Liposome-encapsulated ciprofloxacin for inhalation (CFI) was investigated as a putative postexposure therapeutic for two strains of Francisella tularensis. The efficacies of oral ciprofloxacin and intranasally instilled CFI could not be distinguished in a mouse model of infection with the F. tularensis live vaccine strain (LVS), where a single dose of either formulation offered full protection against a lethal challenge. However, mouse studies with the more virulent Schu S4 strain of F. tularensis demonstrated that a higher level of protection against a lethal aerosol infection is provided by CFI than by oral ciprofloxacin. In addition, using this infection model, it was possible to discriminate the efficacy of intranasally instilled CFI from that of aerosolized CFI, with aerosolized CFI providing full protection after just a single dose. The improved efficacy of CFI compared to oral ciprofloxacin is likely due to the high sustained concentrations of ciprofloxacin in the lung. In summary, CFI may be a promising therapy, perhaps enabling the prophylactic regimen to be shortened, for use in the event of a deliberate release of F. tularensis. The prophylactic efficacy of CFI against other biological warfare (BW) threat agents also warrants investigation.
机构:
Med Coll Wisconsin, Dept Microbiol & Mol Genet, Milwaukee, WI 53226 USAMed Coll Wisconsin, Dept Microbiol & Mol Genet, Milwaukee, WI 53226 USA
Pechous, Roger D.
McCarthy, Travis R.
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Med Coll Wisconsin, Dept Microbiol & Mol Genet, Milwaukee, WI 53226 USAMed Coll Wisconsin, Dept Microbiol & Mol Genet, Milwaukee, WI 53226 USA
McCarthy, Travis R.
Mohapatra, Nrusingh P.
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Ohio State Univ, Dept Mol Biol, Immunol & Med Genet, Columbus, OH USAMed Coll Wisconsin, Dept Microbiol & Mol Genet, Milwaukee, WI 53226 USA
Mohapatra, Nrusingh P.
Soni, Shilpa
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Ohio State Univ, Dept Mol Biol, Immunol & Med Genet, Columbus, OH USAMed Coll Wisconsin, Dept Microbiol & Mol Genet, Milwaukee, WI 53226 USA
Soni, Shilpa
Penoske, Renee M.
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Med Coll Wisconsin, Dept Microbiol & Mol Genet, Milwaukee, WI 53226 USAMed Coll Wisconsin, Dept Microbiol & Mol Genet, Milwaukee, WI 53226 USA
Penoske, Renee M.
Salzman, Nita H.
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Med Coll Wisconsin, Dept Microbiol & Mol Genet, Milwaukee, WI 53226 USA
Med Coll Wisconsin, Dept Pediat, Milwaukee, WI USAMed Coll Wisconsin, Dept Microbiol & Mol Genet, Milwaukee, WI 53226 USA
Salzman, Nita H.
Frank, Dara W.
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Med Coll Wisconsin, Dept Microbiol & Mol Genet, Milwaukee, WI 53226 USAMed Coll Wisconsin, Dept Microbiol & Mol Genet, Milwaukee, WI 53226 USA
Frank, Dara W.
Gunn, John S.
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Ohio State Univ, Dept Mol Biol, Immunol & Med Genet, Columbus, OH USAMed Coll Wisconsin, Dept Microbiol & Mol Genet, Milwaukee, WI 53226 USA
Gunn, John S.
Zahrt, Thomas C.
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Med Coll Wisconsin, Dept Microbiol & Mol Genet, Milwaukee, WI 53226 USAMed Coll Wisconsin, Dept Microbiol & Mol Genet, Milwaukee, WI 53226 USA
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Univ Virginia, Dept Med, Charlottesville, VA 22908 USAUniv Virginia, Dept Med, Charlottesville, VA 22908 USA
Ramakrishnan, Girija
Meeker, Alexis
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Univ Virginia, Dept Med, Charlottesville, VA 22908 USAUniv Virginia, Dept Med, Charlottesville, VA 22908 USA
Meeker, Alexis
Dragulev, Bojan
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Univ Virginia, Dept Med, Charlottesville, VA 22908 USA
Univ Virginia, Sch Med Core Facil, Charlottesville, VA 22908 USAUniv Virginia, Dept Med, Charlottesville, VA 22908 USA