Therapeutic strategies and outcomes of MDR and pre-XDR-TB in Italy: a nationwide study

2021 ◽  
Vol 25 (5) ◽  
pp. 395-399
Author(s):  
N. Riccardi ◽  
L. Saderi ◽  
E. Borroni ◽  
E. Tagliani ◽  
D. M. Cirillo ◽  
...  

BACKGROUND: Treatment outcomes in multidrug‐resistant TB (MDR‐TB) patients are suboptimal in several low‐incidence countries.METHODS: The primary outcome measure was the proportion of successfully treated patients in Italy during an 18‐year period. Secondary outcomes were treatment outcomes in certain drug‐containing regimens and the possibility for the WHO shorter MDR‐TB regimen.RESULTS: In the 191 patients included (median age at admission: 33 years; 67.5% male, following drug‐resistance patterns were found: MDR‐TB in 68.6%, pre‐extensively drug‐resistant TB (pre‐XDR‐TB) in 30.4% and XDR‐TB in 1.1% patients. The most frequently prescribed drugs were fluoroquinolones in 84.6% cases, amikacin in 48.7%, linezolid in 34.6% and meropenem/clavulanic acid in 29.5%. The median duration of treatment was 18 months. Treatment success was achieved in 71.2% patients, of whom, 44% were cured and 27.2% completed treatment. Treatment success rates did not statistically differ between the MDR‐ (68.8%) and pre‐XDR‐TB (77.6%) groups (P = 0.26). Treatment success rates had large variability between North and South of Italy (81.3% vs. 53.3%). Only 22.5% of the cases would have been eligible for shorter MDR‐TB regimensCONCLUSION: Our study highlights variability in treatment outcomes in MDR‐ and pre‐XDR‐TB patients. Study findings confirmed the potential utility of linezolid and, for patients with limited oral options, meropenem/clavulanic acid and amikacin.

2020 ◽  
Vol 24 (2) ◽  
pp. 233-239
Author(s):  
S. Park ◽  
K-W. Jo ◽  
T. S. Shim

BACKGROUND: Pyrazinamide (PZA) is an important anti-tuberculosis drug for multidrug-resistant tuberculosis (MDR-TB). However, PZA has recently been demoted within the hierarchy of TB drugs used for MDR-TB.METHODS: We conducted a retrospective cohort study to investigate treatment outcomes for simple MDR-TB (susceptible to both second-line injectable drugs and fluoroquinolones) according to PZA susceptibility.RESULTS: Among 216 pulmonary MDR-TB patients included in the study, 68 (31.5%) were PZA-resistant (PZA-R). The mean age was 41.8 years, and 63.4% were male. Baseline characteristics such as comorbidity, previous TB history, acid-fast bacilli (AFB) smear positivity and cavitation were similar in PZA-susceptible (PZA-S) and PZA-R patients. The number of potentially effective drugs was slightly higher among PZA-S patients than among the PZA-R (5.1 vs. 4.8, respectively; P = 0.003). PZA was more frequently used in PZA-S patients (73.0%) than in the PZA-R (14.7%), while para-aminosalicylic acid was more frequently used in PZA-R than in PZA-S patients (76.5% vs. 50.7%). The treatment success rate was similar in PZA-S (77.7%) and PZA-R (75.0%) patients. PZA resistance was not associated with treatment success in multivariate analysis.CONCLUSIONS: PZA-resistant simple MDR-TB patients had the same treatment success rate as the PZA-susceptible group even without using novel anti-TB drugs.


2020 ◽  
Vol 114 (10) ◽  
pp. 733-741
Author(s):  
Muhammad Atif ◽  
Wajiha Ahmad ◽  
Nafees Ahmad ◽  
Iram Malik ◽  
Sajjad Sarwar

Abstract Background This study aims to evaluate the treatment outcomes and factors associated with unsuccessful treatment outcomes among multidrug-resistant TB (MDR-TB) patients. Method This was a retrospective observational study conducted at the Bahawal Victoria Hospital, Bahawalpur, Pakistan. The sociodemographic, clinical and treatment-related data of MDR-TB patients registered at the study site between June 2014 and December 2016 were retrospectively collected. Patients’ treatment outcomes were categorized on the basis of WHO-recommended criteria. Multivariate binary logistic regression analysis was used to find the independent factors associated with unsuccessful treatment outcomes. Results Out of 179 MDR-TB patients, 106 (59.2%) completed their treatment successfully. The remaining 73 patients (40.8%) had unsuccessful treatment outcomes, among whom 45 (25.1%) died, while 18 (10.1%) were lost to follow-up. Factors associated with unsuccessful treatment outcomes included age ≥40 y (AOR 4.310; p = 0.006), unsuccessful interim treatment outcomes (AOR 5.810; p = 0.032), occurrence of adverse events (AOR 0.290; p = 0.029) and ofloxacin resistance (AOR 2.952; p = 0.042). Conclusion The treatment success rate among the selected cohort of MDR-TB patients was less than the target of ≥75% set by the WHO in the End TB Strategy. The lower treatment success rate at the study site requires urgent attention from clinicians and program managers.


