Antibacterial activities of ciprofloxacin, norfloxacin, oxolinic acid, cinoxacin, and nalidixic acid

Abstract

In vitro studies were performed comparing ciprofloxacin (Bay o 9867) and norfloxacin with three related organic acids. Ciprofloxacin was two to eight times more active than norfloxacin against 658 bacterial isolates representing 30 species. For all species tested, ciprofloxacin MICs for 90% inhibition were c 2.0 pL-g/ ml. Additional tests with 5,994 isolates detected only 37 (0.6%) strains resistant to 2.0 pLg of ciprofloxacin per ml and 106 (1.8%) resistant to 1.0 F.g/ml. Only 6 (0.1%) of the 5,994 strains were resistant to 16 j±g of norfloxacin per ml, and 129 (2.1%) were resistant to 4.0 ,ug/ml. The majority of resistant strains were streptococci or Pseudomonas spp. Resistance among the Enterobacteriaceae was extremely rare (i.e., > 99.8% susceptible to both drugs).Ciprofloxacin (Bay o 9867) is a new quinolone carboxylic acid derivative that is being developed for oral and parenteral use in treatment of systemic infections as well as urinary tract infections (1,3,5,7,9). Structurally, ciprofloxacin closely resembles norfloxacin, except that ciprofloxacin has a cyclopropyl group in the 1 position, whereas norfloxacin has an ethyl group in that position. In this report, we compare the in vitro activity of ciprofloxacin with that of norfloxacin and three related organic acids currently being used for treatment of urinary tract infections. Broth microdilution tests were first performed with 658 isolates representative of common bacterial species. To further document the incidence of resistance among isolates currently being encountered, all isolates selected for susceptibility testing in four different clinical laboratories were tested against ciprofloxacin and norfloxacin for 30 to 45 days.MATERIALS AND METHODS Antimicrobial agents. Ciprofloxin was supplied as laboratory standard powder by Miles Pharmaceuticals (West Haven, Conn.). Norfloxacin was provided by Merck Institute for Therapeutic Research, Rahway, N.J. Nalidixic acid was obtained from Sterling Winthrop Research Institute, Rensselaer, N.Y. Eli Lilly Research Laboratories, Indianapolis, Ind., provided cinoxacin and oxolinic acid. Ciprofloxacin was dissolved and diluted in sterile water, and the other drugs were dissolved in 0.1 N NaOH and diluted in sterile water.Bacterial isolates. The 658 aerobic or facultatively anaerobic bacterial isolates used in the first phase of this study were collected from six geographically separate medical centers, and additional isolates were contributed by the Centers for Disease Control, Atlanta, Ga. The contributing laboratories include The Cleveland Clinic Foundation,

Liquid Chromatographic Determination of Ciprofloxacin and Some Metabolites in Human Body Fluids

“…Ciprofloxacin is a very potent antimicrobial agent äs compared with other groups of antibiotics (1)(2)(3)(4)(5)(6)(7)(8). E. g., MIC90 values of 0.015 to 2 mg/1 were reported for several Gram-negative species (2).…”

Quinolonas: Perspectivas actuales y mecanismos de resistencia

“…La investigación de compuestos similares, como 1,8 naftiridonas, resultó en el descubrimiento del ácido nalidíxico (1-etil-7-metil-4-oxo-1,8-naftiridina-3-ácido carboxílico) en 1962, convirtiéndose en la primera quinolona sintética con actividad antimicrobiana, especialmente para el tratamiento de infecciones de vías urinarias no complicadas 6 . Esto llevó al desarrollo de otros antimicrobianos basados en el anillo 4-quinolona, como el ácido oxolínico, cinoxacina y flumequina, usados clínicamente para tratar infecciones causadas por bacterias gramnegativas [7][8][9] . A través de los años, el ácido nalidíxico ha sido modificado con el objetivo de obtener un espectro más amplio de cobertura antimicrobiana, dando origen a las primeras fluoroquinolonas.…”

Molecular Background of Fluoroquinolone Resistance in Pathogenic Human Mycoplasmas

“…В 1984 г., когда применение фторхинолонов еще только входило в клиническую практику, при тестировании 5994 изолятов 30 различ-ных видов было найдено всего 37 устойчивых изолятов [4]. Спустя 30 лет доля устойчивых к фторхинолонам изолятов различных видов значительно возросла и составляет 10-25% в Европе и до 45% -в Гонконге [16].…”