Rifampicin-resistant Tuberculosis Patients Research Articles

Safety of high-dose amikacin in the first week of all-oral rifampicin-resistant tuberculosis treatment for the prevention of acquired resistance (STAKE): protocol for a single-arm clinical trial

IntroductionAn effective rifampicin-resistant tuberculosis (RR-TB) treatment regimen should include prevention of resistance amplification. While bedaquiline (BDQ) has been recommended in all-oral RR-TB treatment regimen since 2019, resistance is rising at...

Determinant of catastrophic costs associated with treatment for rifampicin-resistant TB in households in the Republic of Moldova.

The Republic of Moldova is a lower-middle-income country. Patients with TB face some barriers to accessing TB services. Welfare benefits are available during TB treatment. We aimed to determine the proportion of rifampicin-resistant TB (RR-TB) households that experienced catastrophic costs due to TB at a threshold of ≥20% of household income and investigate the associated risk factors. A cross-sectional countrywide study comprised 430 patients with RR-TB who had received TB treatment as an inpatient or outpatient for at least 2 months. RR-TB patients lost 30% of their household income in inpatient and 70% in outpatient TB care. TB-related costs were associated with being unofficially employed or unemployed (aOR 1.9, 95% CI 1.1-3.3), having fewer household members (aOR 2.1, 95% CI 1.3-3.5), having an income that accounted for over 50% of household income (aOR 2.4, 95% CI 1.5-3.8), and being a poor household (aOR 2.2, 95% CI 1.2-3.9). Although TB health services are provided to patients free of charge, 26% of RR-TB households experienced catastrophic TB costs. The associated factors should be considered to improve patient-centred TB care, especially in vulnerable groups. Welfare payments mitigate TB costs.

TB and poverty: the effect of rifampicin-resistant TB on household income.

The Republic of Moldova, one of Europe's poorest countries, also bears one of the highest burdens of rifampicin-resistant TB (RR-TB). To trace the patients' journey through TB in terms of the relationship with poverty and assess its determinants. This cross-sectional study used secondary data from a survey assessing catastrophic costs in RR-TB-affected households. Data were obtained from 430 RR-TB patients. The percentage of poor TB-affected households rose from 65% prior to TB to 86% after TB treatment completion (P < 0.001). Social factors leading to poverty were identified for each stage: diagnostic period (history of incarceration: cOR 2.3, 95% CI 1.1-5.2); treatment period (being unemployed or unofficially employed: cOR 6.7, 95% CI 4.3-10.0); and post-treatment (being married or cohabiting: cOR 5.7, 95% CI 2.9-11.0). Participants who had ≥3 members in their households were more likely to be poor at all TB stages: diagnostic period (cOR 5.7, 95% CI 3.7-8.8), treatment period (cOR 3.8, 95% CI 2.5-5.6) and post-treatment (cOR 7.2, 95% CI 3.6-14.3). The study identified risk factors associated with poverty at each stage of TB. These findings outline that innovative social protection policies are required to protect TB patients against poverty.

Management of rifampicin-resistant tuberculosis in conflict-affected areas: The case of Iraq.

Since December 2019, the World Health Organization (WHO) has encouraged National Tuberculosis Programs to deprioritize the use of injectable-containing regimens and roll-out all-oral bedaquiline-containing regimens for rifampicin-resistant tuberculosis (RR-TB) treatment. Consequently, Iraq gradually replaced the injectable-containing regimen with an all-oral regimen, including bedaquiline. To assess treatment enrolment and outcomes of both regimens during a transitioning phase in Iraq, where health system services are recovering from decades of war, we conducted a nationwide retrospective cohort study using routinely collected programmatic data for patients enrolled between 2019-2021. We describe treatment enrolment and use logistic regression to identify predictors of unfavorable treatment outcomes (failure, death, or lost to follow-up), including regimen type. Nationwide, a total of 301 RR-TB patients started treatment, of whom 167 concluded treatment. The proportion of patients enrolled on the all-oral regimen increased from 53.2% (50/94) in 2020, to 75.5% (80/106) in 2021. Successful treatment was achieved in 82.1% (32/39) and 63.3% (81/128), for all-oral and injectable-containing regimens respectively. Moreover, the proportion of lost to follow-up was lower among those treated with the all-oral versus the long injectable-containing regimen; respectively 2.6% (1/39) versus 17.9% (23/128: p = 0.02). Unfavorable treatment outcome was associated with male gender (aOR 2.12, 95%CI:1.02-4.43) and age <15 years (vs 30-49 years, aOR 5.80, 95%CI:1.30-25.86). Regimen type (aOR 2.37, 95%CI: 0.91-6.13) was not significantly associated with having an unfavorable treatment outcome. In Iraq, the use of bedaquiline-containing all-oral regimen resulted in a high treatment success and reduced lost to follow-up.

