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The efficacy of ciprofloxacin and doxycycline against experimental tularaemia
Abstract:
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.
Insights
This study evaluated doxycycline and ciprofloxacin for treating tularaemia in mice. Both antibiotics showed efficacy, but relapse occurred post-treatment, suggesting extended administration may be necessary.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Tularaemia is a severe infectious disease caused by Francisella tularensis.
- Antibiotic treatment is crucial, but optimal regimens and relapse potential require further investigation.
Purpose of the Study:
- To assess the efficacy of doxycycline and ciprofloxacin against experimental tularaemia.
- To compare the protective effects of different antibiotic dosages and treatment durations.
- To investigate the occurrence and prevention of relapse after antibiotic withdrawal.
Main Methods:
- Experimental tularaemia infection induced by Francisella tularensis Schu4 in Porton outbred mice.
- Administration of doxycycline and ciprofloxacin at varying doses (40 mg/kg bd, 20 mg/kg bd) and initiation times (48h before, 24h after infection).
- Comparison of median lethal dose (MLD) in antibiotic-treated versus untreated mice; assessment of relapse post-antibiotic withdrawal.
Main Results:
- Both ciprofloxacin and doxycycline provided protection against tularaemia at higher doses (40 mg/kg bd).
- Lower doses (20 mg/kg bd) and delayed initiation of treatment reduced protective efficacy.
- A significant relapse rate (90%) was observed after antibiotic withdrawal, regardless of dose or type.
- Extended treatment to 10 days post-infection prevented relapse.
Conclusions:
- Ciprofloxacin and doxycycline demonstrate potential for treating tularaemia.
- Relapse is a significant concern following standard antibiotic courses.
- Extended antibiotic administration may be necessary to prevent relapse in tularaemia treatment.