Primary Drug-resistant Tuberculosis Research Articles

Primary Pre-Extensively Drug-Resistant (Pre-XDR) Tuberculosis with Meningoencephalitis in Nineteen Years Old Young Woman : A Case Report

Introduction. Mycobacterium tuberculosis (MTB) is continually evolving in order to resist treatment. This has resulted in drug-resistant tuberculosis, which has a greater rate of therapy failure and mortality, as well as the necessity for other ways of disease transmission prevention. Pre-extensively drug-resistant tuberculosis (Pre-XDR TB) is caused by MTB strains that are resistant to isoniazid, rifampicin, and any fluoroquinolone medicines. Case Report. A 19-year-old HIV-negative immunocompetent female presented to our emergency department with dyspnea and severe headache. She also complained of a cough, a low-grade temperature, and weight loss. She has no relevant medical history and has never been exposed to tuberculosis. A chest X-ray revealed infiltrates with cavities and fibrosis in both lungs, while a brain CT suggested meningoencephalitis. We performed a sputum drug sensitivity test and discovered that this patient was resistant to rifampin, isoniazid, levofloxacin, and moxifloxacin. She was later diagnosed with Pre-XDR TB and was given a tailored lengthier regimen that included Bedaquiline, Cycloserin, Linezolide, Clofazimine, and Etambutol. Her symptoms improved significantly as a result of this program. Discussion. Primary pre-XDR TB in an immunocompetent patient is uncommon, and our case is even more unusual due to meningoencephalitis involvement. The treatment of pre-XDR TB requires a personalized regimen that is tailored to the patient's clinical status and comorbidities. The possibility of transmission via a positive contact was raised in this patient, prompting us to conduct a more thorough contact inquiry to prevent future spread. Conclusion. In our region, there is a risk of'silent' drug resistant tuberculosis. Early detection and treatment of such patients are critical to preventing uncontrollable pan-resistant TB. Successful management with cautious contact investigation will minimize the mortality rate and spread rate of drug-resistant TB. Keywords. Drug-Resistant Lung Tuberculosis, Drug-Resistant Meningoencephalitis Tuberculosis

Computed Tomography Manifestations in Patients with Rifampin Primary Drug-Resistant Tuberculosis in an Infectious Disease Hospital in the Yi Autonomous Prefecture, China

Computed Tomography Manifestations in Patients with Rifampin Primary Drug-Resistant Tuberculosis in an Infectious Disease Hospital in the Yi Autonomous Prefecture, China

Patterns and trends of primary drug-resistant tuberculosis in Chongqing, China, from 2012 to 2020.

Primary drug-resistant tuberculosis (DR-TB) contributes significantly to the global TB epidemic, particularly in countries with high TB burdens. This study aimed to investigate the characteristics of primary DR-TB prevalence in Chongqing, China, from 2012 to 2020. A total of 4546 newly diagnosed and 2769 relapse TB patients admitted to the hospital from 2012 to 2020 were included. Categorical variables were compared using Pearson chi-square test or Fisher exact test, as appropriate. Logistic regression analysis was performed to determine factors associated with primary DR-TB. The rate of primary DR-TB was 24.5%, whereas that of acquired DR-TB was 67.8%. Among newly diagnosed TB cases, the percentage of DR-TB (from 48.9 to 44.2%), mono-resistant TB (from 11.8 to 9.7%), multidrug-resistant TB (MDR-TB; from 25.3 to 6.9%), and pre-extensive drug-resistant TB (from 13.7 to 5.8%) showed a decreasing trend from 2012 to 2020. Age from 15 to 64 years was a risk factor for the development of primary DR-TB (15-44 years: adjusted odds ratio = 2.227, 95% confidence interval: 1.053-4.710; 45-64 years: adjusted odds ratio = 2.223, 95% confidence interval: 1.048-4.717). The rates of primary DR-TB (P = .041) and MDR-TB (P = .007) were significantly higher in the age group of 15 to 64 years than in the age groups of ≤14 years and ≥65 years. Noticeably, rising trends of primary DR-TB (from 0 to 27.3%) and MDR-TB (from 0 to 9.1%) in the population of ≤14 years were observed from 2012 to 2020. Although the rate of primary DR-TB showed a downward trend, a rising drug-resistance rate among some particular subgroups was still observed. Further control of primary DR-TB should focus more on TB patients aged 15 to 64 years.