Predictors of Death in Rifampicin Resistant Tuberculosis Patients Treated with the Short Course in Conakry, Guinea.

The emergence of rifampicin-resistant tuberculosis (RR-TB) is a major issue for TB control programs due to high risk of treatment failure and death. The objective of this study was to describe survival and to determine predictors of death in RR-TB patients treated with the short regimen (9-11 months) in the Conakry TB treatment centers. Sociodemographic, clinical, and survival data were collected prospectively between 2016 and 2021 on RR-TB patients in the Department of Pneumo-Phtisiology, the Carrière and the Tombolia TB centers. The Kaplan-Meier method was used to estimate the cumulative incidence of death of patients. The Cox regression model was used to identify the predictors independently associated with death. Of 869 patients, 164 (18.9%) patients died during treatment, 126 of them within 120 days of treatment initiation. The factors associated with death during treatment were as follows: patients treated in the Carrière TB center (adjusted hazard ratio [aHR] = 1.65; 95% CI: 1.06-2.59) and in the Department of Pneumo-Phtisiology (aHR = 3.26; 95% CI: 2.10-5.07), patients ≥ 55 years old (aHR = 4.80; 95% CI: 2.81-8.19), patients with no history of first-line TB treatment (aHR = 1.51; 95% CI: 1.05-2.16), and patients living with HIV (aHR = 2.81; 95% CI: 1.94-4.07). The results of this study can help the national TB control program to reconsider its therapeutic strategy to improve patient care in case of RR-TB. Large prospective clinical studies should be conducted to provide evidence of the impact of such factors like previous history of TB treatment and HIV infection on survival of RR-TB patients.

Impact of line probe assay-based molecular testing on individualized treatment in patients with rifampicin-resistant tuberculosis: data from the prospective INNOVA4TB cohort study in Ukraine.

Ukraine remains a high World Health Organization priority country for drug-resistant tuberculosis (TB). Rifampicin-resistant TB (RR-TB) has a more protracted, more complicated, and more expensive treatment. In 2021, Ukraine reported 4025 RR-TB cases - 5.4 times more (751) than all 30 European Union/ European Economic Area countries together. The objective of the study was to determine the diagnostic accuracy of line probe assay (LPA), AID Autoimmun Diagnostika GmbH, for detecting resistance to anti-TB drugs and its clinical application for selecting treatment regimens. A prospective observational cohort study. From May 2019 to June 2020, we consecutively enrolled patients with active TB hospitalized at the Regional Phthisiopulmonology Center (Vinnytsia, Ukraine), aged between 18 and 82 years. The LPA was performed in the Genetic Research Laboratory at National Pirogov Memorial Medical University, Vinnytsia, Ukraine. A total of 84 clinical specimens and 97 culture isolates from 126 TB patients were tested during the study. Accuracy (95% confidence interval) of LPA for clinical samples in comparison with phenotypic drug susceptibility test (DST) was 80.1 (68.5-89.0) for isoniazid (H), 74.7 (62.4-84.6) for rifampicin (R), 74.4 (62.5-84.1) for ethambutol, 71.4 (41.9-91.6) for streptomycin, 84.6 (62.4-96.5) for prothionamide/ethionamide, and 84.6 (73.6-92.3) for levofloxacin (Lfx), respectively. We found a significantly higher sensitivity of LPA for H, R, and Lfx for the culture isolates compared to clinical specimens (p < 0.05). LPA detected different mutations in 6 out of 17 (35.5%) patients susceptible to R by Xpert. A shorter treatment regimen with an injectable agent demonstrated a low suitability rate of 5% (8/156) in a cohort of RR-TB patients from Ukraine. Initial LPA testing accurately identifies resistance to anti-TB drugs and facilitates the selection of an appropriate treatment regimen, minimizing exposure to empirical therapy.

