title: Transformation of the antibacterial agent norfloxacin by environmental mycobacteria.
abstract: Because fluoroquinolone antimicrobial agents may be released into the environment, the potential for environmental bacteria to biotransform these drugs was investigated. Eight Mycobacterium sp. cultures in a sorbitol-yeast extract medium were dosed with 100 microg ml(-1) of norfloxacin and incubated for 7 days. The MICs of norfloxacin for these strains, tested by an agar dilution method, were 1.6 to 25 microg ml(-1). Cultures were extracted with ethyl acetate, and potential metabolites in the extracts were purified by high-performance liquid chromatography. The metabolites were identified using mass spectrometry and nuclear magnetic resonance spectroscopy. N-Acetylnorfloxacin (5 to 50% of the total absorbance at 280 nm) was produced by the eight Mycobacterium strains. N-Nitrosonorfloxacin (5 to 30% of the total absorbance) was also produced by Mycobacterium sp. strain PYR100 and Mycobacterium gilvum PYR-GCK. The MICs of N-nitrosonorfloxacin and N-acetylnorfloxacin were 2- to 38- and 4- to 1,000-fold higher, respectively, than those of norfloxacin for several different bacteria, including the two strains that produced both metabolites. Although N-nitrosonorfloxacin had less antibacterial activity, nitrosamines are potentially carcinogenic. The biotransformation of fluoroquinolones by mycobacteria may serve as a resistance mechanism.
authors.affiliation: National Center for Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Adjei
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Heinze
authors.forename: Joanna
authors.initials: J
authors.lastname: Deck
authors.forename: James P
authors.initials: JP
authors.lastname: Freeman
authors.forename: Anna J
authors.initials: AJ
authors.lastname: Williams
authors.forename: John B
authors.initials: JB
authors.lastname: Sutherland
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D004783:Environmental Microbiology; D004785:Environmental Pollutants / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D009161:Mycobacterium / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D009643:Norfloxacin / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000900:Anti-Bacterial Agents; D004785:Environmental Pollutants; D009643:Norfloxacin