Central Nervous System Antimicrobial Exposure and Proposed Dosing for Anthrax Meningitis

Area of Science:

• Pharmacology
• Infectious Diseases
• Neuroscience

Background:

• Systemic anthrax mortality is linked to central nervous system inflammation in anthrax meningitis.
• Adequate cerebrospinal fluid (CSF) antimicrobial concentrations are essential for effective treatment.

Purpose of the Study:

• To evaluate antimicrobial efficacy in CSF for Bacillus anthracis infections.
• To determine optimal antimicrobial dosages for treating anthrax meningitis.

Main Methods:

• Literature and regulatory document review for antimicrobial serum and CSF exposures.
• Population pharmacokinetic modeling and Monte Carlo simulations using in vitro susceptibility data.
• Assessment of antimicrobial activity against Bacillus anthracis with varying meningeal inflammation.

Main Results:

• High probability of success (≥95%) for ciprofloxacin, levofloxacin, meropenem, imipenem/cilastatin, penicillin G, ampicillin, ampicillin/sulbactam, doxycycline, and minocycline.
• Acceptable probability (90%-95%) for piperacillin/tazobactam and higher-dose levofloxacin.
• Low probability (<90%) for vancomycin, amikacin, clindamycin, and linezolid.

Conclusions:

• Prompt empiric antimicrobial therapy can reduce anthrax meningitis morbidity and mortality.
• β-lactam, fluoroquinolone, and tetracycline classes are recommended as first-line or alternative agents.
• Clindamycin and linezolid may be beneficial in combination therapy due to toxin inhibition.