Active case detection of rifampicin sensitive and resistant tuberculosis by systematic screening among household contacts of rifampicin-resistant tuberculosis patients in Dhaka, Bangladesh

Background/Aim: Patients with rifampicin resistant-tuberculosis (RRTB) may remain a source of infection longer than patients with rifampicin sensitive-tuberculosis (RS-TB). This study aimed to detect active cases of RS-TB and RR-TB through systematic screening among household contacts of RR-TB patients in Dhaka, Bangladesh. Methods: This cross-sectional study was conducted among the 355 household contacts (HHCs) of 93 RR-TB primary cases identified from various centres in Dhaka, diagnosed between November 2020 and October 2021. For the identification of active cases of tuberculosis (TB), systematic screening among HHCs was done, where verbal screening was performed to check the presence of symptoms of TB. Those who had at least one symptoms of TB were considered as symptomatic contacts. Later GeneXpert analysis of sputum was done among the screened symptomatic contacts. Data was collected using a pretested, semi-structured, interviewer-administered questionnaire. Results: An estimated 30.4 % of respondents were ≤ 15 years of age. TBlike symptoms were prevalent among 9.9 % of respondents. Loss of appetite (45.7 %), unexplained weight loss (40.0 %) and cough (37.1 %) were the most common symptoms. Among the contacts with TB-like symptoms, 6.7 % were diagnosed as a case of TB (3.35 % were RR-TB and 3.35 % were RS-TB). The number needed to be screened to find an active case of TB was established at 178 among the HHCs of RR-TB. Conclusions: About one in ten RR-TB HHCs showed TB-like symptoms. One in fifteen HHCs with TB-like symptoms was an active case of TB. Regular, effective screening of RR-TB contacts is needed to stop the transmission.

Changing trend analysis on early detection of rifampicin resistant tuberculosis patients in southwestern area of China, 2016-2020.

There were no data about prevention and control status of RR-TB in a poor area with high burden of TB in China. In order to develop evidence-based RR-TB response strategies and improve enrollment of RR-TB patients in Yunnan province, China, this study was aimed at analyzing the changing trends in the detection and enrollment of RR-TB patients and examining the factors that may have implication on enrollment in treatment. Data, which includes demographics, screening and testing, and treatment enrollment, was collected from the TB Management Information System. Retrospective data analysis and factors analysis were applied. Descriptive statistics, Chi-square test, Rank sum test and logistic regression analysis were used. From 2016 and 2018, the province had been challenged by low levels of screening, detection and enrollment of RR-TB. During the period between 2019 and 2020, a comprehensive model of RR-TB prevention and control was established in Yunnan, characterized by a robust patient-centered approach for RR-TB care and multiple, targeted interventions through the cascade of care from detection to treatment. In 2020, 93.8% of the bacteriologically positive TB patients were screened for RR-TB, which had been significantly increased by 146.9% from 38.0% in 2016. The interval from initial consultation at RR-TB facility to diagnosis (inter-quartile range) was reduced from 29.5 (1-118) days in 2016 to 0 (0-7) days in 2020. Despite the increasing rates of enrollment of RR-TB patients over the years, non-enrollment of those detected was still high (32.3%) in 2020. The main reasons for non-enrollment identified were refusal of treatment due to financial difficulties, loss to follow-up or death before starting treatment. Multivariate analysis showed that the elderly patients aged 65 or above (OR = 2.7, CI: 1.997-3.614), new patients (OR = 0.7, CI: 0.607-0.867), conventional DST used for confirmatory diagnosis of RR-TB (OR = 1.9, CI: 1.620-2.344) and diagnosis of RR-TB being conducted by the RR-TB care facilities at the prefecture and municipal level (OR = 4.4, CI: 3.608-5.250) have implications on RR-TB non-enrollment. As a comprehensive RR-TB model was implemented in Yunnan with scaled up use of molecular test for rapid detection of RR-TB, initial screening of RR-TB were decentralized to the county- and district-level to strengthen rapid, early detection of RR-TB, achieving a higher coverage of screening in the end. However, there remains a major gap in enrollment of RR-TB. The main barriers include: limited knowledge and awareness of RR-TB and financial burdens among patients, delayed diagnosis, loss to follow-up, difficulties in self care and travel for elderly patients, and limited capacity of clinical management at the lower-level RR-TB care facilities. The situation of the RR-TB epidemic in Yunnan could be improved and contained as soon as possible by continuous strengthening of the comprehensive, patient-centered model with targeted interventions coordinated through multi-sectoral engagement to improve enrollment of RR-TB patients.

