Intensive Phase Of Treatment Research Articles

High Pretreatment Level of Neutrophil to Lymphocyte Ratio, Monocyte to Lymphocyte Ratio and Other Factors Associated with Delayed Sputum Conversion in Patients with Pulmonary Tuberculosis.

IntroductionPatients with delayed intensive phase sputum conversion have a higher risk of multidrug resistant-tuberculosis (MDR-TB) and poorer treatment outcomes. Both, host (immune response and comorbidity) and pathogen factors play important roles in determining sputum conversion after treatment initiation. Impaired host immune response, especially the cellular components, as defined by the increased pre-treatment level of neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR) and other additional factors, were associated with severe active TB.PurposeTo evaluate whether impaired immune responses (high pre-treatment level of NLR and MLR) and other factors associate with delayed sputum conversion at the end of the intensive phase treatment.Patients and MethodsThis was a case–control study from 2016 to 2020, which retrospectively analyzed the pre-treatment level of NLR, MLR and other factors among patients with new cases of pulmonary tuberculosis (PTB).ResultsA total of 62 patients (31 cases and 31 control). The cut-off value of high pretreatment level of NLR and MLR was 5.065 and 0.585, respectively. Bivariate analysis showed that pretreatment NLR ≥5.065 (OR 8.23, CI 95% 2.48–27.32, p < 0.001), MLR ≥0.585 (OR 10.18, 95% CI 3.13–33.18, p < 0.001) and BMI <18.5 (OR 2.91, 95% CI 1.03–8.20, p = 0.041) were associated with an increased risk of delayed sputum conversion. Multivariate analysis, however, showed that pretreatment NLR ≥5.065 was not significantly associated with delayed sputum conversion (AOR 3.370, 95% CI 0.71–15.91, p value 0.125). A high pretreatment of MLR (AOR 30.802, 95% CI 3.22–287.55, p value 0.003) and lower BMI (AOR 10.942, 95% CI 1.121–98.563, p value 0.033) were significantly associated with an increased risk of delayed intensive phase sputum conversion.ConclusionHigh MLR pretreatment and a low BMI were significantly associated with an increased risk of delayed sputum conversion at the end of the PTB intensive phase treatment. High NLR pretreatment, smoking, diabetes, and HIV were not associated with sputum conversion.

Sex Differences in Active Pulmonary Tuberculosis Outcomes in Mali, West Africa.

Men and women often respond differently to infectious diseases and their treatments. Tuberculosis (TB) is a life-threatening communicable disease that affects more men than women globally. Whether male sex is an independent risk factor for unfavorable TB outcomes, however, has not been rigorously investigated in an African context, where individuals are likely exposed to different microbial and environmental factors. We analyzed data collected from a cohort study in Mali by focusing on newly diagnosed active pulmonary TB individuals who were treatment naive. We gathered baseline demographic, clinical, and microbiologic characteristics before treatment initiation and also at three time points during treatment. More males than females were affected with TB, as evidenced by a male-to-female ratio of 2.4:1. In addition, at baseline, males had a significantly higher bacterial count and shorter time to culture positivity as compared with females. Male sex was associated with lower smear negativity rate after 2 months of treatment also known as the intensive phase of treatment, but not at later time points. There was no relationship between patients' sex and mortality from any cause during treatment. This study suggests that sex-based differences in TB outcomes exist, with sex-specific effects on disease outcomes being more pronounced before treatment initiation and during the intensive phase of treatment rather than at later phases of treatment.

Anemia Is a Strong Predictor of Wasting, Disease Severity, and Progression, in Clinical Tuberculosis (TB).

A typical trait of chronic tuberculosis (TB) is substantial weight loss that concurs with a drop in blood hemoglobin (Hb) levels, causing anemia. In this observational study, we explored Hb levels in 345 pulmonary TB patients. They were divided into anemic or non-anemic groups which related to clinical symptoms, anthropometric measurements, and immune status. Data was obtained in a randomized controlled trial that we previously conducted using nutritional supplementation of TB patients in Ethiopia. A post hoc analysis demonstrated that anemic patients have a higher composite clinical TB score at baseline than non-anemic patients. Consequently, Hb values were significantly lower in underweight patients with moderate to severe disease and/or cavitary TB compared to normal weight patients with mild disease or non-cavitary TB. Anemia was associated with a low body mass index (BMI), low mid-upper arm circumference (MUAC), lower peripheral CD4 and CD8 T cells counts and IFN-γ levels, and a higher erythrocyte sedimentation rate (ESR). Chronic inflammation and TB disease progression appeared to be driven by elevated systemic levels of pro-inflammatory IL-6 in anemic patients. Multivariable modeling confirmed that a low Hb and a low BMI were key variables related to an unfavorable TB disease status. Although Hb levels increased with successful chemotherapy, anemic TB patients maintained a slower clinical recovery compared to non-anemic patients during the intensive phase treatment (two months). In conclusion, anemia is a strong predictor of wasting, disease severity, inflammation, and slower recovery in patients with pulmonary TB.

