The highest estimated prevalence of MDR-TB is in India and China. However, the largest number of patients who have been diagnosed with MDR-TB live in the European Region of the WHO. In Belarus, Kazakhstan, Kyrgyzstan, the Republic of Moldova, the Russian Federation and Ukraine, more than 25% of all new patients who have not received treatment for TB in the past, have MDR-TB. 1 Less than one third of notified TB patients worldwide are evaluated with drug susceptibility testing (DST) for RMP; only half of patients with RMP resistance or MDR-TB undergo DST for FQs and second-line injectable drugs. 1 Only 20% of MDR-TB cases have access to adequate treatment. 3,4 It is predicted that the number of patients with MDR-TB and XDR-TB in highburden countries will continue to rise in the coming decades. 5 Treatment for MDR-TB is challenging for patients, relatives, healthcare providers and health systems. 6 The level of drug resistance of the causative strain of M. tuberculosis can be highly variable. 7 Depending on the DST results, current WHO treatment recommendations range from 9 to 20 months of daily combination antibiotic treatment. 8 The treatment is characterised by a high frequency of adverse drug events, often leading to changes in the regimen. 9 Due to high costs, some of the second-line drugs are not available in countries where they are needed most. 10 Despite all of our efforts, according to the latest WHO report, only 55% of patients with MDR-TB and 34% of patients with XDR-TB achieve a successful treatment outcome. 1 Treatment outcomes in MDR-TB and XDR-TB are highly dependent upon available resources. It was recently shown that relapse-free cure-rates in patients with M/XDR-TB can be similar to patients with drug-susceptible TB (DS-TB) when sufficient resources are provided, 11 and treatment can be personalised. 12 The aim of the present article is to update previous TBNET (Tuberculosis Network European Trials) recommendations on the optimal management of patients with M/XDR-TB. 6

Tuberculosis is a bacterial infectious disease that is mainly transmitted from human to human via infectious aerosols. Currently, tuberculosis is the leading cause of death by an infectious disease worldwide. In the past decade, the number of patients affected by tuberculosis has increased by ∼20 percent and the emergence of drug-resistant strains of Mycobacterium tuberculosis challenges the goal of elimination of tuberculosis in the near future. For the last 50 years, management of patients with tuberculosis has followed a standardized management approach. This standardization neglects the variation in human susceptibility to infection, immune response, the pharmacokinetics of drugs, and the individual duration of treatment needed to achieve relapse-free cure. Here we propose a package of precision medicine-guided therapies that has the prospect to drive clinical management decisions, based on both host immunity and M. tuberculosis strains genetics. Recently, important scientific discoveries and technological advances have been achieved that provide a perspective for individualized rather than standardized management of patients with tuberculosis. For the individual selection of best medicines and host-directed therapies, personalized drug dosing, and treatment durations, physicians treating patients with tuberculosis will be able to rely on these advances in systems biology and to apply them at the bedside.

According to the World Health Organization (WHO), tuberculosis is the leading cause of death attributed to a single microbial pathogen worldwide. In addition to the large number of patients affected by tuberculosis, the emergence of Mycobacterium tuberculosis drug-resistance is complicating tuberculosis control in many high-burden countries. During the past 5 years, the global number of patients identified with multidrug-resistant tuberculosis (MDR-TB), defined as bacillary resistance at least against rifampicin and isoniazid, the two most active drugs in a treatment regimen, has increased by more than 20% annually. Today we experience a historical peak in the number of patients affected by MDR-TB. The management of MDR-TB is characterized by delayed diagnosis, uncertainty of the extent of bacillary drug-resistance, imprecise standardized drug regimens and dosages, very long duration of therapy and high frequency of adverse events which all translate into a poor prognosis for many of the affected patients. Major scientific and technological advances in recent years provide new perspectives through treatment regimens tailor-made to individual needs. Where available, such personalized treatment has major implications on the treatment outcomes of patients with MDR-TB. The challenge now is to bring these adances to those patients that need them most.