Transmission of multidrug-resistant tuberculosis in Jiangxi, China, and associated risk factors.

In order to effectively combat the urgent threat of multidrug-resistant tuberculosis (MDR-TB), it is imperative to gain a comprehensive understanding of the drug-resistant profiles, transmission dynamics, and associated risk factors. Our study encompassed a population-based retrospective analysis with 130 MDR-TB patients from 2018 to 2021. The research methodology incorporated whole-genome sequencing, drug susceptibility testing , and logistic regression analysis to discern the risk factors of genomic clustering linked to recent transmission. The findings from phenotypic drug resistance assessments revealed notable resistance rates: ethambutol at 62.3% (81/130), streptomycin at 72.3% (94/130), levofloxacin at 51.5% (67/130), and moxifloxacin at 50.0% (65/130). Furthermore, among all patients, 38 individuals (29.23%, 38/130) were found to be part of 17 clusters, indicating instances of recent MDR-TB transmission. The genomic clustering patients were deeply investigated. Lineage 2.2.1 was established as the primary sub-lineage (86.15%, 112/130), followed by lineage 4 (9.23%, 12/130). Moreover, the logistic regression analysis underscored that unemployment, farming occupations, and prior TB treatment were identified as significant risk factors for recent transmission. IMPORTANCE: The high prevalence of multidrug-resistant tuberculosis (MDR-TB) in Jiangxi Province highlights the importance of understanding the genetic background and drug resistance patterns of these strains. This knowledge is crucial for developing effective control methods. Furthermore, in light of the significance of preventing transmission among tuberculosis patients, whole-genome sequencing was utilized to investigate the recent transmission of MDR-TB and identify associated risk factors. The findings revealed that individuals in the farming sector, those who are unemployed, and patients with a history of tuberculosis treatment are at elevated risk. Consequently, targeted public interventions for these at-risk groups are imperative.

Efficacy and safety of shorter multidrug-resistant or rifampicin-resistant tuberculosis regimens: a network meta-analysis.

BACKGROUND: Drug-resistant tuberculosis (DR-TB) remains a threat to public health. Shorter regimens have been proposed as potentially valuable treatments for multidrug or rifampicin resistant tuberculosis (MDR/RR-TB). We undertook a systematic review and network meta-analysis to evaluate the efficacy and safety of shorter MDR/RR-TB regimens. METHODS: We searched PubMed/MEDLINE, Cochrane Center for Clinical Trials (CENTRAL), Scopus, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, US Food and Drug Administration, and Chinese Clinical Trial Registry for primary articles published from 2013 to July 2023. Favorable (cured and treatment completed) and unfavorable (treatment failure, death, loss to follow-up, and culture conversion) outcomes were assessed as the main efficacy outcomes, while adverse events were assessed as the safety outcomes. The network meta-analysis was performed using R Studio version 4.3.1 and the Netmeta package. The study protocol adhered to the PRISMA-NMA guidelines and was registered in PROSPERO (CRD42023434050). RESULT: We included 11 eligible studies (4 randomized control trials and 7 cohorts) that enrolled 3,548 patients with MDR/RR-TB. Treatment with a 6-month combination of BdqLzdLfxZTrd/Eto/H had two times more favorable outcomes [RR 2.2 (95% CI 1.22, 4.13), P = 0.0094], followed by a 9-11 month combination of km/CmMfx/LfxPtoCfzZEHh [RR1.67 (95% CI 1.45, 1.92), P < 0.001] and a 6-month BdqPaLzdMfx [RR 1.64 (95% CI 1.24, 2.16), P < 0.0005] compared to the standard longer regimens. Treatment with 6 months of BdqPaLzdMfx [RR 0.33 (95% CI 0.2, 0.55), P < 0.0001] had a low risk of severe adverse events, followed by 6 months of BdqPaLzd [RR 0.36 (95% CI 0.22, 0.59), P ≤ 0.001] and BdqPaLzdCfz [RR 0.54 (95% CI 0.37, 0.80), P < 0.0001] than standard of care. CONCLUSION: Treatment of patients with RR/MDR-TB using shorter regimens of 6 months BdqLzdLfxZTrd/Eto/H, 9-11 months km/CmMfx/LfxPtoCfzZEHh, and 6 months BdqPaLzdMfx provides significantly higher cure and treatment completion rates compared to the standard longer MDR/RR-TB. However, 6BdqPaLzdMfx, 6BdqPaLzd, and 6BdqPaLzdCfz short regimens are significantly associated with decreased severity of adverse events. The findings are in support of the current WHO-recommended 6-month shorter regimens.

