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BACKGROUND: Increasing evidence suggests that post-TB lung disease (PTLD) causes significant morbidity and mortality. The aim of these clinical standards is to provide guidance on the assessment and management of PTLD and the implementation of pulmonary rehabilitation (PR).METHODS: A panel of global experts in the field of TB care and PR was identified; 62 participated in a Delphi process. A 5-point Likert scale was used to score the initial ideas for standards and after several rounds of revision the document was approved (with 100% agreement).RESULTS: Five clinical standards were defined: Standard 1, to assess patients at the end of TB treatment for PTLD (with adaptation for children and specific settings/situations); Standard 2, to identify patients with PTLD for PR; Standard 3, tailoring the PR programme to patient needs and the local setting; Standard 4, to evaluate the effectiveness of PR; and Standard 5, to conduct education and counselling. Standard 6 addresses public health aspects of PTLD and outcomes due to PR.CONCLUSION: This is the first consensus-based set of Clinical Standards for PTLD. Our aim is to improve patient care and quality of life by guiding clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage PTLD.

The management of resistant tuberculosis (tb) can be extremely difficult, especially in case of novel unpredicted complications. In this report, we present a case of a 48-year-old patient with pre-extensively drug-resistant (XDR) tb who received a treatment regimen including pretomanid, bedaquiline, linezolid, cycloserine, and amikacin and died due to myocarditis. Acquired resistance to first- and second-line drugs developed due to previous poor adherence to medication. The clinical presentation of the patient, along with her initial ultrasonographical, electrocardiogram (ECG), and laboratory examinations, were typical for acute myocarditis; however, the patient was considered unstable, and further investigations, including magnetic resonance imaging (MRI), pericardiocentesis, and endomyocardial biopsy were not performed. To our knowledge, this is the first case of myocarditis in such a patient, the clinical features of which raised a high suspicion of drug induction that could be attributed to the treatment regimen that was administered. Clinicians who manage cases of drug-resistant tb should be aware of this newly reported, potentially lethal, adverse event.

Mycobacterium abscessus is a difficult-to-treat, multidrug-resistant human pathogen. Relebactam has been shown to inhibit M. abscessus β-lactamase (BLA Mab ) and increase the activity of imipenem and amoxicillin. We present two cases of lung infection due to M. abscessus , one caused by M. abscessus subsp . massiliense and the other by subsp . abscessus . Both strains showed moderate sensitivity to imipenem, and the second strain was also resistant to macrolides. A multidrug antibiotic regimen was administered in both cases, which included imipenem/cilastatin/relebactam adjusted to the estimated glomerular filtration rate (eGFR) and amoxicillin for three months. The regimen was well tolerated and both patients improved both clinically and radiologically after the first phase of treatment. The results of our patients indicate that the combination of imipenem/cilastatin/relebactam and amoxicillin could be used in the future in difficult infections by M. abscessus ., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Vogiatzoglou et al.)

In this review, two cases of testicular tuberculosis (TB) are presented, and another 58 cases published in PubMed between January 1, 2012, and July 31, 2023, are reviewed. Testicular TB remains a disease mainly of the developing world, with one notable exception - the infections caused as a result of Bacillus Calmette-Guérin infusion immunotherapy for bladder cancer. Its clinical course is subacute; however, it might get disseminated and become life-threatening; therefore, prompt diagnosis is very important. The diagnosis can be quite challenging, and testicular tissue is the sample with the highest diagnostic yield, either for microbiological or histopathological diagnosis. On the other hand, its treatment follows the standard guidelines for TB treatment; however, the avoidance of an unnecessary orchiectomy is important., (Copyright © 2024 Copyright: © 2024 International Journal of Mycobacteriology.)

