Antibodies against native proteins of Mycobacterium tuberculosis can detect pulmonary tuberculosis patients.

Accurate point-of-care testing (POCT) is critical for managing tuberculosis (TB). However, current antibody-based diagnosis shows low specificity and sensitivity. To find proper antigen candidates for TB diagnosis by antibodies, we assessed IgGs responsiveness to Mycobacterium tuberculosis proteins in pulmonary TB (PTB) patients. We employed major secreted proteins, such as Rv1860, Ag85C, PstS1, Rv2878c, Ag85B, and Rv1926c that were directly purified from M. tuberculosis. In the first screening, we found that IgG levels were significantly elevated in PTB patients only against Rv1860, PstS1, and Ag85B among tested antigens. However, recombinant PstS1 and Ag85B from Escherichia coli (E. coli) couldn't distinguish PTB patients and healthy controls (HC). Recombinant Rv1860 was not checked due to its little expression. Then, the 59 confirmed PTB patients from Soetomo General Academic Hospital, Surabaya, Indonesia, and 102 HC were tested to Rv1860 and Ag85B only due to the low yield of the PstS1 from M. tuberculosis. The ROC analysis using native Ag85B and Rv1860 showed an acceptable area under curve for diagnosis, which is 0.812 (95% CI 0.734-0.890, p < 0.0001) and 0.821 (95% CI 0.752-0.890, p < 0.0001). This study indicates that taking consideration of native protein structure is key in developing TB's POCT by antibody-based diagnosis.

Mental Health Status and Its Associated Factors Related to Pulmonary Tuberculosis Patients in Primary Health Care Centre in Surabaya, Indonesia.

BACKGROUND: Mental disorders in TB patients are due to long-term treatment, drug side effects, and relapse. This study aimed to analyse the mental health status among TB patients and its associated factors. METHODS: The study was carried out on 107 Pulmonary TB patients from 5 Primary Healthcare centres in Surabaya, Indonesia. Furthermore, Mental Health Inventory (MHI-18) was used to measure the mental health status. The MHI-18 has four subscales including, anxiety, depression, behaviour control, and positive affection. In addition, the score range of MHI and its subscales is 0-100, where the higher score showed a better mental health status. RESULTS: The results showed no difference in the score of mental health status, anxiety, depression, and positive affect in all factors. However, behaviour control depicted a significant difference between sex and marital status. In conclusion, mental health problems can occur in all TB patients irrespective of their characteristics. CONCLUSION: Screening is required for the prevention of severe disease in the early treatment phase and various factors related to mental health should be considered during the implementation of TB management to optimize treatment outcomes.

The effect of isolated probiotics from Indonesian Passiflora edulis sims. on interferon gamma levels in peripheral blood mononuclear cell of adult tuberculosis patients in vitro.

Background: Mycobacterium tuberculosis (M.tb) is unique because the bacteria live intracellularly and hide in macrophages so that they can escape from phagocytosis. This is one of the factors that complicate the treatment of M.tb infections. Interferongamma (IFN-γ) is a compound that plays an important role in macrophage activation to control intracellular pathogens. Objective: The purpose of this research is to analyze the concentration of IFN-γ in peripheral blood mononuclear cells of adult Tuberculosis patients (TB) after in vitro administration of multistrain probiotics from indigeneous Indonesian red passion fruit (Passiflora edulis Sims.). Method: The probiotics isolated from red passion fruit were introduced into Peripheral Blood Mononuclear Cell (PBMC) adult TB patients who were undergoing Anti-tuberculosis Drug Therapy (ATD) category one at the Trosobo Primary Health Center (Sidoarjo, East Java, Indonesia), and the patients who were undergoing ATD category one treatment were willing to be involved in this study.Result: The probiotics isolated from fermentation-broth of Indonesian red passion fruit were able to increase IFN-γ levels in PBMC of adult TB patients. Conclusion: The red passion fruit probiotics isolated can increase IFN-γ of adult TB patients increased from 0.82% to 23.17% after in vitro administration.

