In vitro antibacterial activity of norfloxacin (MK-0366)

WIN 49375 (amifloxacin) is a synthetic antibacterial agent of the quinolone class. It is similar in chemical structure to pefloxacin but differs by containing a methylamino, rather than an ethyl, substituent at the 1-N position. The activity of WIN 49375 in vitro was comparable to those of norfloxacin and pefloxacin against Enterobacteriaceae and generally greater than those of tobramycin and cefotaxime. WIN 49375 was more active in vitro than carbenicillin and mezlocillin against Pseudomonas aeruginosa isolates and showed moderate activity against Staphylococcus aureus, with MICs of <2 ,ug/ml. The in vitro activity of WIN 49375 was not markedly affected by the presence of human serum, the size of the bacterial inoculum, or changes in pH between 6 and 8. Against systemic, gram-negative bacterial infections in mice, WIN 49375 was generally less active than cefotaxime but more active than gentamicin. WIN 49548, the major piperazinyl-N-desmethyl metabolite of WIN 49375, was as effective as the parent drug against experimental infections in mice when given parenterally. When administered orally, however, this metabolite was less potent than WIN 49375. WIN 49375 was highly active by the oral route, with 50% effective doses within two-to threefold of those obtained with parenteral medication.

Section: Discussionsupporting

confidence: 80%

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confidence: 99%

In vitro and in vivo antibacterial activities of the fluoroquinolone WIN 49375 (amifloxacin)

Cornett¹,

Wagner²,

Dobson³

et al. 1985

“…It should be pointed out, however, that in several recent reports (8,13,15) In previous investigations, the quinoline drugs oxolinic and nalidixic acids, to which norfloxa-VOL. 23,1983 on May 12, 2018 by guest http://aac.asm.org/ Downloaded from cin is structurally related, were found to be active both in vitro (6,16) and in vivo (10,17) against antibiotic-resistant shigellae. Furthermore, the efficacy of oxolinic acid in treating chronic Shigella carriers has been reported (32 Although the development of resistance to nalidixic and oxolinic acids during treatment of urinary tract infections has been shown (1, 7), it is believed that the quinolines still have a significant advantage over other commonly used agents in that resistance appears not to be mediated by R factors (1,5), a property which in theory should greatly limit the spread of resistant strains.…”

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confidence: 99%

“…Its increased potency and expanded antibacterial spectrum compare with those of nalidixic acid (9,13,20,22,23), and its desirable pharmacokinetic properties (4) The anaerobic bacterium Clostridium difficile was less susceptible to norfloxacin (MIC90, 128 ,ug/ml) and to nalidixic acid (MIC90, >128 ,ug/ml) than to other agents and was most susceptible to vancomycin (MIC90, 0.5 ,ug/ml). The MIC9os of norfloxacin against all the aerobic isolates tested were less than 1 ,ug/ml, ranging from 0.008 ,ug/ml for E. coli to 0.5 ,ug/ml for Campylobacter fetus subsp.…”

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confidence: 99%

In vitro antibacterial activity of norfloxacin (MK-0366, AM-715) and other agents against gastrointestinal tract pathogens

Shungu¹,

Weinberg²,

Gadebusch³

1983

A comparison was made of the in vitro activities of norfloxacin and of nine other orally administered antibacterial agents against 180 clinical isolates representing the bacterial species most frequently implicated in infections of the gastrointestinal tract in humans. The 90% minimal inhibitory concentrations showed norfloxacin to be 4, 15, 4, 17, 17, 17, and 33 times more active than the next best compound tested against Campylobacter fetus subsp. jejuni, Escherichia coli, Salmonella spp., Shigella spp., Vibrio cholerae, Vibrio parahaemolyticus, and Yersinia enterocolitica, respectively, with an overall 90% minimal inhibitory concentration of less than or equal to 0.5 micrograms/ml. Norfloxacin was least active against Clostridium difficile (90% minimal inhibitory concentration, 128 micrograms/ml). These results should encourage further evaluation of norfloxacin as a potential chemotherapeutic agent in the treatment of enteric bacterial infections for which antibiotic therapy is indicated.

