Effect of Delaying Treatment on Efficacy of Ciprofloxacin and Levofloxacin in the African Green Monkey Model of Pneumonic Plague
Abstract
BACKGROUND
Ciprofloxacin and levofloxacin, 2 fluoroquinolone antimicrobials, are ≥90% effective for the treatment of inhalational plague when administered within 2-6 hours of fever onset in African green monkeys (AGM). Based on data in the AGM model, these antimicrobials were approved under the Food and Drug Administration's Animal Efficacy Rule. However, that data did not address the issue of how long treatment with these antimicrobials would remain effective after fever onset.
METHODS
The AGM model of pneumonic plague was used to explore the effect of delaying treatment with ciprofloxacin and levofloxacin on efficacy. In 2 studies, AGMs were challenged with inhaled lethal doses of Yersinia pestis. Treatment with ciprofloxacin and levofloxacin was initiated from 0 to up to 30 hours after fever onset.
RESULTS
Challenged animals all developed fever within 78 hours and were treated with ciprofloxacin (n = 27) or levofloxacin (n = 29) at various predetermined time points postfever. When administered 10 hours after fever onset, 10 days of ciprofloxacin and levofloxacin treatment remained very effective (90 or 100%, respectively). The efficacy of both antimicrobials declined as treatment initiation was further delayed. Statistical analyses estimated the treatment delay times at which half of the AGMs were no longer expected to survive as 19.7 hours for ciprofloxacin and 26.5 hours for levofloxacin.
CONCLUSIONS
This study demonstrates that there is a narrow window following fever…
Read the paper
Related studies
- Penicillins for Treatment of Pneumococcal Pneumonia: Does In Vitro Resistance Really Matter?
- Thiophenes—Naturally Occurring Plant Metabolites: Biological Activities and In Silico Evaluation of Their Potential as Cathepsin D Inhibitors
- Inhalable Mannosylated Rifampicin–Curcumin Co-Loaded Nanomicelles with Enhanced In Vitro Antimicrobial Efficacy for an Optimized Pulmonary Tuberculosis Therapy
- Development and validation of microbial bioassay for quantification of Levofloxacin in pharmaceutical preparations
- GC-MS Analysis and Biomedical Therapy of Oil from n-Hexane Fraction of Scutellaria edelbergii Rech. f.: In Vitro, In Vivo, and In Silico Approach
- Propranolol, chlorpromazine and diclofenac restore susceptibility of extensively drug-resistant (XDR)-Acinetobacter baumannii to fluoroquinolones
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.