Mycobacterium tuberculosis - atpE gene profile of bedaquiline-treated pulmonary tuberculosis patients at the referral hospital Dr. Soetomo, Indonesia.

Background: The atpE gene is a target for bedaquiline (Bdq)-activating drug action and mutations in the gene are fixed to cause resistance. However, changes in the amino acid of ATPase have been little reported from a clinical setting since it was first used in 2015 in Indonesia. This study aims to observe the sequence of nucleotide and amino acid from rifampicin-resistant (RR) pulmonary tuberculosis (TB) patients, both new and relapse cases treated with Bdq. Methods: This is an observational descriptive study performed in the referral hospital Dr Soetomo, Indonesia, at August 2022-November 2022. We performed Sanger sequencing and comparison of the atpE gene from the patient's sputum from August to November 2022 to wild-type Mycobacterium tuberculosis H37Rv and species of mycobacteria using BioEdit version 7.2 and BLAST NCBI software. We also conducted an epidemiological study on patients' characteristics. This study uses a descriptive statistic to show the percentage of data. Results: The total of 12 M. tuberculosis isolates showed that the atpE gene sequence was 100% similar to the wild-type M. tuberculosis H37Rv. No single-nucleotide polymorphisms or mutations were found, and no change in the amino acid structure at position 28 (Asp), 61 (Glu), 63 (Ala), and 66 (Ile). The percentage identity of atpE to M. tuberculosis H37Rv and M. tuberculosis complex was 99%-100%, while the similarity with the other mycobacteria species other than TB (Mycobacterium avium complex, Mycobacterium abscessus, and Mycobacterium lepraemurium) was 88%-91%. Conclusions: This study revealed M. tuberculosis -atpE gene sequence profile of RR-TB patients had no mutations, as the specific gene region, and no change in the amino acid structure. Therefore, Bdq can be continually trusted as an effective anti-tubercular drug in RR-TB patients.

Characteristics of Previous Tuberculosis Treatment History in Patients with Treatment Failure and the Impact on Acquired Drug-Resistant Tuberculosis.

Tuberculosis (TB) treatment failure is a health burden, as the patient remains a source of infection and may lead to the development of multi-drug resistance (MDR). Information from cases of treatment failure that develop into MDR, which is related to a history of previous TB treatment, in accordance with the pharmacokinetic aspect, is one important thing to prevent TB treatment failure and to prevent drug resistance. This was an observational descriptive study in an acquired MDR-TB patient who had a prior history of treatment failure. A structured questionnaire was used to collect information. The questionnaire consisted of a focus on the use of TB drug formulas during the treatment period, as well as when and how to take them. This study included 171 acquired MDR-TB patients from treatment failure cases. An amount of 64 patients received the separated TB drug, and 107 patients received the fixed dose combination (FDC) TB drug. An amount of 21 (32.8%) patients receiving separated TB drug and six (5.6%) patients receiving FDC TB drug took their drug in divided doses. In addition, three (4.7%) patients receiving separated TB drug and eight (7.5%) patients receiving FDC TB drug took their drug with food. An amount of 132 out of 171 (77.2%) patients had a history of incorrect treatment that developed into MDR-TB. Education on how to take the correct medication, both the separate version and the FDC TB drug, according to the pharmacokinetic aspect, is important before starting TB treatment.

Development of population pharmacokinetics model and Bayesian estimation of rifampicin exposure in Indonesian patients with tuberculosis.

