The association between sterilizing activity and drug distribution into tuberculosis lesions

Nature Medicine
Brendan PrideauxVéronique Dartois

Abstract

Finding new treatment-shortening antibiotics to improve cure rates and curb the alarming emergence of drug resistance is the major objective of tuberculosis (TB) drug development. Using a matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging suite in a biosafety containment facility, we show that the key sterilizing drugs rifampicin and pyrazinamide efficiently penetrate the sites of TB infection in lung lesions. Rifampicin even accumulates in necrotic caseum, a critical lesion site where persisting tubercle bacilli reside. In contrast, moxifloxacin, which is active in vitro against a subpopulation of Mycobacterium tuberculosis that persists in specific niches under drug pressure and has achieved treatment shortening in mice, does not diffuse well in caseum, concordant with its failure to shorten therapy in recent clinical trials. We suggest that such differential spatial distribution and kinetics of accumulation in lesions may create temporal and spatial windows of monotherapy in specific niches, allowing the gradual development of multidrug-resistant TB. We propose an alternative working model to prioritize new antibiotic regimens based on quantitative and spatial distribution of TB drugs in the major ...Continue Reading

References

Oct 1, 1992·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·N RastogiP Cruaud
Oct 28, 2003·American Journal of Respiratory and Critical Care Medicine·Eric L NuermbergerJacques H Grosset
Sep 18, 2004·American Journal of Respiratory and Critical Care Medicine·Kwok C ChangCheuk M Tam
Jul 26, 2006·Pharmacology·Claudia WagnerChristian Joukhadar
Dec 23, 2006·Current Opinion in Chemical Biology·Michelle L Reyzer, Richard M Caprioli
May 23, 2007·Antimicrobial Agents and Chemotherapy·Anne J LenaertsRandall J Basaraba
Feb 27, 2008·Journal of Pharmaceutical Sciences·Nigel J WatersBindi Sohal
Mar 19, 2008·Infection and Immunity·Laura E ViaClifton E Barry
Dec 25, 2009·Lung·Matthew J MacCarrickBalagangadhar R Totapally
Jan 9, 2010·Current Opinion in Microbiology·Anna D Tischler, John D McKinney
Oct 12, 2011·Antimicrobial Agents and Chemotherapy·Maria C KjellssonVéronique Dartois
May 31, 2012·Open Biology·Selvakumar SubbianGilla Kaplan
Jul 31, 2012·Journal of Proteomics·Brendan Prideaux, Markus Stoeckli
Mar 29, 2013·Journal of the American Society for Mass Spectrometry·Guillaume RobichaudDavid C Muddiman
Oct 9, 2013·Antimicrobial Agents and Chemotherapy·Jongseok LeeMoses L Joloba
Feb 4, 2014·Nature Reviews. Microbiology·Véronique Dartois
May 7, 2014·Antimicrobial Agents and Chemotherapy·Scott M IrwinAnne J Lenaerts
Sep 10, 2014·The New England Journal of Medicine·Stephen H GillespieUNKNOWN REMoxTB Consortium
Oct 23, 2014·The New England Journal of Medicine·Amina JindaniUNKNOWN RIFAQUIN Trial Team
Jan 15, 2015·The Journal of Antimicrobial Chemotherapy·Suresh B LakshminarayanaSrinivasa P S Rao
Feb 24, 2015·Immunological Reviews·Carl Nathan, Clifton E Barry
Apr 29, 2015·Antimicrobial Agents and Chemotherapy·Si-Yang LiEric L Nuermberger

❮ Previous
Next ❯

Citations

Mar 5, 2016·Frontiers in Microbiology·Wilfried MoreiraThomas Dick
Feb 24, 2016·The Journal of Antimicrobial Chemotherapy·Noton K DuttaPetros C Karakousis
Feb 13, 2016·EBioMedicine·Suzaan Marais, Robert J Wilkinson
Sep 14, 2016·ACS Infectious Diseases·Clifton E Barry
Nov 26, 2015·The New England Journal of Medicine·C Robert HorsburghChristoph Lange
Nov 19, 2015·Seminars in Immunopathology·Constance J MartinSarah M Fortune
Apr 1, 2016·Expert Review of Respiratory Medicine·Neesha RockwoodRobert J Wilkinson
Apr 5, 2016·Nature Medicine·Mohlopheni J MarakalalaEric J Rubin
Apr 27, 2016·The Journal of Experimental Medicine·Yancheng LiuDavid G Russell
Jul 28, 2016·Tuberculosis·S LipworthS H Gillespie
Jun 5, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·João P SilvaF Miguel Gama
Jun 9, 2016·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Christian LienhardtChristine F Sizemore
Sep 15, 2016·ACS Infectious Diseases·Jansy P SarathyVéronique Dartois
Jun 22, 2016·Assay and Drug Development Technologies·Kaitlyn SchaafJim Sun
Jul 1, 2016·Proceedings of the National Academy of Sciences of the United States of America·Kirill RichardsonBree B Aldridge
Jul 9, 2016·Nitric Oxide : Biology and Chemistry·Krishna C ChintaAdrie J C Steyn
Jul 5, 2016·Expert Review of Clinical Pharmacology·Arnold MafukidzeJennifer Furin
Aug 16, 2016·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Payam NahidAndrew Vernon
Sep 9, 2016·Immunotherapy·Nancy GuptaRakesh Kumar
Oct 16, 2016·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Shashikant SrivastavaTawanda Gumbo
Oct 26, 2016·Drug Discovery Today·Vitor Mendes, Tom L Blundell
Feb 6, 2016·Expert Opinion on Emerging Drugs·S HofmanJ W C Alffenaar
Nov 1, 2016·The Journal of Antimicrobial Chemotherapy·Moloko C CholoRonald Anderson
Dec 14, 2016·International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases·S E McAnawC R Horsburgh
Sep 18, 2016·Médecine et maladies infectieuses·T MaitreUNKNOWN CNR-MyRMA
Feb 17, 2017·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Neesha RockwoodRobert J Wilkinson
Jun 1, 2017·Clinical and Translational Science·I H BartelinkR M Savic
Jun 1, 2017·Proceedings of the National Academy of Sciences of the United States of America·Kohta SaitoCarl F Nathan
Jun 26, 2017·The Journal of Infection·Alexander C OuthredBen J Marais
Dec 1, 2017·The Journal of Antimicrobial Chemotherapy·M Tobias HeinrichsRussell R Kempker
Feb 22, 2018·Antimicrobial Agents and Chemotherapy·Chao ChenVéronique Dartois
Jun 9, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Joshua T MattilaCarolyn J Anderson
Dec 13, 2017·Antimicrobial Agents and Chemotherapy·Dereje A NegatuThomas Dick
Dec 6, 2017·Antimicrobial Agents and Chemotherapy·Jansy P SarathyVéronique A Dartois
Dec 21, 2017·MBio·Kristine M Guinn, Eric J Rubin
Dec 1, 2017·Frontiers in Molecular Biosciences·Michael A ReicheValerie Mizrahi
Jan 13, 2018·Frontiers in Immunology·Hayley C WarsinskeDenise E Kirschner

❮ Previous
Next ❯

Methods Mentioned

BETA
biopsies
contraception
pregnancy test
dissection

Clinical Trials Mentioned

NCT00816426
NCT00018044

Software Mentioned

MSiReader
ImageQuest
Thermo
Analyst
Excel

Related Concepts

Related Feeds

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Antitubercular Agents

Antitubercular agents are pharmacologic agents for treatment of tuberculosis. Discover the latest research on antitubercular agents here.

Antitubercular Agents (ASM)

Antitubercular agents are pharmacologic agents for treatment of tuberculosis. Discover the latest research on antitubercular agents here.