Forgiveness Is the Attribute of the Strong: Nonadherence and Regimen Shortening in Drug-sensitive Tuberculosis.

Rationale: "Forgiveness" charts the ability of a drug or regimen to withstand nonadherence without negative clinical consequences. Objectives: We aimed to determine the influence of regimen length, regimen drugs, and dosing, and when during treatment nonadherence occurs on the forgiveness of antituberculosis regimens. Methods: Using data from three randomized controlled trials comparing experimental 4-month regimens for drug-sensitive tuberculosis with the standard 6-month regimen, we used generalized linear models to examine how the risk of a negative composite outcome changed as dose-taking decreased. The percentage of doses taken and the absolute number of doses missed were calculated during the intensive and continuation phases of treatment, and overall. A mediation analysis was undertaken to determine how much the association between intensive phase dose-taking and the negative composite outcome was mediated through continuation phase dose-taking. Measurements and Main Results: Forgiveness of the 4- and 6-month regimens did not differ for any treatment period. Importantly, 4-month regimens were no less forgiving of small numbers of absolute missed doses than the 6-month regimen (e.g., for 3-7 missed doses vs. no missed doses [baseline], 6-month regimen adjusted risk ratio 1.65 [95% confidence interval, 0.80-3.41] and 4-month regimens 1.80 [1.33-2.45]). No 4-month regimen was conclusively more forgiving than another. We found evidence of mediation by continuation phase dose-taking on the intensive phase dose-taking and negative composite outcome relationship. Conclusions: With the current appetite for, and progress toward, shorter drug-sensitive tuberculosis regimens worldwide, we offer reassurance that shorter regimens are not necessarily less forgiving of nonadherence. Given the importance of continuation phase adherence, patient support during this period should not be neglected.

Nutritional background of low-income pulmonary tuberculosis patients on anti-tuberculosis therapy at Infectious Disease Hospital, Calabar, Nigeria: A case-control study

Background: Poverty and malnutrition are associated with the risk of developing tuberculosis (TB). Nutritional reintegration with anti-TB therapy may improve treatment success rate. Aim: To investigate the nutritional status of low-income pulmonary TB patients in relation to the different anti-TB treatment phases. Methods: Forty five pulmonary TB patients and 40 controls aged 19-54 years, receiving treatment at Infectious Disease Hospital, Calabar, Nigeria, between September 2018 and July 2019 were studied. Serum total protein, albumin, iron and vitamin A were determined by colorimetric and HPLC methods respectively. Height and weight were measured and BMI computed, and data analysed using Student’s t-test, ANOVA, and Pearson’s correlation at P&lt;0.05. Results: Among TB patients, 66.7%, 35.5%, and 22.22% were albumin, iron, and vitamin A deficient respectively. Total protein and globulins levels were higher while BMI, albumin, iron, and vitamin A were lower in the TB patients compared to the control (P=0.001). Albumin and iron levels of TB patients on continuation phase of anti-TB treatment (CPAT) were higher than those of TB-HIV coinfection on the same phase of treatment, TB patients on intensive phase of anti-TB treatment (IPAT) and controls (p&lt;0.05). Comparing TB patients on CPAT and IPAT, also CPAT-HIV and IPAT-HIV patients, BMI and biochemical indices studied were not significantly different (P&gt;0.05) respectively. Albumin and iron were significantly lower in CPAT-HIV compared with CPAT patients. Albumin correlated positively and significantly with iron (r=0.405, p=0.006) in TB patients. Conclusion: Tuberculosis is associated with decreased BMI, albumin, iron and vitamin A, and higher total protein, and globulin, suggesting that malnutrition may be associated with TB risk, poor treatment compliance and outcomes.

Tuberculosis Treatment Compliance Under Smartphone-Based Video-Observed Therapy Versus Community-Based Directly Observed Therapy: Protocol for a Cluster Randomized Controlled Trial.