BACKGROUND: Interindividual variability in the pharmacokinetics (PK) of anti-tuberculosis (TB) drugs is the leading cause of treatment failure. Herein, we evaluated the influence of demographic, clinical, and genetic factors that cause variability in RIF PK parameters in Indonesian TB patients. METHODS: In total, 210 Indonesian patients with TB (300 plasma samples) were enrolled in this study. Clinical data, solute carrier organic anion transporter family member-1B1 (SLCO1B1) haplotypes *1a, *1b, and *15, and RIF concentrations were analyzed. The population PK model was developed using a non-linear mixed effect method. RESULTS: A one-compartment model with allometric scaling adequately described the PK of RIF. Age and SLCO1B1 haplotype *15 were significantly associated with variability in apparent clearance (CL/F). For patients in their 40s, each 10-year increase in age was associated with a 10% decrease in CL/F (7.85 L/h). Patients with the SLCO1B1 haplotype *15 had a 24% lower CL/F compared to those with the wild-type. Visual predictive checks and non-parametric bootstrap analysis indicated good model performance. CONCLUSION: Age and SLCO1B1 haplotype *15 were significant covariates of RIF CL/F. Geriatric patients with haplotype *15 had significantly greater exposure to RIF. The model could optimize TB pharmacotherapy through its application in therapeutic drug monitoring (clinical trial no. NCT05280886).

The Profile of Multidrug Tuberculosis Regimen and Treatment Outcomes in Pulmonary MDR-TB Patients at the Tertiary Referral Hospital Dr. Soetomo, East Java, Indonesia: A Seven-Year Retrospective Study on Bedaquiline.

BACKGROUND: The use of bedaquiline has been reported to minimize the number of lost to follow-up and fewer rejections from the patients. This study is the first to depict the use of bedaquiline. It aims to provide information related to the profile of the MDR-TB drug regimen in the last 7 years with the treatment outcomes of pulmonary MDR-TB patients at a tertiary referral hospital in East Java. METHODS: This study was a retrospective, descriptive, and data analysis on 1053 pulmonary MDR-TB patients in tertiary referral hospital Dr Soetomo, East Java, Indonesia, with the SPSS software version 25 and Microsoft Excel 2021. RESULTS: The study analyzed the  MDR-TB treatment regimen following the latest guidelines from WHO (2020) at a tertiary referral hospital in East Java. This study shows that a bedaquiline-containing regimen started in January 2015 to July 2022 with the percentage of distribution (1, 3, 11, 4, 18, 13, 29, 21)% consecutively in the regimen. The treatment outcome profile of MDR-TB patients shows the average percentage of cured (15%), died (12%), lost-to-follow-up cases (27%), moved to an individualized regimen or a different health facility (42%), and currently in the evaluation stage (4%). Overall from January 2017 to July  2022, the number of LTFU cases decreased (42, 46, 29, 19, 8, 4)%. However, the cured case fluctuated between 2017-2022 (16, 28, 26, 32)%  respectively after Bdq started to be included in the regimen regularly for treating RR/MDR-TB. CONCLUSION: After seven years of study, we revealed an association between adding bedaquiline to the regimen and the treatment success and decreasing lost-to-follow-up cases.

Line probe assay test in new cases of tuberculosis with rifampicin resistance not detected by Xpert MTB/RIF.

Background: In Indonesia, the National guideline for tuberculosis only recommended taking the DST to check INH resistance only for re-treatment cases of rifampicin-susceptible TB (RS-TB) detected by Xpert MTB/RIF. This study was conducted mainly to evaluate the proportion of isoniazid resistance in new cases of RS-TB according to the Xpert MTB/RIF. Methods: This was an observational descriptive study in RS-TB new patients diagnosed by Xpert MTB/RIF. Sputum samples were examined using first-line LPA and evaluated by culture-based DST. Results of first-line LPA and culture-based DST were compared and presented. Results: Fifty-four new cases of RS-TB (according Xpert MTB/RIF) were enrolled in this study. INH resistance was detected in 4 (7.4%) using FL-LPA and in 5 (9.3%) using culture-based DST. RIF resistance was also found in 1 (1.9%) using FL-LPA and in 2 (3.7%) using culture-based DST. Ethambutol resistance was also detected in 4 (7.4%) using culture-based DST. Conclusion: First-line LPA successfully revealed 4 (7.4%) of Hr-TB in new RS-TB cases detected by the Xpert MTB/RIF. In new cases with RS-TB detected by the Xpert MTB/RIF, FL- LPA can be used as rapid molecular DST to detect RIF and INH resistance followed by culture-based DST to examine other drug resistance.

