Anthrax doesn't develop resistance to long-term Tx with Doxycycline

OB/GYN News, Feb 15, 2002 by Miriam E. Tucker

CHICAGO -- Doxycycline appears to be superior to ciprofloxacin, or any other quinolone or macrolide, for long-term therapy or prophylaxis against anthrax, Dr. Itzhak Brook reported in a poster presentation at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy sponsored by the American Society for Microbiology

Quinolones, macrolides, and doxycycline are all considered effective therapy against anthrax. But the development of antimicrobial resistance against these drugs by Bacillus anthracis could limit their usefulness in the event of any future bioterrorism attacks, said Dr. Brook of the Armed Forces Radiobiology Research Institute, Bethesda, Md.

In a study funded by the U.S. Department of Defense, Dr. Brook and his associates subjected a veterinary anthrax vaccine strain (B. anthracis Sterne) to 21 sequential subcultures in subinhibitory concentrations of doxycycline, ciprofloxacin, alatrofloxacin, and gatifloxacin. They also ran it through 15 such subcultures with the macrolides erythromycin, azithromycin, and clarithromycin.

Significant increases in minimal inhibitory concentration (MIC) occurred with the quinolones and macrolides, but not doxycycline. After 21 subcultures, the MIC for doxycycline increased minimally, from 0.025 mg/L to 0,1 mg/L. In contrast, the MIC for ciprofloxacin jumped from 0.1 to 12.5 mg/L, Dr. Brook said.

All of the quinolone-resistant isolates were also resistant to the other three quinolones but not to doxycycline, while the two doxycycline-exposed isolates were not resistant to any quinolone, he noted.

Ofloxacin and gatifloxacin were effective against B. anthracis longer than were ciprofloxacin or alatrofloxacin, while clarithromycin was effective longer than either erythromycin or azithromycin.

Dr. Brook cautioned that this work was done in vitro only. "There is no proof that such resistance will emerge in patients," he told this newspaper.