학술논문
Central Nervous System Antimicrobial Exposure and Proposed Dosing for Anthrax Meningitis.
Document Type
Academic Journal
Author
Bradley JS; Department of Pediatrics, University of California-San Diego School of Medicine and Rady Children's Hospital, San Diego, California, USA.; Bulitta JB; Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Orlando, Florida, USA.; Cook R; Oak Ridge Institute for Science and Education, CDC Fellowship Program, Division of High Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.; Yu PA; Division of Preparedness and Emerging Infections, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.; Iwamoto C; Division of High Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.; Hesse EM; Division of Preparedness and Emerging Infections, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.; Chaney D; Division of High Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.; Yu Y; Division of Preparedness and Emerging Infections, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.; Kennedy JL; Division of High Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.; Sue D; Division of Preparedness and Emerging Infections, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.; Karchmer AW; Division of Infectious Disease, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.; Bower WA; Division of High Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.; Hendricks K; Division of High Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Source
Publisher: Oxford University Press Country of Publication: United States NLM ID: 9203213 Publication Model: Print Cited Medium: Internet ISSN: 1537-6591 (Electronic) Linking ISSN: 10584838 NLM ISO Abbreviation: Clin Infect Dis Subsets: MEDLINE
Subject
Language
English
Abstract
Background: The high mortality of systemic anthrax is likely a consequence of the severe central nervous system 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 used population pharmacokinetic modeling and Monte Carlo simulations to determine whether a specific antimicrobial dosage would likely achieve effective CSF antimicrobial activity in patients with normal to inflamed meninges (ie, an intact to markedly disrupted blood-brain barrier).
Results: The probability of microbiologic success at achievable antimicrobial dosages was high (≥95%) for ciprofloxacin, levofloxacin (500 mg every 12 hours), meropenem, imipenem/cilastatin, penicillin G, ampicillin, ampicillin/sulbactam, doxycycline, and minocycline; acceptable (90%-95%) for piperacillin/tazobactam and levofloxacin (750 mg every 24 hours); and low (<90%) for vancomycin, amikacin, clindamycin, and linezolid.
Conclusions: 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 suggest antimicrobials that should not be relied on 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.
Competing Interests: Potential conflicts of interest . J. S. B. is supported by an NICHD grant (1 R01 HD095547-01). J. B. B. is supported by NIAID grants (R01 AI130185 and R01 AI136803). K. H., C. I., E. H., and P. Y. are career officers with the CDC. J. B. reports consulting fees from MicuRx Pharmaceuticals Inc, Aerovate Therapeutics, and Lupin and honorarium for a lecture under T32 (William Shafer, Emory) on antimicrobial pharmacology. A. W. K. reports stock from Pfizer, Johnson & Johnson, and AbbVie. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
(Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)
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 used population pharmacokinetic modeling and Monte Carlo simulations to determine whether a specific antimicrobial dosage would likely achieve effective CSF antimicrobial activity in patients with normal to inflamed meninges (ie, an intact to markedly disrupted blood-brain barrier).
Results: The probability of microbiologic success at achievable antimicrobial dosages was high (≥95%) for ciprofloxacin, levofloxacin (500 mg every 12 hours), meropenem, imipenem/cilastatin, penicillin G, ampicillin, ampicillin/sulbactam, doxycycline, and minocycline; acceptable (90%-95%) for piperacillin/tazobactam and levofloxacin (750 mg every 24 hours); and low (<90%) for vancomycin, amikacin, clindamycin, and linezolid.
Conclusions: 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 suggest antimicrobials that should not be relied on 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.
Competing Interests: Potential conflicts of interest . J. S. B. is supported by an NICHD grant (1 R01 HD095547-01). J. B. B. is supported by NIAID grants (R01 AI130185 and R01 AI136803). K. H., C. I., E. H., and P. Y. are career officers with the CDC. J. B. reports consulting fees from MicuRx Pharmaceuticals Inc, Aerovate Therapeutics, and Lupin and honorarium for a lecture under T32 (William Shafer, Emory) on antimicrobial pharmacology. A. W. K. reports stock from Pfizer, Johnson & Johnson, and AbbVie. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
(Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)