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In December 2022, based on the assessment of new evidence, the World Health Organization (WHO) updated its guidelines for the treatment of drug-resistant tuberculosis (TB). The evaluation of both, these recommendations, and the latest study data, makes it necessary to update the existing guidelines on the treatment of at least rifampicin-resistant tuberculosis for the German-speaking region, hereby replacing the respective chapters. A shortened MDR-TB treatment of at least 6 month using the fixed and non-modifiable drug combination of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) is now also recommended for Germany, Austria, and Switzerland under certain conditions. This recommendation applies to TB cases with proven rifampicin resistance, including rifampicin monoresistance. For treatment of pre-extensively drug resistant TB (pre-XDR-TB), an individualized treatment for 18 months adjusted to resistance data continues to be the primary recommendation. The non-modifiable drug combination of bedaquiline, pretomanid, and linezolid (BPaL) may be used alternatively in pre-XDR TB if all prerequisites are met. The necessary prerequisites for the use of BPaLM and BPaL are presented in this amendment to the S2k guideline for 'Tuberculosis in adulthood'., Competing Interests: Informationen zu Interessenkonflikten finden Sie auf den Seiten der AWMF (http://www.awmf.org/leitlinien/awmf-regelwerk.html)., (Thieme. All rights reserved.)

In Germany tuberculosis is a rare disease and usually well treatable. Worldwide it is one of the most common infectious diseases with approximately 10 million new cases every year. Even with low incidences in Germany, tuberculosis is an important differential diagnosis especially due to international developments and migration movements. With a decreasing experience there's a continuous demand on accurate and up-to-date information. This guideline covers all aspects of microbiological diagnostics, basic principles of standard therapy, treatment of extrapulmonary tuberculosis, management of side effects, special features of diagnosis and treatment of resistant tuberculosis, and treatment in TB-HIV coinfection. Also, it explains when treatment in specialized centers is required, aspects of care and legal regulations and the diagnosis and preventive therapy of latent tuberculosis infection. The update of the S2k guideline "Tuberculosis in Adults" is intended to serve as a guideline for prevention, diagnosis, and treatment of tuberculosis for all those involved in tuberculosis care and to help meet the current challenges in dealing with tuberculosis in Germany., Competing Interests: Eine Übersicht der Interessenkonflikte findet sich im Internet unter http://awmf.org; AWMF-Registriernummer 020-019, (Thieme. All rights reserved.)

Background:  While the risk of tuberculosis (TB) reactivation is adequately documented in relation to TNF-alpha inhibitors (TNFi), the question of what the tuberculosis risk is for newer, non-TNF biologics (non-TNFi) has not been thoroughly addressed., Methods:  We conducted a systematic review of randomized phase 2 and phase 3 studies, and long-term extensions of same, published through March 2019. Of interest was information pertaining to screening and treating of latent tuberculosis (LTBI) in association with the use of 12 particular non-TNFi. Only rituximab was excluded. We searched MEDLINE and the ClinicalTrial.gov database for any and all candidate studies meeting these criteria., Results:  677 citations were retrieved; 127 studies comprising a total of 34,293 patients who received non-TNFi were eligible for evaluation. Only 80 out of the 127 studies, or 63 %, captured active TB (or at least opportunistic diseases) as potential outcomes and 25 TB cases were reported. More than two thirds of publications (86/127, 68 %) mentioned LTBI screening prior to inclusion of study participants in the respective trial, whereas in only 4 studies LTBI screening was explicitly considered redundant. In 21 studies, patients with LTBI were generally excluded from the trials and in 42 out of the 127 trials, or 33 %, latently infected patients were reported to receive preventive therapy (PT) at least 3 weeks prior to non-TNFi treatment., Conclusions:  The lack of information in many non-TNFi studies on the number of patients with LTBI who were either excluded prior to participating or had been offered PT hampers assessment of the actual TB risk when applying the novel biologics. Therefore, in case of insufficient information about drugs or drug classes, the existing recommendations of the German Central Committee against Tuberculosis should be applied in the same way as is done prior to administering TNFi. Well designed, long-term "real world" register studies on TB progression risk in relation to individual substances for IGRA-positive cases without prior or concomitant PT may help to reduce selection bias and to achieve valid conclusions in the future., Competing Interests: R. D. received a grant by the Niedersächsischer Verein zur Bekämpfung der Tuberkulose, Lungen- und Bronchialerkrankungen.M. F. has worked as a paid consultant or speaker for the following companies: Novartis, LEO Pharma, Almirall and AbbVie.C. K. has consulted or lectured for AbbVie, Centogene, Celltrion, Chugai, Gilead, GSK, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche, Sanofi and UCB.U. M. has been a paid consultant and/or speaker and/or recipient of research support and/or participant in clinical trials for AbbVie, Almirall, Eli Lilly, Formycon, Janssen, LEO Pharma and Novartis.R. O.-K. has received fees from Novartis, Gilead, Boehringer Ingelheim, Berlin Chemie, Insmed and Astra Zeneca for lectures that were financially supported or organized by the companies mentioned.T. B., B. H., A. K., A. N. and T. S. do not declare any conflict of interest., (Thieme. All rights reserved.)

Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

The increasing evidence has made it necessary to change international recommendations for the diagnosis and treatment of resistant tuberculosis repeatedly in the recent years. This year, the WHO has published comprehensive recommendations that take into account these developments. The current German tuberculosis guideline was published in 2017 with differing recommendations in some areas. Here the new WHO recommendations of 2020 for rapid diagnosis and therapy of resistant tuberculosis are summarized and the relevant differences are commented for Germany, Austria and Switzerland. A complete re-evaluation of the literature is currently taking place by updating the German-language AWMF 2k guidelines., Competing Interests: Ralf Otto-Knapp hat Honorare der Firmen Novartis, Gilead, Boehringer Ingelheim, Berlin Chemie, Insmed, Astra Zeneca für Vorträge erhalten, die von den genannten Firmen finanziell unterstützt oder organisiert wurden. Die Firmen hatten keinen Einfluss auf die Inhalte der Präsentationen.Brit Häcker: 2018 finanzielle Unterstützung durch Otsuka für Erstellung einer Datenbank für MDR-Patienten.Christoph Lange erhielt Vortragshonorare von Chiesi, Gilead, Janssen, Novartis, Berlin Chemie und Insmed für Vorträge auf Symposien, die von diesen Firmen unterstützt/veranstaltet wurden und hat gegen Honorarzahlung Oxfordimmunotec wissenschaftlich beraten. Er hat beim Europäischen Patentamt ein Patent für einen Biomarker zur Individualisierung der Therapie der Tuberkulose angemeldet (EP20158652.6).Florian Maurer erhielt Honorare der Akademie für Infektionsmedizin und Biomerieux für Vorträge ohne Einfluss auf den Inhalt., (Thieme. All rights reserved.)

Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt be- steht.

Competing Interests: Prof. Stefan H. E. Kaufmann ist Ko-Erfinder des Impfstoffs VPM1002, der an Vakzinze Projekt Management GmbH und Serum Institute of India Ltd. lizenziert wurde.Dr. Brit Häcker: finanzielle Unterstützung der Firma Otsuka für den Aufbau einer Datenbank für MDR-Patienten.Dr. Ralf Otto-Knapp hat Honorare der Firmen Novartis, Gilead, Boehringer Ingelheim, Berlin Chemie, Insmed, Astra Zeneca für Vorträge erhalten, die von den genannten Firmen finanziell unterstützt oder organisiert wurden. Die Firmen hatten keinen Einfluss auf die Inhalte der Präsentationen.

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., Competing Interests: Interessenkonflikt: Siehe Interessenkonflikterklärung auf www.awmf.org, (© Georg Thieme Verlag KG Stuttgart · New York.)

