Journal of Antimicrobial Chemotherapy, Vol 41, 461-465, Copyright © 1998 by The British Society for Antimicrobial Chemotherapy
P Russell, SM Eley, MJ Fulop, DL Bell and RW Titball
The efficacy of doxycycline and ciprofloxacin against an experimental
tularaemia infection was assessed by comparing the median lethal dose (MLD)
of Francisella tularensis Schu4 biotype A strain given intraperitoneally to
antibiotic-treated and untreated mice. In untreated Porton outbred mice
this was <1 cfu. Ciprofloxacin and doxycycline given at 40 mg/kg bd,
initiated 48 h before infection and continued for 5 days after infection,
afforded protection against intraperitoneal challenges of 3.7 x 10(6) cfu
and 6.0 x 10(6) cfu, respectively. Protection was reduced when both
antibiotics were given over a similar period at a lower dose regimen (20
mg/kg bd) to 8.8 x 10(5) cfu and 3.5 x 10(2) cfu, respectively. The greater
reduction in protection offered by doxycycline was a reflection of the
higher in- vitro MIC. Protection also decreased when the antibiotics were
initiated 24 h after challenge. The MLD was 3.2 x 10(5) cfu and 1.6 x 10(6)
cfu for ciprofloxacin and doxycycline respectively given at 40 mg/kg bd and
was reduced further using the lower dose regimen. Overall, 90% of the
deaths occurred following the withdrawal of antibiotic, irrespective of the
antibiotic dose or type. It was possible to prevent this relapse by
extending the antibiotic administration to 10 days after challenge.
Ciprofloxacin and doxycycline may be useful for treating tularaemia,
although the possibility of relapse should be considered.
ORIGINAL ARTICLES
The efficacy of ciprofloxacin and doxycycline against experimental tularaemia
CBD Porton Down, Salisbury, Wiltshire, UK.
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