Background: Tracheostomy is commonly used in intensive care unit (ICU) patients who are expected to be on long-term mechanical ventilation or suffer from emergency upper airway obstruction. However, some studies have conflicting findings regarding the optimal technique and its timing and benefits., Aim: To provide evidence of practice, characteristics, and outcome concerning tracheostomy in an ICU of a tertiary care hospital., Methods: This was a retrospective cohort study including adult critical care patients in a single ICU for two consecutive years. Patients' demographic characteristics, severity of illness (APACHE II score), level of consciousness [Glasgow Coma Scale (GCS)], comorbidities, timing and type of tracheostomy procedure performed and outcome were recorded. We defined late as tracheostomy placement after 8 days or no tracheotomy., Results: Data of 660 patients were analyzed (median age of 60 years), median APACHE II score of 19 and median GCS score of 12 at admission. Tracheostomy was performed in 115 patients, of whom 63 had early and 52 late procedures. Early tracheostomy was mainly executed in case of altered level of consciousness and severe critical illness polyneuromyopathy, however there were no significant statistical results (47.6% vs 36.5%, P = 0.23) and (23.8% vs 19.2%, P = 0.55) respectively. Regarding the method selected, early surgical tracheostomy (ST) was conducted in patients with maxillofacial injuries (50.0% vs 0.0%, P = 0.033), whereas late surgical tracheostomy was selected for patients with goiter (44.4% vs 0.0% P = 0.033). Patients with early tracheostomy spent significantly fewer days on mechanical ventilation (15.3 ± 8.5 vs 22.8 ± 9.6, P < 0.001) and in ICU in general (18.8 ± 9.1 vs 25.4 ± 11.5, P < 0.001). Percutaneous dilatation tracheostomy (PDT) vs ST was preferable in older critical care patients in the case of Central Nervous System underlying cause of admission (62.5% vs 26.3%, P = 0.004). ST was the method of choice in compromised airway (31.6%, vs 7.3% P = 0.008). A large proportion of patients (88/115) with tracheostomy managed to wean from mechanical ventilation and were transferred out of the ICU (100% vs 17.4%, P < 0.001)., Conclusion: PDT was performed more frequently in our cohort. This technique did not affect mechanical ventilation days, ventilator-associated pneumonia (VAP), ICU length of stay, or survival. No complications were observed in the percutaneous or surgical tracheostomy groups. Patients undergoing early tracheostomy benefited in terms of mechanical ventilation days and ICU length of stay but not of discharge status, presence of VAP, or survival., Competing Interests: Conflict-of-interest statement: All authors have no conflicts of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Competing Interests: Competing interests: None declared.

Elexacator/tezacaftor/ivacaftor (ETI) has improved cystic fibrosis (CF) outcomes. A reduction in use of maintenance medication after its initiation has been reported. Seventy-one adult people with CF (PwCF) who are followed in three CF centers and completed one year of treatment with ETI were included in this study. Their use of inhaled dornase-α, colistin, tobramycin, aztreonam and levofloxacin during this period was compared with the corresponding use during one year without ETI, using the Medication Possession Ratio (MPR). MPR was significantly decreased after ETI initiation for dornase-α (67±35% vs 48±40%, p<0.001) and for all four inhaled antibiotics together (62±33% vs 41±37%, p<0.001). The findings of this multi-center, retrospective, study suggest that the initiation of ETI significantly leads to decrease in use of standard inhaled medication in PwCF. The significance of this finding in the course of the disease is yet to be investigated by larger prospective clinical trials., Competing Interests: Declaration of Competing Interest There is no conflict of interest, (Copyright © 2023 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background: Longitudinal cohort data of patients with tuberculosis (TB) and coronavirus disease 2019 (COVID-19) are lacking. In our global study, we describe long-term outcomes of patients affected by TB and COVID-19., Methods: We collected data from 174 centres in 31 countries on all patients affected by COVID-19 and TB between 1 March 2020 and 30 September 2022. Patients were followed-up until cure, death or end of cohort time. All patients had TB and COVID-19; for analysis purposes, deaths were attributed to TB, COVID-19 or both. Survival analysis was performed using Cox proportional risk-regression models, and the log-rank test was used to compare survival and mortality attributed to TB, COVID-19 or both., Results: Overall, 788 patients with COVID-19 and TB (active or sequelae) were recruited from 31 countries, and 10.8% (n=85) died during the observation period. Survival was significantly lower among patients whose death was attributed to TB and COVID-19 versus those dying because of either TB or COVID-19 alone (p<0.001). Significant adjusted risk factors for TB mortality were higher age (hazard ratio (HR) 1.05, 95% CI 1.03-1.07), HIV infection (HR 2.29, 95% CI 1.02-5.16) and invasive ventilation (HR 4.28, 95% CI 2.34-7.83). For COVID-19 mortality, the adjusted risks were higher age (HR 1.03, 95% CI 1.02-1.04), male sex (HR 2.21, 95% CI 1.24-3.91), oxygen requirement (HR 7.93, 95% CI 3.44-18.26) and invasive ventilation (HR 2.19, 95% CI 1.36-3.53)., Conclusions: In our global cohort, death was the outcome in >10% of patients with TB and COVID-19. A range of demographic and clinical predictors are associated with adverse outcomes., Competing Interests: Conflict of interest: The authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2023.)