BPaLM Regimen Against Drug-Resistant Tuberculosis in India: A Need of the Hour.

India has a high burden of drug-resistant tuberculosis (DR-TB) cases. The management of this severe form of TB is associated with a number of issues like long treatment durations, high pill burden, and multiple adverse drug reactions. Efforts are on through various research studies and trials for finding solutions to the issues linked to the current drug regimens against drug-resistant tuberculosis. One such remarkable development is the introduction of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM)-based regimens to fight against two of the most severe forms of tuberculosis, i.e., multidrug- and extensively drug-resistant tuberculosis (MDR-TB and XDR-TB). This editorial throws light on this newer regimen and discusses the same in the Indian context.

Quantification of MDR-TB drug JBD0131 and its metabolite in plasma via UPLC-MS/MS: application in first-in-human study.

Aim: JBD0131, a novel anti-multidrug-resistant tuberculosis (MDR-TB) drug, can target and inhibit the synthesis of mycolic acids, which are crucial components of the cell wall of the Mycobacterium tuberculosis complex. To support the results of this clinical trial in healthy subjects, development of a specific and accurate quantification method for detecting JBD0131 and its metabolite DM131 in human plasma is needed.Materials & methods: Samples with prior added stabilizer were pretreated by protein precipitation method and the extracts were subjected to ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The m/z transitions for the precursor/product ion pairs were 402.1/273 for JBD0131, 333.1/273 for DM131 and 386.1/257 for the internal standard (IS).Results: This method showed good linearity from 1 to 2000 ng/ml for JBD0131 and 0.25 to 500 ng/ml for DM131 and was validated in terms of selectivity, linearity, accuracy, precision, matrix effect, recovery of pretreament and stability.Conclusion: This method was sensitive and specific for measuring the plasma concentrations of JBD0131 and its metabolites. And it was applied for the investigation of the pharmacokinetics of JBD0131 and DM131 in a clinical trial.

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Multi-drug resistant gene mutation analysis in Mycobacterium tuberculosis by molecular techniques.

Background and Objectives: Rifampicin (RIF) and isoniazid (INH), two most potent antibiotics, are prescribed to cure tuberculosis. Mycobacterium tuberculosis, the causative agent of multidrug-resistant tuberculosis (MDR-TB), is resistant to these first-line drugs. Here, two molecular techniques were demonstrated such as PCR sequencing-based and GeneXpert assay for rapidly identifying MDR-TB. Materials and Methods: Pulmonary samples (sputum) were collected from 55 MDR-TB suspected patients from the National Tuberculosis Reference Laboratory (NTRL), Dhaka where the research work was partially accomplished and continued in the department of Microbiology, University of Dhaka, Bangladesh. We strived for sequencing technique as well as GeneXpert assay to identify mutations in rpoB and katG genes in MTB strains and sputum directly. Culture-based drug susceptibility testing (DST) was performed to measure the efficacy of the molecular methods employed. Results: When analyzed, rpoB gene mutations at codons 531 (54.54%), 526 (14.54%), and 516 (10.91%) were found by sequencing in 80% of the samples. Nucleotide substitution at katG315 (AGC→ACC) was spotted in 16 (76.19%) out of 21 samples. When comparing the sequencing results with DST, sensitivity and specificity were investigated to determine drug-resistance (rifampicin-resistance were 98 and 100% whereas isoniazid-resistance were 94 and 100% respectively). Additionally, as a point of comparison with DST, only 85.45% of RIF mono-resistant TB cases were accurately evaluated by the GeneXpert assay. Conclusion: This research supports the adoption of PCR sequencing approach as an efficient tool in detecting MDR-TB, counting the higher sensitivity and specificity as well as the short period to produce the results.