Proposed Algorithm for Integrated Management of TB-SARS-CoV-2 Co-Infection in a TB-Endemic Country.

Tuberculosis (TB) and COVID-19 have become significant health problems globally, especially in countries with high prevalence. Therefore, this research aims to examine all possibilities and predict the impact of TB-SARS-CoV-2 co-infection to anticipate the cascade effect of both diseases in all sectors. The conceptual strategy of the algorithm in TB-COVID-19 is needed to create an integrated management system. It includes the stages of early detection with accurate and effective methods, as well as the synchronization of TB-COVID-19 health services, starting from primary health facilities to secondary and tertiary referral centers. The algorithm in TB-COVID-19 is crucial to prepare future strategies for PTB co-infection viral respiratory infections other than SARS-CoV-2, ILI, ARI, and SARI. Since the implementation involves all health services, there is a need to integrate the governance of TB-COVID-19 and other comorbidities in good health services based on research and multicentre design.

Comparison Epidemiology between Tuberculosis and COVID-19 in East Java Province, Indonesia: An Analysis of Regional Surveillance Data in 2020.

Tuberculosis and COVID-19 are among the infectious diseases that constitute a public health concern. Therefore, this study aims to examine the recent epidemiology of tuberculosis and COVID-19 in East Java Province, Indonesia, in 2020. Case-based surveillance data were acquired with a retrospective design between January and December 2020 by the East Java Health Officer. The data were analyzed using Quantum Geographic Information System (QGIS) for mapping, and Microsoft Excel for recording. Furthermore, the statistical analysis (Spearman correlation test) was carried out via Statistical Package for Social Science (SPSS) applications. A total number of 38,089 confirmed cases of tuberculosis was recorded, with an incidence rate of 95.49/100,000 population, a case fatality rate (CFR) of 3.6%, and an average treatment success rate of 87.78%. COVID-19 is a new viral disease, with a total of 84,133 confirmed COVID-19 cases in East Java, with an incidence rate of 232.9/100,000 population. The highest incidence rate was found in Mojokerto city, while the lowest was found in Sampang. Furthermore, the CFR values of tuberculosis and COVID-19 were 1.4% and 6.8%, respectively. The regional survey in East Java Province showed that the incidence of tuberculosis remains high. This indicated that the search for active cases and preventive promotion was not completed. Therefore, inter-sectoral collaboration can be adapted to provide suitable tuberculosis health care.

Antibiotic Resistance in Non-Typhoidal Salmonella enterica Strains Isolated from Chicken Meat in Indonesia.

The increase in antibiotic resistance in non-typhoidal Salmonella enterica (NTS) has been confirmed in Indonesia by this study. We confirmed the virulence genes and antimicrobial susceptibilities of clinical NTS (n = 50) isolated from chicken meat in Indonesia and also detected antimicrobial resistance genes. Of 50 strains, 30 (60%) were non-susceptible to nalidixic acid (NA) and all of them had amino acid mutations in gyrA. Among 27 tetracycline (TC) non-susceptible strains, 22 (81.5%) had tetA and/or tetB. The non-susceptibility rates to ampicillin, gentamicin or kanamycin were lower than that of NA or TC, but the prevalence of blaTEM or aadA was high. Non-susceptible strains showed a high prevalence of virulence genes compared with the susceptible strains (tcfA, p = 0.014; cdtB, p < 0.001; sfbA, p < 0.001; fimA, p = 0.002). S. Schwarzengrund was the most prevalent serotype (23 strains, 46%) and the most frequently detected as multi-antimicrobial resistant. The prevalence of virulence genes in S. Schwarzengrund was significantly higher than other serotypes in hlyE (p = 0.011) and phoP/Q (p = 0.011) in addition to the genes above. In conclusion, NTS strains isolated from Indonesian chicken had a high resistance to antibiotics and many virulence factors. In particular, S. Schwarzengrund strains were most frequently detected as multi-antimicrobial resistant and had a high prevalence of virulence genes.

