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In December 2022 World Health Organization released a new treatment for multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) guideline. The main novelty of this update is two new recommendations (i) a 6-month treatment regimen composed of bedaquiline, pretomanid, linezolid (600 mg), and moxifloxacin (BPaLM) is recommended in place of the 9-month or longer (18-month) regimens in MDR/RR-TB patients, now including extensive pulmonary TB and extrapulmonary TB (except TB involving central nervous system, miliary TB and osteoarticular TB); (ii) the use of the 9-month all-oral regimen rather than longer (18-months) regimen is suggested in patients with MDR/RR-TB and in whom resistance to fluoroquinolones has been excluded. Longer (18-month) treatments remain a valid option in all cases in which shorter regimens cannot be implemented due to intolerance, drug-drug interactions, extensively drug-resistant tuberculosis, extensive forms of extrapulmonary TB, or previous failure. The new guidelines represent a milestone in MDR/RR-TB treatment landscape, setting the basis for a shorter, all-oral, more acceptable, equitable, and patient-centered model for MDR/RR-TB management. However, some challenges remain to be addressed to allow full implementation of the new recommendations., Competing Interests: Declaration of competing interests Tiberi S. is an employee of GSK, all opinions are his own and not that of the company. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

BACKGROUND: The aim of these clinical standards is to provide guidance on 'best practice´ for diagnosis, treatment and management of drug-susceptible pulmonary TB (PTB). METHODS: A panel of 54 global experts in the field of TB care, public health, microbiology, and pharmacology were identified; 46 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all 46 participants. RESULTS: Seven clinical standards were defined: Standard 1, all patients (adult or child) who have symptoms and signs compatible with PTB should undergo investigations to reach a diagnosis; Standard 2, adequate bacteriological tests should be conducted to exclude drug-resistant TB; Standard 3, an appropriate regimen recommended by WHO and national guidelines for the treatment of PTB should be identified; Standard 4, health education and counselling should be provided for each patient starting treatment; Standard 5, treatment monitoring should be conducted to assess adherence, follow patient progress, identify and manage adverse events, and detect development of resistance; Standard 6, a recommended series of patient examinations should be performed at the end of treatment; Standard 7, necessary public health actions should be conducted for each patient. We also identified priorities for future research into PTB. CONCLUSION: These consensus-based clinical standards will help to improve patient care by guiding clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment for PTB.

Background: Paradoxical reaction after the initiation of tuberculosis treatment is defined as increased inflammation following effective antimycobacterial treatment. This is a phenomenon that can severely complicate a patient's recovery, potentially leading to further morbidity and residual deficits. Paradoxical reaction remains poorly understood regarding its pathophysiology and management. Only a limited number of reports look critically at the available therapeutic options, with evidence of the efficacy of prednisolone therapy being primarily limited to extrapulmonary PR only., Case: We describe two HIV negative patients who were admitted to our department with pulmonary tuberculosis, presenting with inflammatory patterns attributable to PR and their response to adjunctive steroid therapy., Discussion and Conclusions: The presented cases further highlight the need for immunological studies and randomized trials for corticosteroid therapy are needed to better understand this phenomenon as well as provide an evidence-base for anti-inflammatory treatment. Furthermore, by means of this case series, we are also able to highlight the potential variability in the symptomatology of the lesser known PR phenomenon, in which we observed a hypotensive shock-like syndrome not previously described in literature.