Biomédica ◽  
2020 ◽  
Vol 40 (4) ◽  
pp. 616-625
Author(s):  
Ángela Tobón ◽  
Johana Rueda ◽  
Diego H. Cáceres ◽  
Gloria I. Mejía ◽  
Elsa M. Zapata ◽  
...  

Introduction: Multidrug-resistant tuberculosis treatment is effective in 50% of patients due to several factors including antibiotic susceptibility of the microorganism, adverse treatment reactions, social factors, and associated comorbidities.Objectives: In this study, we describe the demographics, clinical characteristics, and factors associated with treatment outcomes in multidrug-resistant tuberculosis (MDR-TB) patients in Medellín, Colombia.Materials and methods: We conducted a retrospective analysis using data from patients diagnosed with MDR-TB attending Hospital La María in Medellín, Colombia, for treatment between 2010 and 2015. Patients were categorized as having successful (cured) or poor (failure, lost to follow-up, and death) treatment outcomes. Associations between demographic, clinical factors, laboratory results, treatment outcomes, and follow-up information were evaluated by univariate, multivariate, and multiple correspondence analyses.Results: Of the 128 patients with MDR-TB, 77 (60%) had successful outcomes. Of those with poor outcomes, 26 were lost to follow-up, 15 died, and 10 were treatment failures. Irregular treatment, the presence of comorbidities, and positive cultures after more than two months of treatment were associated with poor outcomes compared to successful ones (p<0.05 for all). The multiple correspondence analyses grouped patients who were lost to follow-up, had HIV, and drug addiction, as well as patients with treatment failure, irregular treatment, and chronic obstructive pulmonary disease.Conclusion: The recognition of factors affecting treatment is essential and was associated with treatment outcomes in this series of patients. Early identification of these factors should increase the rates of treatment success and contribute to MDR-TB control.


2021 ◽  
Author(s):  
Shao-Jun Zhang ◽  
Yan Yang ◽  
Wen-Wen Sun ◽  
Zhong-Shun Zhang ◽  
He-ping Xiao ◽  
...  

Abstract Objective: To compare the effectiveness and safety of bedaquiline-containing and bedaquiline-free regimens for treatment of patients with refractory rifampicin-resistant/multidrug-resistant tuberculosis (RR/MDR-TB).Methods: Patients with refractory RR/MDR-TB receiving bedaquiline-containing regimens (bedaquiline group, n=102) and bedaquiline-free regimens (non-bedaquiline group, n=100) were included in this retrospective historical control study across East China. The culture conversion, end-of-treatment outcomes, cavity closing rate, and adverse events (AEs) were compared between the two groups. Univariate and multivariate analyses were performed to identify independent predictors of treatment success and culture reversion.Results: The baseline characteristics of the patients were well balanced between the two groups. The culture conversion rates in the bedaquiline group at month 3 (89.2% vs. 66.0%), month 6 (90.2% vs. 72.0%), month 9 (91.2% vs. 66.0%), and month 12 (94.1% vs. 65.0%) were all significantly higher than those in the non-bedaquiline group (all p<0.001). Similar results were observed in the cavity closing rate at month 9 (19.6% vs. 8.0%, p=0.017) and month 12 (39.2% vs. 15.0%, p<0.001). Patients receiving bedaquiline-containing regimens had more treatment success than those receiving bedaquiline-free regimens (p<0.001; cure rate, 69.6% vs. 45.0%; complete the treatment, 22.5% vs. 18.0%; treatment success, 92.2% vs. 63.0%). The use of bedaquiline was identified as an independent predictor of both treatment success (OR=7.356, 95% CI: 2.920–18.530, p<0.001) and culture reversion (OR=0.124, 95% CI: 0.035–0.452, p<0.001). AEs were similarly reported in 26.5% of patients in the bedaquiline group and 19.0% in the non-bedaquiline group (p=0.206).Conclusions: Bedaquiline-containing regimens resulted in better treatment outcomes and similar safety relative to bedaquiline-free regimens for patients with refractory pulmonary RR/MDR-TB.


2020 ◽  
Vol 7 (1) ◽  
pp. e000606 ◽  
Author(s):  
Samiksha Ghimire ◽  
Samriddhi Karki ◽  
Bhagwan Maharjan ◽  
Jos G W Kosterink ◽  
Daan J Touw ◽  
...  

