Update S2k guideline on adult tuberculosis: What's new?

Since mid-2022, the revised S2k guideline on tuberculosis in adults has been available. In a total of 9 chapters and 109 recommendations and explanatory texts, the various aspects of diagnostics, care and therapy as well as special situations such as resistance, HIV-TB co-infection or latent tuberculous infection (LTBI) are discussed in detail. We would like to present a few selected innovations to you here.

DIAGNOSIS

The diagnosis of tuberculosis (TB) should be confirmed by microbiological evidence. In the case of pulmonary tuberculosis, three high-quality sputa are suitable for this purpose. If extrapulmonary tuberculosis is suspected, the diagnosis should also be confirmed using suitable material (e.g. tissue sample WITHOUT formalin). As part of the primary diagnosis, in addition to microscopic and cultural detection of the pathogen from at least one sample, a molecular biological examination including the detection of frequent pathogen mutations should also be carried out. The first available bacterial isolate should be used for cultural resistance testing for the drugs used in standard therapy and, in addition, molecular biological testing should be carried out for the gene segments associated with isoniazid and rifampicin resistance.

STANDARD THERAPY

The standard therapy for sensitive pulmonary tuberculosis has not currently changed. The six-month therapy should be carried out for eight weeks with the drugs rifampicin (RMP), isoniazid (INH), pyrazinamide (PZA) and ethambutol (EMB) and then for four months with RMP and INH. The internationally possible shortening of therapy to 4 months with rifapentine, moxifloxacin, isoniazid and pyrazinamide has not yet been adopted in the EU due to the lack of availability of rifapentine. If possible, all medications should be taken at the same time on an empty stomach in the morning.

CONTROL

Routine laboratory tests, sputum microscopy and culture, ophthalmologic examinations and radiological checks are recommended at regular intervals. At the beginning, an HIV test and, if necessary, hepatitis serology should also be arranged. Clinical and radiological follow-up examinations should be carried out after one, two and six months. Further check-ups are recommended 6 and 12 months after the end of therapy. In the case of extensive findings, some forms of extrathoracic tuberculosis, side effects or concomitant diseases, the duration and composition of the therapy may change.

RESISTANT TUBERCULOSIS

In the case of INH monoresistance, treatment should be carried out for 6 months with rifampicin, levofloxacin, pyrazinamide and ethambutol, whereby a shortened course of PZA and/or EMB is possible in principle.

Multidrug-resistant (MDR) TB requires complex and lengthy treatment, which is why therapy should be carried out in or in cooperation with an experienced TB treatment center. As the international studies and treatment recommendations for MDR-TB are changing rapidly, there may be changes to the recommendation in the near future. In the case of MDR-TB, i.e. in the presence of resistance to rifampicin and isoniazid, the therapy should be individualized and carried out over 18 months. If susceptibility is proven, the three drugs of WHO group A (bedaquiline, moxifloxacin or levofloxacin, linezolid) and at least one drug of WHO group B (terizidone or clofazimine) are used. If, due to other resistances, intolerances or contraindications, a therapy consisting of at least four drugs cannot be put together, group C drugs are added. Shortened treatment regimens should currently only be used in exceptional cases and in consultation with a specialized center. The WHO has announced an adjustment to the treatment recommendation. Shortening therapy to 6-9 months with BPaL(M) (bedaquiline, pretomanid, linezolid, (moxifloxacin)) is to be recommended as an alternative. An early update of the German recommendations for MDR-TB therapy is planned after reviewing the study data, some of which are still unpublished. In cases of suspected treatment failure without evidence of additional drug resistance, potential absorption or elimination disorders, risks of toxicity or interactions (e.g. HIV co-infection) or questionable adherence, the drug levels in the blood should be measured and the dosage of the drugs adjusted accordingly.

SOCIO-MEDICAL ASPECTS AND AFTERCARE

Tuberculosis is an infectious disease that must be reported, but treatment and isolation must also be carried out in consultation with the responsible health authority. This also applies to cost issues relating to isolation measures for infection control reasons and the treatment of uninsured people. The care of patients with tuberculosis is often associated with complex socio-medical challenges that can jeopardize the success of treatment and should therefore be addressed at an early stage. It is helpful to provide information and communication in the patient's native language, provide treatment close to home and, if possible, on an outpatient basis, integrate digital support services, evaluate and clarify comorbidities, social risk factors, financial issues and legal residence problems in advance, and provide support with urgent organizational challenges (e.g. childcare during isolation measures).

Even after successful completion of TB therapy, especially after MDR-TB, symptoms may persist that require clarification of secondary diseases. These are summarized as post-TB lung disease (PTLD) . Radiological and lung function examinations and questionnaires can be used for diagnosis. A possible therapy, need for rehabilitation or symptom relief depends on the clinical picture.

LATENT TUBERCULOUS INFECTION

By definition, a latent tuberculous infection (LTBI) is a positive immunological test (tuberculin skin test/THT or interferon-gamma release assay/IGRA) with simultaneous exclusion of tuberculosis. The available tests only detect an immune response, but cannot differentiate between a disease and an infection, nor can they predict the risk of progression from infection to disease. For this reason, the indication for a test should only be given to high-risk groups and a decision on preventive therapy if an infection is detected should be made together with the person concerned on the basis of an individual risk-benefit assessment and the available framework conditions. Contact persons, people living with HIV (PLWH) with additional risk factors and patients before therapy with TNF inhibitors (TNFi) and possibly other biologics and JAK inhibitors should be screened for LTBI and treated preventively. People with serious underlying diseases with immunosuppression, people before transplants or people from high-prevalence countries should be offered preventive therapy in the event of LTBI. Various preventive treatment regimens are available, with the shorter rifamycin-based regimens (four months of RMP or three months of RMP and INH) being preferred. Rifapentine-based regimens are also theoretically possible, but are currently not a practical alternative due to the lack of availability in Europe. Preventive therapy (based on the index person's resistogram) should also be offered after individual risk-benefit assessment in cases of contact with patients with infectious MDR-TB and subsequent infection.