Non-tuberculous mycobacterioses comprise a group of diseases caused by mycobacteria which do not belong to the Mycobacterium (M.) tuberculosis-complex and are not ascribed to M. leprae. These mycobacteria are characterized by a broad variety as to environmental distribution and adaptation. Some of the species may cause specific diseases, especially in patients with underlying immunosuppressive diseases, chronic pulmonary diseases or genetic predisposition, respectively. Worldwide, a rising prevalence and significance of non-tuberculous mycobacterioses is recognized. The present recommendations summarise current aspects of epidemiology, pathogenesis, clinical aspects, diagnostics - especially microbiological methods including susceptibility testing -, and specific treatment for the most relevant species. Diagnosis and treatment of non-tuberculous mycobacterioses during childhood and in HIV-infected individuals are described in separate chapters., (© Georg Thieme Verlag KG Stuttgart · New York.)

The present guideline provides a new and updated concept of treatment and prevention of adult patients with community-acquired pneumonia. It replaces the previous guideline dating from 2009.The guideline was worked out and agreed on following the standards of methodology of a S3-guideline. This includes a systematic literature search and grading, a structured discussion of recommendations supported by the literature as well as the declaration and assessment of potential conflicts of interests.The guideline has a focus on specific clinical circumstances, an update on severity assessment, and includes recommendations for an individualized selection of antimicrobial treatment as well as primary and secondary prevention., (© Georg Thieme Verlag KG Stuttgart · New York.)

This article summarizes the state of development of new drugs for the treatment of multidrug-resistant tuberculosis. We focused on delamanid, bedaquiline, pretomanid, SQ 109 and sutezolid., (© Georg Thieme Verlag KG Stuttgart · New York.)

Non tuberculous mycobacterial diseases are caused by mycobacteria other than M. tuberculosis complex. NTM are found in the environment and are not transmitted from humans to humans. Infection occurs by the inhalation of dust or aerosols. The finding of NTM is not equal to a diagnosis of active disease. For the diagnosis of active disease well defined clinical and microbiological criteria have to be fulfilled. Gold standard is the detection of NTM by culture, in the case of pulmonary NTM at least two times. There is no established susceptibility testing. Treatment mostly consists of three drugs, given for up to 24 months., (© Georg Thieme Verlag KG Stuttgart · New York.)

Nontuberculous mycobacterioses comprise a group of diseases caused by mycobacteria which do not belong to the Mycobacterium (M.) tuberculosis complex and are not ascribed to M. leprae. These mycobacteria are characterized by a broad variety as to environmental distribution and adaptation. Some of the species may cause specific diseases, especially in patients with underlying immunosuppressive diseases, chronic pulmonary diseases or genetic predisposition, respectively. Worldwide a rising prevalence and significance of nontuberculous mycobacterioses can be recognized. The present recommendations summarise actual aspects of epidemiology, pathogenesis, clinical aspects, diagnostics - especially microbiological methods including susceptibility testing -, and specific treatment for the most relevant species. Diagnosis and treatment of nontuberculous mycobacterioses during childhood and in HIV-infected individuals are described in separate chapters., (© Georg Thieme Verlag KG Stuttgart · New York.)

In March 2013, the first cases of avian influenza virus infections in humans were reported by the authorities of the PR of China to the World Health Organization. This influenza A(H7N9) virus comprises genes of at least four different avian influenza viruses, some segments mimicking human-like influenza-signatures. Until 11 August, 2013 135 humans were infected, 44 (33%) died. The clinical course is characterized by fever, cough, gastrointestinal symptoms, lympho- and thrombopenia as well by the rapid onset of an acute respiratory distress syndrome in nearly 25% of the cases. Although human to human transmission may have occurred only in the context of three clusters, strict hygiene measures should be instituted and any suspect case should be reported to the local health authorities immediately. The detection of influenza A(H7N9) is based on real-time polymerase chain reaction (PCR). Antiviral treatment should be initiated as early as possible for suspect, probable or confirmed cases, even when 48 hours have passed after symptom onset. At present the future development of this epidemic cannot be predicted., (© Georg Thieme Verlag KG Stuttgart · New York.)

