Since 2015 a significant increase in tuberculosis cases is notified in Germany, mostly due to rising numbers of migrants connected to the recent refugee crisis. Because of the low incidence in previous years, knowledge on tuberculosis is more and more limited to specialized centers. However, lung specialist and healthcare workers of other fields have contact to an increasing number of tuberculosis patients. In this situation, guidance for the management of standard therapy and especially for uncommon situations will be essential. This new guideline on tuberculosis in adults gives recommendations on diagnosis, treatment, prevention and prophylaxis. It provides a comprehensive overview over the current knowledge, adapted to the specific situation in Germany. The German Central Committee against Tuberculosis (DZK e. V.) realized this guideline on behalf of the German Respiratory Society (DGP). A specific guideline for tuberculosis in the pediatrics field will be published separately. Compared to the former recommendations of the year 2012, microbiological diagnostics and therapeutic drug management were given own sections. Chapters about the treatment of drug-resistant tuberculosis, tuberculosis in people living with HIV and pharmacological management were extended. This revised guideline aims to be a useful tool for practitioners and other health care providers to deal with the recent challenges of tuberculosis treatment in Germany.

W e read with great interest the mathematical model presented by Fofana et al. (1) on the role of pyrazinamide (PZA) in the emergence of multidrug-resistant tuberculosis (MDR TB), particularly as the results of their model mirror our concerns regarding the amplification of PZA resistance during inappropriate first-line therapy and the dramatic negative consequences that this can have on the subsequent response to second-line therapy. Indeed recent data from Belarus suggest that approximately 50% of PZA resistance is acquired de novo (2). Fofana et al. (1) propose that this problem, a result of using the same important agent in first-and second-line therapy, might be circumvented by using an as-yet-unidentified new agent with characteristics similar to those of PZA in a new second-line regimen. Although considerable effort is being applied to the development of new targets for such agents (3), it is far from certain when or even if these miraculous drugs will be available for routine use. Consequently, PZA is currently a uniquely valuable agent, which we speculate will be very difficult to replace (4, 5). We therefore suggest that in settings where the a priori risk of MDR TB due to transmission is above a certain level, such as in Belarus, prescribing PZA to new patients before they have been screened for rifampin and isoniazid resistance is likely counterproductive. Screening for PZA resistance is still complicated and not in reach for many laboratories. Of course, in an ideal world, a full drug susceptibility test (DST) profile would be available for all patients before TB therapy is prescribed. Unfortunately, in reality, this is seldom the case; at best, there is a considerable delay before DST results are communicated to the physician, and at worst, DST is not performed at all until there is evidence of treatment failure, which may be between 2 and 6 months after starting the patient on first-line agents. As this scenario appears to account for 50% of the PZA resistance seen in MDR-TB cases in many settings (5), action is required now to prevent transmissible PZA-resistant mutants from becoming widely established (6, 7). Thus, we propose that, in settings with a high proportion of MDR-TB patients, PZA be withheld until there is evidence of susceptibility to other first-line agents, because of either a clinical response (acid-fast bacillus [AFB] smear conversion) or a solid laboratory diagnosis. Modeling the exact proportion of primary MDR-TB patients in whom PZA resistance was prevented, a population benefitting from this change, and discussion of the ethics of this approach would be highly informative. Delaying action Citation Anthony RM, Cynamon M, Hoffner S, Werngren J, den Hertog AL, van Soolingen D. 2017. Protecting pyrazinamide, a priority for improving outcomes in multidrug-resistant tuberculosis treatment. Antimicrob Agents Chemother 61:e00258-17. https://doi.

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Ongoing transmission, high levels of drug resistance, and poor diagnostic

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