Background: The high mortality of systemic anthrax is likely a consequence of the severe central nervous system (CNS) inflammation that occurs in anthrax meningitis. Effective treatment of such infections requires, at a minimum, adequate cerebrospinal fluid (CSF) antimicrobial concentrations.
Methods: We reviewed English medical literature and regulatory documents to extract information on serum and CSF exposures for antimicrobials with in vitro activity against Bacillus anthracis. Using CSF pharmacokinetic exposures and in vitro B. anthracis susceptibility data, we employed population pharmacokinetic modeling and Monte Carlo simulations to predict whether a specific antimicrobial dosage would likely achieve effective CSF antimicrobial activity in patients with normal to inflamed meninges (i.e., an intact to markedly disrupted blood brain barrier).
Results: Probability of microbiologic success at achievable antimicrobial dosages was high (≥95%) for ciprofloxacin, levofloxacin (500 mg q12 h), meropenem, imipenem/cilastatin, penicillin G, ampicillin, ampicillin/sulbactam, doxycycline, and minocycline; acceptable (90-95%) for piperacillin/tazobactam and levofloxacin (750 mg q24 h); and low (<90%) for vancomycin, amikacin, clindamycin, and linezolid.
Conclusion: Prompt empiric antimicrobial therapy of patients with suspected or confirmed anthrax meningitis may reduce the high morbidity and mortality. Our data support using several β-lactam-, fluoroquinolone-, and tetracycline-class antimicrobials as first-line and alternative agents for treatment of patients with anthrax meningitis; all should achieve effective microbiologic exposures. Our data also suggest antimicrobials that should not be relied upon to treat suspected or documented anthrax meningitis. Furthermore, the protein synthesis inhibitors clindamycin and linezolid can decrease toxin production and may be useful components of combination therapy.
Keywords: Anthrax; Brain Abscess; Cerebrospinal Fluid; Meningitis; Modeling.
Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.