Postexposure Prophylaxis and Treatment of Bacillus anthracis Infections: A Systematic Review and Meta-analyses of Animal Models, 1947-2019.
Amoxicillin-Potassium Clavulanate Combination
/ therapeutic use
Animals
Anthrax
/ drug therapy
Anti-Bacterial Agents
/ pharmacology
Anti-Infective Agents
/ therapeutic use
Bacillus anthracis
Cilastatin, Imipenem Drug Combination
/ pharmacology
Ciprofloxacin
/ therapeutic use
Doxycycline
/ therapeutic use
Glycopeptides
/ pharmacology
Humans
Levofloxacin
/ therapeutic use
Lipopeptides
/ pharmacology
Models, Animal
Tetracyclines
/ therapeutic use
United States
beta-Lactams
/ therapeutic use
anthrax
antimicrobial
drug-resistant
postexposure prophylaxis
treatment
Journal
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213
Informations de publication
Date de publication:
17 10 2022
17 10 2022
Historique:
entrez:
17
10
2022
pubmed:
18
10
2022
medline:
20
10
2022
Statut:
ppublish
Résumé
Anthrax is endemic to many countries, including the United States. The causative agent, Bacillus anthracis, poses a global bioterrorism threat. Without effective antimicrobial postexposure prophylaxis (PEPAbx) and treatment, the mortality of systemic anthrax is high. To inform clinical guidelines for PEPAbx and treatment of B. anthracis infections in humans, we systematically evaluated animal anthrax treatment model studies. We searched for survival outcome data in 9 scientific search engines for articles describing antimicrobial PEPAbx or treatment of anthrax in animals in any language through February 2019. We performed meta-analyses of efficacy of antimicrobial PEPAbx and treatment for each drug or drug combination using random-effects models. Pharmacokinetic/pharmacodynamic relationships were developed for 5 antimicrobials with available pharmacokinetic data. Monte Carlo simulations were used to predict unbound drug exposures in humans. We synthesized data from 34 peer-reviewed studies with 3262 animals. For PEPAbx and treatment of infection by susceptible B. anthracis, effective monotherapy can be accomplished with fluoroquinolones, tetracyclines, β-lactams (including penicillin, amoxicillin-clavulanate, and imipenem-cilastatin), and lipopeptides or glycopeptides. For naturally occurring strains, unbound drug exposures in humans were predicted to adequately cover the minimal inhibitory concentrations (MICs; those required to inhibit the growth of 50% or 90% of organisms [MIC50 or MIC90]) for ciprofloxacin, levofloxacin, and doxycycline for both the PEPAbx and treatment targets. Dalbavancin covered its MIC50 for PEPAbx. These animal studies show many reviewed antimicrobials are good choices for PEPAbx or treatment of susceptible B. anthracis strains, and some are also promising options for combating resistant strains. Monte Carlo simulations suggest that oral ciprofloxacin, levofloxacin, and doxycycline are particularly robust choices for PEPAbx or treatment.
Sections du résumé
BACKGROUND
Anthrax is endemic to many countries, including the United States. The causative agent, Bacillus anthracis, poses a global bioterrorism threat. Without effective antimicrobial postexposure prophylaxis (PEPAbx) and treatment, the mortality of systemic anthrax is high. To inform clinical guidelines for PEPAbx and treatment of B. anthracis infections in humans, we systematically evaluated animal anthrax treatment model studies.
METHODS
We searched for survival outcome data in 9 scientific search engines for articles describing antimicrobial PEPAbx or treatment of anthrax in animals in any language through February 2019. We performed meta-analyses of efficacy of antimicrobial PEPAbx and treatment for each drug or drug combination using random-effects models. Pharmacokinetic/pharmacodynamic relationships were developed for 5 antimicrobials with available pharmacokinetic data. Monte Carlo simulations were used to predict unbound drug exposures in humans.
RESULTS
We synthesized data from 34 peer-reviewed studies with 3262 animals. For PEPAbx and treatment of infection by susceptible B. anthracis, effective monotherapy can be accomplished with fluoroquinolones, tetracyclines, β-lactams (including penicillin, amoxicillin-clavulanate, and imipenem-cilastatin), and lipopeptides or glycopeptides. For naturally occurring strains, unbound drug exposures in humans were predicted to adequately cover the minimal inhibitory concentrations (MICs; those required to inhibit the growth of 50% or 90% of organisms [MIC50 or MIC90]) for ciprofloxacin, levofloxacin, and doxycycline for both the PEPAbx and treatment targets. Dalbavancin covered its MIC50 for PEPAbx.
CONCLUSIONS
These animal studies show many reviewed antimicrobials are good choices for PEPAbx or treatment of susceptible B. anthracis strains, and some are also promising options for combating resistant strains. Monte Carlo simulations suggest that oral ciprofloxacin, levofloxacin, and doxycycline are particularly robust choices for PEPAbx or treatment.
Identifiants
pubmed: 36251546
pii: 6762167
doi: 10.1093/cid/ciac591
pmc: PMC9649436
doi:
Substances chimiques
Anti-Bacterial Agents
0
Anti-Infective Agents
0
Glycopeptides
0
Lipopeptides
0
Tetracyclines
0
beta-Lactams
0
Ciprofloxacin
5E8K9I0O4U
Levofloxacin
6GNT3Y5LMF
Amoxicillin-Potassium Clavulanate Combination
74469-00-4
Cilastatin, Imipenem Drug Combination
92309-29-0
Doxycycline
N12000U13O
Types de publication
Journal Article
Meta-Analysis
Systematic Review
Research Support, U.S. Gov't, P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
S379-S391Subventions
Organisme : CDC HHS
Pays : United States
Informations de copyright
Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022.
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