ObjectivesThe objectives of this study were to evaluate treatment in patients on current programmatic multidrug-resistant tuberculosis (MDR-TB) regimen and verify eligibility for the 9-month regimen and therapeutic drug monitoring (TDM).MethodsWe performed a retrospective chart review of patients with MDR-TB receiving standardised regimen at the German Nepal TB Project Clinic, Nepal, between 2014 and 2016. Eligibility for the 9-month regimen and indications for TDM were evaluated.ResultsOut of 107 available patients’ medical records, 98 were included. In this centre, the MDR-TB treatment success rates were 69.0% in 2015, 86.6% in 2016 and 86.5% in 2017. The median time to sputum smear conversion was 60 days (60–90 IQR) and culture conversion was 60 days (60–90 IQR). Observed side effects did not impact treatment outcomes. No difference in treatment success rates was observed between patients with predisposing risk factors and those without. Only 49% (36/74) of patients were eligible for the 9-month regimen and 23 patients for TDM according to American Thoracic Society guideline criteria.ConclusionsNepalese patients with MDR-TB on ambulatory care had good treatment outcome after programmatic treatment. Implementation of the new WHO oral MDR-TB treatment regimen may further improve treatment results. The 9-month regimen and TDM should be considered as part of programmatic care.


Author(s):  
Jagadeeswara Rao Muvva ◽  
Sultan Ahmed ◽  
Rokeya Sultana Rekha ◽  
Sadaf Kalsum ◽  
Ramona Groenheit ◽  
...  

Abstract Background Multidrug-resistant tuberculosis (MDR-TB) has low treatment success rates and new treatment strategies are needed. We explored if treatment with vitamin D (vitD) and phenylbutyrate (PBA) could improve conventional chemotherapy by enhancing immune-mediated eradication of Mycobacterium tuberculosis. Methods A clinically relevant model was used consisting of human macrophages infected with M. tuberculosis-isolates (n=15) with different antibiotic-resistance profiles. The antimicrobial effect of vitD+PBA, was tested together with rifampicin or isoniazid. Methods included colony-forming units (intracellular bacterial growth), mRNA expression analyses (LL-37, β-defensin, nitric oxide synthase, and dual oxidase-2), RNA interference (LL-37-silencing in primary macrophages), western blot and confocal microscopy (LL-37 and LC3 protein expression). Results VitD+PBA inhibited growth of clinical MDR-TB strains in human macrophages and strengthened intracellular growth inhibition of rifampicin and isoniazid via induction of the antimicrobial peptide LL-37 and LC3-dependent autophagy. Gene-silencing of LL-37 expression enhanced MDR-TB growth in vitD+PBA-treated macrophages. The combination of vitD+PBA and isoniazid were equally effective to reduce intracellular MDR-TB growth as compared to a &gt;125-fold higher dose of isoniazid alone, suggesting potent additive effects of vitD+PBA with isoniazid. Conclusions Immunomodulatory agents that trigger multiple immune pathways can strengthen standard MDR-TB treatment and contribute to next-generation individualized treatment options for difficult-to-treat pulmonary TB patients.


2020 ◽  
Vol 8 (2) ◽  
pp. 141
Author(s):  
Lailatul Fitriya ◽  
Kurnia Dwi Artanti

Background: Multidrug resistant tuberculosis (MDR TB) is a major public health problem marked by the Mycobacterium tuberculosis strain that is resistant to first line anti TB drugs, including rifampicin and isoniazid simultaneously. A patient confirmed as having MDR TB can transmit this form of TB to other individuals. Therefore, treatment success is the main target when addressing MDR TB. Purpose: This study aimed to assess the treatment outcomes of MDR TB patients in East Java Province from 2014 to 2017. Method: This is a quantitative-descriptive study using the secondary data of drug resistant TB patients sourced from the e-TB Manager website in the East Java Province Health Office. Results: The results show that the average MDR TB patients was 47 years old, 57.44% were male, 37.52% had a negative HIV status, 44.87% were relapse patients, 71.95% had undergone two or less previous treatments, and 69.24% had sputum culture conversion. The treatment outcomes included 161 patients (31.14%) confirmed as cured, 27 patients (5.22%) completing treatment, 174 patients (33.65%) defaulting, two patients (0.38%) confirmed as having failed treatment, and 59 patients (11.41%) dying during the treatment period. Conclusion: The treatment success rate was low and the number of defaults was high. Therefore, it is hoped that there will be support from those closest to the patient and health workers who will maintain and increase the patient's motivation to complete the treatment.


2021 ◽  
Vol 15 (09.1) ◽  
pp. 34S-42S
Author(s):  
Tinatin Jomidava ◽  
Mohammed Khogali ◽  
Yuliia Sereda ◽  
Zaza Avaliani ◽  
Malkhaz Davitashvili ◽  
...  