Study on the resistance of rifampicin-resistant Mycobacterium tuberculosis to anti-tuberculosis drugs in group A

Objective: To summarize the resistance of rifampicin-resistant Mycobacterium tuberculosis to anti-tuberculosis drugs in group A. Methods: In the retrospective study, a total of 1 226 clinical isolates from suspected multidrug-resistant pulmonary tuberculosis patients in Beijing TB control system from 2016 to 2021 were identified as Mycobacterium tuberculosis (MTB) strains by MPB64 antigen detection test. Rifampicin-resistant tuberculosis (RR-TB) strains were screened by the phenotypic drug susceptibility using the proportion method. The drug susceptibilities of Levofloxacin(LFX), Moxifloxacin(MFX), Bedaquiline(BDQ) and Linezolid(LZD)were detected by the phenotypic drug susceptibility with microplate method. The drug resistance rate, drug resistance level and minimum inhibitory concentration (MIC) distribution of four anti-tuberculosis drugs in group A were analyzed. We calculated the demographic distribution of RR-TB, multidrug-resistant tuberculosis(MDR-TB), pre-extensively drug resistant tuberculosis (pre-XDR-TB), extensively drug resistant tuberculosis (XDR-TB) patients and the cross resistance of LFX and MFX, then summarized the drug-resistance spectrum of BDQ-resistant and LZD-resistant strains and the treatment outcome of RR-TB patients. Measurement data were expressed as rate or composition ratio,χ2 test was used between and within groups, and P<0.05 was considered statistically significant. Results: Among the 1 226 suspected multidrug-resistant pulmonary tuberculosis patients, the detection rates of RR/MDR/pre-XDR/XDR-TB patients were 20.8%(255/1 226), 15.2%(186/1 226), 5.7%(70/1 226), 0.5%(6/1 226), respectively. There were statistically significant differences in the distribution of patients with the four types of drug resistance in terms of age and treatment history (χ2=14.95, P=0.020;χ2=15.91, P=0.001). The drug resistance rates of LFX, MFX, BDQ and LZD in RR-TB patients were 27.5% (70/255), 27.5% (70/255), 0.4% (1/255) and 2.4% (6/255), respectively. The MICs of LFX, MFX and LZD-susceptible MTB were mainly at 0.25 mg/L, and the MIC of BDQ-susceptible MTB was mainly concentrated at 0.03 mg/L. 25.1% (64/255) of the RR MTB were resistant to both LFX and MFX, and 6 strains were resistant to LFX or MFX, showing incomplete two-way cross resistance. One BDQ-resistant strain and six LZD-resistant strains were detected. The treatment success rate of RR-TB patients was 74.4% (151/203), and there were statistically significant differences in treatment outcomes between resistant and sensitive patients on the LFX-containing treatment regimen (Fisher's exact test, P=0.012). Conclusions: The prevalence of fluoroquinolones (LFX and MFX) resistance in rifampicin-resistant MTB is very serious. LFX and MFX show incomplete bidirectional cross-resistance. BDQ and LZD have the most promising future in the treatment of MDR-TB. Improve drug-resistance testing will help to further improve the success rate of treatment.

Favourable outcomes in RR-TB patients using BPaL and other WHO-recommended second-line anti-TB drugs.

SETTING: According to reports in South Africa, treatment failure rates for rifampicin-resistant TB (RR-TB) are significant and below the WHO target of ≥70%. HIV infection and the use of highly active antiretroviral therapy (HAART) influence how patients receiving anti-TB drugs respond to therapy. In the treatment of RR-TB, more recent medications, including bedaquiline, pretomanid and linezolid (BPaL), have shown promising results.OBJECTIVE: To assess treatment outcomes in RR-TB patients using BPaL and other second-line anti-TB drugs as recommended by the WHO in the South African population.DESIGN: The databases Medline, PubMed, Google Scholar and Embase were searched for studies between 2015 and 2022, which investigated BPaL outcomes in South Africa.RESULTS: Of the 27,259 participants, 21% were on bedaquiline, 1% were taking pretomanid and 9% were taking linezolid as part of their background regimen. About 68% of the patients were HIV-positive, with 59% of them taking HAART.CONCLUSION: Overall, 66% of patients taking BPaL drugs as part of their background regimen had favourable treatment outcomes. Additionally, patients with RR-TB who were HIV-positive and taking HAART while receiving BPaL drugs as part of a background regimen had improved treatment outcomes.

