title: In vitro resistance of Bacillus anthracis Sterne to doxycycline, macrolides and quinolones.
abstract: Bacillus anthracis is a potential biological warfare agent. Its ability to develop resistance to antimicrobial agents currently recommended for the treatment of anthrax infection is a major concern. B. anthracis Sterne was grown from a live veterinary vaccine and used it to test for the development of resistance after 21 sequential subcultures in sub-inhibitory concentrations of doxycycline and three quinolones (ciprofloxacin, alatrofloxacin and gatifloxacin) and 15 sequential subcultures in sub-inhibitory concentrations of three macrolides (erythromycin, azithromycin and clarithromycin). After 21 subcultures the minimal inhibitory concentrations (MICs) increased from 0.1 to 1.6 mg/l for ciprofloxacin, from 1.6 to 12.5 mg/l for alatrofloxacin, from 0.025 to 1.6 mg/l for gatifloxacin and from 0.025 to 0.1 mg/l for doxycycline. After 15 passages of sequential subculturing with macrolides, the MICs increased from 12.5 to 12.5 or 50.0 mg/l for azithromycin, from 0.2 to 1.6 or 0.4 mg/l for clarithromycin and from 6.25 to 6.25 or 50 mg/l for erythromycin. After sequential passages with a single quinolone or doxycycline, each isolate was cross-tested for resistance using the other drugs. All isolates selected for resistance to one quinolone were also resistant to the other two quinolones, but not to doxycycline. The doxycycline-resistant isolate was not resistant to any quinolone.
authors.affiliation: Radiation Medicine Department, Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603, USA. brook@mx.afrri.usuhs.mil
authors.forename: I
authors.initials: I
authors.lastname: Brook
authors.forename: T B
authors.initials: TB
authors.lastname: Elliott
authors.forename: H I
authors.initials: HI
authors.lastname: Pryor
authors.forename: T E
authors.initials: TE
authors.lastname: Sautter
authors.forename: B T
authors.initials: BT
authors.lastname: Gnade
authors.forename: J H
authors.initials: JH
authors.lastname: Thakar
authors.forename: G B
authors.initials: GB
authors.lastname: Knudson
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001408:Bacillus anthracis / Q000187:drug effects* / Q000254:growth & development; D004318:Doxycycline / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones; D018942:Macrolides; D008826:Microbial Sensitivity Tests
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D018942:Macrolides; D004318:Doxycycline