The purpose of the study was to evaluate painful procedures in ICU patients and to investigate their effect as well as the role of analgesia in the outcome. We measured pain level and vital signs before, during and after potentially painful procedures by using the Behavioral Pain Scale (BPS) and the Critical Care Pain Observation Tool (CPOT). We analyzed the correlation of these measurements and of analgesia with the outcome. Twenty-eight patients were subjected to 160 stimuli. There were statistically significant differences in pain scores and most vital signs between the different timepoints (before-during, during-after). Most of them were significantly correlated with each other. Physiotherapy proved to be the most painful procedure. Regarding the outcome, the administration of extra analgesia predicted less days of mechanical ventilation ( p  = 0.015) and of ICU stay ( p  = 0.016). The higher change in BPS was correlated with more days of mechanical ventilation [B (95% CI) = 3.640 (1.001-6.280), p  = 0.007] and of ICU stay [B (95% CI) = 3.645 (1.035-6.254), p  = 0.006]. The higher change in CPOT and the nonuse of extra analgesia were related to increased mortality [OR (95% CI) = 1.492 (1.107-2.011), p  = 0.009 and OR (95% CI) = 2.626 (1.013-6.806), p  = 0.047]. Increased pain in ICU patients was successfully assessed by the BPS and CPOT and correlated to worse outcomes, which the administration of extra analgesia might improve.

Background: We aimed to evaluate the pharmacokinetic profile of tigecycline in plasma and its penetration to sputum in moderately ill patients with an infectious acute exacerbation of chronic obstructive pulmonary disease (COPD)., Methods: Eleven patients hospitalized with acute respiratory failure due to an acute COPD exacerbation with clinical evidence of an infectious cause received tigecycline 50 mg twice daily after an initial loading dose of 100 mg. Blood and sputum samples were collected at steady state after dose seven., Results: In plasma, mean C max pl was 975.95 ± 490.36 ng/mL and mean C min pl was 214.48 ±140.62 ng/mL. In sputum, mean C max sp was 641.91 ± 253.07 ng/mL and mean C min sp was 308.06 ± 61.7 ng/mL. In plasma, mean AUC 0-12 pl was 3765.89 ± 1862.23 ng*h/mL, while in sputum mean AUC 0-12 sp was 4023.27 ± 793.37 ng*h/mL. The mean penetration ratio for the 10/11 patients was 1.65 ± 1.35. The mean Free AUC 0-24 pl /MIC ratio for Streptococcus pneumoniae and Haemophilus influenzae was 25.10 ± 12.42 and 6.02 ± 2.97, respectively., Conclusions: Our findings support the clinical effectiveness of tigecycline against commonly causative bacteria in COPD exacerbations and highlight its sufficient lung penetration in pulmonary infections of moderate severity.