The epidemiological situation of tuberculosis (TB) in Germany has improved considerably during the past few years. However, those in unprotected contact with infectious tuberculosis patients frequently and/or over longer periods of time and/or intensively continue to have a higher risk for TB infection. Rapid diagnosis, prompt initiation of effective treatment, and adequate infection control measures are of particular importance to prevent infection. The present recommendations depict the essentials of infection control as well as specific measures in the hospital (isolation, criteria for its duration and technical requirements, types of respiratory protection, disinfection measures, waste disposal). The specific requirements for outpatients (medical practice), at home, for ambulance services, and in congregate settings, including prisons, are also addressed. Compared with the previous recommendations the pattern of respiratory protection measures has been simplified. As a rule, hospital staff and those visiting infectious tuberculosis patients are advised to wear respiratory protection that satisfies the criteria of FFP2-masks (DIN EN 149), while patients should wear mouth-nose protectors (surgical masks) in the presence of others and outside the isolation room. A detailed depiction of criteria for isolation and its duration in smear positive and only culturally confirmed pulmonary tuberculosis has been added., (© Georg Thieme Verlag KG Stuttgart · New York.)

The "International Standards for Tuberculosis Care" (ISTC) were developed by the World Health Organisation (WHO) and others to provide internationally agreed and, if possible, evidence-based standards for tuberculosis care including the care by private providers who are not part of national tuberculosis programmes or health-care systems. Hence, the ISTC primarily address resource-restrained countries with high tuberculosis prevalence. In this article, the German translation of the 21 standards from 2009 is presented - addressing diagnostic and therapeutic standards, co-infection (especially with HIV) and public-health issues. The accompanying comments show how these standards have to be modified for Germany due to the medical resources available here and country-specific characteristics respectively., (© Georg Thieme Verlag KG Stuttgart · New York.)

Several new international recommendations have been published since the German Central Committee against Tuberculosis (DZK) published its recommendations for drug treatment of tuberculosis (TB) in 2001 and for chemoprevention of latent tuberculosis infection (LTBI) in 2004. These international publications have been integrated in the present new recommendations which describe both the treatment of active TB and preventive treatment, pointing out specific adaptations for Germany. Separate sections deal with the current management of mono-, poly-, and multiresistance or drug intolerance, of TB in children, of different forms of extrapulmonary TB, of LTBI and of special situations such as HIV infection, renal or hepatic insufficiency, infection following BCG instillation in bladder cancer or in case of adverse drug reactions. The following aspects differ from the previous recommendations: A three-drug regimen for the so-called fully susceptible minimal TB is no longer recommended in adults. A dosage of 15 mg/kg body weight of ethambutol for adults is regarded as sufficient. Four secondline drugs (supplemented by pyrazinamide, where appropriate) are recommended for multidrug-resistant tuberculosis (MDR-TB). MDR-TB should be treated over a period of at least 20 months, with an injectable drug administered for a minimum of 8 months (initial phase). Ciprofloxacine and ofloxacine are no longer used to treat TB. It is also recommended to offer an HIV test to all TB patients to complement antiretroviral therapy, if necessary, and to adapt the antituberculous therapy accordingly., (© Georg Thieme Verlag KG Stuttgart · New York.)

Tuberculosis is one of the leading causes, if not the leading cause of death in human history. Worldwide TB still belongs to the ten most frequent causes of death and represents one of the most urgent public health problems globally. In Germany as in almost all industrialised countries, the incidence and mortality has been continuously declining but globally the situation is worsening dramatically due to HIV coinfection and the increase of polyresistant TB strains. Only rapid and internationally concerted action with the cooperation of the affected countries and combined with intensified research efforts into new diagnostics, therapeutics, and vaccines will be able to prevent a development that will no longer be manageable even with 21st century technology., (Copyright Georg Thieme Verlag KG Stuttgart . New York.)

