antibacterial potency, the activity of the new fluoro- quinolones far surpasses that of the original quinolone, nalidixic acid (NAL, I). The most significant changes made in the quinolone nucleus, addition of fluorine and piperazine have provided these fluoroquinolones with activity against gram- negative bacteria that rivals that of the major classes of antibiotics. The increased potency of the new fluoroquinolones holds promise for a greatly expanded clinical use. This includes the potential for treatment of bacterial prostatitis, gastroenteritis, osteo-myelitis, some pneumonias and infections caused by multiply-resistant Enterobacteriaceae and methicillin-resistant staphylococci. Engagement in the R&D of quinolone antibacterials has resulted in clinical trials with at least eight different fluoroquinolones throughout the world, of which four have received approval for clinical use outside the US. Relative to the first commercially introduced fluoroquinolone, NOR, subsequent analogues have shown greater oral absorption (PEF, ENO) and increased serum. This chapter complements recent reviews describing the mechanism of action and resistance, toxicity, pharmacology and SAR's of the quinolone antibacterials. The chapter discusses cirofloxacin (the most potent of the quinolone antibacterials), norfloxacin, ofloxacin, enoxacin, pefloxacin, amiflcucacin, difloxacin (A-56619), A-56620, CI-934, S-25930, S-25932, and other new quinolones—their usefulness against various microbes, and also the comparison of one compound's effectiveness to another.

Influence of ofloxacin, norfloxacin, nalidixic acid, pyromidic acid and pipemidic acid on human γ-interferon production and blastogenesis

Abstract: Several new quinolone derivatives were investigated for their influence on human lymphocyte blastogenesis and gamma-interferon production following concanavalin A stimulation. All the antimicrobials induced inhibition of lymphocyte DNA synthesis. The gamma-interferon measurements showed that nalidixic acid and norfloxacin have a negative influence on lymphokine production and release.

In vitro activity of A-56619 (difloxacin), A-56620, and other new quinolone antimicrobial agents against genital pathogens.

Abstract: The in vitro activities of two new carboxyquinolones, A-56619 (difloxacin) and A-56620, were compared with those of ciprofloxacin, norfloxacin, and ofloxacin against genital tract pathogens. All the quinolones were highly active against Neisseria gonorrhoeae. A-56619 had the lowest MICs against Chlamydia trachomatis (MIC range, 0.125 to 0.25 micrograms/ml) and Haemophilus ducreyi (MIC for 90% of isolates tested, 0.1 micrograms/ml).

Comparative in vitro Activities of Ciprofloxacin, Enoxacin, Norfloxacin, Ofloxacin and Pefloxacin against Bacteroides fragilis and Clostridium difficile

Abstract: The in vitro activity of ciprofloxacin, enoxacin, norfloxacin, ofloxacin and pefloxacin against 99 Bacteroides fragilis strains and 105 Clostridium difficile strains were determined by the agar dilution method. Ofloxacin was the most potent agent. The MIC for 90% of the B. fragilis and C. difficile strains was 8 mg/l. Ciprofloxacin had MIC90's of 16 mg/l for B. fragilis and C. difficile. The MIC90's of pefloxacin against B, fragilis and C. difficile were 32 mg/l. 90% of the B. fragilis strains were inhibited by 32 mg/l enoxacin, while the MIC90's of enoxacin as well as of norfloxacin against C. difficile were 64 mg/l. The lowest activity against B. fragilis was obtained with norfloxacin (MIC90's of 128 mg/l). Since serum levels of these agents are reported to be between 1 and 3 mg/l after orally administered doses, B. fragilis and C. difficile should be regarded as insusceptible to these quinolone compounds.

New oral quinolone compounds in chronic bronchitis

Abstract: Clinical, microbiological and pharmacokinetic results are presented from studies in 186 patients treated with the new quinolone antimicrobial agents enoxacin, pefloxacin, ciprofloxacin or ofloxacin. Almost all had been admitted to hospital for acute purulent exacerbations of chronic bronchitis, associated mainly with Haemophilus influenzae, Streptococcus pneumoniae, Branhamella catarrhalis or Pseudomonas aeruginosa. The H. influenzae and B. catarrhalis strains were generally very sensitive to the quinolones and sputum concentrations of 1.3 to 4.5 mg/l exceeded the MICs (geometric mean values 0.07 to 0.44 mg/l) by a factor of more than 10. In contrast, P. aeruginosa was slightly less sensitive (geometric mean MICs 0.4 to 4.4 mg/l) and S. pneumoniae much less so (with geometric mean MICs between 0.84 and 6.7 mg/l) and a number of treatment failures were noted with these organisms. Various unwanted drug effects (mostly upper gastro-intestinal) were seen, particularly with enoxacin. The best clinical results were observed with ofloxacin, even with once daily dosage, but the results with the other quinolones could only be described as moderate.