BackgroundThe health care system in Thailand has struggled to cope with the COVID-19 pandemic, resulting in decreased administration of community-based directly observed therapy (DOT) for tuberculosis (TB). As an alternative to failed DOT, video-observed therapy (VOT) or the Thai asynchronous VOT system, “TH VOT,” was devised. We developed a protocol for a study to test the superiority of VOT over DOT in ensuring treatment compliance.ObjectiveWe aim to compare the mean cumulative compliance days of TB patients and their observers under the VOT program with that of individuals under the DOT program during the intensive phase of TB treatment.MethodsA cluster randomized controlled trial of pulmonary TB patients and their observers will be conducted over a 2-month period. This study will be conducted in the Hat Yai and Meuang Songkhla districts of Songkhla Province, Southern Thailand. A total of 38 observers working at 38 primary care units (PCUs) will be randomized equally into VOT and DOT groups. The TH VOT system will be implemented in 19 PCUs in the VOT group while the other 19 PCUs will continue with the traditional DOT program. Approximately 1-5 TB patients will be under observation, depending on the PCU jurisdiction in which the patients reside. The inclusion criteria for TB patients will be as follows: patients diagnosed with newly active pulmonary TB with a positive acid-fast bacilli sputum smear, aged >18 years, own a smartphone, and are able to use the LINE (Line Corporation) app. The exclusion criteria will be patients with a condition that requires the intervention of a specialist, rifampicin resistance according to a cartridge-based nucleic acid amplification test (GeneXpert MTB/RIF), unable to continue the treatment, and/or alcohol dependence. After the 2-month observation period, all sessions and follow-up clinical outcomes recorded will be retrieved. An intention-to-treat analysis will be performed to assess the compliance of both patients undergoing drug administration and their observers.ResultsThe Human Research Ethics Committee, Faculty of Medicine, Prince of Songkla University approved the trial on February 19, 2021 (approval number 64-03618-9). The trial was funded in May 2021. The recruitment period will be from January 2022 to July 2022. The observation is scheduled to end by September 2022.ConclusionsIf the VOT shows superiority in observational compliance among patients and observers, the existing DOT policy will be replaced with VOT.Trial RegistrationThai Clinical Trials Registry TCTR20210624002; https://www.thaiclinicaltrials.org/show/TCTR20210624002International Registered Report Identifier (IRRID)DERR1-10.2196/38796

Magnitude of Depression and Associated Factors Among Patients on Tuberculosis Treatment at Public Health Facilities in Harari Regional State, Eastern Ethiopia: Multi-Center Cross-Sectional Study.

BackgroundDepression among tuberculosis patients remains a significant public health concern. Its burden and severity is increasing in low-income countries, especially in sub-Saharan Africa. Although it has negative impacts on quality of life, depression among tuberculosis patients is rarely studied in Ethiopia, particularly in the study area. Therefore, this study aimed to determine the magnitude of depression and associated factors among tuberculosis patients in Eastern Ethiopia.MethodsA facility-based cross-sectional study was conducted from April 15 to May 15, 2021, among 213 tuberculosis patients in public health facilities of the Harari Regional State, Eastern Ethiopia. Study participants were selected using a systematic sampling technique. Data were collected using interviewer-administered questionnaire. Depression was assessed using Patients Health Questionnaire-9 (PHQ-9). Epi-data and SPSS were used for data processing and analysis. Bi-variable and multivariable logistic regressions were employed to determine the effects of predictors on depression. Statistical significance was considered at a p-value <0.05.ResultsThe magnitude of depression among tuberculosis patients was 52.1% [95% CI (45.4, 58.8%)]. Patient’s age of 25–34 years [AOR = 0.31, 95% CI (0.128, 0.75)], female sex [AOR = 5.04; 95% CI (2.18, 11.62)], intensive phase of tuberculosis treatment [AOR = 2.56; 95% CI (1.118, 5.876)], HIV-positive status [AOR = 7.143; 95% CI (1.55, 32.93)], smoking history [AOR = 9.08; 95% CI (3.35, 24.61)] and having poor social support [AOR = 4.13; 95% CI (1.29, 13.22)] were factors statistically associated with depression.ConclusionIn this study, the magnitude of depression was relatively high as more than half of the participants had depression. Advanced age, female sex, intensive phase of tuberculosis treatment, HIV-positive status, smoking history, and poor social support were identified as associated factors with depression. Therefore, this result calls all stakeholders to give duly emphasis on incorporating and integrating mental health support programs as routine practice in tuberculosis follow-up clinics, as screening, early detection and treatment, and training for all health care providers are very crucial in tackling depression among tuberculosis patients.

Comparative analysis of efficacy and safety of various anti-tuberculosis therapy regimens in patients with MDR/XDR tuberculosis