Immune Disorders in Patients with Pulmonary Tuberculosis with Primary and Acquired Drug-Resistance of <i>Mycobacterium Tuberculosis</i>

The objective: to evaluate main parameters of cellular, humoral immunity and natural resistance in tuberculosis patients with primary and acquired multiple drug resistance; to study the correlation of these parameters with clinical and radiological manifestations.Subjects and Methods. A prospective study was conducted which included 169 patients with pulmonary tuberculosis, 80 of them were new cases of drug susceptible pulmonary tuberculosis and they made the Comparison Group (CG), and 89 patients suffered from multiple drug resistant tuberculosis and they made the Main Group (MG). The Main Group was divided into 2 subgroups: MG-1 – 40 patients with primary multiple drug resistant tuberculosis; MG-2 ‒ 49 patients who acquired drug resistance of Mycobacterium tuberculosis during treatment of tuberculosis.The immune assays included the lymphocyte blast transformation reaction (LBTR) to phytohemagglutinin and tuberculin (PPD), immunophenotyping of CD3+ and CD19+ cells; phagocytic index and phagocytic number were calculated; nitro blue tetrazolium test was used, concentrations of immunoglobulins and antimycobacterial antibodies were determined.Results. The clinical laboratory data demonstrated a more severe course of the disease in patients with multiple drug resistant tuberculosis, especially in those with acquired multiple drug resistant tuberculosis which was confirmed by the severity of immune deficiencies of the cellular immunity and innate resistance as well as by the overactivity of humoral immunity. The levels of CD3+ and LBTR reaction to PPD had a negative correlation with clinical manifestations and radiological features demonstrating the severity of pulmonary tuberculosis in patients with multiple drug resistance, especially in those with acquired multiple drug resistance; and CD19+ and antimycobacterial antibodies positively correlated with clinical manifestations and radiological signs.Conclusions. Parameters of cellular immunity and natural resistance were the lowest in the patients with acquired multiple drug resistance of Mycobacterium tuberculosis versus primary multiple drug resistance and drug susceptible Mycobacterium tuberculosis. Parameters of humoral immunity demonstrated the increased activity to compensate for the insufficiency of cellular immunity regardless of the type of resistance of Mycobacterium tuberculosis.

Level of Mycobacteria in Pre-Treatment Sputum and Susceptibility of M. tuberculosis Strains Isolated from Patients with non-Multidrug-Resistant Pulmonary Tuberculosis AFB (+) and Factors Influencing MGIT Results after the First 8 Weeks of Anti-Tuberculosi

