The efficacy of ciprofloxacin and doxycycline against experimental tularaemia.
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.
Russell
P
P
CBD Porton Down, Salisbury, Wiltshire, UK.
Eley
S M
SM
Fulop
M J
MJ
Bell
D L
DL
Titball
R W
RW
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D019072:Antibiotic Prophylaxis; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004318:Doxycycline / Q000008:administration & dosage / Q000627:therapeutic use*; D005604:Francisella tularensis / Q000187:drug effects; D051379:Mice; D008826:Microbial Sensitivity Tests; D014406:Tularemia / Q000188:drug therapy* / Q000517:prevention & control*
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D002939:Ciprofloxacin; D004318:Doxycycline