The objective: to evaluate the efficacy and safety of various anti-tuberculosis therapy regimens for multiple drug resistant (MDR) and extensive drug resistant pulmonary tuberculosis in the intensive phase of treatment lasting for 8 months minimum.Subjects and Methods. A single-center cohort prospective-retrospective clinical study was conducted, which included 166 patients aged 18 to 70 years with active pulmonary tuberculosis and proven MDR of Mycobacterium tuberculosis, who received chemotherapy according to regimens IV and V. The treatment regimen of patients in Group I (n = 96) included modern anti-tuberculosis drugs (TBdrugs) – bedaquiline, linezolid, respiratory fluoroquinolone (levofloxacin, moxifloxacin, sparfloxacin), cycloserine, pyrazinamide, and perchlozone at a dose of 8-10 mg/kg, 1 time per day after meals during the intensive phase of treatment, that was at least 8 months. Patients from Group II (n = 70) received a respiratory fluoroquinolone (levofloxacin, moxifloxacin, sparfloxacin), aminoglycoside (amikacin), cycloserine, pyrazinamide, ethambutol, and prothionamide.Results. After 3 months of treatment, symptoms of intoxication disappeared in 22 (81.5%) patients in Group I, and only 41 (61.2%) in Group II (p = 0.04; TTF). In patients of Group I versus Group II, the body temperature returned to normal within a shorter time: 2.8 and 4.3 weeks, respectively (p &lt; 0.05). By the end of the intensive phase of treatment (8 months), sputum conversion confirmed by culture was observed more often in patients of Group I compared to Group II (85 and 80%, pχ2 = 0.003). Adverse events (AE) caused by TB drugs in Group I were observed significantly more often versus Group II: gastroenterological adverse events (pχ2 = 0.05), cardiac adverse events (pTTP = 0.05), and endocrinological adverse events (pTTP = 0.05). Neurotoxic AEs tended to develop more often in Group I (pTTP = 0.06). Ototoxic AEs were more frequently observed in Group II where the treatment regimens included aminoglycosides (pχ2 = 0.05). To maintain adequate chemotherapy regimens IV or V over long-term treatment, MDR tuberculosis patients need continuous monitoring of AEs, intravenous administration of two or three TB drugs, and timely therapy to manage manifestations of AEs.

HUBUNGAN KEPATUHAN DAN DUKUNGAN KELUARGA DENGAN CLINICAL OUTCOME PASIEN TB

Background: Tuberculosis is an infectious disease caused by mycobacterium tuberculosis. The low compliance of tuberculosis treatment caused resistance and affected clinical outcomes. Purpose: This study aimed to determine the relationship between medication compliance and family support with clinical outcomes in tuberculosis patients. Method: This analytical study used a cross-sectional design. The population was tuberculosis patients who used intensive phase of tuberculosis treatment at several primary health care. This study used a consecutive sampling technique. After we met the criteria and the patient signed informed consent, then microscopic smear and measurement of body weight were done to find clinical outcomes. After that, we gave a Medication Adherence Report Scale (MARS-5) questionnaire to measure medication compliance and a family support questionnaire to measure family support. The collected data were analyzed by fisher-test.Results: This study showed a relationship between medication compliance and clinical outcome with a p-value of 0.003 0.05. Respondents with high adherence had 16.625 times the possibility of achieving clinical outcomes compared to respondents who had low compliance. In addition, it was also found that there was a relationship between family support with clinical outcomes with a p-value of 0.006 0.05, and respondents with good family support had 11.333 times the possibility to achieve good clinical outcomes compared to respondents with sufficient family support. Conclusion: Hight medication compliance on treatment and good family support is essential in achieving good clinical outcomes at the end of the intensive phase.

Acceptability of video observed treatment vs. directly observed treatment for tuberculosis: a comparative analysis between South and Central India

Background Directly Observed Treatment (DOT) is a requirement in the management of Tuberculosis (TB) globally. With the transition from alternate day treatment to daily treatment in India, monitoring treatment adherence through DOT is a logistic challenge. The pervasiveness of mobile phones in India provides a unique opportunity to address this challenge remotely. This study was designed to compare the acceptability of mobile phones for antitubercular treatment (ATT) support in two distinct regions of India. Methodology This was a cross-sectional exploratory study that enrolled 351 patients with TB, of whom 185 were from Bangalore, South India, and 166 from Ujjain, Central India. Trained research assistants administered a pretested questionnaire comprising demographics, phone usage patterns, and acceptability of mobile phone technology to support treatment adherence to TB medicines. Results The mean age of the 351 participants was 32±13.6 years of whom 140 (40%) were women. Of the participants, 259 (74%) were urban, 221 (63%) had &gt;4 years of education. A significantly greater number of participants were newly diagnosed with TB and were in the intensive phase of treatment. Overall, 218 (62%) preferred vDOT over DOT. There was an overall difference in preference between the two sites which is explained by differences in socio-economic variables. Conclusion Mobile phone adherence support is acceptable to patients on Antitubercular treatment ATT with minor variations in design based on demographic and cultural differences. In India, the preference for voice calls over text messages/SMS while designing mHealth interventions cannot be ignored. Of importance is the preference for DOT over vDOT in central India, unlike South India. However, in time, the expanding use of mobile technology supplemented with counseling, could overcome the barriers of privacy and stigma and promote the transition from in-person DOT to vDOT or mobile phone adherence monitoring and support for ATT in India.

Acute psychiatric care: approaches to increasing the range of services and improving access and quality of care.