Background: Adherence to pulmonary medication is pivotal in delaying the progression of lung disease in cystic fibrosis (CF). Further exploring the consequences of poor adherence and its impact on disease severity may be valuable to personalize CF treatment strategy., Aim: To evaluate indicators of disease severity among children and adults with CF and investigate which of them are related to pulmonary medication adherence., Methods: This is a retrospective cohort study. Data of children and adults followed up in one pediatric and one adult CF Unit were evaluated over 4 years. Disease severity was assessed by measuring body mass index (BMI), lung function, history of pulmonary exacerbations, and medication complexity. Adherence was assessed by calculating a 12-month medication possession ratio (MPR) for each pulmonary medication and then averaged for a composite MPR (cMPR) for each patient. Regression analysis was performed to explore the association of adherence with disease severity., Results: Ninety-five patients were included in our study, 52 children and 43 adults. The overall cMPR was 0.74 (SD = 0.25); 0.68 (SD = 0.24) for children and 0.81 (SD = 0.24) for adults. Adults presented higher adherence, with overall mean cMPR 0.81 (SD = 0.24) compared to children with mean cMPR 0.68 (SD = 0.24) (p < 0.05, 95% CI = -0.27 to -0.03). Adherence was inversely related to FEV 1 % predicted (β = -0.002, 95% CI = -0.004 to 0, p = 0.023) and FVC% predicted (β = -0.003, 95% CI = -0.005 to -0.001, p = 0.006) in regression analysis. Adherence was not found to be associated with BMI, history of exacerbations and medication complexity. The analysis of each medication showed that adherence to Dornase-alpha, Tobramycin and Colomycin was significantly related to specific disease severity indicators., Conclusion: An overall moderate to high level of adherence was found among our study population. Adults presented higher adherence compared to children. FEV1% and FVC% predicted were related to a significant decrease in adherence. Among our group of CF patients with an overall moderate to high level of adherence, adherence to pulmonary medication was inversely related to disease severity., (© 2022 Wiley Periodicals LLC.)

Background: The aim of the present study was the application of the latest phenotype recommendations in Greek patients, in order to identify specific clinical, imaging and spirometric characteristics, at initial diagnosis of sarcoidosis, related to disease phenotypes., Methods: Our cohort included 147 patients coming from Northern Greece, recruited from the Outpatient Sarcoidosis Clinic, of Aristotle University of Thessaloniki. The observation period was 5 years. The Scadding staging system and the World Association of Sarcoidosis and other Granulomatous Disorders (WASOG) Clinical Outcome Status instrument were used. Phenotypes were defined by the latest DELPHI consensus recommendations., Results: The following clinical phenotypes were identified: asymptomatic 59%, acute 14.3%, chronic 12.9% and advanced 33.3%. The observed phenotypes were not related to Scadding stages. Lung function decline was in line with phenotype severity. The presence of fibrosis to any extent upon diagnosis differed among phenotypes (asymptomatic 13.8%, acute 38.1%, chronic 57.9%, advanced 61.2%, P<0.001) and was common for relapsing patients (P<0.001). In spontaneously remitting patients, fibrosis upon diagnosis was found less often than in non-remitting patients (P<0.001). Renal involvement was more frequently found in the advanced phenotype (P=0.032). Skin involvement was more common for patients with acute onset (P<0.001) and spontaneous remission (P=0.012). Ocular involvement was mainly found in relapsing patients (P<0.001)., Conclusions: In our cohort, sarcoidosis clinical phenotypes have certain clinical, imaging and functional characteristics, at initial diagnosis of the disease, which could be assessed in everyday practice., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-21-1760/coif). The authors have no conflicts of interest to declare., (2022 Journal of Thoracic Disease. All rights reserved.)

Competing Interests: KGC declares salary support to serve as US Agency for International Development (USAID) senior TB scientific advisor through an Inter-governmental Personnel Act award between Emory University and the USAID. FN and AZ acknowledge support from the EU European & Developing Countries Clinical Trials Partnership-funded Pan-African Network for Rapid Research, Response, Relief and Preparedness for infectious diseases epidemics (PANDORA-ID-NET), Central African Network on Tuberculosis, HIV/AIDS and Malaria (CANTAM-3), and East African Consortium for Clinical Research (EACCR3) programmes. AZ is in receipt of a UK National Institutes for Health Research Senior Investigator award and is a Mahathir Foundation Science Award and Pascoal Mocumbi Prize laureate. All other authors declare no competing interests. The views expressed in this Comment are entirely those of the authors and do not reflect the views of their respective institutions.

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.

