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Antimicrobial Agents and Chemotherapy, March 1998, p. 675-681, Vol. 42, No. 3
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Antibiotic Treatment of Experimental Pneumonic Plague in Mice

William R. Byrne,* Susan L. Welkos, M. Louise Pitt, Kelly J. Davis,dagger Ralf P. Brueckner,Dagger John W. Ezzell, Gene O. Nelson,§ Joseph R. Vaccaro,parallel Luann C. Battersby, and Arthur M. Friedlander

United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland 21702-5011

Received 21 August 1997/Returned for modification 26 September 1997/Accepted 19 December 1997

A mouse model was developed to evaluate the efficacy of antibiotic treatment of pneumonic plague; streptomycin was compared to antibiotics with which there is little or no clinical experience. Infection was induced by inhalation of aerosolized Yersinia pestis organisms. Antibiotics were administered by intraperitoneal injection every 6 hours for 5 days, at doses that produced levels of drug in serum comparable to those observed in humans treated for other serious infections. These studies compared in vitro to in vivo activity and evaluated the efficacy of antibiotics started at different times after exposure. Early treatment (started 24 h after challenge, when 0 of 10 mice tested had positive blood cultures) with netilmicin, ciprofloxacin, ofloxacin, ceftriaxone, ceftazidime, aztreonam, ampicillin, and rifampin (but not cefazolin, cefotetan, or ceftizoxime) demonstrated efficacy comparable to streptomycin. Late treatment (started 42 h after exposure, when five of five mice tested had positive blood cultures) with netilmicin, ciprofloxacin, ofloxacin, and a high dose (20 mg/kg of body weight every 6 h) of gentamicin produced survival rates comparable to that with streptomycin, while all of the beta-lactam antibiotics (cefazolin, cefotetan, ceftriaxone, ceftazidime, aztreonam, and ampicillin) and rifampin were significantly inferior to streptomycin. In fact, all groups of mice treated late with beta-lactam antibiotics experienced accelerated mortality rates compared to normal-saline-treated control mice. These studies indicate that netilmicin, gentamicin, ciprofloxacin, and ofloxacin may be alternatives for the treatment of pneumonic plague in humans. However, the beta-lactam antibiotics are not recommended, based upon poor efficacy in this mouse model of pneumonic plague, particularly when pneumonic plague may be associated with bacteremia.

* Corresponding author. Mailing address: U.S. Army Medical Research Institute of Infectious Diseases, ATTN: MCMR-UIB-G, 1425 Porter St., Fort Detrick, MD 21702-5011. Phone: (301) 619-7341. Fax: (301) 619-4894. E-mail: ByrneWR{at}DETRICK.Army.Mil.

dagger Present address: U.S. Army Medical Research and Materiel Command, Fort Detrick, MD 21702-5012.

Dagger Present address: Dept of Clinical Pharmacology, Walter Reed Army Institute of Research, Washington, DC 20307.

§ Present address: 4477 20th Ave., Peterson, IA 51047.

parallel Present address: 32 Berkshire Dr., Jacksonville, NC 28546.

Antimicrobial Agents and Chemotherapy, March 1998, p. 675-681, Vol. 42, No. 3
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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