scholarly journals Promising shorter and more effective treatment regimens for drug-resistant tuberculosis: recent research found

2018 ◽  
Vol 5 (2) ◽  
pp. 65-65
Author(s):  
Cheepsattayakorn Attapon ◽  
Ruangrong Cheepsattayakorn
Author(s):  
Yu.I. Feshchenko ◽  
N.A. Litvinenko ◽  
N.V. Grankina ◽  
M.V. Pogrebna ◽  
Yu.O. Senko ◽  
...  

Objective — to study the effectiveness of treatment of MDR-TB (multidrug-resistant tuberculosis) and preXDR-TB/XDR-TB (pre-extensively and extensively drug resistant tuberculosis), depending on the composition of ITRs (individualized treatment regimens). Materials and methods. Тhe prospective observational study included 566 patients with MDR/preXDR-TB and XDR-TB during 2016—2020 on the scientific clinical bases of the SI «National Institute of Phthisiology and Pulmonology named after F.G. Yanovsky NAMS of Ukraine» and ME «Kryvyi Rih Anti-tuberculosis Dispensary» Dnipropetrovsk Regional Council Department. Patients were prescribed individualized treatment regimens in cases where short (standard or modified) regimens could not be prescribed. Patients were divided into comparison groups: 469 of them were treated with antimycobacterial therapy including bedaquiline and other effective antimycobacterial drugs groups A—C (without delamanid) — group 1. And 97 patients who were treated with the inclusion of both new antimycobacterial drugs (bedaquiline and delamanid) — group 2. Results and discussion. Regardless of whether the delamanid, in addition to bedaquiline and other drugs selected for the scheme according to WHO recommendations, «effective treatment» was found in 91.3 against 88.6 % of patients. In the remote period (6-month — 4-year follow-up period) there was no recurrence of the disease, regardless of the composition of the regime. The loss of treatment effectiveness was due to deaths from non-tuberculosis reasons and those lost for follow-up. Conclusions. For highly effective treatment, individualized regimens should include bedaquidine and linezolid from group A, and for previously ineffectively treated patients, clofazimine and carbapenems must be included (possibility to include 4 or more effective AMDs in ITR). For patients with fluoroquinolone resistance, treatment should include delamanid.


2020 ◽  
Vol 18 (2) ◽  
pp. 115-121
Author(s):  
Mariia V. Pavlova ◽  
Tatiana I. Vinogradova ◽  
Natalia V. Zabolotnykh ◽  
Elena S. Ershova ◽  
Nadezhda V. Sapozhnikova ◽  
...  

The aim of this work was an experimental and clinical study of increasing of the efficiency of therapy of respiratory tuberculosis with drug resistant pathogen by including a combination of anti-tuberculosis drugs of new generation Bedaquiline (Bq) and Thioureidoiminomethylpyridi-nium perchlorate (perchlozone, Tpp) into treatment regimens. The presented results were obtained: in the experiment on a model of tuberculosis infection in 103 male C57black / 6 mice, reproduced by inserting into the lateral vein of the tail of a suspense of clinical strains of Mycobacterium tuberculosis with multi-drug resistance (MDR) and with various combinations of mutations in the genes; in the clinic on the basis of examination and treatment of 148 patients with multidrug-resistant respiratory tuberculosis. It is shown that the application of the therapy schemes for multiple and broad drug resistant tuberculosis, containing Bq and Tpp in combination with drugs, selected taking into account the drug sensitivity of mycobacteria, allows to significantly reduce the periods of relief of symptoms of intoxication, regression of inflammatory changes, abacillation and achieving positive X-ray dynamics. Undesirable phenomena against the background of combined prescription of new generation drugs, as a rule, corresponded to light and moderate severity, and in frequency of development and expression did not differ from control groups of observation.


PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0241065
Author(s):  
Florence O. Bada ◽  
Nick Blok ◽  
Evaezi Okpokoro ◽  
Saswata Dutt ◽  
Christopher Akolo ◽  
...  

Background Globally, drug resistant tuberculosis (DR-TB) continues to be a public health threat. Nigeria, which accounts for a significant proportion of the global burden of rifampicin/multi-drug resistant-TB (RR/MDR-TB) had a funding gap of $168 million dollars for TB treatment in 2018. Since 2010, Nigeria has utilized five different models of care for RR/MDR-TB (Models A-E); Models A, B and C based on a standardized WHO-approved treatment regimen of 20–24 months, were phased out between 2015 and 2019 and replaced by Models D and E. Model D is a fully ambulatory model of 9–12 months during which a shorter treatment regimen including a second-line injectable agent is utilized. Model E is identical to Model D but has patients hospitalized for the first four months of care while Model F which is to be introduced in 2020, is a fully ambulatory, oral bedaquiline-containing shorter treatment regimen of 9–12 months. Treatment models for RR/MDR-TB of 20–24 months duration have had treatment success rates of 52–66% while shorter treatment regimens have reported success rates of 85% and above. In addition, replacing the second-line injectable agent in a shorter treatment regimen with bedaquiline has been found to further improve treatment success in patients with fluoroquinolone-susceptible RR/MDR-TB. Reliable cost data for RR/MDR-TB care are limited, specifically costs of models that utilize shorter treatment regimens and which are vital to guide Nigeria through the provision of RR/MDR-TB care at scale. We therefore conducted a cost analysis of shorter treatment regimens in use and to be used in Nigeria (Models D, E and F) and compared them to three models of longer duration utilized previously in Nigeria (Models A, B and C) to identify any changes in cost from transitioning from Models A-C to Models D-F and opportunities for cost savings. Methods We obtained costs for TB diagnostic and monitoring tests, in-patient and out-patient care from a previous study, inflated these costs to 2019 NGN and then converted to 2020 USD. We obtained other costs from the average of six health facilities and drug costs from the global drug facility. We modeled treatment on strict adherence to two Nigerian National guidelines for programmatic and clinical management of drug-resistant tuberculosis. Results We estimated that the total costs of care from the health sector perspective for Models D, E and F were $4,334, $7,705 and $3,420 respectively. This is significantly lower than the costs of Models A, B and C which were $14,781, $12, 113, $7,572 respectively. Conclusion Replacing Models A–C with Models D and E reduced the costs of RR/MDR-TB care in Nigeria by approximately $5,470 (48%) per patient treated and transitioning from Models D and E to Model F would result in further cost savings of $914 to $4,285 (21 to 56%) for every patient placed on Model F. If the improved outcomes of patients managed using bedaquiline-containing shorter treatment regimens in other countries can be attained in Nigeria, Model F would be the recommended model for the scale up of RR/MDR-TB care in Nigeria.