Background: This study examined the drug-specific and overall adherence of teenagers and adults with cystic fibrosis (CF) to inhaled therapies, to assess the degree of adherence, stability over a period of 4 years, and its association with health outcomes., Methods: Fifty-five participants (30 women and 25 men) aged 14 years or older from two CF centers were enrolled in a retrospective review of inhaled medication adherence over 4 years. Adherence was assessed by the number of doses that were obtained by each participant based on the "e-prescription.gr" platform and the calculation of the medication possession ratio (MPR)., Results: The mean composite MPR (cMPR) for the entire research period was 0.75 ± 0.19. A total of 43.4% of participants showed a variance of adherence <25%. Participants with stable adherence had a significantly higher mean cMPR compared with those with variable adherence (0.86 ± 0.16 vs. 0.66 ± 0.17, p < 0.001). A statistically significant difference between groups of patients with different degrees of mean cMPR and mean weight was observed (p = 0.011). Patients with a mean cMPR ≥0.80 weighed significantly more than those with moderate and low adherence. In addition, mean weight correlated significantly with the mean cMPR (Β [95% confidence interval] = 14.845 [0.191-29.498], r = 0.269, p = 0.047)., Conclusions: In our setting, the cMPR was easy to assess and showed that adherence was probably better than expected. The association of cMPR with weight should be further investigated. Stable adherence seemed to be related to high adherence. This observation could enhance our understanding of people with CF and their approach to treatment., (© 2022 Wiley Periodicals LLC.)

Background and Objective: Data on natural killer (NK)- and natural killer T (NKT)- like cells in the immunopathogenesis of sarcoidosis remain limited. The aim was to assess NK- and NKT-like cells across different stages in bronchoalveolar lavage (BALF) versus peripheral blood (PB) in comparison to controls., Methods: Forty four patients (32 women and 12 men, mean age 46.6±14.4 years) with biopsy-proven sarcoidosis and 10 healthy individuals (6 women, 4 men mean age 52.6±19.1 years) were submitted to BALF. Total cells and cell differentials were counted, while CD45+, CD3+, CD4+, CD8+, CD19+, CD3-CD16/56 (NK cells) and CD3+CD16/56+ (NKT-like cells) were determined by dual flow cytometry in BALF and PB., Results: A significantly lower percentage of both NK and NKT-like cells was observed in BALF of controls and sarcoid patients (SP) compared to PB. Both BALF NK and NKT-cell counts were significantly higher in SP than in controls (NK: p=0.046, NKT-like: p=0.012) In addition BALF NK cell percentage differed among sarcoidosis stages (p=0.005). In PB NK-cell count was lower in sarcoidosis patients but the difference did not reach statistical significance. Also, in sarcoid patients' BALF NK-cell percentage negatively correlated with lymphocyte percentage (r=-0.962, p<0.001)., Conclusions: The increased count of BALF NK and NKT-like cells in sarcoidosis compared to controls along with the increase of NK cells with stage progression are in line with a growing number of investigations suggesting the involvement of NK- and NKT-like cells in the pathogenesis of sarcoidosis., (Copyright: © 2021 SARCOIDOSIS VASCULITIS AND DIFFUSE LUNG DISEASES.)

Pulmonary tuberculosis caused by Mycobacterium caprae was diagnosed in a 65-year-old goat breeder from northern Greece. This case represents a documented occupational transmission of M. caprae and highlights the importance of enhanced laboratory screening and increased surveillance for zoonotic tuberculosis control.

Severe Mycolicibacter kumamotonensis-pulmonary disease was diagnosed in a 68-year-old immunocompetent woman in Greece; the disease was initially treated as tuberculosis. The patient responded favorably to a new treatment regimen of azithromycin, amikacin, moxifloxacin, and linezolid. Complete symptom resolution and radiologic improvement resulted.

Introduction: Longitudinal data regarding changes in exercise capacity among adult cystic fibrosis (CF) patients are currently scarce. The aim of this brief report was to assess changes in exercise capacity among adult CF patients with stable and mild-to-moderate disease eight years after their initial evaluation., Material and Methods: Maximum cardiopulmonary exercise testing (CPET) was utilized. Other assessments included Doppler echocardiography, the 6-minute walking test, spirometry, and lung volume evaluation., Results: Eleven (6 male, 5 female) patients completed both evaluations (initial and after eight years). During follow-up, indices of ventilatory impairment (such as ventilatory reserve; p=0.019, and ventilatory equivalent for carbon dioxide; p = 0.047) deterio-rated significantly following a decline in respiratory function measurements. Peak oxygen uptake (VO2), both as an absolute (26.6 ± 8.46 vs 23.89 ± 6.16 mL/kg/min; p = 0.098) and as a % of predicted value (71.21 ± 16.54 vs 70.60 ± 15.45; p = 0.872), did not deteriorate. This is also true for oxygen pulse (p = 0.743), left heart ejection fraction (p = 0.574), and pulmonary artery systolic pressure (p = 0.441). However, the anaerobic threshold, both as an absolute (p = 0.009) and as a % of predicted value (p = 0.047), was significantly lower during follow-up., Conclusion: In adult CF patients with stable, mild-to-moderate disease, a peak VO2 may be preserved for several years. However, even in these patients, deconditioning is present.