Background: The holistic management of tuberculosis (TB) patients can improve life expectancy and lost organ function., Rehabilitation: Chronic sequelae are very common among patients who survive TB, which can lead to a further decline in lung function. There is still no guidance for 'cured' patients with impaired lung function who need pulmonary rehabilitation. Additional tests for evaluation should be given after the end of treatment, as recent studies have shown the good effect of pulmonary rehabilitation for TB patients., Optimized Nutritional Care: Malnutrition is very common among TB patients and is related to malabsorption. The latter can cause lower drug exposure, which may result in treatment failure, increasing the risk of death, and can lead to acquired drug resistance. Malnutrition should be assessed according to the Global Leadership Initiative on Malnutrition (GLIM) criteria and the diagnosis should lead to an individualized treatment plan, including sufficient proteins and preferably in combination with adequate training., Protective Immune Responses: Under normal circumstances, most immune cells use a glucose-based mechanism to generate energy. Therefore the patient's nutritional status is a key factor in shaping immune responses. Disease-related malnutrition leads to proteolysis and lipolysis. In the end, the identification of individuals who will benefit from immune-modulatory strategies may lead to clinically relevant markers., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To investigate the potency of a hand-held point-of-care electronic-nose to diagnose pulmonary tuberculosis (PTB) among those suspected of PTB., Methods: Setting: Lung clinics and Dr. Sardjito Hospital, Yogyakarta, Indonesia. Participants: patients with suspected PTB and healthy controls. Sampling: 5 minutes exhaled breath. Sputum-smear-microscopy, culture, chest-radiography, and follow-up for 1.5-2.5 years, were used to classify patients with suspected PTB as active PTB, probably active PTB, probably no PTB, and no PTB. After building a breath model based on active PTB, no PTB, and healthy controls (Calibration phase), we validated the model in all patients with suspected PTB (Validation phase). In each variable (sex, age, Body Mass Index, co-morbidities, smoking status, consumption of alcohol, use of antibiotics, flu symptoms, stress, food and drink intake), one stratum's Receiver Operating Characteristic (ROC)-curve indicating sensitivity and specificity of the breath test was compared with another stratum's ROC-curve. Differences between Area-under-the-Curve between strata (p<0.05) indicated an association between the variable and sensitivity-specificity of the breath test. Statistical analysis was performed using STATA/SE 15., Results: Of 400 enrolled participants, 73 were excluded due to extra-pulmonary TB, incomplete data, previous TB, and cancer. Calibration phase involved 182 subjects, and the result was validated in 287 subjects. Sensitivity was 85% (95%CI: 75-92%) and 78% (95%CI: 70-85%), specificity was 55% (95%CI: 44-65%) and 42% (95%CI: 34-50%), in calibration and validation phases, respectively. Test sensitivity and specificity were lower in men., Conclusion: The electronic-nose showed modest sensitivity and low specificity among patients with suspected PTB. To improve the sensitivity, a larger calibration group needs to be involved. With its portable form, it could be used for TB screening in remote rural areas and health care settings., Competing Interests: A.M.S., Y.S., Y.W.S., N.R., S., O.A., and T.S.W. declare no conflict of interest. J.W.G. and H.O. are employed by the eNose Company, Zutphen, the Netherlands. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Treatment outcomes for multidrug-resistant tuberculosis remain poor. We aimed to estimate the association of treatment success and death with the use of individual drugs, and the optimal number and duration of treatment with those drugs in patients with multidrug-resistant tuberculosis., Methods: In this individual patient data meta-analysis, we searched MEDLINE, Embase, and the Cochrane Library to identify potentially eligible observational and experimental studies published between Jan 1, 2009, and April 30, 2016. We also searched reference lists from all systematic reviews of treatment of multidrug-resistant tuberculosis published since 2009. To be eligible, studies had to report original results, with end of treatment outcomes (treatment completion [success], failure, or relapse) in cohorts of at least 25 adults (aged >18 years). We used anonymised individual patient data from eligible studies, provided by study investigators, regarding clinical characteristics, treatment, and outcomes. Using propensity score-matched generalised mixed effects logistic, or linear regression, we calculated adjusted odds ratios and adjusted risk differences for success or death during treatment, for specific drugs currently used to treat multidrug-resistant tuberculosis, as well as the number of drugs used and treatment duration., Findings: Of 12 030 patients from 25 countries in 50 studies, 7346 (61%) had treatment success, 1017 (8%) had failure or relapse, and 1729 (14%) died. Compared with failure or relapse, treatment success was positively associated with the use of linezolid (adjusted risk difference 0·15, 95% CI 0·11 to 0·18), levofloxacin (0·15, 0·13 to 0·18), carbapenems (0·14, 0·06 to 0·21), moxifloxacin (0·11, 0·08 to 0·14), bedaquiline (0·10, 0·05 to 0·14), and clofazimine (0·06, 0·01 to 0·10). There was a significant association between reduced mortality and use of linezolid (-0·20, -0·23 to -0·16), levofloxacin (-0·06, -0·09 to -0·04), moxifloxacin (-0·07, -0·10 to -0·04), or bedaquiline (-0·14, -0·19 to -0·10). Compared with regimens without any injectable drug, amikacin provided modest benefits, but kanamycin and capreomycin were associated with worse outcomes. The remaining drugs were associated with slight or no improvements in outcomes. Treatment outcomes were significantly worse for most drugs if they were used despite in-vitro resistance. The optimal number of effective drugs seemed to be five in the initial phase, and four in the continuation phase. In these adjusted analyses, heterogeneity, based on a simulated I 2 method, was high for approximately half the estimates for specific drugs, although relatively low for number of drugs and durations analyses., Interpretation: Although inferences are limited by the observational nature of these data, treatment outcomes were significantly better with use of linezolid, later generation fluoroquinolones, bedaquiline, clofazimine, and carbapenems for treatment of multidrug-resistant tuberculosis. These findings emphasise the need for trials to ascertain the optimal combination and duration of these drugs for treatment of this condition., Funding: American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: Few innovative anti-microbial products have been brought to market in recent years to combat the global multidrug resistant-tuberculosis (MDR-TB) epidemic. Bedaquiline, a novel oral diarylquinoline, was approved by the US FDA as a part of combination therapy in adults with pulmonary MDR-TB based on phase II trials., Area Covered: Pubmed searches were conducted using search terms bedaquiline, diarylquinoline, R207910, and TMC207 was performed. Supplementary sources included World Health Organization, Clinicaltrial.gov, US Food and Drug Administration. Bedaquiline is an ATP synthase inhibitor specific for M. tuberculosis and some nontuberculous mycobacteria. It is metabolized by CYP3A4 and it's drug exposure can be influenced by inducers and inhibitors of this enzyme. Phase II studies showed promising results on efficacy of bedaquiline when being used in combination with a background regimen for MDR-TB. Main safety concerns include QTc prolongation and hepatotoxicity. Phase III trials are ongoing to confirm efficacy findings from phase II studies and provide additional evidence of safety and efficacy. Expert commentary: Critical data for long-term efficacy and safety are incomplete and scarce, supporting the cautious use of bedaquiline.