Acute services for mental health crises are very important to service users and their supporters, and consume a substantial share of mental health resources in many countries. However, acute care is often unpopular and sometimes coercive, and the evidence on which models are best for patient experience and outcomes remains surprisingly limited, in part reflecting challenges in conducting studies with people in crisis. Evidence on best ap-proaches to initial assessment and immediate management is particularly lacking, but some innovative models involving extended assessment, brief interventions, and diversifying settings and strategies for providing support are potentially helpful. Acute wards continue to be central in the intensive treatment phase following a crisis, but new approaches need to be developed, evaluated and implemented to reducing coercion, addressing trauma, diversifying treatments and the inpatient workforce, and making decision-making and care collaborative. Intensive home treatment services, acute day units, and community crisis services have supporting evidence in diverting some service users from hospital admission: a greater understanding of how best to implement them in a wide range of contexts and what works best for which service users would be valuable. Approaches to crisis management in the voluntary sector are more flexible and informal: such services have potential to complement and provide valuable learning for statutory sector services, especially for groups who tend to be underserved or disengaged. Such approaches often involve staff with personal experience of mental health crises, who have important potential roles in improving quality of acute care across sectors. Large gaps exist in many low- and middle-income countries, fuelled by poor access to quality mental health care. Responses need to build on a foundation of existing community responses and contextually relevant evidence. The necessity of moving outside formal systems in low-resource settings may lead to wider learning from locally embedded strategies.

Population pharmacokinetics of ethambutol in African children: a pooled analysis.

Ethambutol protects against the development of resistance to co-administered drugs in the intensive phase of first-line anti-TB treatment in children. It is especially relevant in settings with a high prevalence of HIV or isoniazid resistance. We describe the population pharmacokinetics of ethambutol in children with TB to guide dosing in this population. We pooled data from 188 intensively sampled children from the DATiC, DNDi and SHINE studies, who received 15-25 mg/kg ethambutol daily according to WHO guidelines. The median (range) age and weight of the cohort were 1.9 (0.3-12.6) years and 9.6 (3.9-34.5) kg, respectively. Children with HIV (HIV+; n = 103) received ART (lopinavir/ritonavir in 92%). Ethambutol pharmacokinetics were best described by a two-compartment model with first-order elimination and absorption transit compartments. Clearance was estimated to reach 50% of its mature value by 2 months after birth and 99% by 3 years. Typical steady-state apparent clearance in a 10 kg child was 15.9 L/h. In HIV+ children on lopinavir/ritonavir, bioavailability was reduced by 32% [median (IQR) steady-state Cmax = 0.882 (0.669-1.28) versus 1.66 (1.21-2.15) mg/L). In young children, bioavailability correlated with age. At birth, bioavailability was 73.1% of that in children 3.16 years or older. To obtain exposure within the 2-6 mg/L recommended range for Cmax, the current doses must be doubled (or tripled with HIV+ children on lopinavir/ritonavir) for paediatric patients. This raises concerns regarding the potential for ocular toxicity, which would require evaluation.

Coincidence of drug induced liver injury and cholecystitis on human immunodeficiency virus patient with anti-tuberculosis treatment

Tuberculosis (TB) is a serious health problem. Anti-TB treatment has good efficacy, but in some cases side effects can occur that can affect medication adherence and development of drug resistance. One of the serious side effects of anti-TB treatment is drug induced liver injury. We reported the case of a 56 year old male patient with TB-HIV confection who developed symptoms of hepatotoxicity after 3 weeks of intensive phase of anti-TB treatment.

Tuberculosis treatment intermittency in the continuation phase and mortality in HIV-positive persons receiving antiretroviral therapy