Implementation strategies for decentralized management of multidrug-resistant tuberculosis: insights from community health systems in Zambia.

BACKGROUND: Decentralized management approaches for multi-drug-resistant tuberculosis (MDR TB) have shown improved treatment outcomes in patients. However, challenges remain in the delivery of decentralized MDR TB services. Further, implementation strategies for effectively delivering the services in community health systems (CHSs) in low-resource settings have not been fully described, as most strategies are known and effective in high-income settings. Our research aimed to delineate the specific implementation strategies employed in managing MDR TB in Zambia. METHODS: Our qualitative case study involved 112 in-depth interviews with a diverse group of participants, including healthcare workers, community health workers, patients, caregivers, and health managers in nine districts. We categorized implementation strategies using the Expert Recommendations for Implementing Change (ERIC) compilation and later grouped them into three CHS lenses: programmatic, relational, and collective action. RESULTS: The programmatic lens comprised four implementation strategies: (1) changing infrastructure through refurbishing and expanding health facilities to accommodate management of MDR TB, (2) adapting and tailoring clinical and diagnostic services to the context through implementing tailored strategies, (3) training and educating health providers through ongoing training, and (4) using evaluative and iterative strategies to review program performance, which involved development and organization of quality monitoring systems, as well as audits. Relational lens strategies were (1) providing interactive assistance through offering local technical assistance in clinical expert committees and (2) providing support to clinicians through developing health worker and community health worker outreach teams. Finally, the main collective action lens strategy was engaging consumers; the discrete strategies were increasing demand using community networks and events and involving patients and family members. CONCLUSION: This study builds on the ERIC implementation strategies by stressing the need to fully consider interrelations or embeddedness of CHS strategies during implementation processes. For example, to work effectively, the programmatic lens strategies need to be supported by strategies that promote meaningful community engagement (the relational lens) and should be attuned to strategies that promote community mobilization (collective action lens).

Tracking multidrug resistant tuberculosis: a 30-year analysis of global, regional, and national trends.

Objectives: To provide valuable insights for targeted interventions and resource allocation, our analysis delved into the multifaceted burden, trends, risks, and projections of multi drug resistant tuberculosis (MDR-TB). Methods: This research employed data from the Global Burden of Disease (GBD) 2019 dataset, which used a comparative risk assessment to quantify the disease burden resulting from risk factors. Initially, this database was utilized to extract details concerning the disability-adjusted life years (DALYs), mortality, incidence, and the number of individuals afflicted by MDR-TB. Subsequently, regression analyses were conducted using the Joinpoint program to figure average annual percent change (AAPC) to ascertain the trend. Thirdly, the age-period-cohort model (APCM) was adopted to analyze evolutions in incidence and mortality. Finally, utilizing the Nordpred model within R software, we projected the incidence and mortality of MDR-TB from 2020 to 2030. Results: MDR-TB remained a pressing global health concern in regions with lower socio-demographic indexes (SDI), where the AAPC in DALYs topped 7% from 1990 to 2019. In 2019, the cumulative DALYs attributed to MDR-TB tallied up to 4.2 million, with India, the Russian Federation, and China bearing the brunt. Notably, the incidence rates have shown a steadfast presence over the past decade, and a troubling forecast predicts an uptick in these areas from 2020 to 2030. Additionally, the risk of contracting MDR-TB grew with advancing age, manifesting most acutely among men aged 40+ in lower SDI regions. Strikingly, alcohol consumption had been identified as a significant contributor, surpassing the impacts of smoking and high fasting plasma glucose, leading to 0.7 million DALYs in 2019. Conclusions: A robust strategy is needed to end tuberculosis (TB) by 2030, especially in lower SDI areas.

Synergy of Xpert (MTB/RIF) and Line probe assay for detection of rifampicin resistant strains of Mycobacterium tuberculosis.

