Update of drug-resistant tuberculosis treatment guidelines: A turning point

In December 2022 World Health Organization released a new treatment for multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) guideline. The main novelty of this update is two new recommendations (i) a 6-month treatment regimen composed of bedaquiline, pretomanid, linezolid (600 mg), and moxifloxacin (BPaLM) is recommended in place of the 9-month or longer (18-month) regimens in MDR/RR-TB patients, now including extensive pulmonary TB and extrapulmonary TB (except TB involving central nervous system, miliary TB and osteoarticular TB); (ii) the use of the 9-month all-oral regimen rather than longer (18-months) regimen is suggested in patients with MDR/RR-TB and in whom resistance to fluoroquinolones has been excluded. Longer (18-month) treatments remain a valid option in all cases in which shorter regimens cannot be implemented due to intolerance, drug-drug interactions, extensively drug-resistant tuberculosis, extensive forms of extrapulmonary TB, or previous failure. The new guidelines represent a milestone in MDR/RR-TB treatment landscape, setting the basis for a shorter, all-oral, more acceptable, equitable, and patient-centered model for MDR/RR-TB management. However, some challenges remain to be addressed to allow full implementation of the new recommendations

Clinical presentation of pulmonary and extrapulmonary tuberculosis

This chapter presents an overview of the clinical presentation of PTB and EPTB. The signs and syptoms of PTB are discussed, as well as several forms of EPTB, including disseminated TB, central nervous system TB, spinal TB, pleural TB, lymph node TB, abdominal TB, joint and extraspinal TB, urogenital TB, cutaneous TB, ocular TB, airway TB and pericardial TB. Diagnostic delay is considered, and the extra transmission risk this causes. No symptom or sign is specific for TB; it therefore remains important that symptoms and signs are examined carefully.</p

Clinical presentation of pulmonary and extrapulmonary tuberculosis

This chapter presents an overview of the clinical presentation of PTB and EPTB. The signs and syptoms of PTB are discussed, as well as several forms of EPTB, including disseminated TB, central nervous system TB, spinal TB, pleural TB, lymph node TB, abdominal TB, joint and extraspinal TB, urogenital TB, cutaneous TB, ocular TB, airway TB and pericardial TB. Diagnostic delay is considered, and the extra transmission risk this causes. No symptom or sign is specific for TB; it therefore remains important that symptoms and signs are examined carefully.</p

New and repurposed drugs to treat multidrug- and extensively drug-resistant tuberculosis

Submitted by Regiane Silva ([email protected]) on 2018-07-18T17:12:04Z No. of bitstreams: 1 Novos fármacos e fármacos repropostos para o tratamento da tuberculose multirresistente e extensivamente resistente.pdf: 381637 bytes, checksum: e3eeca9cf210b91986da18db130a071b (MD5)Approved for entry into archive by Regiane Silva ([email protected]) on 2018-07-20T13:32:22Z (GMT) No. of bitstreams: 1 Novos fármacos e fármacos repropostos para o tratamento da tuberculose multirresistente e extensivamente resistente.pdf: 381637 bytes, checksum: e3eeca9cf210b91986da18db130a071b (MD5)Made available in DSpace on 2018-07-20T13:32:22Z (GMT). No. of bitstreams: 1 Novos fármacos e fármacos repropostos para o tratamento da tuberculose multirresistente e extensivamente resistente.pdf: 381637 bytes, checksum: e3eeca9cf210b91986da18db130a071b (MD5) Previous issue date: 2018Universidade Federal do Rio Grande do Sul. Faculdade de Medicina. Porto Alegre, RS, Brasil.Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sérgio Arouca, Centro de Referência Professor Hélio Fraga. Rio de Janeiro, RJ, Brasil.Royal London Hospital, London, United KingdomSecretaria de Estado da Saúde do Estado de São Paulo, Hospital Nestor Goulart Reis, Américo Brasiliense, SP, Brasil / Universidade de Araraquara, Faculdade de Medicina. Araraquara, SP, Brasil.Instituto Nacional de Enfermedades Respiratorias, Clínica de Tuberculosis, Ciudad de México, México.Centro Hospitalar de Vila Nova de Gaia-Espinho, Serviço de Pneumologia, Porto, Portugal / Universidade do Porto, Instituto de Saúde Pública, Porto, Portugal / Universidade do Porto, Faculdade de Medicina. Porto, Portugal.Fondazione Salvatore Maugeri, Istituto di Ricovero e Cura a Carattere Scientifico, Tradate, Italia / Public Health Consulting Group, Lugano, Switzerland.Fondazione Salvatore Maugeri, Istituto di Ricovero e Cura a Carattere Scientifico, Division of Pulmonology, Tradate, Italia.Universidad de Monterrey, Centro de Investigación, Prevención y Tratamiento de Infecciones Respiratorias, Monterrey, México.Athens Chest Hospital, 7th Respiratory Medicine Department, Athens, Greece.University College London and NIHR Biomedical Research Centre, London, United Kingdom.Fondazione Salvatore Maugeri, Istituto di Ricovero e Cura a Carattere Scientifico, Tradate, Italia.A tuberculose multirresistente (TB-MDR, do inglês multidrug-resistant) e a extensivamente resistente (TB-XDR, do inglês extensively drug-resistant) continuam representando um desafio para os clínicos e as autoridades de saúde pública. Infelizmente, embora haja relatos encorajadores de taxas de sucesso maiores, a taxa global de desfechos favoráveis do tratamento da TB-MDR/XDR é de apenas 54%, ou muito menor quando o espectro de resistência aos fármacos vai além do da TB-XDR. O tratamento da TB-MDR/XDR continua sendo uma tarefa difícil, em razão da alta incidência de eventos adversos, do longo tempo de tratamento, do alto culto dos esquemas utilizados e da drenagem dos recursos de saúde. Diversos ensaios e estudos foram realizados recentemente (alguns já publicados e outros em andamento), todos visando a melhorar os desfechos do tratamento da TB-MDR/XDR por meio da alteração da abordagem geral, redução do tempo de tratamento e desenvolvimento de um esquema universal. O objetivo desta revisão foi resumir o que se conseguiu até o momento, no que se refere a novos fármacos e fármacos repropostos, dando foco especial para delamanid, bedaquilina, pretomanida, clofazimina, carbapenêmicos e linezolida. Após mais de 40 anos de negligência, recentemente foi dada mais atenção á necessidade de novos fármacos para se combater a “praga branca”, e resultados promissores estão sendo relatados.Multidrug-resistant and extensively drug-resistant tuberculosis (MDR-TB and XDR-TB, respectively) continue to represent a challenge for clinicians and public health authorities. Unfortunately, although there have been encouraging reports of higher success rates, the overall rate of favorable outcomes of M/XDR-TB treatment is only 54%, or much lower when the spectrum of drug resistance is beyond that of XDR-TB. Treating M/XDR-TB continues to be a difficult task, because of the high incidence of adverse events, the long duration of treatment, the high cost of the regimens used, and the drain on health care resources. Various trials and studies have recently been undertaken (some already published and others ongoing), all aimed at improving outcomes of M/XDR-TB treatment by changing the overall approach, shortening treatment duration, and developing a universal regimen. The objective of this review was to summarize what has been achieved to date, as far as new and repurposed drugs are concerned, with a special focus on delamanid, bedaquiline, pretomanid, clofazimine, carbapenems, and linezolid. After more than 40 years of neglect, greater attention has recently been paid to the need for new drugs to fight the “white plague”, and promising results are being reported