2018 ◽  
Vol 51 (5) ◽  
pp. 1800544 ◽  
Author(s):  
Olatunde Olayanju ◽  
Jason Limberis ◽  
Aliasgar Esmail ◽  
Suzette Oelofse ◽  
Phindile Gina ◽  
...  

Optimal treatment regimens for patients with extensively drug-resistant tuberculosis (XDR-TB) remain unclear. Long-term prospective outcome data comparing XDR-TB regimens with and without bedaquiline from an endemic setting are lacking.We prospectively followed-up 272 South African patients (49.3% HIV-infected; median CD4 count 169 cells·µL−1) with newly diagnosed XDR-TB between 2008 and 2017. Outcomes were compared between those who had not received bedaquiline (pre-2013; n=204) and those who had (post-2013; n=68; 80.9% received linezolid in addition).The 24-month favourable outcome rate was substantially better in the bedaquiline versus the non-bedaquiline group (66.2% (45 out of 68) versus 13.2% (27 out of 204); p<0.001). In addition, the bedaquiline group exhibited reduced 24-month rates of treatment failure (5.9% versus 26.0%; p<0.001) and default (1.5% versus 15.2%; p<0.001). However, linezolid was withdrawn in 32.7% (18 out of 55) of patients in the bedaquiline group because of adverse events. Admission weight >50 kg, an increasing number of anti-TB drugs and bedaquiline were independent predictors of survival (the bedaquiline survival effect remained significant in HIV-infected persons, irrespective of CD4 count).XDR-TB patients receiving a backbone of bedaquiline and linezolid had substantially better favourable outcomes compared to those not using these drugs. These data inform the selection of XDR-TB treatment regimens and roll-out of newer drugs in TB-endemic countries.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Joseph Baruch Baluku ◽  
Richard Katuramu ◽  
Joshua Naloka ◽  
Enock Kizito ◽  
Martin Nabwana ◽  
...  

Abstract Background Patients with drug resistant tuberculosis (DR-TB) with comorbidities and drug toxicities are difficult to treat. Guidelines recommend such patients to be managed in consultation with a multidisciplinary team of experts (the “TB consilium”) to optimise treatment regimens. We describe characteristics and treatment outcomes of DR-TB cases presented to the national DR-TB consilium in Uganda between 2013 and 2019. Methods We performed a secondary analysis of data from a nation-wide retrospective cohort of DR-TB patients with poor prognostic indicators in Uganda. Patients had a treatment outcome documented between 2013 and 2019. Characteristics and treatment outcomes were compared between cases reviewed by the consilium with those that were not reviewed. Results Of 1,122 DR-TB cases, 189 (16.8%) cases from 16 treatment sites were reviewed by the consilium, of whom 86 (45.5%) were reviewed more than once. The most frequent inquiries (N = 308) from DR-TB treatment sites were construction of a treatment regimen (38.6%) and management of side effects (24.0%) while the most frequent consilium recommendations (N = 408) were a DR-TB regimen (21.7%) and “observation while on current regimen” (16.6%). Among the cases reviewed, 152 (80.4%) were from facilities other than the national referral hospital, 113 (61.1%) were aged ≥ 35 years, 72 (40.9%) were unemployed, and 26 (31.0%) had defaulted antiretroviral therapy. Additionally, 141 (90.4%) had hepatic injury, 55 (91.7%) had bilateral hearing loss, 20 (4.8%) had psychiatric symptoms and 14 (17.7%) had abnormal baseline systolic blood pressure. Resistance to second-line drugs (SLDs) was observed among 9 (4.8%) cases while 13 (6.9%) cases had previous exposure to SLDs. Bedaquiline (13.2%, n = 25), clofazimine (28.6%, n = 54), high-dose isoniazid (22.8%, n = 43) and linezolid (6.7%, n = 13) were more frequently prescribed among cases reviewed by the consilium than those not reviewed. Treatment success was observed among 126 (66.7%) cases reviewed. Conclusion Cases reviewed by the consilium had several comorbidities, drug toxicities and a low treatment success rate. Consilia are important “gatekeepers” for new and repurposed drugs. There is need to build capacity of lower health facilities to construct DR-TB regimens and manage adverse effects.


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