INTRODUCTION: Early diagnosis and successful treatment of drug-resistant tuberculosis (TB) demands rapid, precise, and consistent diagnostic methods to minimise the development of resistance. Therefore, this comparative study was designed to evaluate the diagnostic performance of Xpert (MTB/RIF) and Line probe assay (LPA) for detecting drug-resistant TB. METHODOLOGY: This study comprised 389 (279 pulmonary and 110 extrapulmonary) samples from patients suspected of having TB. All samples were subjected to Xpert (MTB/RIF), LPA, solid culture, and drug-susceptibility testing. Out of 320 samples, only 180 culture (gold standard) positive were included in the final evaluation. The diagnostic characteristics for methods used were determined by calculating diagnostic sensitivity, specificity, and predictive values. The agreement between all methods was determined by calculating the kappa coefficient. RESULTS: The sensitivity and specificity for Xpert (MTB/RIF) for detecting TB were 88.5% and 96.4%, respectively, against the solid culture. On the other hand, LPA showed sensitivity and specificity at 94.3% and 100%, respectively. Xpert (MTB/RIF) showed moderate agreement (kappa 0.65, p < 0.01) - (73.3% sensitivity; 97.6% specificity) for the detection of rifampicin resistance. However, LPA achieved better diagnostic accuracy (kappa 0.80, p < 0.01) - (84.6% sensitivity; 98.4% specificity) against drug-resistant TB. CONCLUSIONS: Xpert (MTB/RIF) and LPA have outstanding diagnostic sensitivity and specificity against RIF resistance with a shorter turnaround time, which could result in a substantial therapeutic outcome. Our findings showed LPA superiority over Xpert (MTB/RIF) for drug resistance. However, due to operational challenges, the requirement of technical expertise and infrastructure issues, LPA cannot be used as point-of-care testing in resource-limited countries.

Innovative Bedaquiline-Based Delivery Systems for Multidrug-Resistant Tuberculosis Treatment.

The increasing incidence of multidrug-resistant tuberculosis (MDR-TB) is one of the most challenging tasks in tuberculosis treatment. Conventional TB treatment regimens have proven ineffective in treating MDR-TB, thus demanding the development of new drugs followed by delivery systems. Bedaquiline, a novel anti-TB drug, has been reported to inhibit the ATP synthase required for the growth and replication of TB bacteria. Bedaquiline is able to target the persistent or latent form of TB, which remains difficult to treat with conventional drugs. This makes bedaquiline an important drug in the fight against MDR-TB. The drug has been approved by the US FDA as well as European Medicines Agency and is now widely used as part of combination therapy for the treatment of MDR-TB. Bedaquiline and its ad-vanced drug delivery system play a key role in tackling MDR-TB, providing a much-needed boost to control and eventually eliminate the disease. However, the cost of the drug remains a concern, and efforts are underway to make bedaquiline more accessible and affordable to patients in resource-limited settings. Nevertheless, the development of bedaquiline nanofor-mulations represents a significant step forward in the fight against TB and offers hope to millions of patients across the globe.

Glomerulonephritis during Mycobacterium tuberculosis infection: scoping review.

INTRODUCTION: People with Tuberculosis (TB) infection may present with glomerulonephritis (GN). The range of presentations, renal pathologies, and clinical outcomes are uncertain. Whether clinical features that establish if GN etiology is medication or TB related, and possible benefits of immunosuppression remain uncertain. METHODS: A scoping review was completed, searching MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science and Conference Abstracts from Inception to December, 2023. The study population included patients with TB infection who developed GN and underwent renal biopsy. All data regarding presentation, patient characteristics, renal pathology, management of TB and GN, and outcomes were summarized. RESULTS: There were 62 studies identified, with 130 patients. These cases included a spectrum of presentations including acute kidney injury, nephrotic syndrome and hypertension, and a range of 10 different renal pathology diagnoses. Cases that included immunosuppression and outcomes ranged from complete remission to long-term dialysis dependence. The presence of granulomas (4/4, 100%), anti-glomerular basement membrane disease (3/3, 100%), amyloidosis (75/76, 98.7%), and focal segmental glomerulosclerosis (2/2, 100%) were specific for GN being TB-infection related. On the other hand, minimal change disease was specific for anti-TB therapy related (7/7, 100%). While patients with more aggressive forms of GN commonly were prescribed immunosuppression, this study was unable to confirm efficacy. Only rifampin or isoniazid were implicated in drug-associated GN. DISCUSSION: This study provides a clear rationale for renal biopsy in patients with TB and GN, and outlines predictors for the GN etiology. Thus, this study establishes key criteria to optimize diagnosis and management of patients with TB and GN.

