title: Activity of nitazoxanide and tizoxanide against Mycobacterium tuberculosis in vitro and in whole blood culture.
abstract: Nitazoxanide (NTZ) and its metabolite tizoxanide (TIZ) were studied as antimycobacterial agents in vitro (in mycobacterial growth indicator tube [MGIT] cultures) and in a whole blood bactericidal assay. Both NTZ and TIZ show high protein binding. In MGIT cultures (albumin concentration = 78 μM), inhibition of Mycobacterium tuberculosis growth occurred at total drug concentrations of ≥16 μg/ml, whereas in whole blood cultures (albumin concentration = 350 μM), ≥128 μg/ml was required. Free drug fractions at these two conditions were estimated to be 69% and 2%, respectively. Co-incubation of NTZ and TIZ in human plasma for 72 h nearly completely eliminated their ability to inhibit mycobacterial growth in MGIT. Interactions with plasma proteins may limit the potential of NTZ and TIZ as drugs for human tuberculosis.
authors.affiliation: Department of Medicine, Case Western Reserve University, University Hospitals Case Medical Center, 10900 Euclid Ave, Cleveland, OH 44106, USA. Electronic address: eph29@case.edu.
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Harausz
authors.affiliation: Department of Medicine, Case Western Reserve University, University Hospitals Case Medical Center, 10900 Euclid Ave, Cleveland, OH 44106, USA. Electronic address: kac2@case.edu.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Chervenak
authors.affiliation: Department of Pathology, Case Western Reserve University, University Hospitals Case Medical Center, 10900 Euclid Ave, Cleveland, OH 44106, USA. Electronic address: carynandsteven@yahoo.com.
authors.forename: Caryn E
authors.initials: CE
authors.lastname: Good
authors.affiliation: Department of Pathology, Case Western Reserve University, University Hospitals Case Medical Center, 10900 Euclid Ave, Cleveland, OH 44106, USA. Electronic address: mrj6@case.edu.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Jacobs
authors.affiliation: Aurum Institute, 29 Queens Rd, Parktown, Johannesburg, South Africa. Electronic address: rwallis@auruminstitute.org.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Wallis
authors.affiliation: Lilly Research Laboratories, USA. Electronic address: mvsf@sbcglobal.net.
authors.forename: Manuel
authors.initials: M
authors.lastname: Sanchez-Felix
authors.affiliation: Department of Medicine, Case Western Reserve University, University Hospitals Case Medical Center, 10900 Euclid Ave, Cleveland, OH 44106, USA. Electronic address: whb@case.edu.
authors.forename: W Henry
authors.initials: WH
authors.lastname: Boom
mesh_terms: D000995:Antitubercular Agents / Q000097:blood / Q000494:pharmacology*; D000071997:Blood Culture; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity; D009574:Nitro Compounds; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism; D000075462:Serum Albumin, Human; D015610:Serum Bactericidal Test; D013844:Thiazoles / Q000097:blood / Q000494:pharmacology*; D013997:Time Factors
chemical_list: C422455:ALB protein, human; D000995:Antitubercular Agents; D009574:Nitro Compounds; D012709:Serum Albumin; D013844:Thiazoles; C104067:tizoxanide; C041747:nitazoxanide; D000075462:Serum Albumin, Human
keywords: BCG; Mycobacteria growth indicator tube; Mycobacterium tuberculosis; Nitazoxanide; Tizoxanide; Whole blood assay