Vietnam is among 30 high TB ​​burden countries even though the Vietnam National TB Program has made great efforts to detect and treat tuberculosis. Objectives: Assessment of Mycobacterial level in sputum before treatment, and susceptibility to the first line anti-TB drugs of M. tuberculosis strains isolated from TB patients with AFB (+) and non-multidrug-resistant. Moreover, factors influencing MGIT outcome after the first 8 weeks of first-line anti-TB drugs therapy in patients with pulmonary tuberculosis was also analysed. Methodology: An observational, analytical study was performed in 128 patients with non-multidrug-resistant pulmonary tuberculosis AFB (+) for evaluating the level of Mycobacteria in sputum before treatment by smear microscopy method; the susceptibility of M. tuberculosis isolated from sputum of the patient was analysed by Lowenstein - Jensen method. Factors affecting positive MGIT results after 2 months of treatment were determined by multivariate logistics regression. Results: The patients had AFB 3+ were 28% in new cases and 24,5% retreatment patients. The rate of M. tuberculosis strains was susceptible to the first line anti-TB drugs in new cases was higher than retreatment patients. The percentage of any anti-TB drug resistance in retreatment tuberculosis was 59,6%, higher than that of new case TB (23,6%). There was high rate of M. tuberculosis strains resistant to Streptomycin and Isoniazid (12,5% and 16,8% for new cases; 42,3% and 36,5% for retreatment cases, respectively). Large radiographic chest lesions and high AFB levels in pre-treatment sputum were factors associated with a positive MGIT result after the first 8 weeks of treatment. Conclusion: Most of TB patients had high level of Mycobacteria in sputum samples collected before treatment. The percentage of M. tuberculosis strains isolated from sputum of pulmonary non MDR-TB patients had any anti-TB drug resistance were high. High Mycobacteria level in pre-treatment sputum and radiographic chest lesions related to positive MGIT result after the first 8 weeks of treatment.
 Keywords
 Pulmonary tuberculosis, first-line anti-TB drugs, anti-TB drug resistance, susceptibility, M. tuberculosis.
 References
 [1] World Health Organization, Global Tuberculosis Report 2020. Tuberculosis profiles: Viet Nam (2020) Available: https://worldhealthorg.shinyapps.io/tb_profiles/?_inputs_&entity_type=%22country%22&lan=%22EN%22&iso2=%22VN%22 (accessed 10 April 2020).[2] L.T. Luyen, N.V. Hung, Methods for Diagnosis in Tuberculosis, in Le Thi Luyen (Ed), Tuberculosis - Textbook for General Medical Students. Vietnam National University Press, Hanoi, 2020, pp: 47-69 (in Vietnamese).[3] Ministry of Health - National Tuberculosis Programme Guideline for Standard Operating Procedures of Microbiology Laboratory Methods for Mycobacteria. Vietnam National Tuberculosis Programme, Hanoi (2013) (in Vietnamese).[4] Ministry of Health (2018) Guideline for Management, Diagnosis and Treatment for Tuberculosis. (in Vietnamese) Available: https://kcb.vn/vanban/quyet-dinh-so-3216-qd-byt-ngay-23-5-2018-ve-viec-ban-hanh-huong-dan-chan-doan-dieu-tri-va-du-phong-benh-lao (Accessed 12 January 2019)[5] A.P. Ralph, M. Ardian, A. Wiguna et al. A simple, valid, numerical score for grading chest x-ray severity in adult smear-positive pulmonary tuberculosis. Thorax 2010 Oct;65(10):863-869. https://doi.org/10.1136/thx.2010.136242[6] C.T. Minh, L.T. Luyen, N.T.L. Huong et al. Plasma concentration of anti-tubeculosis drugs in pulmonary tuberculosis patients, who treatment in National Tuberculosis and Lung Diseases Hospital 2008 Journal of Practical Medicine 651(2009) 50-53 (in Vietnamese).[7] N.V. Nhung, N.B. Hoa, D.N. Sy, C.M. Hennig, A.S. Dean (2015) The fourth national anti-tuberculosis drug resistance survey in Viet Nam. Int J Tuberc Lung Dis. Jun 2015 19(6) 670-675. https://doi.org/10.5588/ijtld.14.0785[8] N.T. Hang, S. Maeda, L.T. Lien, et al. Primary drug-resistant tuberculosis in Hanoi, Viet Nam: present status and risk factors. PloS one 8(8) (2013) e71867. https://doi.org/10.1371/journal.pone.0071867[9] R. Hafner, J.A. Cohn, D.J. Wright, et al. Early bactericidal activity of isoniazid in pulmonary tuberculosis. Optimization of methodology. The DATRI 008 Study Group. Am J Respir Crit Care Med 156 (1997) 918–923. https://doi.org/10.1164/ajrccm.156.3.9612016[10] A. Jindani, V.R. Aber, E.A. Edwards, D.A. Mitchison. The early bactericidal activity of drugs in patients with pulmonary tuberculosis. Am J Respir Crit Care Med. 121(1980)(6) 939-949. Available: https://www.atsjournals.org/doi/10.1164/arrd.1980.121.6.939 (Accessed 12 January 2019).[11] H.L. Rieder. Intervention for Tuberculosis Control and Elimination. International Union of Tuberculosis and Lung Diseases, Paris, France, 2002.

Treatment outcomes of pregnant women with drug-resistant tuberculosis in Uganda: A retrospective review of 18 cases

BackgroundThere is a dearth of reports on drug-resistant tuberculosis (DRTB) treatment outcomes among pregnant women in tuberculosis (TB)/HIV high-burdened countries. We report treatment outcomes of 18 pregnant women with DRTB in Uganda. MethodsWe reviewed charts of individuals who received DRTB treatment in Uganda across 16 DRTB treatment sites. We included all women who were pregnant during DRTB treatment and had a treatment outcome documented between 2013 and 2019. ResultsThere were 18 pregnant women with a mean age (standard deviation (SD)) of 27.5 (5.2) years, of whom 8 (44.4%) were HIV co-infected. Among these women, 12 (66.7%) had primary DRTB and 8 (44.4%) had multidrug-resistant TB. Levofloxacin (Lfx), Pyrazinamide, Cycloserine and Kanamycin (Kn) were the most (>78%) used drugs in the treatment regimen and the mean (SD) treatment duration was 17.6 (7.5) months. Elevated liver enzymes (81.8%, n = 11) and hearing loss (33.3%, n = 15) were the most frequently encountered drug adverse events. Treatment success was observed among 15 (83.3%) patients, 2 (11.1%) patients were lost to follow up and 1 (5.6%) patient died. ConclusionThe treatment success among pregnant women with DRTB in Uganda was high despite a high prevalence of HIV co-infection.