Machine learning investigation of tuberculosis with medicine immunity impact.

Tuberculosis (T.B.) remains a prominent global cause of health challenges and death, exacerbated by drug-resistant strains such as multidrug-resistant tuberculosis MDR-TB and extensively drug-resistant tuberculosis XDR-TB. For an effective disease management strategy, it is crucial to understand the dynamics of T.B. infection and the impacts of treatment. In the present article, we employ AI-based machine learning techniques to investigate the immunity impact of medications. SEIPR epidemiological model is incorporated with MDR-TB for compartments susceptible to disease, exposed to risk, infected ones, preventive or resistant to initial treatment, and recovered or healed population. These masses' natural trends, effects, and interactions are formulated and described in the present study. Computations and stability analysis are conducted upon endemic and disease-free equilibria in the present model for their global scenario. Both numerical and AI-based nonlinear autoregressive exogenous NARX analyses are presented with incorporating immediate treatment and delay in treatment. This study shows that the active patients and MDR-TB, both strains, exist because of the absence of permanent immunity to T.B. Furthermore, patients who have recovered from tuberculosis may become susceptible again by losing their immunity and contributing to transmission again. This article aims to identify patterns and predictors of treatment success. The findings from this research can contribute to developing more effective tuberculosis interventions.

Drug resistance in drug-resistant tuberculosis patients with and without diabetes mellitus: a comparative analysis.

BACKGROUND: This dual burden of tuberculosis (TB) and diabetes mellitus (DM) has become a global public health concern. This study aims to compare drug resistance in drug-resistant tuberculosis (DR-TB) patients with and without DM and analyse the risk factors of multidrug-resistant tuberculosis (MDR-TB). METHODS: A total of 893 DR-TB patients were admitted to Wenzhou Central Hospital between January 2018 and December 2022. After excluding 178 cases with incomplete clinical and laboratory data, 715 patients were included in the study. These patients were then categorized into two groups based on the presence of type 2 DM: the DM group (160 cases) and the non-DM group (555 cases). Demographic information, baseline clinical characteristics, laboratory and imaging test results, clinical diagnoses, and other relevant data were collected for analysis. Statistical analysis was conducted on demographic information, clinical parameters, drug resistance spectrum, and risk factors for multidrug resistance. RESULTS: In both the DM and non-DM groups, the order of resistance to first-line anti-tuberculosis drugs is isoniazid, streptomycin, rifampicin, and ethambutol. There is no significant difference in the proportion of mono-resistant tuberculosis, polydrug-resistant tuberculosis, and multidrug-resistant tuberculosis between the two groups (P > 0.05). The prevalence of MDR-TB in both groups shows a downward trend between 2018 and 2022, but the trend is not statistically significant (P > 0.05). Among patients without DM, residence in rural areas, retreatment of tuberculosis, pulmonary cavity, and uric acid ≥ 346 µmol/L are identified as independent risk factors for MDR-TB. Among patients with DM, residence in rural areas, retreatment of tuberculosis, pulmonary cavity, and HbA1c ≥ 9.8% were identified as independent risk factors for MDR-TB. CONCLUSION: Isoniazid is the most resistant drug among DR-TB patients with and without DM. There is no statistically significant difference in drug resistance patterns between the two groups. Some progress has been made in the prevention and control of DR-TB in this area, but the effect is not very significant. There are differences in the risk factors of MDR-TB between patients with and without DM.

