title: Intra- and extracellular activities of trimethoprim-sulfamethoxazole against susceptible and multidrug-resistant Mycobacterium tuberculosis.
abstract: We investigated the activity of trimethoprim-sulfamethoxazole (SXT) against Mycobacterium tuberculosis, the pathogen that causes tuberculosis (TB). The MIC distribution of SXT was 0.125/2.4 to 2/38 mg/liter for the 100 isolates tested, including multi- and extensively drug-resistant isolates (MDR/XDR-TB), whereas the intracellular MIC90 of sulfamethoxazole (SMX) for the pansusceptible strain H37Rv was 76 mg/liter. In an exploratory analysis using a ratio of the unbound area under the concentration-time curve from 0 to 24 h over MIC (fAUC0-24/MIC) using ≥ 25 as a potential target, the cumulative fraction response was ≥ 90% at doses of ≥ 2,400 mg of SMX. SXT is a potential treatment option for MDR/XDR-TB.
authors.affiliation: Unit of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden Department of Infectious Diseases, Karolinska University Hospital Solna, Stockholm, Sweden lina.davies-forsman@karolinska.se.
authors.forename: L
authors.identifier: http://orcid.org/0000-0001-8885-3320
authors.initials: L
authors.lastname: Davies Forsman
authors.affiliation: Department of Medical Microbiology, Linköping University Hospital, Linköping, Sweden Department of Medicine and Optometry, Linnaeus University, Kalmar, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Schön
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
authors.forename: U S H
authors.initials: US
authors.lastname: Simonsson
authors.affiliation: Unit of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden Department of Infectious Diseases, Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Bruchfeld
authors.affiliation: Department of Medical Microbiology, Linköping University Hospital, Linköping, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Larsson
authors.affiliation: Unit for Highly Pathogenic Bacteria, Department of Microbiology, Public Health Agency of Sweden, Solna, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Juréen
authors.affiliation: Department of Clinical Microbiology, Regional and University Laboratories, Region Skåne, Malmö, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Sturegård
authors.affiliation: Department of Clinical Microbiology, MTC, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: C G
authors.initials: CG
authors.lastname: Giske
authors.affiliation: Department of Clinical Microbiology, MTC, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden Department of Microbiology, The University of the West Indies, Kingston, Jamaica.
authors.forename: K
authors.initials: K
authors.lastname: Ängeby
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D002460:Cell Line; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D015870:Gene Expression; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000494:pharmacology*; D018088:Tuberculosis, Multidrug-Resistant / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D008156:Luciferases