Objective: To compare the former tuberculosis treatment regimen including one fluoroquinolone (ofloxacin, levofloxacin, or moxifloxacin) and a second-line injectable drug (amikacin, kanamycin, or capreomycin) plus three to five oral drugs (regimen 1) with the current regimen including the three WHO group A drugs (regimen 2) in terms of efficacy and safety at two tuberculosis referral centers in Mexico. Methods: This was a retrospective study based on a review of the clinical records of all consecutive rifampin-resistant or multidrug-resistant tuberculosis (RR/MDR-TB) patients treated from January of 2010 to October of 2023. Patients included were microbiologically confirmed cases of RR/MDR-TB with pulmonary involvement and who received at least 30 days of regimen 1 or regimen 2. Outcomes and adverse events were classified in accordance with WHO definitions. Results: One hundred and twenty-six RR/MDR-TB patients met the inclusion criteria. Of those, 87 were treated with regimen 1 and 39 received regimen 2. Success rates were not significantly different between the two groups of patients, although those treated with the oral regimen including bedaquiline from regimen 2 had higher success rates. Regimen 2 patients experienced a shorter time to culture conversion, and the regimen length was shortened accordingly, the median duration being 16.1 months [IQR, 15-17.3 months]. In patients receiving the all-oral regimen 2, adverse events were significantly associated with a history of type 2 diabetes mellitus (OR = 15.4; 95% CI, 2.73-87.29; p = 0.002) and were mainly related to linezolid use. Conclusions: Oral regimens appear to be effective, although toxicity to linezolid requires strict patient monitoring.

Keywords: Mexico; Tuberculosis, multidrug-resistant; Bedaquiline; Linezolid; Treatment outcome.

Given the global burden of tuberculosis, shortened treatment regimens with existing or repurposed drugs are needed to contribute to tuberculosis control. The long duration of treatment of drug-susceptible tuberculosis (DS-TB) is associated with nonadherence and loss to follow up, and the treatment success rate of multidrug-resistant tuberculosis (MDR-TB) is low (approximately 50%) with longer regimens. In this review article, we report recent advances and ongoing clinical trials aimed at shortening regimens for DS-TB and MDR-TB. We discuss the role of high-dose rifampin, as well as that of clofazimine and linezolid in regimens for DS-TB. There are at least 5 ongoing clinical trials and 17 observational studies and clinical trials evaluating shorter regimens for DS-TB and MDR-TB, respectively. We also report the results of observational studies and clinical trials evaluating a standardized nine-month moxifloxacin-based regimen for MDR-TB. Further studies, especially randomized clinical trials, are needed to evaluate regimens including newer drugs, drugs proven to be or highly likely to be efficacious, and all-oral drugs in an effort to eliminate the need for injectable drugs.

Keywords: Tuberculosis/drug therapy; Tuberculosis, multidrug-resistant/drug therapy; Drug resistance, bacterial.

Multidrug-resistant and extensively drug-resistant tuberculosis (MDR-TB and XDR-TB, respectively) continue to represent a challenge for clinicians and public health authorities. Unfortunately, although there have been encouraging reports of higher success rates, the overall rate of favorable outcomes of M/XDR-TB treatment is only 54%, or much lower when the spectrum of drug resistance is beyond that of XDR-TB. Treating M/XDR-TB continues to be a difficult task, because of the high incidence of adverse events, the long duration of treatment, the high cost of the regimens used, and the drain on health care resources. Various trials and studies have recently been undertaken (some already published and others ongoing), all aimed at improving outcomes of M/XDR-TB treatment by changing the overall approach, shortening treatment duration, and developing a universal regimen. The objective of this review was to summarize what has been achieved to date, as far as new and repurposed drugs are concerned, with a special focus on delamanid, bedaquiline, pretomanid, clofazimine, carbapenems, and linezolid. After more than 40 years of neglect, greater attention has recently been paid to the need for new drugs to fight the "white plague", and promising results are being reported.

Keywords: Tuberculosis/therapy; Tuberculosis, multidrug-resistant; Extensively drug-resistant tuberculosis; Antitubercular agents.