Different Contributions of embB and ubiA Mutations to Variable Level of Ethambutol Resistance in Mycobacterium tuberculosis Isolates.

Objective: To explore the association between the variant mutations within embB and ubiA, and the degree of ethambutol (EMB) resistance of Mycobacterium tuberculosis (M. tuberculosis) isolates. Methods: A total of 146 M. tuberculosis isolates were used to determine the minimum inhibitory concentrations (MICs) of EMB with a 96-well microplate-based assay. The mutations within embB and ubiA among these isolates were identified with DNA sequencing. Moreover, a multivariate regression model and a computer model were established to assess the effects of mutations on EMB resistance. Results: Our data showed that overall 100 isolates exhibited 28 mutated patterns within the sequenced embB and ubiA. Statistical analysis indicated that embB mutations Met306Val, Met306Ile, Gly406Ala, and Gln497Arg, were strongly associated with EMB resistance. Of these mutations, Met306Val and Gln497Arg were significantly associated with high-level EMB resistance. Almost all multiple mutations occurred in high-level EMB-resistant isolates. Although the mutation within ubiA accompanied with embB mutation presented exclusively in EMB-resistant isolates, four single ubiA mutations (Ala39Glu, Ser173Ala, Trp175Cys, and Val283Leu) leading to protein instability were observed in EMB-susceptible isolates. Conclusion: This study highlighted the complexity of EMB resistance. Some individual mutations and multiple mutations within embB and ubiA contributed to the different levels of EMB resistance.

Study of adverse drug reactions during the treatment of drug resistant tuberculosis.

BACKGROUND: Pharmacovigilance entails monitoring of patients for timely detection of ADR and reporting them so that more information about drug safety can be obtained. This may help in the future for dose modification or alteration of regimen. In NTEP, ADSm (Active Drug Safety monitoring) is part of pharmacovigilance. In this study we shall be studying ADRs to Anti TB drugs in DRTB. METHODOLOGY: This study is observational, retrospective and record based, of patients admitted from 2021 to 2023 in the DOTS ward of Respiratory Medicine Department of a tertiary care hospital in Goa. Data such as age, sex, regimen, date of AKT initiation and adverse effects documented has been noted and compiled. RESULTS: ADRs have been tabulated in the form of tables. Statistical analysis is done to find out the commonest ADR, time when they are likely to occur, which age and gender are most likely affected and if there are any other associated risk factors for ADRs. CONCLUSION: This study will enable in future to better monitor patients with regard to particular adverse drug reaction, patient safety and if needed to alter the regimen as early as possible.

Xpert MTB/XDR implementation in South Africa: cost outcomes of centralised vs. decentralised approaches.

INTRODUCTION: In South Africa, Xpert® MTB/RIF Ultra (Ultra) is the recommended diagnostic assay for TB with line-probe assays for first- (LPAfl) and second-line drugs (LPAsl) providing additional drug susceptibility testing (DST) for samples that were rifampicin-resistant (RR-TB). To guide implementation of the recently launched Xpert® MTB/XDR (MTB/XDR) assay, a cost-outcomes analysis was conducted comparing total costs for genotypic DST (gDST) for persons diagnosed with RR-TB considering three strategies: replacing LPAfl/LPAsl (centralised level) with MTB/XDR vs. Ultra reflex testing (decentralised level). Further, DST was performed using residual specimen following RR-TB diagnosis. METHODS: The total cost of gDST was determined for three strategies, considering loss to follow-up (LTFU), unsuccessful test rates, and specimen volume. RESULTS: For 2019, 9,415 persons were diagnosed with RR-TB. A 35% LTFU rate between RR-TB diagnosis and LPAfl/LPAsl-DST was estimated. Unsuccessful test rates of 37% and 23.3% were reported for LPAfl and LPAsl, respectively. The estimated total costs were $191,472 for the conventional strategy, $122,352 for the centralised strategy, and $126,838 for the decentralised strategy. However, it was found that sufficient residual volume for reflex MTB/XDR testing is a limiting factor at the decentralised level. CONCLUSION: Centralising the implementation of XDR testing, as compared to LPAfl/LPAsl, leads to significant cost savings.

