title: Meropenem-clavulanic acid shows activity against Mycobacterium tuberculosis in vivo.
abstract: The carbapenems imipenem and meropenem in combination with clavulanic acid reduced the bacterial burden in Mycobacterium tuberculosis-infected macrophages by 2 logs over 6 days. Despite poor stability in solution and a short half-life in rodents, treatment of chronically infected mice revealed significant reductions of bacterial burden in the lungs and spleens. Our results show that meropenem has activity in two in vivo systems, but stability and pharmacokinetics of long-term administration will offer significant challenges to clinical evaluation.
authors.affiliation: Tuberculosis Research Section, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: England
authors.forename: Helena I M
authors.initials: HI
authors.lastname: Boshoff
authors.forename: Kriti
authors.initials: K
authors.lastname: Arora
authors.forename: Danielle
authors.initials: D
authors.lastname: Weiner
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Dayao
authors.forename: Daniel
authors.initials: D
authors.lastname: Schimel
authors.forename: Laura E
authors.initials: LE
authors.lastname: Via
authors.forename: Clifton E
authors.initials: CE
authors.lastname: Barry
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D002460:Cell Line; D019818:Clavulanic Acid / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D008264:Macrophages / Q000382:microbiology; D000077731:Meropenem; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D013845:Thienamycins / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D019818:Clavulanic Acid; D000077731:Meropenem