Primary Drug-Resistance Pattern and Trend in Elderly Tuberculosis Patients in Shandong, China, from 2004 to 2019.

BackgroundWith an aging population, China is facing a huge burden of elderly patients with drug resistant tuberculosis (DR-TB), which has become a significant obstacle for the global TB control. There is still little study on DR-TB in the elderly in China so far. Thus, more research on the epidemiological characteristics and trend of primary DR-TB among the elderly will be necessary.MethodsA retrospective study was conducted in Shandong, China from 2004 to 2019. We collected 12,661 primary TB cases, of which 4368 elderly (≥60 years) primary TB cases were involved. Clinical characteristics including age, sex, cavity, smoking, drinking, comorbidity and drug susceptibility data were collected from 36 TB prevention and control institutions of Shandong Province. Sputum samples were collected by each surveillance site, and examined in the TB Reference Laboratory of SPCH. Descriptive statistical analysis, chi-square and linear regression were used for analyzing.ResultsAmong 4368 elderly patients with primary TB, the DR-TB and multi-resistant tuberculosis (MDR-TB) accounted for 17.19% and 2.29%, respectively. During 2004–2019, the proportions of MDR-TB, polydrug resistant tuberculosis (PDR-TB), rifampin (RFP)-resistance increased by 160.00%, 18.18%, 231.82%, respectively and the rate of DR-TB among elderly patients with primary cavitary TB increased by 255%. Among the elderly with primary DR-TB during 2004–2019, the proportion of male (from 85.19 to 89.06), cavity (from 7.41 to 46.88), RFP-resistance (from 3.70 to 21.88), and streptomycin (SM)-resistance (from 37.04 to 62.5) increased significantly (P<0.05). And the proportion of female (from 14.81 to 10.94), non-cavity (from 92.59 to 32.81), INH-resistance (from 66.67 to 57.81) decreased significantly (P<0.05).ConclusionAmong the elderly, the proportions of MDR-TB, PDR-TB, RFP-resistance and cavitary DR-TB increased significantly. The pattern of DR-TB changed from female, non-cavity and INH-resistant groups to male, cavity, RFP or SM-resistant groups. For a better control on the elderly DR-TB in the future, we should pay more attention to male, smoking, drinking, chronic obstructive pulmonary disease (COPD) and diabetes subgroups and take targeted measures to control these subgroups.

Dynamic characteristics of drug resistant tuberculosis in Leiyang, Hunan, 2013–2017

ObjectiveTo analyze the dynamic trend of drug resistance of Mycobacterium tuberculosis in Leiyang city, Hunan province from 2013 to 2017, and to understand the local drug resistance spectrum of M. tuberculosis, so as to provide evidences for the formulation of chemotherapy regimen of tuberculosis (TB) and TB prevention and control. MethodsThe strains of M. tuberculosis collected in Leiyang from 2013 to 2017 were analyzed retrospectively. After identification by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS), all the M. tuberculosis strains were subjected to susceptibility tests of 8 first and second line anti-TB drugs by using microtiter plate method to understand the minimum inhibitory concentration. Statistical description and Chi-square for trend test were used to analyze the drug resistance trend. ResultsA total of 568 clinical strains of M. tuberculosis were included in this study, of which 18.49% (105/568) were from retreated TB cases, and 81.51% (463/568) form new TB cases. Overall, the drug resistance rate was 22.13% (120/568), the multi-drug resistance rate was 6.34% (36/568) and the extensively drug resistance rate was 0.35% (2/568). Drug resistance trend analysis showed that only the resistance rate to fluoroquinolones increased year by year (trend χ2＝8.585, P＝0.003), while the fluctuations of the drug resistance rate to other drugs, overall drug resistance rate and multi-drug resistance rate were not obvious, the differences were not statistically significant. ConclusionOverall, the drug resistance of tuberculosis in Leiyang was serious, the resistance rate to fluoroquinolones showed an increasing trend, and close attention should be paid on that. The standardized use of fluoroquinolones should be strengthened. Cross-drug resistance should be fully considered in the treatment of patients with drug resistant TB. In addition, the management of MDR-TB patients should be strengthened to reduce the incidence of primary drug resistant TB.