BackgroundSome tuberculosis (TB) treatment guidelines recommend daily TB treatment in both the intensive and continuation phases of treatment in HIV-positive persons to decrease the risk of relapse and acquired drug resistance. However, guidelines vary across countries, and treatment is given 7, 5, 3, or 2 days/week. The effect of TB treatment intermittency in the continuation phase on mortality in HIV-positive persons on antiretroviral therapy (ART), is not well-described.MethodsWe conducted an observational cohort study among HIV-positive adults treated for TB between 2000 and 2018 and after enrollment into the Caribbean, Central, and South America network for HIV epidemiology (CCASAnet; Brazil, Chile, Haiti, Honduras, Mexico and Peru). All received standard TB therapy (2-month initiation phase of daily isoniazid, rifampin or rifabutin, pyrazinamide ± ethambutol) and continuation phase of isoniazid and rifampin or rifabutin, administered concomitantly with ART. Known timing of ART and TB treatment were also inclusion criteria. Kaplan–Meier and Cox proportional hazards methods compared time to death between groups. Missing model covariates were imputed via multiple imputation.Results2303 patients met inclusion criteria: 2003(87%) received TB treatment 5–7 days/week and 300(13%) 2–3 days/week in the continuation phase. Intermittency varied by site: 100% of patients from Brazil and Haiti received continuation phase treatment 5–7 days/week, followed by Honduras (91%), Peru (42%), Mexico (7%), and Chile (0%). The crude risk of death was lower among those receiving treatment 5–7 vs. 2–3 days/week (HR = 0.68; 95% CI = 0.51—0.91; P = 0.008). After adjusting for age, sex, CD4, ART use at TB diagnosis, site of TB disease (pulmonary vs. extrapulmonary), and year of TB diagnosis, mortality risk was lower, but not significantly, among those treated 5–7 days/week vs. 2–3 days/week (HR 0.75, 95%CI 0.55–1.01; P = 0.06). After also stratifying by study site, there was no longer a protective effect (HR 1.42, 95%CI 0.83–2.45; P = 0.20).ConclusionsTB treatment 5–7 days/week was associated with a marginally decreased risk of death compared to TB treatment 2–3 days/week in the continuation phase in multivariable, unstratified analyses. However, little variation in TB treatment intermittency within country meant the results could have been driven by other differences between study sites. Therefore, randomized trials are needed, especially in heterogenous regions such as Latin America.

ОТДЕЛЬНЫЕ АСПЕКТЫ ЛЕЧЕНИЯ ПАЦИЕНТОВ С ВПЕРВЫЕ ВЫЯВЛЕННЫМ ТУБЕРКУЛЕЗОМ ЛЕГКИХ С МНОЖЕСТВЕННОЙ ЛЕКАРСТВЕННОЙ УСТОЙЧИВОСТЬЮ В СОЧЕТАНИИ И ХРОНИЧЕСКОЙ ОБСТРУКТИВНОЙ БОЛЕЗНЬЮ ЛЕГКИХ: В ФОКУСЕ ИНГАЛЯЦИОННЫЕ ГЛЮКОКОРТИКОСТЕРОИДЫ

Introduction. The problem of treating tuberculosis (TB) remains relevant, due to the growth of drug-resistant forms of mycobacterium tuberculosis and an increase in the incidence of TB in persons with comorbid bronchopulmonary pathology, which requires comprehensive management of this category of patients, with mandatory drug correction of concomitant pathology. Aim. The aim of this study was to assess the effect of inhaled glucocorticosteroids (budesonide / formoterol 160 / 4.5 in an Inhaler device) on the efficacy of TB therapy in patients with newly diagnosed multidrug-resistant tuberculosis (MDR) who developed in the presence of chronic obstructive pulmonary disease (COPD). Material and methods. A simple, prospective, comparative study in accordance with the inclusion criteria included 40 patients admitted to an anti-tuberculosis dispensary with newly diagnosed MDR tuberculosis with COPD. The diagnosis of TB and COPD was confirmed using radiographic, functional and laboratory research methods. Group 1, age Me (25; 75) 55.5 (46; 58) years - 22 patients with MDR + COPD tuberculosis who, simultaneously with TB chemotherapy, received a short-acting M-anticholinergic blocker, 2 inhalations 4 times a day, group 2, age 54.5 (51; 58) years - 18 patients with MDR + COPD tuberculosis, simultaneously with TB chemotherapy received a combination of ICS with a long-acting bronchodilator (beta-2-agonist (LABA)), budesonide + formoterol 160 / 4.5 μg dose - 2 inhalations 2 times a day (in an inhaler device). Duration of observation is 9 months. Results and discussion. After 9 months of observation, closure of decay cavities in 63.6% in group 1 and 83.3% in group 2 (χ² = 0.3; p = 0.581), smear negativity in 90.9% of cases in group 1 and in 100, 0% in group 2, respectively (χ² = 0.04 p = 0.834), abacillated 63.3% and 100.0% in groups 1 and 2, respectively (χ² = 0.46; p = 0.496). Against the background of the use of ICS in the intensive phase of TB chemotherapy simultaneously with antibiotic therapy, there was a decrease in the time of abacillation and closure of decay cavities in comparison with the group that did not receive ICS. At the same time in broncholics, the use of ICS made it possible to quickly stop the broncho-obstructive syndrome, improve the quality of life and compliance with long-term anti-tuberculosis therapy. An additional nonspecific anti-inflammatory effect of ICS promoted the active resorption of infiltrative changes and the cure of a specific process, reducing the duration of the main course of treatment, including in patients with MDR. Conclusion. Patients of the anti-tuberculosis dispensary with concomitant bronchopulmonary pathology need complex treatment aimed at correcting comorbid conditions, simultaneously with chemotherapy for tuberculosis. The use of ICS in addition to long-acting bronchodilators (LABA, LDAH) in patients with COPD for the correction of broncho-obstructive syndrome in the intensive phase of TB treatment can reduce the time of smear negativity, abacillation and closure of decay cavities.