This update summarized the hospital experience from the first wave of the new influenza A/H1/N1 pandemic., (Copyright Georg Thieme Verlag KG Stuttgart . New York.)

Multi-drug resistant tuberculosis (MDR-Tb), caused by Mycobacterium tuberculosis, is long known, and it is defined to be resistant to both isonizid and rifampicin with or without resistance to other drugs. In addition to MDR-Tb, XDR-Tb (extensively drug-resistant tuberculosis) is resistant to any fluoroquinolone, and at least one of three injectable drugs, in addition to MDR-Tb. For some years these highly resistant Tb have been isolated world wide, which was named XDR 2006. Once no reliable therapy is available, the best way to prevent XDR-Tb is to ensure the efficacy of national TB control programs. The treatment must be in accordance with the results of drug susceptibility testing. Further, there is an urgent need to develop new Tb drugs. However, treatment is made difficult due to specific characteristics of Tb, e. g. the presences of metabolically silent, persistent or dormant bacteria within host lesions, which are not susceptible to antimycobacterial drugs, and its capability to rapidly develop drug resistance. This article informs about the current threat of the emerging XDR-Tb and summarizes possible options to curb with this phenomenon.

In practice, antimicrobial treatment is usually thought to be regularly indicated in the treatment of patients with acute exacerbations of COPD. However, data supporting this practice are very limited. Most placebo-controlled studies do not satisfy currently required methodological quality standards. We develop a concept of restrictive indications for antimicrobial treatment from the available data. Cornerstones of this concept include the selection of treatment setting as well as the indication for antimicrobial treatment according to the severity of the acute exacerbation (not primarily of COPD) and to the type of exacerbation (Anthonisen type I). The selection of antimicrobial agents is based on an intraindividual rotation concept in order to limit antimicrobial selection pressure. The concept presented here can at the same time be used as a clinical guide as well as a framework for future studies dealing with currently unresolved issues.

Up to now the diagnosis of latent tuberculosis infection (LTBI) was based solely on the tuberculin skin test. However, this method offers neither 100 % sensitivity nor -- and this is in particular due to its cross-reactivity with BCG and environmental mycobacteria -- a 100 % specificity. The demand in Germany for a more reliable in vitro test is currently enhanced by the change from the multipuncture test to the intradermal (Mendel-Mantoux) test and by the uncertainty resulting from the ceased production of the tuberculin previously used in Germany. The manufacturers of immunologic test methods such as the QuantiFERON-TB Gold In-Tube (ELISA assay) and the T SPOT-TB Test (ELISPOT assay), which are based on the Interferon-gamma (IFN-gamma) production of sensitized T lymphocytes, offer their products as possible alternatives. This article explains the function of the IFN-gamma tests and gives an overview of the most recent data, possible indications and the open scientific questions to be investigated by future clinical studies. Although the new test methods have the potential to eventually prevail as an additional helpful diagnostic tool, the authors consider a complete replacement of the tuberculin skin test as premature. The IFN-gamma tests may, however, prove already now to be a useful additional diagnostic method.

New methods for diagnosing active tuberculosis (TB) and/or latent tuberculosis infection have been offered increasingly during recent years, also in Germany. The Tuberculosis Rapid Assay ('Tuberkulose Schnelltest [TB-ST]') from DiaVita is a serologic test method aiming to detect, within a few minutes, tuberculosis-specific antibodies in whole blood or serum of tuberculosis patients. Due to a lack of data, it is, however, hardly possible to assess this test on a scientific basis. With a relatively high specificity (according to DiaVita over 95 %) but inadequate sensitivity (approximately 60 - 80 %), particularly in paucibacillary types of TB, we consider this method of limited value for routine testing. If active TB is strongly suspected, a positive test result may corroborate the tentative diagnosis, whereas a negative test result is not helpful for differential diagnosis considering the great number of false-negative test results to be expected. The greatest value of the test seems to be in bacteriologically confirmed TB, in which however there may be no need for additional diagnostics. The test has not been evaluated, and in our opinion is probably unsuitable for detecting latent TB infection. Data is also lacking for a number of patient groups in urgent need of a reliable alternative to the tuberculin skin test (e. g., immunocompromised patients, children). It is not clear whether this method will find a place in routine TB diagnostics. We therefore cannot recommend this test as a routine diagnostic tool for TB at present.