Primary drug resistance of mycobacterium tuberculosis in Shandong, China, 2004\u20132018

BackgroundPrimary drug-resistant tuberculosis (DR-TB) has contributed to a significant health and economic burden on a global scale, especially in China. we sought to estimate epidemiological characteristics of primary DR-TB in China from 2004 to 2018.MethodsEleven thousand four hundred sixty-seven newly diagnosed and 1981 retreated TB cases with drug susceptibility data were included. Chi-Square test for trends, linear regression, a joinpoint regression model and temporal trend in proportions of the different resistance patterns were carried out.ResultsThe proportion of primary DR-TB and mono-resistant TB (MR-TB) in China had reduced by more than 12% since 2004, and were 21.38%, 13.35% in 2018 respectively. Among primary DR-TB cases (2173,18.95%), the percentage of multiresistant TB (MDR-TB, from 5.41 to 17.46%), male (from 77.03 to 84.13%), cavity (from 13.51 to 43.92%), rifampicin(RFP)-resistant TB (from 8.11 to 26.98%), streptomycin(SM)-resistant TB (from 50.00 to 71.43%) increased significantly (P < 0.05). On the contrary, the proportion of female, non-cavity, isoniazide(INH)-resistant TB (from 55.41 to 48.15%) and MR-TB (from 82.43 to 62.43%) decreased significant (P < 0.05). The primary drug resistance rate among female, cavity, smoking, drinking, 15 to 44 year-old TB subgroups increased by 0.16, 6.24, 20.95, 158.85, 31.49%, respectively. The percentage of primary DR-TB, RFP-resistant TB dropped significantly during 2004–2007 in Joinpoint regression model.ConclusionThe total rate of drug resistance among new TB cases showed a downward trend in Shandong, China, from 2004 to 2018. Primary drug resistance patterns were shifting from female, non-cavity, INH-resistant TB, and MR-TB groups to male, cavity, RFP/SM-resistant TB, and MDR-TB groups. Considering the rising drug resistance rate among some special population, future control of primary DR-TB in China may require an increased focus on female, cavity, smoking, drinking, or 15 to 44 year-old TB subgroups.

Second-line anti-tuberculosis drug resistance testing in Ghana identifies the first extensively drug-resistant tuberculosis case.

BackgroundDrug resistance surveillance is crucial for tuberculosis (TB) control. Therefore, our goal was to determine the prevalence of second-line anti-TB drug resistance among diverse primary drug-resistant Mycobacterium tuberculosis complex (MTBC) isolates in Ghana.Materials and methodsOne hundred and seventeen MTBC isolates with varying first-line drug resistance were analyzed. Additional resistance to second-line anti-TB drugs (streptomycin [STR], amikacin [AMK] and moxifloxacin [MOX]) was profiled using the Etest and GenoType MTBDRsl version 2.0. Genes associated with resistance to AMK and MOX (gyrA, gyrB, eis, rrs, tap, whiB7 and tlyA) were then analyzed for mutation.ResultsThirty-seven (31.9%) isolates had minimum inhibitory concentration (MIC) values ≥2 µg/mL against STR while 12 (10.3%) isolates had MIC values ≥1 µg/mL for AMK. Only one multidrug-resistant (MDR) isolate (Isolate ID: TB/Nm 919) had an MIC value of ≥0.125 µg/mL for MOX (MIC = 3 µg/mL). This isolate also had the highest MIC value for AMK (MIC = 16 µg/mL) and was confirmed as resistant to AMK and MOX by the line probe assay GenoType MTBDRsl version 2.0. Mutations associated with the resistance were: gyrA (G88C) and rrs (A514C and A1401G).ConclusionOur findings suggest the need to include routine second-line anti-TB drug susceptibility testing of MDR/rifampicin-resistant isolates in our diagnostic algorithm.