Correlation of Moxifloxacin Concentration, C-Reactive Protein, and Inflammatory Cytokines on QTc Interval in Rifampicin-Resistant Tuberculosis Patients Treated with Shorter Regimens.

BACKGROUND: Drug-resistant tuberculosis (DR-TB) is a global health concern. QTc prolongation is a serious adverse effect in DR-TB patients receiving a shorter regimen. This study aimed to evaluate the correlation of moxifloxacin concentration, CRP, and inflammatory cytokines with QTc interval in DR-TB patients treated with a shorter regimen. METHODS: This study was performed in 2 groups of rifampicin-resistant (RR-TB) patients receiving shorter regimens. Correlation for all variables was analyzed. RESULTS: CRP, IL-1ß, and QTc baseline showed significant differences between 45 RR-TB patients on intensive phase and continuation phase with p-value of <0.001, 0.040, and <0.001, respectively. TNF-α and IL-6 between RR-TB patients on intensive phase and continuation phase showed no significant difference with p=0.530 and 0.477, respectively. CRP, TNF-α, IL-1 ß, and IL-6 did not correlate with QTc interval in intensive phase (p=0.226, 0.281, 0.509, and 0.886, respectively), and also in continuation phase (0.805, 0.865, 0.406, 0.586, respectively). At 2 hours after taking the 48th-dose, moxifloxacin concentration did not correlate with QTc interval, both in intensive phase (p=0.576) and in continuation phase (p=0.691). At 1 hour before taking the 72nd-hour dose, moxifloxacin concentration also did not correlate with QTc interval in intensive phase (p=0.531) and continuation phase (p=0.209). CONCLUSION: Moxifloxacin concentration, CRP, and inflammatory cytokines did not correlate with QTc interval in RR-TB patients treated with shorter regimens. The use of moxifloxacin is safe but should be routinely monitored and considered the presence of other risk factors for QTc prolongation in RR-TB patients who received shorter regimens.

Development of population pharmacokinetics model of isoniazid in Indonesian patients with tuberculosis.

OBJECTIVES: No population pharmacokinetics (PK) model of isoniazid (INH) has been reported for the Indonesian population with tuberculosis (TB). Therefore, we aimed to develop a population PK model to optimize pharmacotherapy of INH on the basis of therapeutic drug monitoring (TDM) implementation in Indonesian patients with TB. MATERIALS AND METHODS: INH concentrations, N-acetyltransferase 2 (NAT2) genotypes, and clinical data were collected from Dr. Soetomo General Academic Hospital, Indonesia. A nonlinear mixed-effect model was used to develop and validate the population PK model. RESULTS: A total of 107 patients with TB (with 153 samples) were involved in this study. A one-compartment model with allometric scaling for bodyweight effect described well the PK of INH. The NAT2 acetylator phenotype significantly affected INH clearance. The mean clearance rates for the rapid, intermediate, and slow NAT2 acetylator phenotypes were 55.9, 37.8, and 17.7 L/h, respectively. Our model was well-validated through visual predictive checks and bootstrapping. CONCLUSIONS: We established the population PK model for INH in Indonesian patients with TB using the NAT2 acetylator phenotype as a significant covariate. Our Bayesian forecasting model should enable optimization of TB treatment for INH in Indonesian patients with TB.

The espD full gene as a potential biomarker in active pulmonary tuberculosis.