Objective: To evaluate the impact of smoking on pulmonary tuberculosis (PTB) treatment outcomes and the two-month conversion rates for Mycobacterium tuberculosis sputum cultures among patients with culture-confirmed PTB in an area with a moderate incidence of tuberculosis in Brazil. Methods: This was a retrospective cohort study of PTB patients diagnosed and treated at the Thoracic Diseases Institute of the Federal University of Rio de Janeiro between 2004 and 2012. Results: Of the 298 patients diagnosed with PTB during the study period, 174 were included in the outcome analysis: 97 (55.7%) were never-smokers, 31 (17.8%) were former smokers, and 46 (26.5%) were current smokers. Smoking was associated with a delay in sputum culture conversion at the end of the second month of TB treatment (relative risk = 3.58 [95% CI: 1.3-9.86]; p = 0.01), as well as with poor treatment outcomes (relative risk = 6.29 [95% CI: 1.57-25.21]; p = 0.009). The association between smoking and a positive culture in the second month of treatment was statistically significant among the current smokers (p = 0.027). Conclusions: In our sample, the probability of a delay in sputum culture conversion was higher in current smokers than in never-smokers, as was the probability of a poor treatment outcome.

Keywords: Tuberculosis; Treatment outcome; Smoking.

Tuberculosis continues to be a major public health problem. Although efforts to control the epidemic have reduced mortality and incidence, there are several predisposing factors that should be modified in order to reduce the burden of the disease. This review article will address some of the risk factors associated with tuberculosis infection and active tuberculosis, including diabetes, smoking, alcohol use, and the use of other drugs, all of which can also contribute to poor tuberculosis treatment results. Tuberculosis can also lead to complications in the course and management of other diseases, such as diabetes. It is therefore important to identify these comorbidities in tuberculosis patients in order to ensure adequate management of both conditions.

Keywords: Tuberculosis/epidemiology; Tuberculosis/prevention & control; Diabetes mellitus/prevention & control; Smoking/adverse effects; Alcohol drinking/adverse effects; Street drugs/adverse effects.

The World Health Organization (WHO) has recently recommended new technologies for the diagnosis of tuberculosis. The WHO recommendations include the development of a strategic plan for bringing the network up to grade; investment in supervision and quality control; and implementation of a system of laboratory environmental management. Without those measures having been taken, no new technology can be effectively incorporated. We surveyed the tuberculosis laboratory network in Brazil in order to identify possible bottlenecks for the incorporation of new technologies. We identified a lack of resources allocated to supervision and quality control; a low number of requests for cultures; a lack of effective laboratory information systems; and a lack of awareness regarding the future infrastructure needs of the laboratory network at the municipal level.

Keywords: Quality control; Tuberculosis; Laboratories; Clinical laboratory information systems; Technology

The objective of this study was to describe country-specific lockdown measures and tuberculosis indicators collected during the first year of the COVID-19 pandemic. Data on lockdown/social restrictions (compulsory face masks and hand hygiene; international and local travel restrictions; restrictions to family visits, and school closures) were collected from 24 countries spanning five continents. The majority of the countries implemented multiple lockdowns with partial or full reopening. There was an overall decrease in active tuberculosis, drug-resistant tuberculosis, and latent tuberculosis cases. Although national lockdowns were effective in containing COVID-19 cases, several indicators of tuberculosis were affected during the pandemic.

Keywords: COVID-19; Tuberculosis; Physical distancing; Health policy; Global health; Communicable disease control.

Objective: To develop and apply a competency-based test to assess learning among internal medicine residents during a respiratory ICU rotation at a university hospital. Methods: We developed a test comprising 19 multiple-choice questions regarding knowledge of mechanical ventilation (MV) and 4 self-assessment questions regarding the degree of confidence in the management of MV. The test was applied on the first and last day of a 30-day respiratory ICU rotation (pre-rotation and post-rotation, respectively). During the rotation, the residents had lectures, underwent simulator training, and shadowed physicians on daily bedside rounds focused on teaching MV management. Results: Fifty residents completed the test at both time points. The mean score increased from 6.9 ± 1.2 (pre-rotation) to 8.6 ± 0.8 (post-rotation; p < 0.001). On questions regarding the approach to hypoxemia, the recognition of patient-ventilator asynchrony, and the recognition of risk factors for extubation failure, the post-rotation scores were significantly higher than the pre-rotation scores. Confidence in airway management increased from 6% before the rotation to 22% after the rotation (p = 0.02), whereas confidence in making the initial MV settings increased from 31% to 96% (p < 0.001) and confidence in adjusting the ventilator modes increased from 23% to 77% (p < 0.001). Conclusions: We developed a competency-based test to assess knowledge of MV among residents before and after an rotation in a respiratory ICU. Resident performance increased significantly after the rotation, as did their confidence in caring for patients on MV.

