Expanded options for treatments directed against pathogens that can be used for bioterrorism are urgently needed. Treatment regimens directed against such pathogens can be identified only by using data derived from in vitro and animal studies. It is crucial that these studies reliably predict the efficacy of proposed treatments in @entity1 . The objective of this study was to identify a @entity800 treatment regimen that will serve as an effective therapy for @entity6192 infections and postexposure prophylaxis. An in vitro hollow-fiber @entity281 model that replicates the pharmacokinetic profile of @entity800 observed in @entity1 (half-life [t(1/2)], 7.5 h) or in animals, such as the @entity19 or the @entity2608 (t(1/2), approximately 2 h), was used to evaluate a proposed indication for @entity800 (500 mg once daily) for the treatment of @entity6192 infections. The results obtained with the in vitro model served as the basis for the doses and the dose schedules that were evaluated in the @entity19 inhalational @entity6192 model. The effects of @entity800 and @entity2177 treatment were compared to those of no treatment (untreated controls). The main outcome measure in the in vitro hollow-fiber @entity281 model was a persistent reduction of culture density (> or = 4 log10 reduction) and prevention of the emergence of @entity800 -resistant organisms. In the @entity19 inhalational @entity6192 model the main outcome measure was survival. The results indicated that @entity800 given once daily with simulated @entity1 pharmacokinetics effectively sterilized @entity6192 cultures. By using a simulated animal pharmacokinetic profile, a once-daily dosing regimen that provided a @entity1 -equivalent exposure failed to sterilize the cultures. Dosing regimens that "partially humanized" @entity800 exposures within the constraints of animal pharmacokinetics reproduced the antimicrobial efficacy seen with @entity1 pharmacokinetics. In a @entity19 inhalational @entity6192 model, once-daily dosing was significantly inferior (survival end point) to regimens of dosing every 12 h or every 6 h with identical total daily @entity800 doses. These results demonstrate the predictive value of the in vitro hollow-fiber @entity281 model with respect to the success or the failure of treatment regimens in animals. Furthermore, the model permits the evaluation of treatment regimens that "humanize" antibiotic exposures in animal models, enhancing the confidence with which animal models may be used to reliably predict the efficacies of proposed antibiotic treatments in @entity1 in situations (e.g., the release of pathogens as agents of bioterrorism or emerging @entity166 ) where @entity1 trials cannot be performed. A treatment regimen effective in @entity2608 was identified.

Effective antimicrobial regimens for use in @entity1 for therapy of XXXX infections and postexposure prophylaxis.

@entity1 :: ('9606', 'Species') :: ['humans', 'human'] @entity6192 :: ('1392', 'Species') :: ['Bacillus anthracis', 'anthrax'] @entity19 :: ('10090', 'Species') :: ['mouse'] @entity2177 :: ('MESH:D002939', 'Chemical') :: ['ciprofloxacin'] @entity281 :: ('MESH:D007239', 'Disease') :: ['infection'] @entity166 :: ('MESH:D003141', 'Disease') :: ['infectious diseases'] @entity2608 :: ('9544', 'Species') :: ['rhesus monkey', 'rhesus monkeys'] @entity800 :: ('MESH:D015242', 'Chemical') :: ['levofloxacin']
@entity6192 :: (1392,Species) :: ['Bacillus anthracis']