Prevalence and genetic determinant of drug-resistant tuberculosis among patients completing intensive phase of treatment in a Tertiary Referral Center in Nigeria

Drug-resistant tuberculosis (DR-TB) continues to be a challenge in developing countries with poor resources. Despite the high prevalence of primary DR-TB, its routine screening prior to the treatment is not performed in public hospitals in Nigeria. Data regarding drug resistance and its genetic determinant among follow-up patients with TB are lacking in Nigeria. Hence, the aim of this study was to determine the prevalence and genetic determinant of drug resistance among the follow-up patients with TB in a tertiary hospital in Nigeria. This was a cross-sectional, laboratory-based study conducted on 384 sputum samples collected from consented follow-up patients with TB. Standard microbiology methods (Ziehl-Neelsen staining and microscopy) and polymerase chain reaction (PCR; line probe assay [LIPA]) were used to analyze the collected samples. Pearson's Chi-square test was used to analyze the generated data. Out of 384 sputum samples analyzed for Mycobacterium tuberculosis and DR-TB, 25 (6.5%) tested positive for acid-fast bacilli. These samples were subjected to PCR (LIPA), of which 18 (72%) tested positive for DR-TB. Of these 18 samples, mutations conferring resistance to rifampicin (rpoB) and isoniazid (katG and/or inhA) were detected in 12 (66.7%) and 6 (33.3%) samples, respectively. Transmission dynamics of DR-TB was not significantly (P > 0.05) dependent on demographic characteristics. There is a need to strengthen the laboratory capacity for the diagnosis of TB and drug resistance testing and make these services available, affordable, and accessible to the patients who need them.

Prevalence and Risk Factors of Primary Drug-Resistant Tuberculosis in China

ObjectiveTo investigate the prevalence of primary drug-resistant tuberculosis (TB) and associated risk factors in China. We also explored factors contributing to the transmission of multidrug-resistant tuberculosis (MDR-TB). MethodsA total of 2794 representative, Mycobacterium tuberculosis isolates from treatment-naive patients were subjected to drug susceptibility testing, and risk factors for drug-resistant TB were analyzed. We also analyzed MDR-TB strain sublineages, drug-resistance-conferring mutations, and risk factors associated with clustered primary MDR strains. ResultsAmong 2794 Mycobacterium tuberculosis isolates from treatment-naive patients, the prevalence of any resistance to first-line drugs was 33.2% and the prevalence of MDR-TB was 5.7%. We did not find any risk factors significantly associated with resistance to first-line drugs. The 93 primary MDR-TB isolates were classified into six sublineages, of which, 75 (80.6%) isolates were the RD105-deleted Beijing lineage. The largest sublineage included 65 (69.9%) isolates with concurrent deletions of RD105, RD207, and RD181. Twenty-nine (31.2%) primary MDR strains grouped in clusters; MDR isolates in clusters were more likely to have S531L rpoB mutation. ConclusionThis study indicates that primary drug-resistant TB and MDR-TB strains are prevalent in China, and multiple measures should be taken to address drug-resistant TB.

Prevalence of primary drug resistant tuberculosis in a tertiary care hospital, Nepal

Background &amp; objectives: Tuberculosis is a transmissible disease mainly due to inhalation of infected droplet nuclei. The burden of drug resistant tuberculosis is very high in our neighboring countries India and China. Prevalence of primary drug resistant disease is difficult to estimate in our country because culture and sensitivity is not done routinely. This study was an attempt to find out the prevalence of drug resistant in newly diagnosed tuberculosis patients serving in the Nepalese Armed Forces. Methodology: Medical records of patients serving in the Nepalese Armed Forces who had the provisional diagnosis of pulmonary tuberculosis for the first time from July 2012 to June 2014 were analyzed. They had their sputum subjected for both smear and culture with sensitivity testing. Out of 134 patients, 62 had culture positive for Mycobacterium tuberculosis and drug sensitivity was done for the first line 4 antitubercular drugs. Results: Drug resistant strains were found in 5 cases (8.1%) of which 2 (3.2%) were resistant to 4 first line drugs - rifampicin, isoniazid, ethambutol and streptomycin. Prevalence of isoniazid resistance was the highest, found in 3 cases (4.8%). Conclusion: Primary drug resistant tuberculosis in newly diagnosed cases was high even in young healthy adults, and isoniazid resistant strains were the commonest.DOI: http://dx.doi.org/10.3126/jcmc.v4i4.11970

