Is doxycycline effective in treating Bacillus infections?

Doxycycline is Effective for Treating Bacillus anthracis Infections

Doxycycline is highly effective for both postexposure prophylaxis and treatment of susceptible Bacillus anthracis (anthrax) infections, with demonstrated efficacy comparable to ciprofloxacin in animal models and FDA approval for this indication. 1, 2

Evidence for Efficacy

Postexposure Prophylaxis

• Doxycycline demonstrated significant efficacy for postexposure prophylaxis against susceptible B. anthracis strains (OR 5.4,95% CI 3.2–9.0), with efficacy similar to ciprofloxacin. 1
• Monte Carlo simulations predict that oral doxycycline achieves adequate unbound drug exposures in humans to cover the minimal inhibitory concentrations for naturally occurring B. anthracis strains. 1
• The tetracycline class showed efficacy for prophylaxis with odds ratios ranging from 5.4 for doxycycline to 1489 for minocycline. 1

Active Treatment

• For treatment of infections from susceptible B. anthracis strains, doxycycline improved survival compared to no treatment, with efficacy similar to ciprofloxacin. 1
• Doxycycline's efficacy for treatment was comparable to newer tetracyclines (eravacycline OR 369, omadacycline OR 9.8) and to first-line fluoroquinolones. 1
• All 110 B. anthracis strains isolated in Italy from 1984-2017 showed susceptibility to doxycycline in vitro. 3

FDA-Approved Indication

The FDA specifically approves doxycycline for "Anthrax due to Bacillus anthracis, including inhalational anthrax (post-exposure): to reduce the incidence or progression of disease following exposure to aerosolized Bacillus anthracis." 2

CDC-Recommended Dosing

For Adults

• Inhalational/systemic anthrax treatment: 100 mg IV every 12 hours initially, then switch to 100 mg orally twice daily when clinically appropriate, continuing for 60 days total (IV and oral combined). 1
• Cutaneous anthrax treatment: 100 mg orally twice daily for 60 days. 1

For Children

• >8 years and >45 kg: 100 mg every 12 hours 1
• >8 years and <45 kg: 2.2 mg/kg every 12 hours 1
• ≤8 years: 2.2 mg/kg every 12 hours 1
• Ciprofloxacin or doxycycline is recommended for antimicrobial prophylaxis and treatment of children with B. anthracis infection. 4

For Pregnant Women

• Same dosing as nonpregnant adults (100 mg every 12 hours), as the high death rate from anthrax infection outweighs the risk posed by the antimicrobial agent. 1

Critical Resistance Considerations

Doxycycline is NOT effective against doxycycline-resistant B. anthracis strains. 1

• Neither doxycycline nor tetracycline were efficacious for postexposure prophylaxis of doxycycline-resistant B. anthracis (Table 2 data). 1
• In vivo studies showed no therapeutic effect of doxycycline in treatment of anthrax caused by tetracycline-resistant strains containing plasmid pBC16. 5
• Minocycline retained efficacy against doxycycline-resistant strains (OR 3.9,95% CI 2.0–7.8) and was 99 times more efficacious than doxycycline when compared head-to-head. 1

Combination Therapy for Resistant Strains

For ciprofloxacin-resistant B. anthracis, combination regimens including doxycycline showed efficacy:

• Ciprofloxacin + meropenem + doxycycline demonstrated treatment efficacy compared to no treatment in animal models. 1
• Three-drug combinations (ciprofloxacin + β-lactam + protein synthesis inhibitor) all showed efficacy against resistant strains. 1

Important Clinical Caveats

Meningitis Concerns

• If meningitis is suspected, doxycycline may be less optimal because of poor central nervous system penetration. 1
• For anthrax meningitis in rabbit models, penicillins and clindamycin showed efficacy, but doxycycline data for CNS infections are limited. 1

Duration of Therapy

• Because of the potential persistence of spores after aerosol exposure, antimicrobial therapy should be continued for 60 days. 1
• This extended duration applies to both postexposure prophylaxis and treatment following inhalational exposure. 1

Susceptibility Testing

• When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. 2
• Susceptibility testing is essential to identify potentially engineered resistant strains following any intentional release. 1

Alternative Agents

If doxycycline cannot be used:

• Ciprofloxacin remains the primary alternative with similar efficacy (OR 11.5 for prophylaxis, OR 12.5 for treatment). 1
• Amoxicillin is an option for prophylaxis in children and pregnant women when B. anthracis is susceptible to penicillin. 4
• Newer tetracyclines (omadacycline, eravacycline) showed excellent efficacy and may overcome some resistance mechanisms. 1