The in-vitro comparative activity of quinolones against bacteria from urinary tract infections in general practice

Abstract: In a study of lower urinary tract infection in general practice over twelve hundred strains have been isolated. Eight hundred and sixty-six consecutive strains were tested against four quinolone compounds. Sixty-nine per cent of the isolates were Escherichia coli and 15% coagulase-negative staphylococci (mostly Staphylococcus saprophyticus). The diffusion method, according to I.C.S. recommendation, was used and standardized for extrapolation of MIC results. Ciprofloxacin followed by norfloxacin and pefloxacin, was the most active quinolone compound (MIC 0 X 015-2 mg/l) against all strains, including multiresistant ones.

In vitro activity of A-56619 and A56620, two new aryl-fluoroquinolone antimicrobial agents.

Abstract: The in vitro antimicrobial activity of two new aryl-fluoroquinolone antibiotics, A-56619 and A-56620, was compared with those of norfloxacin and several other antibiotics against 448 bacterial isolates. A-56620 was the most active agent tested. The usual 90% MIC of A-56620 was less than or equal to 2 micrograms/ml, except for enterococci, gentamicin-resistant Serratia marcescens, and gentamicin-resistant Pseudomonas aeruginosa, for which the 90% MIC was 4 micrograms/ml. A-56619 and norfloxacin were generally severalfold less active than A-56620. Cross resistance was observed between the quinolone antibiotics and other unrelated antibiotic classes.

The comparative in-vitro activity of norfloxacin, ciprofloxacin, enoxacin and nalidixic acid against 423 strains of Gram-negative rods and staphylococci isolated from infected hospitalised patients

Abstract: The in-vitro activities of four quinolone carboxylic acids against 423 clinical isolates of Gram-negative rods and staphylococci from infected hospitalised patients were compared. The antibiotics included nalidixic acid and the newer compounds, norfloxacin (MK-0366), ciprofloxacin (Bay 09867) and enoxacin (AT 2266 or CI919). Norfloxacin showed slightly more activity than enoxacin, but both agents had markedly greater potencies and broader antibacterial spectrums than nalidixic acid. Ciprofloxacin was the most active quinolone tested against both gentamicin-susceptible and gentamicin-resistant stains, having an MIC90 equal or less than 1 mg/l for all species studied.

Chemotherapeutic effects of ofloxacin (HOE 280) and other quinolone-carboxylic derivates in the treatment of experimental lung infections due to Klebsiella pneumoniae DT-S in mice.

Abstract: The chemotherapeutic activity of ofloxacin (HOE 280), a new pyridone-carboxylic acid derivative, was compared with that of other drugs in the same group, including norfloxacin, ciprofloxacin, enoxacin and in some cases pipemidic acid and nalidixic acid. The test model used was experimental pneumonia caused byKlebsiella pneumoniae DT-S in mice. In the treatment of pneumonic mice, ofloxacin was 4 to 18 times more effective than norfloxacin and enoxacin and in most cases slightly more effective than ciprofloxacin. Pipemidic acid and nalidixic acid showed only low activity or proved to be inactive. In studies on the bactericidal activity of the compoundsin vivo, ofloxacin produced a more pronounced effect than ciprofloxacin. With norfloxacin and enoxacin, a bactericidal effect in the infected tissue of the animals was only observed during the first hours after treatment.

Quinolones in vitro.

Abstract: The first quinolone compound, nalidixic acid, showed activity against a limited number of Gram-negative micro-organisms. ‘One step’ resistance developed hiin vitro and during treatment. Resistance was not mediated by transfer of R-plasmids, which is a characteristic of all quinolones. Newer quinolones like oxolinic acid, piromidic acid, cinoxacin and pipemidic acid exhibit an extended spectrum of activity against Gram-negative bacteria at lower MIC values. In recent years fluorinated quinolones were introduced like ciprofloxacin, norfloxacin, pefloxacin, ofloxacin, enoxacin and amifloxacin. These compounds exhibitin vitro a broad spectrum of activity against Gram-negative and Gram-positive bacteria at MIC values seventy to four hundred times less than those for nalidixic acid. Thein vitro activity of these compounds has been investigated in a large study of uncomplicated urinary tract infections in general practice (PINISU). No resistance was found. The fluorinated quinolones are very promising antimicrobial agents for a limited number of indications.

International experiences with ofloxacin, a new quinolone.

Abstract: In vitro andin vivo antibacterial activities of ofloxacin, a new quinolone, are presented. Ofloxacin was found to be characterized by potent bactericidal activity due to its strong inhibition of bacterial DNA gyrase. The high antibacterial activity of ofloxacinin vivo was discussed with respect to its physicochemical properties, i.e., hydrophobicity and bioavailability including high serum concentrations and easy entry into bacterial cells.