Table 1.

Current standards and future perspectives for Precision Medicine for tuberculosis.

Measure	Current standard	Future perspective for precision medicine	When to apply
Rapid selection of effective anti-tuberculosis drugs to form a treatment regimen.	Rapid molecular Rifampicin-resistance testing followed by phenotypic drug susceptibility testing in liquid and/or solid media cultures.	Rapid, sputum-based automated sequencing of the entire genome of M. tuberculosis or of genetic regions (amplicons) of the genome of M. tuberculosis where mutations do predict drug resistance. Algorithm-based treatment decisions based on molecular prediction of drug resistance.	At the time of diagnosis.
Supporting the host immunity by endotype-guided decisions for host-directed therapies.	Endotypes of tuberculosis are still not well defined and identification of endotypes to guide host directed therapies is not performed at present.	Optimal testing needs to be discerned, but likely will include a mixture of metabolism, genetic, epigenetic and/or immune functional studies to identify the host endotype. For example, if host immunity was found to be exuberant, then an endotype-specific therapy might consist of a glucocorticoid, NSAID, calcineurin inhibitor (cyclosporin or tacrolimus) or mTOR inhibitor (rapamycin). In contrast, if evaluations identified anergic or exhausted immunity, than immune boosting regimens may be chosen.	Within the first week: of the diagnosis. Should be repeated 4–8 weeks to evaluate dynamic transitions.
Analysis of host genetic variability to predict adverse events and to provide precise therapeutically interventions.	Host genetic markers are currently not identified in clinical practice. At specialized centers and on special request genetic markers such as mutations associated with specific immune deficiencies are evaluated.	Genetic testing before the start of treatment to (1) define dosing of anti-tuberculous treatment and to (2) identify patients susceptible to adverse drug events and (3) to tailor host-directed therapy to the individual patient.	At the time of diagnosis.
Therapeutic drug monitoring.	Only very few centers world-wide perform measurement of drug levels and PK/PD profiles of anti-tuberculosis drugs in routine clinical practice. Even at these centers there are no analytic capacities to monitor several of the 2nd-line anti-tuberculosis drugs.	Regular therapeutic drug monitoring with same-day-results for all anti-tuberculosis drugs for individual dosage adjustments.	For the first month once a week, once a month thereafter throughout the course of treatment.
Individualizing the duration of anti-tuberculosis therapy.	There are no biomarkers available for routine clinical practice to guide clinicians in the decision of the duration of anti-tuberculosis therapy.	Defining the duration of therapy to achieve relapse-free cure based on the measurement of a robust validated biomarker that also identifies patients having the risk for experiencing recurrent disease at early time points during therapy. Ideally, this biomarker should be measurable in a point-of-care test system.	Once a month throughout the course of treatment starting at month 4.