Introduction: Adherence to second-line antituberculosis drug is challenging. A combination of strategies needs to be implemented to achieve adherence. In Georgia an optimized adherence support (OAS) – a package of education, psychosocial support and adherence counselling – was added to the already existing package of adherence support (supervised treatment, adherence incentives, transport cost reimbursement) to improve adherence and increase treatment success. We assessed the additive benefits of OAS on adherence and treatment outcomes. Methodology: This was a before and after cohort study using routine programme data in the National Center for Tuberculosis and Lung Diseases in Tbilisi. All adult rifampicin- and multidrug-resistant tuberculosis (RR/MDR-TB) patients enrolled for treatment under directly observed therapy in the NCTLD during the period before (June 2015 – January 2016) and after (June 2017 – January 2018) were included in the study. Primary outcomes were: i) adequate adherence defined as ≥ 85% of days covered by TB medication during the whole treatment period; ii) final treatment outcomes. Results: Of 221 RR/MDR-TB, most patients were male (76%, N = 167) with a mean age of 41 ± 14 years. Adherence data was available for 111 patients in the ‘before’ and 97 patients in the ‘after’ cohort. Adequate adherence was achieved by 62% (69/111) in the ‘before’ and 70% (68/97) in the ‘after’ cohort (p = 0.290). Overall treatment success was 64% (73/114) and 63% (67/107) in the ‘before’ and ‘after’ cohorts respectively (p = 0.937). Conclusions: Implementation of OAS had modest effect on adherence and had no additive benefits on treatment outcomes among RR/MDR-TB patients on 18-20 months regimen.


Author(s):  
Khasan Safaev ◽  
Nargiza Parpieva ◽  
Irina Liverko ◽  
Sharofiddin Yuldashev ◽  
Kostyantyn Dumchev ◽  
...  

Uzbekistan has a high burden of drug-resistant tuberculosis (TB). Although conventional treatment for multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) has been available since 2013, there has been no systematic documentation about its use and effectiveness. We therefore documented at national level the trends, characteristics, and outcomes of patients with drug-resistant TB enrolled for treatment from 2013–2018 and assessed risk factors for unfavorable treatment outcomes (death, failure, loss to follow-up, treatment continuation, change to XDR-TB regimen) in patients treated in Tashkent city from 2016–2017. This was a cohort study using secondary aggregate and individual patient data. Between 2013 and 2018, MDR-TB numbers were stable between 2347 and 2653 per annum, while XDR-TB numbers increased from 33 to 433 per annum. At national level, treatment success (cured and treatment completed) for MDR-TB decreased annually from 63% to 57%, while treatment success for XDR-TB increased annually from 24% to 57%. On multivariable analysis, risk factors for unfavorable outcomes, death, and loss to follow-up in drug-resistant TB patients treated in Tashkent city included XDR-TB, male sex, increasing age, previous TB treatment, alcohol abuse, and associated comorbidities (cardiovascular and liver disease, diabetes, and HIV/AIDS). Reasons for these findings and programmatic implications are discussed.


Author(s):  
Swathi Karanth M.P ◽  
Somashekar M ◽  
Anushree Chakraborty ◽  
Swapna R ◽  
Akshata J.S ◽  
...  

Background: The shorter regimen was widely accepted and advocated for MDR-TB treatment compared tothe conventional longer regimen. Evaluating the performance of both regimens in a programmatic setting will help in tailoring the treatment regimen of MDR-TB. Objectives: 1. To estimate the duration of sputum smear conversion in the shorter MDR-TB regimen. 2. To compare the treatment outcomes of the shorter MDR-TB regimen with that of the longer conventional MDR regimen in a programmatic set up in India. 3. To estimate the adverse drug reactions in the shorter MDR-TB regimen. Methods: A retrospective cross-sectional study was conducted on 320 patients enrolled under programmatic management of drug resistant tuberculosis (PMDT) from April 2017 to May 2019 at a nodal DRTB center and a tertiary care hospital in India. Demographic and clinical characteristics of those who received a shorter MDR-TB regimen were recorded. Treatment outcomes of both regimens were recorded. Treatment success is defined as ‘disease cured and treatment completed’, whereas treatment failure was considered when the treatment was either terminated or changed due to lack of bacteriological conversion at the end of an extended intensive phase or culture reversion in the continuation phase. Results: The treatment success observed in the shorter MDR-TB regimen was 61.25%, which was significantly higher than the conventional longer regimen (p=0.0007). Treatment failures were higher with a shorter MDR-TB regimen (p=0.0001). Conclusion: Treatment success with the shorter MDR-TB regimen though higher than the conventional regimen, is still way behind the target treatment success rate. Improving treatment adherence remains pivotal for achieving end TB targets.


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