“…This compound, like the structurally related norfloxacin (1)(2)(3)(4)(5)10), has a high order of activity against a broad spectum of gram-positive, gram-negative, and glucose-nonfermenting bacteria. Its activity is in general superior to that of pipemidic acid, nalidixic acid, oxolinic acid, cephalexin, ampicillin, carbenicillin, and gentamicin in vitro and in vivo (11).…”

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confidence: 99%

In vitro and in vivo antibacterial activity of AT-2266

Kouno¹,

Inoue²,

Mitsuhashi³

1983

AT-2266 [1-ethyl 6fluoro-1,44dihydro4oxo-7-(l-piperazinyl)-1 ,8naphthyridine-3-carboxylic acid] showed a broad spectrum of antibacterial activity against grampositive and gram-negative microorganisms, including Pseudomonas aeruginosa. The in vitro antibacterial activity of AT-2266 was in general comparable to that of norfloxacin, but much higher than that of pipemidic or nalidixic acid. The 90% minimal inhibitory concentrations (MIC90s) of AT-2266 for P. aeruginosa resistant to gentamicin (MIC range, 25 to >200 ,ug/ml) and Enterobacteriaceae resistant to nalidixic acid (25 to >1,600 ,ug/ml) were 3.13 and 12.5 Ijg/ml, respectively. TheMICs of AT-2266 were only slightly affected by the addition of horse serum or sodium cholate, by the pH of the medium, and by inoculum size. AT-2266 was bactericidal at concentrations near its MIC value. The 50%o effective doses of AT-2266 after oral administration against systemic infections in mice were about 1/2 those of norfloxacin, about 1/10 those of pipemidic acid, and between 1/20 and 1/40 those of nalidixic acid.acid] is a new pyridonecarboxylic acid derivative synthesized by Matsumoto et al. (7). This compound, like the structurally related norfloxacin (1-5, 10), has a high order of activity against a broad spectum of gram-positive, gram-negative, and glucose-nonfermenting bacteria. Its activity is in general superior to that of pipemidic acid, nalidixic acid, oxolinic acid, cephalexin, ampicillin, carbenicillin, and gentamicin in vitro and in vivo (11). Oral administration of AT-2266 to animals produced concentrations in body fluids and tissues high enough to cover the minimal inhibitory concentrations (MICs) of a large variety of bacterial pathogens (9). Because there was no evidence of cross-resistance with agents such as streptomycin, chloramphenicol, tetracycline, ampicillin, or cephalexin (11,12), AT-2266 might be a potentially useful drug against various pathogens which are now resistant to these antibiotics. To estimate the chemotherapeutic value of AT-2266, we compared its in vitro and in vivo antibacterial activities with those of norfloxacin, pipemidic acid, and nalidixic acid.MATERIALS AND METHODS Drugs. AT-2266 sesquihydrate and pipemidic acid trihydrate were obtained from Dainippon Pharmaceutical Co., Ltd.; norfloxacin was from Kyorin Pharmaceutical Co., Ltd.; nalidixic acid was from Daiichi Seiyaku Co., Ltd.; and gentamicin was from Shionogi Co., Ltd.Organisms. The organisms used were reference strains stored in our laboratories and recent clinical isolates randomly collected in various hospitals in Japan.Determination of MICs. MICs were determined by the twofold agar dilution method. The media used for preculture and MIC determination were brain heart infusion broth and agar (Difco Laboratories), respectively, for streptococci; brain heart infusion broth and agar (Difco) supplemented with hemin (10 /ml) and P-NAD (Sigma Chemical Co.) for Haemophilus influenzae; GAM broth and agar (Nissui) for obligate anaerobes, and sensitivity test broth and agar (Nissui) ...