High Intrapulmonary Rifampicin and Isoniazid Concentrations Are Associated With Rapid Sputum Bacillary Clearance in Patients With Pulmonary Tuberculosis.

Intrapulmonary pharmacokinetics may better explain response to tuberculosis (TB) treatment than plasma pharmacokinetics. We explored these relationships by modeling bacillary clearance in sputum in adult patients on first-line treatment in Malawi. Bacillary elimination rates (BER) were estimated using linear mixed-effects modelling of serial time-to-positivity in mycobacterial growth indicator tubes for sputum collected during the intensive phase of treatment (weeks 0-8) for microbiologically confirmed TB. Population pharmacokinetic models used plasma and intrapulmonary drug levels at 8 and 16 weeks. Pharmacokinetic-pharmacodynamic relationships were investigated using individual-level measures of drug exposure (area-under-the-concentration-time-curve [AUC] and Cmax) for rifampicin, isoniazid, pyrazinamide, and ethambutol, in plasma, epithelial lining fluid, and alveolar cells as covariates in the bacillary elimination models. Among 157 participants (58% human immunodeficiency virus [HIV] coinfected), drug exposure in plasma or alveolar cells was not associated with sputum bacillary clearance. Higher peak concentrations (Cmax) or exposure (AUC) to rifampicin or isoniazid in epithelial lining fluid was associated with more rapid bacillary elimination and shorter time to sputum negativity. More extensive disease on baseline chest radiograph was associated with slower bacillary elimination. Clinical outcome was captured in 133 participants, with 15 (11%) unfavorable outcomes recorded (recurrent TB, failed treatment, or death). No relationship between BER and late clinical outcome was identified. Greater intrapulmonary drug exposure to rifampicin or isoniazid in the epithelial lining fluid was associated with more rapid bacillary clearance. Higher doses of rifampicin and isoniazid may result in sustained high intrapulmonary drug exposure, rapid bacillary clearance, shorter treatment duration and better treatment outcomes.

Lactobacillus casei modulates inflammatory cytokines and metabolites during tuberculosis treatment: A post hoc randomized controlled trial.

Inflammatory cytokines and metabolic abnormalities are common in patients with tuberculosis. Observational studies have indicated that probiotics modulate inflammatory cytokines and metabolites; however, clinical evidence of the effect of probiotics on patients with tuberculosis is lacking. This study investigated the effects of Lactobacillus casei on inflammatory cytokines and metabolites during tuberculosis treatment. A randomized controlled trial was conducted. A total of 47 inpatients were included and randomly assigned to receive standard antituberculosis therapy only (control group) or that treatment together with 1 × 1010 colony-forming units per day of Lactobacillus casei (low-dose group) or 2 × 1010 colony-forming units per day of Lactobacillus casei (high-dose group) for 4 weeks of intensive treatment during hospitalization. Plasma samples were analyzed for inflammatory cytokines and metabolomics with ELISA kits and ultrahigh performance liquid chromatography quadrupole time-of-flight mass spectrometry. Daily Lactobacillus casei supplementation of up to 2 × 1010 colony-forming units significantly lowered the concentrations of tumor necrosis factor-α, interleukin-6, interleukin-10, and interleukin-12 (p=0.007, p=0.042, p=0.002, p<0.001, respectively) in patients with tuberculosis. Compared with the control and low-dose groups, the plasma metabolites of phosphatidylserine, maresin 1, phosphatidylcholine, L-saccharopine, and pyridoxamine were significantly upregulated, and N-acetylmethionine, L-tryptophan, phosphatidylethanolamine, and phenylalanine were downregulated in the high-dose group. Strong correlations were observed between metabolites and inflammatory cytokines. Lactobacillus casei supplementation during the intensive phase of tuberculosis treatment can significantly modulate inflammatory cytokines and metabolites. Decreased inflammatory cytokines may be related to metabolite changes.

Vitamin C Supplementation Improves Pulmonary Tuberculosis Patients' Sputum Conversion During Intensive Phase Category I Treatment in Medan