Keywords: Education, medical; Respiration, artificial; Surveys and questionnaires; internship and residency; Competency-based education; Educational measurement.

Objective: To evaluate the impact of thoracic radiotherapy on respiratory function and exercise capacity in patients with breast cancer. Methods: Breast cancer patients in whom thoracic radiotherapy was indicated after surgical treatment and chemotherapy were submitted to HRCT, respiratory evaluation, and exercise capacity evaluation before radiotherapy and at three months after treatment completion. Respiratory muscle strength testing, measurement of chest wall mobility, and complete pulmonary function testing were performed for respiratory evaluation; cardiopulmonary exercise testing was performed to evaluate exercise capacity. The total radiotherapy dose was 50.4 Gy (1.8 Gy/fraction) to the breast or chest wall, including supraclavicular lymph nodes (SCLN) or not. Dose-volume histograms were calculated for each patient with special attention to the ipsilateral lung volume receiving 25 Gy (V25), in absolute and relative values, and mean lung dose. Results: The study comprised 37 patients. After radiotherapy, significant decreases were observed in respiratory muscle strength, chest wall mobility, exercise capacity, and pulmonary function test results (p < 0.05). DLCO was unchanged. HRCT showed changes related to radiotherapy in 87% of the patients, which was more evident in the patients submitted to SCLN irradiation. V25% significantly correlated with radiation pneumonitis. Conclusions: In our sample of patients with breast cancer, thoracic radiotherapy seemed to have caused significant losses in respiratory and exercise capacity, probably due to chest wall restriction; SCLN irradiation represented an additional risk factor for the development of radiation pneumonitis.

Keywords: Breast neoplasms; Radiotherapy; Radiation pneumonitis; Respiratory function tests; Exercise test.

Objective: To investigate the impact of a pulmonary rehabilitation program on the functional capacity and on the quality of life of patients on waiting lists for lung transplantation. Methods: Patients on lung transplant waiting lists were referred to a pulmonary rehabilitation program consisting of 36 sessions. Before and after the program, participating patients were evaluated with the six-minute walk test and the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36). The pulmonary rehabilitation program involved muscle strengthening exercises, aerobic training, clinical evaluation, psychiatric evaluation, nutritional counseling, social assistance, and educational lectures. Results: Of the 112 patients initially referred to the program, 58 completed it. The mean age of the participants was 46  14 years, and females accounted for 52%. Of those 58 patients, 37 (47%) had pulmonary fibrosis, 13 (22%) had pulmonary emphysema, and 18 (31%) had other types of advanced lung disease. The six-minute walk distance was significantly greater after the program than before (439 ± 114 m vs. 367 ± 136 m, p = 0.001), the mean increase being 72 m. There were significant point increases in the scores on the following SF-36 domains: physical functioning, up 22 (p = 0.001), role-physical, up 10 (p = 0.045); vitality, up 10 (p < 0.001); social functioning, up 15 (p = 0.001); and mental health, up 8 (p = 0.001). Conclusions: Pulmonary rehabilitation had a positive impact on exercise capacity and quality of life in patients on lung transplant waiting lists.

Keywords: Rehabilitation; Lung transplantation; Quality of life; Exercise; Exercise tolerance.

Objective: Multidrug-resistant tuberculosis (MDR-TB) is a life-threatening infectious disease. Treatment requires multiple antimicrobial agents used for extended periods of time. The present study sought to evaluate the treatment success rate of bedaquiline-based regimens in MDR-TB patients. Methods: This was a systematic review and meta-analysis of studies published up to March 15, 2021. The pooled treatment success rates and 95% CIs were assessed with the fixed-effect model or the random-effects model. Values of p < 0.05 were considered significant for publication bias. Results: A total of 2,679 articles were retrieved by database searching. Of those, 29 met the inclusion criteria. Of those, 25 were observational studies (including a total of 3,536 patients) and 4 were experimental studies (including a total of 440 patients). The pooled treatment success rate was 74.7% (95% CI, 69.8-79.0) in the observational studies and 86.1% (95% CI, 76.8-92.1; p = 0.00; I2 = 75%) in the experimental studies. There was no evidence of publication bias (p > 0.05). Conclusions: In patients with MDR-TB receiving bedaquiline, culture conversion and treatment success rates are high even in cases of extensive resistance.