Effectiveness and safety of a modified short-term regimen of antimycobacterial therapy to treat rifampicin-resistant tuberculosis in elderly patients with concomitant diabetes (a clinical case)

Aim. To analyze the effectiveness and safety of a modified short-term regimen (mSTR) of antimycobacterial therapy (AMBT) for rifampicin-resistant tuberculosis (RR-TB) in a 71-year-old patient with type 2 diabetes mellitus (T2DM) on the clinical case example of own observation. Materials and methods. A clinical case from own observation of the patient who was treated at the clinical base of the Department of Phthisiology and Pulmonology of Zaporizhzhia State Medical University – Pulmonary Tuberculosis Department No. 2 of the Communal Non-profit Organization “Zaporizhzhia Regional Phthisio-Pulmonology Clinical Treatment and Diagnostic Center” is presented. Results. The presented case demonstrates the high safety and efficacy of all oral mSTR, including Lfx-Bdq-Lzd-Cfz-Cs, in the elderly person with RR-TB and concomitant decompensated T2DM who was smear-negative after 4 months as a result of treatment with 9-month mSTR AMBT (Lfx, Bdq, Lzd, Cfz, Сs). Positive radiological dynamics were observed all the time and residual changes in the lungs after tuberculosis were diagnosed at the end of the treatment course. These results complement indications for the use of mSTR, including Lfx-Bdq-Lzd-Cfz-Cs, in RR-TB patients. Conclusions. mSTR AMBT (Lfx, Bdq, Lzd, Cfz, Сs) is effective and safe in elderly patients with RR-TB and concomitant decompensated type 2 diabetes mellitus when adequate treatment of diabetes and timely correction of antimycobacterial drug side effects are undertaken.

Progress in research of prophylactic therapy in contacts of rifampicin-resistant tuberculosis patients

Tuberculosis (TB) prophylactic therapy for latent infection, which can reduce the risk for the development of active TB, is an important measure in TB control. China recommends prophylactic therapy for latent tuberculosis infection (LTBI) in some key populations to reduce the risk for TB. Contacts of patients with multi-drug and rifampicin-resistant TB (MDR/RR-TB) are at high risk for the infection with drug-resistant pathogen, however, no unified prophylactic therapy regimen has been recommended for LTBI due to exposure to MDR/RR-TB patients. This paper summarizes the current MDR/RR-TB prophylactic therapy regimen and its protection effect based on the results of the retrieval of literature, guidelines, expert consensus and technical specifications to provide reference for the prevention and control of LTBI.

A Scoring System Based on Laboratory Parameters and Clinical Features to Predict Unfavorable Treatment Outcomes in Multidrug- and Rifampicin-Resistant Tuberculosis Patients.

The growth of antibiotic resistance to Mycobacterium TB represents a major barrier to the goal of "Ending the global TB epidemics". This study aimed to develop and validate a simple clinical scoring system to predict the unfavorable treatment outcomes (UTO) in multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB) patients. A total of 333 MDR/RR-TB patients were recruited retrospectively. The clinical, radiological and laboratory features were gathered and selected by lasso regression. These variables with area under the receiver operating characteristic curve (AUC)>0.6 were subsequently submitted to multivariate logistic analysis. The binomial logistic model was used for establishing a scoring system based on the nomogram at the training set (N = 241). Then, another independent set was used to validate the scoring system (N = 92). The new scoring system consists of age (8 points), education level (10 points), bronchiectasis (4 points), red blood cell distribution width-coefficient of variation (RDW-CV) (7 points), international normalized ratio (INR) (7 points), albumin to globulin ratio (AGR) (5 points), and C-reactive protein to prealbumin ratio (CPR) (6 points). The scoring system identifying UTO has a discriminatory power of 0.887 (95% CI=0.835-0.939) in the training set, and 0.805 (95% CI=0.714-0.896) in the validation set. In addition, the scoring system is used exclusively to predict the death of MDR/RR-TB and has shown excellent performance in both training and validation sets, with AUC of 0.930 (95% CI=0.872-0.989) and 0.872 (95% CI=0.778-0.967), respectively. This novel scoring system based on seven accessible predictors has exhibited good predictive performance in predicting UTO, especially in predicting death risk.

