title: Individualizing management of extensively drug-resistant tuberculosis: diagnostics, treatment, and biomarkers.
abstract: Success rates for treatment of extensively drug resistant tuberculosis (XDR-TB) are low due to limited treatment options, delayed diagnosis and inadequate health care infrastructure. Areas covered: This review analyses existing programmes of prevention, diagnosis and treatment of XDR-TB. Improved diagnostic procedures and rapid molecular tests help to select appropriate drugs and dosages. Drugs dosages can be further tailored to the specific conditions of the patient based on quantitative susceptibility testing of the M. tuberculosis isolate and use of therapeutic drug monitoring. Pharmacovigilance is important for preserving activity of the novel drugs bedaquiline and delamanid. Furthermore, biomarkers of treatment response must be developed and validated to guide therapeutic decisions. Expert commentary: Given the currently poor treatment outcomes and the association of XDR-TB with HIV in endemic regions, a more patient oriented approach regarding diagnostics, drug selection and tailoring and treatment evaluation will improve treatment outcome. The different areas of expertise should be covered by a multidisciplinary team and may involve the transition of patients from hospitalized to home or community-based treatment.
authors.affiliation: a Dept of Clinical Pharmacy and Pharmacology , University of Groningen, University Medical Center Groningen , Groningen , The Netherlands.
authors.forename: Jan-Willem C
authors.initials: JC
authors.lastname: Alffenaar
authors.affiliation: b University of Groningen, University Medical Center Groningen, Tuberculosis Center Beatrixoord , Haren , The Netherlands.|c Department of Pulmonary Diseases and Tuberculosis , University of Groningen, University Medical Center Groningen , Groningen , The Netherlands.
authors.forename: Onno W
authors.initials: OW
authors.lastname: Akkerman
authors.affiliation: d Royal Tropical Institute (KIT), KIT Biomedical Research , Amsterdam , The Netherlands.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Anthony
authors.affiliation: e Division of Infection , Barts Healthcare NHS Trust , London , United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Tiberi
authors.affiliation: f Division of Infectious Diseases and International Health , University of Virginia , Charlottesville , VA , USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Heysell
authors.affiliation: g Center of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Division of Internal Medicine, Academic Medical Center , University of Amsterdam , Amsterdam , The Netherlands.
authors.forename: Martin P
authors.initials: MP
authors.lastname: Grobusch
authors.affiliation: h Department of Global Health, Academic Medical Centre , University of Amsterdam , Amsterdam , The Netherlands.|i Amsterdam Institute for Global Health and Development , Amsterdam , The Netherlands.|j KNCV Tuberculosis Foundation , The Hague , The Netherlands.
authors.forename: Frank G
authors.initials: FG
authors.lastname: Cobelens
authors.affiliation: k National Tuberclosis Reference Laboratory , National Institute for Public Health and the Environment (RIVM) , Bilthoven , The Netherlands.|l Radboud University Nijmegen Medical Center , Departments of Pulmonary Diseases and Medical Microbiology , Nijmegen , The Netherlands.
authors.forename: Dick
authors.initials: D
authors.lastname: Van Soolingen
mesh_terms: D000995:Antitubercular Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis; D002986:Clinical Trials as Topic; D060085:Coinfection / Q000175:diagnosis / Q000188:drug therapy; D064687:Diarylquinolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D054908:Extensively Drug-Resistant Tuberculosis / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000378:metabolism; D009593:Nitroimidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D010080:Oxazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D017410:Practice Guidelines as Topic; D057285:Precision Medicine
chemical_list: D000995:Antitubercular Agents; D015415:Biomarkers; D064687:Diarylquinolines; D009593:Nitroimidazoles; C516022:OPC-67683; D010080:Oxazoles; C493870:bedaquiline
keywords: Extensive drug resistant tuberculosis; biomarkers; diagnostics; individualised treatment; therapeutic drug monitoring; treatment