A 29-year-old pregnant woman from Syria was screened for tuberculosis upon arrival in the Netherlands. The chest X-ray showed a smooth sharply demarcated mass in her left upper lobe. A low-dose CT showed that the mass was lobulated and surrounded by a hyperlucent pulmonary segment. To protect the foetus from further exposure to radiation, an MRI was performed, which confirmed bronchial atresia with a mucocele of the distal bronchus.

The incidence of tuberculosis in the Netherlands has dropped dramatically over the past 50 years. With declining experience of tuberculosis, misdiagnosis can easily happen. Laryngeal tuberculosis often presents as a tumorous mass that may initially be mistaken for cancer. As laryngeal tuberculosis is usually highly infectious, this poses a risk to the patient as well as his/her contacts including healthcare providers. We describe three patients with (suspected) laryngeal tuberculosis and discuss potential pitfalls. Pivotal for a correct diagnosis are thorough history-taking, physical examination and relatively simple radiological and laboratory tests. Risk groups have been identified for tuberculosis and this can provide a clue. Differentiation between tuberculosis and cancer can be difficult, and the two diseases may concur. Even in low-incidence settings for tuberculosis, knowledge of the disease remains necessary as it is curable and further spread can be prevented with simple measures.

An animal keeper was diagnosed with pulmonary tuberculosis (TB) after bi-annual screening for latent TB infection in zoo employees. In the same period, several bonobos of the zoo were suffering from TB as well. The Mycobacterium tuberculosis strains from both the animal keeper and the bonobos appeared identical. We provide evidence that the animals infected their keeper.