Distribution of Rifampicin-Resistant Tuberculosis Patients based on Presumptive Drug-Resistant Tuberculosis Criteria at Dr. Hasan Sadikin Hospital 2016–2019

Background: Diagnosis of drug-resistant tuberculosis (DR-TB) begins with identifying presumptive DR-TB patients using Xpert MTB/RIF, as a diagnostic test to detect resistance to rifampicin. The study aimed to identify the distribution of rifampicin-resistant tuberculosis (RR-TB) patients based on presumptive DR-TB criteria at Dr. Hasan Sadikin General Hospital Bandung. Moreover, this study also explored the Xpert MTB/RIF Ct values.Methods: This was a descriptive-retrospective study from 570 medical records of DR-TB patients collected at the Multidrug-resistant tuberculosis (MDR-TB) clinic of Dr. Hasan Sadikin General Hospital from 2016 to 2019. The inclusion criteria were suspected patients with the Xpert MTB/RIF Ct values in the very low-low and medium-high categories. Data were analyzed using frequency distribution. Results: The most common presumptive DR-TB criteria among DR-TB patients were relapse cases (52.3%). Presumptive DR-TB criteria, with a high percentage result of medium-high Ct values, were category II treatment failure (80.9%).Conclusion: Relapse case and category II treatment failure are presumptive DR-TB criteria, which need more attention from clinicians.

1433. Factors Associated with Unsuccessful Treatment Outcomes among Patients with Rifampicin Resistant Tuberculosis - Tajikistan, 2015-2020

Abstract Background Tajikistan has a high burden of multidrug resistant TB, including rifampicin-resistant TB (RR-TB). Treatment options are more limited and include standard treatment (T1), bedaquiline/delamanid contained individual treatment (T2), short treatment (T3), modified short treatment (T4), and bedaquiline/pretomanid/linezolid treatment (T5). To inform national treatment plans, we assessed trends in RR-TB and determined factors associated with unsuccessful treatment. Methods We conducted a retrospective cohort study in Dushanbe, Tajikistan, from 2015 to 2020 using patient records. Patients had successful treatment outcomes if they completed treatment or were cured, and unsuccessful if they had treatment failure, were lost-to-follow-up, or died. We report relative risk (RR) and 95% confidence interval from multivariable Poisson regression. Results From 2015 to 2020, there was a decrease in incidence of TB (68.6 to 47.2 per 100,000) and RR-TB (10.6 to 7.2) with a 33% drop 2019 to 2020. Proportion of unsuccessful outcomes also decreased (30% to 15% 2015-2020). Of 522 patients, 515 had RR-TB. Of these, 39% received T1, 43% T2, 15% T3, 2% T4, and 0.4% T5 (Table 1). Overall, 23% had unsuccessful treatment outcomes. Patients on T1 had higher unsuccessful outcome compared to those on T2 - T5 (31% vs 19%, 14%, 0% and 0%, respectively). Unsuccessful outcomes were associated with combined isoniazid, rifampin and streptomycin resistance, alcohol and drug use. For patients receiving T1, unsuccessful outcome was associated with unemployment (RR: 2.7; 1.1-6.8), HIV (RR: 2.3, 1.5-3.4), hepatitis C (RR: 2.2, 1.4-3.4), and concomitant disease (RR: 2.1, 1.4-3.1). For patients receiving T2, risk of unsuccessful outcome was lower for females (RR: 0.4, 0.2-0.7) (Table 2). Conclusion Decrease in incidence is promising. Results highlight the need to transition RR-TB patients to non-standard treatment. Closer follow-up of patients with combined resistance, alcohol or drug use, HIV, hepatitis C, and concomitant diseases may contribute to successful outcome. Disclosures All Authors: No reported disclosures.

