title: Trimethoprim/sulfamethoxazole (co-trimoxazole) prophylaxis is effective against acute murine inhalational melioidosis and glanders.
abstract: Burkholderia pseudomallei is the causative agent of the disease melioidosis, which is prevalent in tropical countries and is intractable to a number of antibiotics. In this study, the antibiotic co-trimoxazole (trimethoprim/sulfamethoxazole) was assessed for the post-exposure prophylaxis of experimental infection in mice with B. pseudomallei and its close phylogenetic relative Burkholderia mallei, the causative agent of glanders. Co-trimoxazole was effective against an inhalational infection with B. pseudomallei or B. mallei. However, oral co-trimoxazole delivered twice daily did not eradicate infection when administered from 6h post exposure for 14 days or 21 days, since infected and antibiotic-treated mice succumbed to infection following relapse or immunosuppression. These data highlight the utility of co-trimoxazole for prophylaxis both of B. pseudomallei and B. mallei and the need for new approaches for the treatment of persistent bacterial infection.
authors.affiliation: Biomedical Sciences Department, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
authors.forename: Kay B
authors.initials: KB
authors.lastname: Barnes
authors.forename: Jackie
authors.initials: J
authors.lastname: Steward
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Thwaite
authors.forename: M Stephen
authors.initials: MS
authors.lastname: Lever
authors.forename: Carwyn H
authors.initials: CH
authors.lastname: Davies
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Armstrong
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Laws
authors.forename: Neil
authors.initials: N
authors.lastname: Roughley
authors.forename: Sarah V
authors.initials: SV
authors.lastname: Harding
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Atkins
authors.forename: Andrew J H
authors.initials: AJ
authors.lastname: Simpson
authors.forename: Helen S
authors.initials: HS
authors.lastname: Atkins
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D042726:Burkholderia mallei / Q000187:drug effects; D016957:Burkholderia pseudomallei / Q000187:drug effects; D018890:Chemoprevention / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D005896:Glanders / Q000517:prevention & control*; D019570:Inhalation Exposure / Q000517:prevention & control*; D008554:Melioidosis / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D056990:Post-Exposure Prophylaxis / Q000379:methods*; D016896:Treatment Outcome; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage*
chemical_list: D000900:Anti-Bacterial Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination