Drug-resistant tuberculosis: emerging treatment options

Figures & data

Figure 1 TB drug development time-line.

Abbreviations: TB, tuberculosis; MDR, multidrug-resistant.

Table 1 Tuberculosis clinical development programs

Groups	Compound	Development stage	Sponsor/coordinator
Rifamycins	Rifapentine	Phase II/III	CDC TBTC, sanofi-aventis
Fluoroquinolone	Gatifloxacin	Phase III	European Commission; IRD; WHO/TDR; Lupin
	Moxifloxacin	Phase II/III	Bayer; TB Alliance; CDC; University College London; Johns Hopkins University
	DC-159a	Preclinical	Japan Anti-Tuberculosis Association, JATA Daiichi-Sankyo Pharmaceutical Co
Oxazolidinone	Linezolid (low dose)	Phase II	CDC TBTC, Pfizer, various universities
	PNU-100480	Phase I	Pfizer
	AZD5847	Phase I	AstraZeneca
Diarylquinoline	TMC207	Phase II	Johnson & Johnson (Tibotec)
Nitroimidazole	OPC67683	Phase II	Otsuka Pharmaceutical
	PA824	Phase II	TB Alliance
Pyrrole	LL3858	Phase I	Lupin
Diamine	SQ109	Phase II	Sequella
Dipiperidines	SQ609	EBA	Sequella
Capuramycins	SQ641	EBA	Sequella
Isothiazoloquinolone	ACH-702	Preclinical	Achillion Pharmaceuticals
Caprazene nucleoside	Caprazamycin	Preclinical	MCRF, Tokyo, Japan Lilly TB Drug Discovery Initiative NIAID, IDRI, Lilly, YourEncore
Benzothiozinones	BZT043	EBA	EPFL School of Life Sciences
Imidazopyridine	Q201	EBA	Quro Science, Inc
Riminophenazines	Phenoxazine and asymmetrical riminophenazine series	EBA and Phase I	Institute of Materia Medica, China and Beijing Tuberculosis and Thoracic Tumor Research Institute

Abbreviations: CDC, Centers for Disease Control and Prevention; TBTC, Tuberculosis Trials Consortium; TDR, Special Programme for Research and Training in Tropical Diseases; EBA, early bactericidal activity; MCRF, Microbial Chemistry Research Foundation; NIAID, National Institute of Allergy and Infectious Diseases; EPFL, École Polytechnique Fédérale de Lausanne; GSK, GlaxoSmithKline; IDRI, Infectious diseases research institute; WHO, World Health Organization; TB, tuberculosis.

Figure 2 TB drug regimen goal.

Abbreviation: TB, tuberculosis.

Table 2 TB vaccine constructs in phase II clinical trials (as of July 2011)

Agent	Strategy	Type	Sponsors	Status
MVA85A/AERAS-485	Prime boost	Viral vector	Oxford-Emergent Tuberculosis Consortium, Aeras	Phase IIb
AERAS-402/Crucell Ad35	Prime boost	Viral vector	Crucell N.V., Aeras	Phase IIb
GSKM72	Prime boost	Recombinant protein	GSK Biologicals, Aeras	Phase II
RUTI	Immunotherapeutic	Fragmented MTB	Archivel farma	Phase II

Note: Reproduced with permission from the Treatment Action Group (http://www.treatmentactiongroup.org/pipeline-report/2011).

Abbreviations: GSK, GlaxoSmithKline; MTB, Mycobacterium tuberculosis.

Table 3 TB Diagnostic Test or Processes in the Pipeline, 2011

Name of test	Sponsor/Developer	Technique	What it measures	Estimated date of WHO review
Peripheral laboratories
Manual loop-mediated isothermal amplification process (LAMP)	Eiken Chemical/Foundation for Innovative New Diagnostics (FIND)	Manual nucleic acid amplification	MTB DNA	2012
Clearview^® TB ELISA	Alere	ELISA to detect Lipoarabinomannan (LAM) in urine	MTB LAM antigen	2013
Colorimetric Thin Layer Agar (TLA) DST	London School of Hygiene and Tropical Medicine/FIND	Colorimetric DST by culturing TB on a TLA plate and using microscopy to identify MTB growth	MTB culture growth	2012
Reference laboratories
GenoType^® MTBDRs	Hain Lifescience/FIND	Line probe assay to identify drug susceptibility to second-line TB drugs on TB culture isolate; is being tested on sputum samples	MTB DNA indicating resistance to fluoroquinolones, ethambutol, and aminoglycosides/cyclic peptides (amikcin, kanamycin, capreomycin)	2012
Sensititre^® MTB minimum inhibitory concentration (MIC) Plate	TREK Diagnostic Systems	Detects MTB growth in TB antibiotic containing plates to identify drug resistance	TB bacilli	2013

Note: Reproduced with permission from the Treatment Action Group (http://www.treatmentactiongroup.org/pipeline-report/2011).

Abbreviations: DST, drug susceptibility testing; ELISA, enzyme linked immunosorbent assay; DNA, deoxyribonucleic acid; TB, tuberculosis; MTB, Mycobacterium tuberculosis.