Background: Pulmonary tuberculosis (PTB) is still a major health problem worldwide. The espD has a potential to be a new biomarker because it is important for the espA, espC, and ESX-1 protein secretion system that are actively expressed in active multiplication of Mycobacterium tuberculosis complex. Methods: A total of 55 sputum samples and 41 culture isolates from newly diagnosed PTB patients at Dr. Soetomo Academic Hospital were collected from September 2016 to April 2019. The tested samples using polymerase chain reaction targeted 555 bp of espD gene and sequencing. Clone Manager Version 6 and NCBI BLAST were used to align the gene sequence against wild-type M. tuberculosis. The prediction of T-cell epitope in espD gene was detected by GENETYX. The three-dimensional (3D) structure of espD was modeled by SWISS-MODEL and I-TASSER and was visualized with PyMOL. Results: From 55 sputum samples, 43 (78.18%) showed positive results, and all culture isolates showed positive results. In addition, all sequenced samples showed 100% homolog with M. tuberculosis H37Rv gene without detected variant or mutation. There were four T-cell epitopes that could be obtained. The 3D model had a I-TASSER confidence score of 3.91 with estimated RMSD of approximately 14.5 Å. The structure consists of a main fold of a three-stranded antiparallel ß-sheet and a long α-helix surrounded by several minor secondary structures. Conclusions: This study provides a brief information about the sequence, epitope prediction, and 3D structure of EspD protein from M. tuberculosis strains in Indonesia.

Determinant factors for loss to follow-up in drug-resistant tuberculosis patients: the importance of psycho-social and economic aspects.

BACKGROUND: Drug-resistant tuberculosis (DR-TB) is the barrier for global TB elimination efforts with a lower treatment success rate. Loss to follow-up (LTFU) in DR-TB is a serious problem, causes mortality and morbidity for patients, and leads to wide spreading of DR-TB to their family and the wider community, as well as wasting health resources. Prevention and management of LTFU is crucial to reduce mortality, prevent further spread of DR-TB, and inhibit the development and transmission of more extensively drug-resistant strains of bacteria. A study about the factors associated with loss to follow-up is needed to develop appropriate strategies to prevent DR-TB patients become loss to follow-up. This study was conducted to identify the factors correlated with loss to follow-up in DR-TB patients, using questionnaires from the point of view of patients. METHODS: An observational study with a cross-sectional design was conducted. Study subjects were all DR-TB patients who have declared as treatment success and loss to follow-up from DR-TB treatment. A structured questionnaire was used to collect information by interviewing the subjects as respondents. Obtained data were analyzed potential factors correlated with loss to follow-up in DR-TB patients. RESULTS: A total of 280 subjects were included in this study. Sex, working status, income, and body mass index showed a significant difference between treatment success and loss to follow-up DR-TB patients with p-value of 0.013, 0.010, 0.007, and 0.006, respectively. In regression analysis, factors correlated with increased LTFU were negative attitude towards treatment (OR = 1.2; 95% CI = 1.1-1.3), limitation of social support (OR = 1.1; 95% CI = 1.0-1.2), dissatisfaction with health service (OR = 2.1; 95% CI = 1.5-3.0)), and limitation of economic status (OR = 1.1; 95% CI = 1.0-1.2)). CONCLUSIONS: Male patients, jobless, non-regular employee, lower income, and underweight BMI were found in higher proportion in LTFU patients. Negative attitude towards treatment, limitation of social support, dissatisfaction with health service, and limitation of economic status are factors correlated with increased LTFU in DR-TB patients. Non-compliance to treatment is complex, we suggest that the involvement and support from the combination of health ministry, labor and employment ministry, and social ministry may help to resolve the complex problems of LTFU in DR-TB patients.

The role of C-Reactive protein as an inflammatory marker to predict prolonged QTc interval in rifampicin-resistant tuberculosis patients: A case-control study.