INTRODUCTION: En Afrique du Sud, Xpert® MTB/RIF Ultra (Ultra) est le test de diagnostic recommandé pour la TB avec des tests par sonde de ligne pour les médicaments de première (LPAfl) et de deuxième ligne (LPAsl) fournissant des tests de sensibilité aux médicaments (DST) supplémentaires pour les échantillons résistants à la rifampicine (RR-TB). Afin d'orienter la mise en œuvre du test Xpert® MTB/XDR (MTB/XDR) récemment lancé, une analyse coûts-résultats a été réalisée en comparant les coûts totaux de la DST génotypique (gDST) pour les personnes diagnostiquées avec une RR-TB en tenant compte de trois stratégies : remplacer le LPAfl/LPAsl (niveau centralisé) par le MTB/XDR par rapport au test Ultra reflex (niveau décentralisé). De plus, l'heure d'été a été réalisée à l'aide d'un échantillon résiduel après le diagnostic de RR-TB. MÉTHODES: Le coût total de la gDST a été déterminé pour trois stratégies, en tenant compte de la perte de suivi (LTFU), des taux d'échec des tests et du volume d'échantillons. RÉSULTATS: En 2019, 9 415 personnes ont reçu un diagnostic de RR-TB. Un taux de LTFU de 35% entre le diagnostic de RR-TB et le diagnostic de LPAfl/LPAsl-DST a été estimé. Des taux d'échec de 37% et de 23,3% ont été signalés pour LPAfl et LPAsl, respectivement. Les coûts totaux estimés étaient de 191 472 dollars pour la stratégie conventionnelle, de 122 352 dollars pour la stratégie centralisée et de 126 838 dollars pour la stratégie décentralisée. Cependant, il a été constaté qu'un volume résiduel suffisant pour les tests réflexes MTB/XDR est un facteur limitant au niveau décentralisé. CONCLUSION: La centralisation de la mise en œuvre des tests XDR, par rapport à LPAfl/LPAsl, permet de réaliser d'importantes économies.

Acupuncture as adjunctive treatment for linezolid-induced peripheral neuropathy: a case series report.

Background: The treatment of multidrug-resistant tuberculosis (MDR-TB) and pre-extensively drug-resistant tuberculosis (pre-XDR-TB) remains challenging due to the limited availability of effective drugs. Linezolid has emerged as a promising therapeutic option for these cases. However, its long-term use can lead to complications such as peripheral and optic neuropathies. Acupuncture, a cornerstone of traditional Chinese medicine, has been shown to be effective in the treatment of peripheral neuropathy (PN). This study examines the potential benefits of acupuncture in the treatment of linezolid-induced peripheral neuropathy (LIPN). Methods: Four patients, aged 27 to 60 years, diagnosed with LIPN, underwent daily acupuncture treatments. The main endpoint was to assess the efficacy of acupuncture in reducing neuropathic pain associated with LIPN in patients. This was primarily measured using changes in the Short Form McGill Pain Questionnaire (SF-MPQ) scores before and after acupuncture treatment. Results: Three of the patients experienced significant symptom remission, while one experienced marginal improvement. Treatments ranged from 7 to 18 sessions. Specifically, the first patient reported substantial relief with a score reduction from 33 to 13; the second patient observed minimal change; the third patient's score decreased dramatically from 10 to 2 after eight sessions; the last patient had a score reduction from 21 to 12 after five sessions, but did not continue treatment for a second assessment. Conclusion: Acupuncture is a promising therapeutic approach for LIPN. However, larger and more thorough studies are needed to determine its full potential.

Apramycin has high in vitro activity against Mycobacterium tuberculosis.