Keywords: Tuberculosis; Drug resistance; Tuberculosis, multidrug-resistant; Efficacy.

Objective: Multidrug-resistant tuberculosis (MDR-TB) remains a global public health challenge, complicating treatment strategies and requiring advanced therapeutic approaches. The persistence of MDR-TB has led to a demand for regimens that are more effective in improving treatment outcomes and controlling transmission. This systematic review and meta-analysis sought to examine the efficacy of linezolid (LZD) and bedaquiline (BDQ) in MDR-TB treatment regimens, evaluating their roles in enhancing therapeutic success and informing optimized management of MDR-TB. Methods: A comprehensive search was conducted across MEDLINE (PubMed), EMBASE, the Cochrane Central Register of Controlled Trials, Scopus, and Web of Science for randomized controlled trials assessing the efficacy of LZD and BDQ in MDR-TB patients up to September 14, 2024. We analyzed treatment outcomes, reporting favorable outcomes (cured and treatment completed) and unfavorable outcomes (death, treatment failure, and loss to follow-up) with a 95% confidence interval. Results: Our analysis included 11 trials, with a total of 1,999 participants. The findings indicate that BDQ+LZD-containing regimens yield significantly higher favorable treatment outcomes (84.5%; 95% CI, 79.8%-88.2%) and lower unfavorable outcomes (15.4%; 95% CI, 11.6%-20.2%). In contrast, regimens lacking either LZD or BDQ show lower efficacy, with favorable outcomes at 66.8% (95% CI, 59.5%-73.4%) and unfavorable outcomes at 33.0% (95% CI, 25.6%-41.4%). Conclusions: MDR-TB treatment regimens including BDQ and LZD lead to significantly better patient outcomes. The combined bactericidal and protein synthesis-inhibiting effects of BDQ and LZD create a powerful therapeutic synergy. Adding pretomanid further enhances this effectiveness, highlighting its value in complex cases. Future research should focus on optimizing these regimens for safety and efficacy and explore adjunctive therapies to improve MDR-TB outcomes even further.

Keywords: Linezolid; Tuberculosis; Tuberculosis, multidrug-resistant; Treatment outcome; Systematic review.

The correlation between resistance to pyrazinamide (PZA) and resistance to other first-line antituberculosis drugs was investigated in 395 Mycobacterium tuberculosis strains isolated from clinical specimens, representing 14% of the overall number of M. tuberculosis isolates obtained between 2003 and 2008 at the laboratory of a referral university hospital for tuberculosis. A high correlation was found between resistance to PZA and multidrug resistance, as well as between PZA resistance and resistance to rifampin, isoniazid, and ethambutol (p < 0.01 for all). These results highlight the importance of performing PZA susceptibility testing prior to the prescription of this drug in order to treat drug-resistant and multidrug-resistant tuberculosis.

Keywords: Tuberculosis/drug therapy; Tuberculosis/microbiology; Antibiotics, antitubercular.

Objective: To determine the drug resistance profile of Mycobacterium tuberculosis in Mozambique. Methods: We analyzed secondary data from the National Tuberculosis Referral Laboratory, in the city of Maputo, Mozambique, and from the Beira Regional Tuberculosis Referral Laboratory, in the city of Beira, Mozambique. The data were based on culture-positive samples submitted to first-line drug susceptibility testing (DST) between January and December of 2011. We attempted to determine whether the frequency of DST positivity was associated with patient type or provenance. Results: During the study period, 641 strains were isolated in culture and submitted to DST. We found that 374 (58.3%) were resistant to at least one antituberculosis drug and 280 (43.7%) were resistant to multiple antituberculosis drugs. Of the 280 multidrug-resistant tuberculosis cases, 184 (65.7%) were in previously treated patients, most of whom were from southern Mozambique. Two (0.71%) of the cases of multidrug-resistant tuberculosis were confirmed to be cases of extensively drug-resistant tuberculosis. Multidrug-resistant tuberculosis was most common in males, particularly those in the 21-40 year age bracket. Conclusions: M. tuberculosis resistance to antituberculosis drugs is high in Mozambique, especially in previously treated patients. The frequency of M. tuberculosis strains that were resistant to isoniazid, rifampin, and streptomycin in combination was found to be high, particularly in samples from previously treated patients.

Keywords: Extensively drug-resistant tuberculosis; Tuberculosis; Tuberculosis, multidrug-resistant.