Background: Many factors influence the success of the acceleration of Acid-Fast Bacilli (AFB) sputum conversion in the treatment of the intensive phase of pulmonary tuberculosis (TB). One of these factors is the nutritional status or nutrition of pulmonary TB patients. Through a fenton reaction, Vitamin C is known to be able to sterilize Mycobacterium tuberculosis. This study aims to determine the effect of giving vitamin C on the conversion of AFB sputum in the intensive phase of pulmonary TB treatment. Method: This study was an inferential, quasi-experimental evaluation of the acceleration of AFB sputum conversion following vitamin C supplementation in patients with category I pulmonary TB. The study group was separated into two groups: 40 TB patients getting Anti Tuberculosis Treatment (ATT) with vitamin C, and 40 TB patients receiving ATT with placebo. Every two weeks, AFB sputum was examined, and vitamin C levels were measured before and after two months of therapy. Results: Conversion of AFB occurred sooner in the vitamin C group of pulmonary TB patients, with as many as 29 patients (72.5%) experiencing conversion of AFB sputum at the end of the second week of therapy, whereas there was no conversion in the placebo group. At the end of the fourth week, all patients (100%) given vitamin C showed AFB sputum conversion, whereas only eight patients (20%) in the placebo group had conversion at the end of the fourth week of treatment. Vitamin C levels increased significantly in the group of pulmonary tuberculosis patients who received vitamin C supplementation. Conclusion: Vitamin C supplementation in the treatment of pulmonary TB can accelerate the conversion of AFB sputum, which is statistically significant.

Effectiveness of chemotherapy of multidrug-resistant tuberculosis using bedaquiline

The aim of the study was to evaluate the effectiveness of MDR/XDR TB treatment with bedaquiline. Methods. The author analyzed the treatment results of 56 patients in Staint Petersburg in 2017 with MDR/XDR TB whose treatment regimen included bedaquiline. All patients were smear/ culture-positive: 43 (67.8%) cases with XDR MBT; 7 (12.5%) with pre-XDR MBT and only 6 (10.7 %) cases with MDR TB. Results. 35 (62.5%) patients received full bedaquiline course, 16 received the treatment for a few days to 4 months and did not complete the course, 5 patients with XDR tuberculosis who underwent surgery were treated for more than 6 months. The average duration of bedaquiline course was 4.7 ± 0.3 months. Among the 27 (48.2%) patients who completed the treatment effectively, 22 had XDR TB, 3 – pre-XDR TB, and 2 – MDR TB. The median sputum conversion period was 4.00 ± 0.42 months (CI: 3.14 – 4.86). 13 (23.2%) patients interrupted the treatment, but 9 of them had negative cultures for MBT at this time. These patients received bedaquiline for 1 to 14 months. Treatment failure was recorded in 12 (21.4%) patients, and 4 (7.14%) patients died during the intensive treatment phase. In general, 27 patients with a successful outcome had negative cultures at the end of the intensive phase and 9 patients who effectively completed the intensive phase but interrupted the treatment continuation phase. In total, 36 patients (64.3%) had a successful treatment outcome. Conclusion. The analysis showed that routine administration of the drug without consideration for treatment compliance increases the effectiveness of the intensive phase (64.3%) and does not significantly affect general effectiveness of the treatment (48.2%). The high frequency of treatment interruption remains a serious obstacle to improving the treatment effectiveness.

POS-716 BURKHOLDERIA PSEUDOMALLEI (MELIOIDOSIS) PERITONEAL DIALYSIS PERITONITIS

Melioidosis is known to be endemic in Southeast Asian countries, including Malaysia where it commonly presents as severe pneumonia or abscesses. In end stage renal disease (ESRD) patients on peritoneal dialysis (PD), melioidosis is rarely reported as the cause of peritonitis. These are retrospective case series of PD for the past 6bmonths secondary to Melioidosis. Clinical features and managements of these two patients are being described. Case series: We reported 2 cases of ESRD patients on continuous ambulatory peritoneal dialysis (CAPD). Both patients were diabetics and presented with typical symptoms of peritoneal dialysis peritonitis where the dialysate effluents grew Burkholderia pseudomallei. Patient 1 was hypotensive on presentation and started on broad spectrum antibiotics, intravenous (IV) ceftazidime. He responded well and completed 4 weeks of intensive IV ceftazidime and was switched to oral Bactrim as eradication therapy upon discharged. Patient 2 was hemodynamically stable and promptly started on intraperitoneal (IP) ceftazidime. Unfortunately, he did not respond despite escalation to intraperitoneal imipenem. His Tenckhoff catheter was removed subsequently and he was converted to haemodialysis (HD). Both patients completed the intensive phase of treatment and were discharged on oral eradication therapy for the treatment of melioidosis. Both are currently well with no relapse. Discussion: There have been few treatment options for melioidosis peritonitis. Treatment comprises of intensive phase, usually IV ceftazidime or meropenem, followed by a prolonged course of eradications phase. If IV antibiotics fail to treat the peritonitis, prompt Tenckhoff catheter removal will be the next appropriate course of action. In our cases, one patient had catheter loss due to melioidosis peritonitis while the other was able to continue on PD. PD peritonitis due to melioidosis is uncommon but it may be associated with catheter loss and possibly fatal if not treated early as systemic melioidosis is associated with high mortality. Early diagnosis, high awareness and prompt management are important in treating melioidosis PD peritonitis.