Introduction. Aminoglycoside antibiotics such as amikacin and kanamycin are important components in the treatment of Mycobacterium tuberculosis (Mtb) infection. However, more and more clinical strains are found to be aminoglycoside antibiotic-resistant. Apramycin is another kind of aminoglycoside antibiotic that is commonly used to treat infections in animals.Hypothesis. Apramycin may have in vitro activity against Mtb.Aim. This study aims to evaluate the efficacy of apramycin against Mtb in vitro and determine its epidemiological cut-off (ECOFF) value.Methodology. One hundred Mtb isolates, including 17 pansusceptible and 83 drug-resistant tuberculosis (DR-TB) strains, were analysed for apramycin resistance using the MIC assay.Results. Apramycin exhibited significant inhibitory activity against Mtb clinical isolates, with an MIC50 of 0.5 µg ml-1 and an MIC90 of 1 µg ml-1. We determined the tentative ECOFF value as 1 µg ml-1 for apramycin. The resistant rates of multidrug-resistant tuberculosis (MDR-TB), pre-extensively drug-resistant (pre-XDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains were 12.12 % (4/33), 20.69 % (6/29) and 66.67 % (14/21), respectively. The rrs gene A1401G is associated with apramycin resistance, as well as the cross-resistance between apramycin and other aminoglycosides.Conclusion. Apramycin shows high in vitro activity against the Mtb clinical isolates, especially the MDR-TB clinical isolates. This encouraging discovery calls for more research on the functions of apramycin in vivo and as a possible antibiotic for the treatment of drug-resistant TB.

Real-life use of delamanid: results from the European post-authorisation safety study.

BACKGROUND: A post-authorisation safety study (PASS) on delamanid (DLM) was conducted as part of a post-approval commitment to the European Medicines Agency. The aim of this study was to evaluate the use of DLM in a real-life setting, its safety, and treatment outcomes in patients with multidrug-resistant TB (MDR-TB). METHODS: This was a prospective, multicentric, non-interventional study conducted in the European Union. MDR-TB Regimen selection and patient monitoring were conducted in accordance with existing medical practices. Data on the use of DLM, related adverse events, and treatment outcomes were collected for up to 30 months after the first DLM dose. Descriptive summary statistics were used for continuous and categorical variables. RESULTS: Out of 86 patients, one had extrapulmonary TB. Two-thirds of the patients were treated with DLM for more than 24 weeks. The most frequent adverse drug reaction to DLM was QT interval prolongation. Resistance to DLM was detected in one patient during treatment. The treatment success rate was 77%. CONCLUSION: No new safety concerns were revealed, including in patients treated with DLM for more than 24 weeks. QT interval prolongations were well managed and did not lead to any clinically significant cardiac effects. The treatment outcomes were in line with the WHO target for Europe.

CONTEXTE: Une étude de sécurité post-autorisation (PASS) sur le délamanide (DLM) a été menée dans le cadre d'un engagement post-approbation auprès de l'Agence européenne des médicaments. L'objectif de cette étude était d'évaluer l'utilisation du DLM dans un contexte réel, son innocuité et les résultats du traitement chez les patients atteints de TB multirésistante (MDR-TB). MÉTHODES: Il s'agissait d'une étude prospective, multicentrique et non interventionnelle menée dans l'Union européenne. La sélection du schéma thérapeutique de la MDR-TB et le suivi des patients ont été effectués conformément aux pratiques médicales existantes. Les données sur l'utilisation du DLM, les effets indésirables connexes et les résultats du traitement ont été recueillies jusqu'à 30 mois après la première dose de DLM. Des statistiques sommaires descriptives ont été utilisées pour les variables continues et catégorielles. RÉSULTATS: Sur 86 patients, un avait une TB extrapulmonaire. Les deux tiers des patients ont été traités avec du DLM pendant plus de 24 semaines. L'effet indésirable le plus fréquent du DLM était l'allongement de l'intervalle QT. Une résistance au DLM a été détectée chez un patient pendant le traitement. Le taux de réussite du traitement était de 77%. CONCLUSION: Aucun nouveau problème de sécurité n'a été révélé, y compris chez les patients traités par le DLM pendant plus de 24 semaines. Les allongements de l'intervalle QT ont été bien gérés et n'ont pas entraîné d'effets cardiaques cliniquement significatifs. Les résultats du traitement étaient conformes à l'objectif de l'OMS pour l'Europe.