Primary Drug-Resistant Tuberculosis in Hanoi, Viet Nam: Present Status and Risk Factors

IntroductionResistance of Mycobacterium tuberculosis (MTB) to anti-tuberculosis (TB) drugs presents a serious challenge to TB control worldwide. We investigated the status of drug resistance, including multidrug-resistant (MDR) TB, and possible risk factors among newly diagnosed TB patients in Hanoi, the capital of Viet Nam.MethodsClinical and epidemiological information was collected from 506 newly diagnosed patients with sputum smear- and culture-positive TB, and 489 (96.6%) MTB isolates were subjected to conventional drug susceptibility testing, spoligotyping, and 15-locus variable numbers of tandem repeats typing. Adjusted odds ratios (aORs) were calculated to analyze the risk factors for primary drug resistance.ResultsOf 489 isolates, 298 (60.9%) were sensitive to all drugs tested. Resistance to isoniazid, rifampicin, streptomycin, ethambutol, and MDR accounted for 28.2%, 4.9%, 28.2%, 2.9%, and 4.5%, respectively. Of 24 isolates with rifampicin resistance, 22 (91.7%) were MDR and also resistant to streptomycin, except one case. Factors associated with isoniazid resistance included living in old urban areas, presence of the Beijing genotype, and clustered strains [aOR = 2.23, 95% confidence interval (CI) 1.15–4.35; 1.91, 1.18–3.10; and 1.69, 1.06–2.69, respectively). The Beijing genotype was also associated with streptomycin resistance (aOR = 2.10, 95% CI 1.29–3.40). Human immunodeficiency virus (HIV) coinfection was associated with rifampicin resistance and MDR (aOR = 5.42, 95% CI 2.07–14.14; 6.23, 2.34–16.58, respectively).ConclusionIsoniazid and streptomycin resistance was observed in more than a quarter of TB patients without treatment history in Hanoi. Transmission of isoniazid-resistant TB among younger people should be carefully monitored in urban areas, where Beijing strains and HIV coinfection are prevalent. Choosing an optimal treatment regimen on the basis of the results of drug susceptibility tests and monitoring of treatment adherence would minimize further development of drug resistance strains.

Epidemiology and management of childhood multidrug-resistant tuberculosis

SUMMARY: Multidrug-resistant tuberculosis (TB) in children is mainly caused by transmission of drug-resistant strains causing infection and disease (i.e., primary drug-resistant TB) and, therefore, follows adult multidrug-resistant TB trends. Diagnosis is made by culture and phenotypic or genotypic drug susceptibility testing, either from the child’s or the adult source case’s Mycobacterium tuberculosis isolate. Treatment is mainly with second-line anti-TB drugs, building a regimen with four effective drugs; the principles of management are the same as for adults. Monitoring for adverse events is important as second-line drugs are more toxic than first-line treatment. With early diagnosis and treatment, outcome is better than in adults. New drugs and drug combinations are in development and should also be evaluated in children.

Relatively low primary drug resistant tuberculosis in southwestern Ethiopia

BackgroundThe prevalence of drug resistant tuberculosis (TB) in Ethiopia in general, and Jimma area in particular, is not well documented. We conducted a study at Jimma University specialized hospital in southwest Ethiopia among new cases of smear positive TB patients to determine the pattern of resistance to first-line drugs.MethodsA health institution based cross sectional study was conducted from November 2010 to September 2011. Any newly diagnosed smear positive TB patient 18 years and above was included in the study. Demographic and related data were collected by trained personnel using a pretested structured questionnaire. Mycobacterial drug susceptibility testing (DST) to the first line drugs isoniazid (INH), rifampicin (RIF), ethambutol (EMB) and streptomycin (STM) was performed on cultures using the indirect proportion method. M. tuberculosis complex (MTBC) was identified with the Capilia TB-Neo test.Results136 patients were enrolled in the study. Resistance to at least one drug was identified in 18.4%. The highest prevalence of resistance to any drug was identified against INH (13.2%) followed by STM (8.1%). There was no statistically significant difference in the proportion of any resistance by sex, age, HIV status and history of being imprisoned. The highest mono resistance was observed against INH (7.4%). Mono resistance to streptomycin was associated with HIV infection (crude OR 15.63, 95%CI: 1.31, 187). Multidrug-resistance TB (MDR-TB) was observed in two patients (1.5%).ConclusionResistance to at least one drug was 18.4% (INH-13.2% and STM-8.1%). STM resistance was associated with HIV positivity. There was relatively low prevalence of MDR-TB yet INH resistance was common around Jimma. The capacity of laboratories for TB culture and DST should be strengthened, in order to correctly manage TB patients and avoid amplification of drug resistance.

