title: Efficacy of liposome-encapsulated ciprofloxacin in a murine model of Q fever.
abstract: Encapsulation of antibiotics may improve treatment of intracellular infections by prolonging antibiotic release and improving antibiotic uptake into cells. In this study, liposome-encapsulated ciprofloxacin for inhalation (CFI) was evaluated as a postexposure therapeutic for the treatment of Coxiella burnetii, the causative agent of Q fever. Intranasal treatment of male A/Jola (A/J) mice with CFI (50 mg/kg of body weight) once daily for 7 days protected mice against weight loss and clinical signs following an aerosol challenge with C. burnetii. In comparison, mice treated twice daily with oral ciprofloxacin or doxycycline (50 mg/kg) or phosphate-buffered saline (PBS) lost 15 to 20% body weight and exhibited ruffled fur, arched backs, and dehydration. Mice were culled at day 14 postchallenge. The weights and bacterial burdens of organs were determined. Mice treated with CFI exhibited reduced splenomegaly and reduced bacterial numbers in the lungs and spleen compared to mice treated with oral ciprofloxacin or doxycycline. When a single dose of CFI was administered, it provided better protection against body weight loss than 7 days of treatment with oral doxycycline, the current antibiotic of choice to treat Q fever. These data suggest that CFI has potential as a superior antibiotic to treat Q fever.
authors.affiliation: Defence Science and Technology Laboratory, Porton Down, Salisbury, United Kingdom.
authors.forename: I H
authors.initials: IH
authors.lastname: Norville
authors.affiliation: Public Health England, Porton Down, Salisbury, United Kingdom.
authors.forename: G J
authors.initials: GJ
authors.lastname: Hatch
authors.affiliation: Public Health England, Porton Down, Salisbury, United Kingdom.
authors.forename: K R
authors.initials: KR
authors.lastname: Bewley
authors.affiliation: Defence Science and Technology Laboratory, Porton Down, Salisbury, United Kingdom.
authors.forename: D J
authors.initials: DJ
authors.lastname: Atkinson
authors.affiliation: Defence Science and Technology Laboratory, Porton Down, Salisbury, United Kingdom.
authors.forename: K A
authors.initials: KA
authors.lastname: Hamblin
authors.affiliation: Aradigm Corporation, Hayward, California, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Blanchard
authors.affiliation: Defence Science and Technology Laboratory, Porton Down, Salisbury, United Kingdom.
authors.forename: S J
authors.initials: SJ
authors.lastname: Armstrong
authors.affiliation: Public Health England, Porton Down, Salisbury, United Kingdom.
authors.forename: J K
authors.initials: JK
authors.lastname: Pitman
authors.affiliation: Public Health England, Porton Down, Salisbury, United Kingdom.
authors.forename: E
authors.initials: E
authors.lastname: Rayner
authors.affiliation: Public Health England, Porton Down, Salisbury, United Kingdom.
authors.forename: G
authors.initials: G
authors.lastname: Hall
authors.affiliation: Public Health England, Porton Down, Salisbury, United Kingdom.
authors.forename: J
authors.initials: J
authors.lastname: Vipond
authors.affiliation: Defence Science and Technology Laboratory, Porton Down, Salisbury, United Kingdom College of Life and Environmental Sciences, University of Exeter, Exeter, United Kingdom tpatkins@dstl.gov.uk.
authors.forename: T P
authors.initials: TP
authors.lastname: Atkins
mesh_terms: D000280:Administration, Inhalation; D000281:Administration, Intranasal / Q000379:methods; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D002939:Ciprofloxacin / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004318:Doxycycline / Q000008:administration & dosage; D008081:Liposomes / Q000008:administration & dosage*; D008168:Lung / Q000382:microbiology; D008297:Male; D051379:Mice; D011778:Q Fever / Q000188:drug therapy* / Q000382:microbiology; D013154:Spleen / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D008081:Liposomes; D002939:Ciprofloxacin; D004318:Doxycycline