Distribution and frequency of common mutations in rpoB gene of Mycobacterium tuberculosis detected by Xpert MTB/RIF and identification of residential areas of rifampicin resistant-TB cases: A first retrospective study from Mizoram, Northeast India

BackgroundRifampicin resistance (RR) is a surrogate marker of multidrug-resistant tuberculosis. The aim of this study is to determine the frequency of the commonly mutated probes for rpoB gene and locate the residential areas of the Rifampicin Resistant-TB (RR-TB) patients in a high endemic zone of Northeast India. MethodsArchived data of 13,454 Xpert MTB/RIF reports were evaluated retrospectively between 2014 and 2021. Socio-demographic and available clinical information were reviewed and analyzed for RR-TB cases only. Logistic Regression was used to analyze the parameters with respect to probe types. P-value ≤ 0.05 was considered to be statistically significant. Results2,894 patients had Mycobacterium tuberculosis infection out of which 460 were RR-TB, which was most prevalent among 25–34 years. The most common mutation occurred in probe A (25.9 %) followed by E (23.5 %), D (9.8 %), B (2.6 %) and the least in C (0.2 %). High prevalence (34.3 %) of probe mutation combinations were also found: probes AB (0.4 %), AD (32.8 %), AE (0.4 %), DE (0.2 %) and ADE (0.4 %). Seventeen patients (3.7 %) were found without any missing probes. RR-TB patients were mostly located in Aizawl North –III, South –II and East –II constituencies. ConclusionThis study provides genetic pattern of drug resistance accountable for RR over the past years in Mizoram which will help local clinicians in the initiation of correct treatment. Also, our findings provide a baseline data on the magnitude of RR-TB within the state and identification of the residential areas can help local health authorities in planning surveillance programs to control the spread of RR-TB.

Delay to Treatment Initiation among Rifampicin Resistant Tuberculosis Patients in Kenya

Drug-resistant tuberculosis surveillance attempts to detect and treat drug-resistant tuberculosis as early as possible in order to avoid transmission, illness, and mortality among people who are afflicted. In Kenya, the delay in starting RR TB treatment has not been established, and its relationship to treatment outcomes is unknown. To investigate the relationship between delayed RR TB therapy commencement and treatment results in Kenyan patients enrolled between January 2010 and June 2013. A retrospective cohort review of 208 randomly chosen RR TB patients treated between January 2010 and June 2013 was conducted. Delay was defined as the interval in days between sample collection and treatment beginning that was on the right side of the median. Logistic regression was used to determine the relationship between the delay in starting RR TB treatment and treatment outcomes, as well as the factors related with the delay. The male to female ratio in the 208 cases was 1.7:1. The youngest and oldest were 2 and 66 years old, respectively. The average age at registration was 34.48 years old [95% CI 32.7,36.3] and the average weight was 50kg [95% CI: 47.73,50.94]. 26.92% (56) were HIV +, and 95% (53) were on ART. 64% Culture and traditional DST were used to diagnose 65% of the patients, while GeneXpert was used to diagnose 35%. The average time to therapy (delay) was 99 days, with a range of 0 to 599 days. The treatment was 82% successful (59% cured, 23% completed). Unfavorable outcomes accounted for 18% of all outcomes. As indicated by X2 = (0.1858), p =0.666, which is more than 0.05, there was no significant difference between delayed and undelayed treatment outcomes. Male patients were 0.03048 times more likely to have an unfavorable outcome than female patients, and patients from the North Eastern region were 23.46 times more likely to have an unfavorable outcome than patients from the Central region.&nbsp; According to a single study, using culture and DST for RR TB diagnosis was substantially linked with delaying treatment beginning and starting treatment in the second quarter of the year (P of 0.000 and 0.005 respectively). Delay in starting treatment is not connected with treatment results in RR TB patients. When compared to culture and DST, GeneXpert considerably lowers time to therapy initiation. Early diagnostic and treatment efforts should be increased to prevent TB transmission and morbidity. Keywords: Delay to treatment, Rifampicin, Resistant, Tuberculosis, Patients

Linezolid-related adverse effects in the treatment of rifampicin resistant tuberculosis: a retrospective study