Background: Ventilator-associated pneumonia is the most common nosocomial infection occurring in intensive care units. Objective: To determinate the impact of multidrug-resistant bacteria on morbidity and mortality in patients with ventilator-associated pneumonia. Method: Retrospective cohort study. Over 40 consecutive months, 91 patients on mechanical ventilation developed pneumonia. Cases were grouped into those caused by multidrug-resistant microorganisms and those caused by drug-sensitive microorganisms. Results: Multidrug-resistant bacteria were isolated in 75 cases (82.4%) and drug-sensitive bacteria in 16 (17.6%). Clinical and epidemiological characteristics were not statistically different between the groups. Staphylococcus aureus was responsible for 27.5% of ventilator-associated pneumonia episodes and Pseudomonas aeruginosa for 17.6%. Early-onset ventilator-associated pneumonia occurred in 33 patients (36.3%) and late-onset in 58 (63.7%). Time on mechanical ventilation, length of intensive care unit stay and overall length of hospital stay were not statistically different between groups. Empirical treatment was considered inadequate in 42 patients with pneumonia caused by multidrug-resistant microorganisms (56%) and in 4 with pneumonia caused by drug-sensitive microorganisms (25%) (p = 0.02). Death occurred in 46 patients with pneumonia caused by multidrug-resistant microorganisms (61.3%) and in 4 with pneumonia caused by drug-sensitive microorganisms (25%) (p = 0.008). Conclusion: Bacterial multidrug-resistance had no impact on morbidity but was associated with higher mortality.

Keywords: Pneumonia bacterial/etiology. Respiration artificial/complications. Indicators of morbidity and mortality.

Objective: To determine the prevalence of primary hyperhidrosis in the city of Botucatu, Brazil, and to evaluate how this disorder affects the quality of life in those suffering from it. Methods: A population survey was conducted in order to identify cases of hyperhidrosis among residents in the urban area of the city, selected by systematic cluster sampling. In accordance with the census maps of the city, the sample size should be at least 4,033 participants. Ten interviewers applied a questionnaire that evaluated the presence of excessive sweating and invited the subjects who reported hyperhidrosis to be evaluated by a physician in order to confirm the diagnosis. Results: A total of 4,133 residents, in 1,351 households, were surveyed. Excessive sweating was reported by 85 residents (prevalence = 2.07%), of whom 51 (60%) were female. Of those 85 respondents, 51 (60%) agreed to undergo medical evaluation to confirm the diagnosis and only 23 (45%) were diagnosed with primary hyperhidrosis (prevalence = 0.93%). Of the 23 subjects diagnosed with primary hyperhidrosis, 11 (48%) reported poor or very poor quality of life. Conclusions: Although the prevalence of self-reported excessive sweating was greater than 2%, the actual prevalence of primary hyperhidrosis in our sample was 0.93% and nearly 50% of the respondents with primary hyperhidrosis reported impaired quality of life.

Keywords: Hyperhidrosis/epidemiology; Hyperhidrosis/diagnosis; Quality of life.

Objective: There is evidence that asthma is associated with an increase in psychiatric symptoms and mental disorders. This association can make it difficult to achieve asthma control. The purpose of this study was to determine whether the level of asthma control is associated with anxiety and depression. Methods: A cross-sectional study involving 78 patients with confirmed moderate or severe asthma and under regular treatment at the Asthma Outpatient Clinic of the Federal University of São Paulo Hospital São Paulo, in the city of São Paulo, Brazil. The patients were divided into two groups by asthma control status, as assessed by the asthma control test, and were subsequently compared in terms of demographic, clinical, and spirometric data, as well as scores for asthma quality of life and hospital anxiety/depression. Results: The sample was predominantly female. Of the 78 patients, 49 (63%) were classified as having uncontrolled asthma. The prevalence of anxiety and of anxiety+depression was significantly higher among patients with uncontrolled asthma than among those with controlled asthma (78% and 100%; p = 0.04 and p = 0.02, respectively), whereas there were no differences between the two groups in terms of the prevalence of depression, spirometry results, or quality of life score. Conclusions: In this sample, the prevalence of anxiety symptoms was higher in the patients with uncontrolled asthma than in those with controlled asthma.In the evaluation of asthma patients, the negative impact of mood states ought to be taken into consideration when asthma control strategies are being outlined.

Keywords: Asthma; Anxiety; Depression; Cross-sectional studies.