Background: Greece is one of the few countries in the European Union/European Economic Area, which do not report tuberculosis (TB) treatment outcome. This study aimed to assess treatment outcomes and identify possible intervening factors in patients with TB in Thessaloniki, Greece, over the period 2012-2017., Methods: All patients diagnosed with TB -excluding rifampicin-resistant/multidrug-resistant (RR/MDR)-TB- during 2015-2017 were included in the study. Data on demographic characteristics, localization, diagnostic methods, resistance, and treatment outcome were recorded and compared to the period 2012-2014., Results: During the period 2015-2017, 82 patients (48 men) with a mean age of 53.8 ± 15.6 years were diagnosed with TB. No significant differences in demographics, microbiological, or treatment characteristics were detected between the two three-year periods, except for the percentage of immunocompromised patients, which was higher during 2015-2017 (15.9 % vs 5.6 %, p =0.029). In the total number of patients, two factors were significantly different between patients with a positive and negative outcome. The percentage of favorable outcome was higher for patients with extrapulmonary compared to pulmonary TB (90.9 % vs 70.5 %, p =0.044). Furthermore, the percentage of immunocompetent patients with a positive outcome was significantly higher in the second treatment period compared to the first (treatment success rate 66.7 % in 2012-2014 vs 84.1 % in 2015-2017, p =0.014). This difference was attributed to the presence of a social nurse who joined the center in 2015., Conclusions: TB treatment success rate in Greece is below the World Health Organization standards. Interventions such as appropriate multidisciplinary staffing of TB centers may prove valuable in improving TB care in Greece. HIPPOKRATIA 2019, 23(4): 154-159., Competing Interests: Authors declare no conflict of interest., (Copyright 2019, Hippokratio General Hospital of Thessaloniki.)

Therapeutic drug monitoring (TDM) of moxifloxacin is recommended to improve the response to tuberculosis treatment and reduce acquired drug resistance. Limited sampling strategies (LSSs) are able to reduce the burden of TDM by using a small number of appropriately timed samples to estimate the parameter of interest, the area under the concentration-time curve. This study aimed to develop LSSs for moxifloxacin alone (MFX) and together with rifampin (MFX+RIF) in tuberculosis (TB) patients. Population pharmacokinetic (popPK) models were developed for MFX ( n  = 77) and MFX+RIF ( n  = 24). In addition, LSSs using Bayesian approach and multiple linear regression were developed. Jackknife analysis was used for internal validation of the popPK models and multiple linear regression LSSs. Clinically feasible LSSs (one to three samples, 6-h timespan postdose, and 1-h interval) were tested. Moxifloxacin exposure was slightly underestimated in the one-compartment models of MFX (mean -5.1%, standard error [SE] 0.8%) and MFX+RIF (mean -10%, SE 2.5%). The Bayesian LSSs for MFX and MFX+RIF (both 0 and 6 h) slightly underestimated drug exposure (MFX mean -4.8%, SE 1.3%; MFX+RIF mean -5.5%, SE 3.1%). The multiple linear regression LSS for MFX (0 and 4 h) and MFX+RIF (1 and 6 h), showed mean overestimations of 0.2% (SE 1.3%) and 0.9% (SE 2.1%), respectively. LSSs were successfully developed using the Bayesian approach (MFX and MFX+RIF; 0 and 6 h) and multiple linear regression (MFX, 0 and 4 h; MFX+RIF, 1 and 6 h). These LSSs can be implemented in clinical practice to facilitate TDM of moxifloxacin in TB patients., (Copyright © 2019 American Society for Microbiology.)