Linezolid (LZD) is an effective drug in treating multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis. This study aimed to evaluate the safety of LZD in the treatment of patients with rifampicin resistant tuberculosis. This was a multicenter retrospective study. A total of 184 patients of the rifampicin resistant tuberculosis patients treated with LZD from Jan 2018 to Apr 2020 in three hospitals were involved, and their clinical symptoms were recorded and analyzed. Meanwhile, the types and incidence of adverse effects associated with LZD were evaluated. It showed that peripheral neuritis (51, 27.7%) and hemochromatosis (42, 22.8%) were the most common adverse effects observed among these patients. The median time of symptoms after LZD treatment was 45.5 and 120.0 days, respectively. Furthermore, female patients had a significantly higher risk for leukopenia (P = 0.002) and hemochromatosis (P = 0.033) when compared with male patients. History of underlying disease was the risk factor for thrombocytopenia (P = 0.022). Patients with long duration of medication (RR = 1.004, 95%CI: 1.002–1.006, P < 0.001) and daily dosage ≥600mg (RR = 3.059, 95%CI: 1.238–7.558, P = 0.015) were at higher risk of hemochromatosis. Age was the risk factor for rash (P = 0.008) and nausea and vomiting (P = 0.018). In addition, LZD administration time was the risk factor for optic neuritis (P < 0.001) and peripheral neuritis (P < 0.001). LZD can cause adverse symptoms in patients with rifampicin resistant tuberculosis. Gender, history of underlying disease, LZD use time, LZD dosage, and age are the risk factors in the LZD treatment of these patients. During medication, bone marrow suppression and neuropathy should be closely monitored. This study could potentially provide useful information for the clinical practice.

Caregiver willingness to give TPT to children living with drug-resistant TB patients.

BACKGROUND:Pediatric household contacts (HHCs) of patients with multidrug-resistant TB (MDR-TB) are at high risk of infection and active disease. Evidence of caregiver willingness to give MDR-TB preventive therapy (TPT) to children is limited.METHODS:This was a cross-sectional study of HHCs of patients with MDR-TB to assess caregiver willingness to give TPT to children aged <13 years.RESULTS:Of 743 adult and adolescent HHCs, 299 reported caring for children aged <13 years of age. The median caregiver age was 35 years (IQR 27–48); 75% were women. Among caregivers, 89% were willing to give children MDR TPT. In unadjusted analyses, increased willingness was associated with TB-related knowledge (OR 5.1, 95% CI 2.3–11.3), belief that one can die of MDR-TB (OR 5.2, 95% CI 1.2–23.4), concern for MDR-TB transmission to child (OR 4.5, 95% CI 1.6–12.4), confidence in properly taking TPT (OR 4.5, 95% CI 1.6–12.6), comfort telling family about TPT (OR 5.5, 95% CI 2.1–14.3), and willingness to take TPT oneself (OR 35.1, 95% CI 11.0–112.8).CONCLUSIONS:A high percentage of caregivers living with MDR- or rifampicin-resistant TB patients were willing to give children a hypothetical MDR TPT. These results provide important evidence for the potential uptake of effective MDR TPT when implemented.

Programmatic management of rifampicin-resistant tuberculosis with standard regimen in Cameroon: a retrospective cohort study

ObjectivesTo describe treatment outcomes for rifampicin-resistant tuberculosis (Rr-TB) started on standard regimen and the frequency of acquired drug resistance in patients treated using the standard treatment regimen (STR) in Cameroon between 2015-2019. MethodsThis is a retrospective cohort study. Rr-TB patients were initiated on the STR, including a fluoroquinolone (FQ), a second-line injectable drug (SLI), and companion drugs. In case of resistance to fluoroquinolones (FQr) at baseline, FQ, SLI and ethionamide were replaced by bedaquiline, delamanid, and linezolid in a modified treatment regimen (mTR), FQr-mTR. In case of resistance to SLI (SLIr) at baseline, SLI was replaced by linezolid (LZD), SLIr-mTR. Logistic regression and competing risk regression were used to estimate predictors of early (first eight weeks) mortality and overall mortality, respectively. ResultsOf 709 patients started on a standard regimen, treatment success occurred in 84.7% (587/693), 72.7% (8/11) and 100% (10/10) of patients treated with STR, FQr-mTR and SLIr-mTR as final regimens, respectively. Three (0.6%) patients acquired FQr during treatment. Early mortality occurred in 4.1% (29/709) and was associated with being HIV positive, male sex and being underweight. Overall mortality was associated with missing drug-susceptibility testing results at baseline, being HIV positive, age>40 and male sex. ConclusionProgrammatic management of Rr-TB, with additional second-line drug resistance treated with mTR, resulted in excellent treatment outcomes.