BACKGROUND: long-term use of anti-tuberculosis drugs (ATD) increases the risk of QTc prolongation, while C-reactive protein (CRP) can be used as an inflammatory marker of Mycobacterium tuberculosis infection.Objective: correlation of CRP on the QTc interval in Rifampicin-resistant tuberculosis (RR-TB) patients with the short regimen. METHODS: An observational study was conducted in Rifampicin-resistant tuberculosis (RR-TB) patients from 2 groups, patients on intensive phase and patients on continuation phase. CRP levels were measured from blood samples and measured automatically using the immunoturbidimetric assay. QTc interval was calculated using electrocardiography. Levels of CRP levels and QTc interval between the 2 groups were analyzed. The statistical analysis used includes the independent t-test, Mann Whitney test, and Rank Spearman test with p = 0.05. RESULTS: Forty-five eligible RR-TB patients were included in this study. CRP levels and QTc intervals between 2 groups (intensive and continuation phase) showed significant difference with p < 0.001 but found no significant correlation of CRP levels and QTc interval in both intensive and continuation phase with p = 0.226 and 0.805, respectively. A higher level of CRP strongly indicated the inflammation caused by RR-TB infection at the early phase of the disease, but not correlated with QTc interval in RR-TB patients. CONCLUSION: Levels of CRP and QTc interval do not correlate in RR-TB patients and can not be used to be the marker of QTc prolongation in RR-TB Patients.

Correlation of inflammatory cytokines on corrected QT interval in rifampicin-resistant tuberculosis patients.

BACKGROUND: The cases of Rifampicin-Resistant Tuberculosis (RR-TB) in our country have increased every year and RR-TB deaths are thought to be caused by prolongation of the QTc interval due to side effects of anti-tuberculosis drugs. Thus, cytokines are needed to be used as early markers of prolongation of the QTc interval in RR-TB patients. OBJECTIVE: This study aims to analyze the correlation of inflammatory cytokines on QTc interval in RR-TB patients who received shorter regimens. METHODS: This study uses a case-control study with a time series conducted in the period September 2019 to February 2020 in one of the referral hospitals for Tuberculosis in Indonesia. Cytokines levels from blood samples were measured using the ELISA method, while QTc intervals were automatically recorded using an electrocardiography machine. The statistical analysis used was the Chi-square test, Man Whitney test, Independence t-test, and Spearman-rank test with p < 0.05. RESULTS: There was no significant correlation between inflammatory cytokines and QTc prolongation in intensive phase which TNF-α value (6.8 pg/ml; r = 0.207; p = 0.281), IL-1ß (20.13 pg/ml; r = 0.128; p = 0.509), and IL-6 (43.17 pg/ml; r = -0.028; p = 0.886). Meanwhile, in the continuation phase, the values for TNF-α (4.79 pg/ml; r = 0.046; p = 0.865), IL-1ß (7.42 pg/ml; r = -0.223; p = 0.406), and IL- 6 (40.61 pg/ml; r = -0.147; p = 0.586). CONCLUSION: inflammatory cytokines (TNF-α, IL-1ß, and IL-6) cannot be used to identify QTc interval prolongation in RR-TB patients who received shorter regimens.

Microbiome in sputum as a potential biomarker of chronicity in pulmonary resistant to rifampicin-tuberculosis and multidrug-resistant-tuberculosis patients.

Background: Cases of tuberculosis (TB) and multidrug-resistant TB (MDR-TB) in South-east Asia including Indonesia are still high. The presence of mixed infections in TB cases has been reported. Several studies revealed the role of the human microbiome in TB. This study purposes to characterize microbiome which can be a potential biomarker of chronicity in TB or MDR-TB. Methods: Sputum samples of pulmonary TB patients confirmed MDR-TB and resistant to rifampicin TB (RR-TB) were conducted Metagenomic next-generation sequencing. Principal coordinate analysis of UniFrac's showing the community structure of microbiome in MDR-TB comorbid diabetes mellitus (DM) is different from RR-TB noncomorbid DM (P = 0.003). Results: Proteobacteria microbiome in MDR-TB comorbid DM was more abundant than in RR-TB noncomorbid DM. Actinobacteria found in the small quantity in RR-TB and MDR-TB. Diversity of microbiome genera was greater in RR-TB. The linear discriminant analysis effect size analysis represents a genus biomarker whose abundance shows significant differences between groups, genus Rothia as a potential biomarker for RR-TB noncomorbid DM. Conclusions: Interesting findings is the community structure of microbiome in MDR-TB and RR-TB. In chronic TB such as recurrent, associated MDR-TB should attention to the findings of a small number of Actinobacteria could be a biomarker of TB which is also a determinant in patient taking combined anti-TB drugs of choice.