In case of a viral pandemic without availability of effective vaccination, one can expect to be faced with additional 250 to 300 new admissions per hospital per week given the worst case scenario. Major complications are expected to occur in the respiratory system with the focus on viral pneumonia often complicated by bacterial superinfection. Frequently these patients will require artificial ventilation. The present infrastructure will not be capable of dealing sufficiently with such high numbers of casualties. These recommendations of the German Society for Pneumonology are based on the successful application of non-invasive ventilation for acute respiratory failure in recent years. It is of importance to achieve effective treatment by the use of relative simple means. The recommendation proposes to use a separate building in order to realize quarantine. In terms of diagnostic tools, a simple x-ray apparatus should be available. To monitor patients pulsoxymetry and ECG devices should be sufficient in most cases. For the treatment of acute respiratory insufficiency a sufficient number of ventilators, masks, tubing systems and filters should be kept in stock. In terms of medical treatment antibiotics to treat superinfections are of major importance. Analgesics, sedatives and intravenous fluids will also be needed. Oxygen should be available for every single patient. The recommendation gives detailed advise for the enforcement of hygiene control, diagnostic as well as therapeutic steps for in hospital treatment of high numbers of casualties of a viral pandemic.

The immunologic mechanisms of latent tuberculosis (TB) infection are complex and hitherto not completely understood. The lifelong risk of an immunocompetent individual of developing active TB after infection with M. tuberculosis is 5-10 % and highest during the first two years after infection. Various factors may considerably increase the risk of developing active TB, e. g., immunosuppressive disease or immunosuppressive medication. However, the development of active TB may be avoided by preventive chemotherapy, the therapy of choice being isoniazid over a 9-month period. Alternative treatment regimens may be indicated in special cases, but it must be borne in mind that the efficacy of these regimens has not been studied sufficiently while they seem to be less well tolerated than isoniazid monotherapy. The tuberculin skin test is still the only sufficiently documented method to detect latent infection with M. tuberculosis which is also suitable for routine application. This test today should be performed exclusively as described by Mendel and Mantoux. Its sensitivity and specificity depend on the prevalence of tuberculosis infection. It should therefore be restricted to individuals at increased risk of latent TB infection. When interpreting the tuberculin skin test, it is necessary to know whether an individual belongs to one of the defined risk groups or has an elevated risk of developing active TB. Among the risk groups are individuals who may have been infected recently with M. tuberculosis (contacts of contagious TB patients) or in whom other factors increase their risk of developing active TB. The indication for chemotherapy for latent TB infection must be based on a careful individual risk-benefit analysis and, besides patient compliance, requires full information of the patient and careful monitoring during therapy. Before initiating treatment, active TB must always be excluded by the proven methods.

These recommendations of the German Central Committee against Tuberculosis give an overview of the current scientific knowledge on the tuberculosis risk of health service employees and on the risk of infection in individual areas of work. The efficacy of face masks and their benefit in tuberculosis control is discussed. There are no reliable data on the efficacy of face masks in preventing infection with M. tuberculosis, nor can such data be expected in the near future, due to the complex interaction of infection-preventing measures. As rapid case finding, isolation, and immediate, effective treatment of infected patients already greatly diminish the risk of transmission, we consider face masks to be of limited use in reducing this risk. However, they may be beneficial in certain areas of work and in certain situations, particularly in the presence of elevated aerosol concentrations. The benefit of face masks depends largely on their correct application. The choice of a particular type of mask requires knowledge of the current epidemiological situation, and a competent assessment of the risk in the area of work for which it is chosen, taking into account the closeness of contact with potentially infectious tuberculosis patients.