Differential diagnosis should never be limited to the obvious diagnoses http://ow.ly/ybTM30obh6H., Competing Interests: Conflict of interest: S.C. Kotoulas has nothing to disclose. Conflict of interest: K. Manika has nothing to disclose. Conflict of interest: G. Pilianidis has nothing to disclose. Conflict of interest: P. Tsikouriadis has nothing to disclose. Conflict of interest: G. Kalopitas has nothing to disclose. Conflict of interest: N. Petridis has nothing to disclose. Conflict of interest: A. Apsemidou has nothing to disclose. Conflict of interest: A. Iakovos has nothing to disclose. Conflict of interest: I. Kioumis has nothing to disclose.

This study aimed to evaluate the pharmacokinetic profile of moxifloxacin (MXF) in serum and sputum/bronchial secretions of 22 patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) hospitalized in the ward and intensive care unit (ICU). The data showed that ICU patients had lower concentrations in secretions ( P = 0.01). However, no other statistically significant differences were observed in pharmacokinetic parameters and penetration in secretions between ward and ICU patients. MXF showed a favorable pharmacokinetic profile, and the pharmacodynamic targets for common pathogens for AECOPD were achieved., (Copyright © 2019 American Society for Microbiology.)

Background: The growing burden of diabetes mellitus (DM) is posing a threat to global tuberculosis (TB) control. DM triples the risk of developing TB, modifies the presenting features of pulmonary TB, and worsens TB treatment outcomes. We aimed to analyze the prevalence of DM among TB patients and to describe the characteristics and clinical presentation of TB-DM patients in Europe., Methods: We performed a cross-sectional survey on the prevalence of DM among consecutively diagnosed adult TB patients in 11 European TB referral centers located in France, Germany, Greece, Italy, Russia, Slovakia, Spain, and the United Kingdom over the period 2007-2015. We also selected DM-TB cases and TB only controls with a 1:3 ratio to perform a case-control analysis, including patients selected from the countries mentioned above plus Norway and Ukraine., Results: Among 3143 TB enrolled patients, DM prevalence overall was 10.7% and ranged from 4.4% in Greece to 28.5% in the United Kingdom. Patients' median ages ranged from 36 to 49 years, and all centers had >60% males; the proportion of foreign-born patients varied widely across sites. In the case-control study, DM was independently associated with older age and, among older patients, with being foreign-born. Among patients with pulmonary involvement, cavities on chest imaging were more frequently observed among those with DM., Conclusions: Diabetes mellitus represents a challenge for TB control in Europe, especially in foreign-born and in elderly patients. Specific screening strategies should be evaluated.

Large studies on bedaquiline used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) are lacking. This study aimed to evaluate the safety and effectiveness of bedaquiline-containing regimens in a large, retrospective, observational study conducted in 25 centres and 15 countries in five continents.428 culture-confirmed MDR-TB cases were analysed (61.5% male; 22.1% HIV-positive, 45.6% XDR-TB). MDR-TB cases were admitted to hospital for a median (interquartile range (IQR)) 179 (92-280) days and exposed to bedaquiline for 168 (86-180) days. Treatment regimens included, among others, linezolid, moxifloxacin, clofazimine and carbapenems (82.0%, 58.4%, 52.6% and 15.3% of cases, respectively).Sputum smear and culture conversion rates in MDR-TB cases were 63.6% and 30.1%, respectively at 30 days, 81.1% and 56.7%, respectively at 60 days; 85.5% and 80.5%, respectively at 90 days and 88.7% and 91.2%, respectively at the end of treatment. The median (IQR) time to smear and culture conversion was 34 (30-60) days and 60 (33-90) days. Out of 247 culture-confirmed MDR-TB cases completing treatment, 71.3% achieved success (62.4% cured; 8.9% completed treatment), 13.4% died, 7.3% defaulted and 7.7% failed. Bedaquiline was interrupted due to adverse events in 5.8% of cases. A single case died, having electrocardiographic abnormalities that were probably non-bedaquiline related.Bedaquiline-containing regimens achieved high conversion and success rates under different nonexperimental conditions., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2017.)