Increased prevalence of primary drug‐resistant pulmonary tuberculosis in immunocompromised patients

Drug-resistant tuberculosis (DR-TB) is difficult and expensive to treat, and is associated with a higher rate of mortality. We conducted a long-term survey to compare the prevalence of primary drug-resistance, adverse effects of drugs and duration of treatment in immunocompetent and immunocompromised patients. Factors associated with primary drug resistance were also investigated. The patients studied had culture-confirmed pulmonary TB but had not previously received anti-TB treatment. These patients were divided into immunocompetent (IMCPe) and immunocompromised (IMCPr) groups. Baseline data, the prevalence of DR-TB, duration of treatment and adverse effects of drugs were analysed. The rates of resistance to individual first-line anti-TB drugs in the two groups and in subgroups of the IMCPr group were calculated. Multinomial regression analysis was performed to investigate the risk factors associated with primary DR-TB. Among the 394 patients, 159 (40.4%) were in the IMCPr group. The baseline data for the two groups were similar, except that the IMCPr group was slightly older. The prevalence of drug-resistance was higher in the IMCPr group (25.8% vs 17.0%, OR 1.69, 95% CI: 1.04-2.77), especially for isoniazid, rifampicin and streptomycin, and patients with liver cirrhosis, malignancies and those receiving immunosuppressants. The incidence of adverse drug effects was similar in the IMCPr and IMCPe groups. Multinomial regression analysis showed that being in the IMCPr group, and especially treatment with immunosuppressants, were independent risk factors for DR-TB. Immunocompromised patients with underlying diseases had an increased prevalence of primary pulmonary DR-TB but a similar incidence of drug-related adverse effects. Diagnosis and investigation of drug-resistance is important before initiating anti-TB treatment in this group of patients.

Tuberculosis chemotherapy in the 21 century: Back to the basics.

The key to successful elimination of tuberculosis (TB) is treatment of cases with optimum chemotherapy. Poor chemotherapy over time has led to drug-resistant disease. Drug resistance of Mycobacterium tuberculosis develops by the selective growth of resistant mutants. The incidence of drug-resistant cases depends on the number of bacilli and the drug-resistant mutants in the lesion. The latter is low for individual drugs and even lower for two and three drugs. Therefore, use of combination chemotherapy with three or more drugs results in cure. However, irregular treatment, inadequate drugs, inadequate drug doses or addition of a single drug to a failing regimen allows selective growth of resistant mutants and acquired drug-resistant TB. Contacts of these resistant cases develop primary drug resistant TB. Thus, drug resistance in tuberculosis is a “man-made problem”. Anti-TB chemotherapy must be given optimally by (i) ensuring adequate absorption of drugs, (ii) timely diagnosis and management of drug toxicities and (iii) treatment adherence. New classes of anti-TB drugs are needed; but are unlikely to become available soon. It is vital that the 21st century physicians understand the basic principles of TB chemotherapy to ensure efficient use of available drugs to postpone or even reverse epidemics drug-resistant TB.

Predictors of primary multiple drug resistant tuberculosis (MDR-TB) transmission in Lima, Peru

Predictors of primary multiple drug resistant tuberculosis (MDR-TB) transmission in Lima, Peru

Drug resistance and genotypic analysis of Mycobacterium tuberculosis strains from Thai tuberculosis patients

The aim of this study was the molecular characterization of primary drug-resistant Mycobacterium tuberculosis strains in Thailand. We examined a group of M. tuberculosis isolates from newly registered tuberculosis (TB) cases, collected at the largest university hospital, the Siriraj Hospital, in Thailand. Of 76 selected drug-resistant M. tuberculosis strains recovered from previously untreated pulmonary TB patients whose sputum samples were sent to this hospital, 29 (38%) were single-drug resistant, 26(34%) multidrug resistant and two (2.6%) extensively drug resistant. Fifty (66%) strains belonged to Beijing genotype. The study demonstrated a severe problem of drug resistance among recently detected TB patients, and two large clusters of genetically similar strains indicated ongoing transmission of drug-resistant TB.