The effect of red passion fruit (Passiflora edulis Sims.) fermentation time on its activity against Extended Strain Methicillin-Resistant (ESBL) Escherichia coli and Methicillin-Resistant Staphylococcus aureus (MRSA).

OBJECTIVES: The purpose of this study is to determine the effect of fermentation techniques on the inhibitory activity of red passion fruit (Passiflora edulis Sims.) fermentation filtrate in De Man Rogosa Sharpe-broth (MRS-B) media against Extended Strain Methicillin-Resistant (ESBL) Escherichia coli and Methicillin-Resistant Staphylococcus aureus (MRSA). METHODS: The fruit pulp was wrapped in banana leaves before compared to direct fermentation processes. This study was divided into three treatment groups. Group 1 was the fruit pulp (5 g) fermented in 45 mL of MRS-B medium for 24 h. Group 2 was the fruit pulp wrapped in banana leaves for 3 days before fermented in MRS-B for 24 h. Group 3 was the fruit pulp wrapped in banana leaves for 3 days before fermentation in MRS-B for 48 h. Fermentation broth of each condition was taken and then filtered using millipore (0.2 µm). As many as 50 µL of filtrates was tested for its inhibitory activity against E. coli ESBL and MRSA using the Kirby Bauer method. RESULTS: Group 2 showed the best antibacterial activity against E. coli ESBL and MRSA with the average zone of inhibition of 38.3 and 37.6 mm respectively. These values were higher than the first and group 3s activities. CONCLUSIONS: The inhibitory activity of group 1s against ESBL and MRSA is categorized as a moderate potency with a diameter of growth inhibition zone of 16-20 mm, whereas the other groups are categorized as strong potency with a diameter higher than 20 mm.

The Risk Factors of Multidrug-Resistant Organisms in Hospitalized Patients with Community-Acquired Pneumonia in Dr. Soetomo Hospital Surabaya, Indonesia.

BACKGROUND: multidrug-resistant organisms (MDRO) caused pneumonia has become a crucial case. MDRO infection has been a problem concern to community-acquired pneumonia (CAP). A lot of factors play roles in CAP with MDRO infection. This study aimed to analyze MDRO as the etiology of hospitalized patients with CAP along with its risk factors in Dr. Soetomo Hospital as one of the top referral hospitals in east Indonesia. METHODS: this retrospective cohort study was conducted from January 2016 to December 2018. Data were collected from patients' medical records. Automatic Rapid Diagnosis (Phoenix TM) was used as a standard method for culture and susceptibility test. Various risk factors were analyzed for MDRO infection. RESULTS: five most common pathogens in hospitalized patients with CAP were Acinetobacter baumannii 244/1364 (17.9%), Klebsiella pneumoniae 134/1364 (9.8%), Pseudomonas aeruginosa 91/1364 (6.7%), Escherichia coli 58/1364 (4.3%), and Enterobacter cloacae 45/1364 (3.3%). There were 294/1364 (21.5%) MDROs isolated from patients with CAP. MDRO infection was linked to previous hospitalization, malignancy, cardiovascular disease, and structural lung disease with p values of 0.002, <0.001, 0.024, and <0.001, respectively. CONCLUSION: the incidence of MDRO in CAP is high (21.5%). The risk factors related were previous hospitalization, malignancy, cardiovascular disease, and structural lung disease.