New and repurposed drugs to treat multidrug- and extensively drug-resistant tuberculosis

ABSTRACT Multidrug-resistant and extensively drug-resistant tuberculosis (MDR-TB and XDR-TB, respectively) continue to represent a challenge for clinicians and public health authorities. Unfortunately, although there have been encouraging reports of higher success rates, the overall rate of favorable outcomes of M/XDR-TB treatment is only 54%, or much lower when the spectrum of drug resistance is beyond that of XDR-TB. Treating M/XDR-TB continues to be a difficult task, because of the high incidence of adverse events, the long duration of treatment, the high cost of the regimens used, and the drain on health care resources. Various trials and studies have recently been undertaken (some already published and others ongoing), all aimed at improving outcomes of M/XDR-TB treatment by changing the overall approach, shortening treatment duration, and developing a universal regimen. The objective of this review was to summarize what has been achieved to date, as far as new and repurposed drugs are concerned, with a special focus on delamanid, bedaquiline, pretomanid, clofazimine, carbapenems, and linezolid. After more than 40 years of neglect, greater attention has recently been paid to the need for new drugs to fight the “white plague”, and promising results are being reported

Prosthetic Valve Candida spp. Endocarditis: New Insights Into Long-term Prognosis—The ESCAPE Study

International audienceBackground: Prosthetic valve endocarditis caused by Candida spp. (PVE-C) is rare and devastating, with international guidelines based on expert recommendations supporting the combination of surgery and subsequent azole treatment.Methods: We retrospectively analyzed PVE-C cases collected in Spain and France between 2001 and 2015, with a focus on management and outcome.Results: Forty-six cases were followed up for a median of 9 months. Twenty-two patients (48%) had a history of endocarditis, 30 cases (65%) were nosocomial or healthcare related, and 9 (20%) patients were intravenous drug users. "Induction" therapy consisted mainly of liposomal amphotericin B (L-amB)-based (n = 21) or echinocandin-based therapy (n = 13). Overall, 19 patients (41%) were operated on. Patients <66 years old and without cardiac failure were more likely to undergo cardiac surgery (adjusted odds ratios [aORs], 6.80 [95% confidence interval [CI], 1.59-29.13] and 10.92 [1.15-104.06], respectively). Surgery was not associated with better survival rates at 6 months. Patients who received L-amB alone had a better 6-month survival rate than those who received an echinocandin alone (aOR, 13.52; 95% CI, 1.03-838.10). "Maintenance" fluconazole therapy, prescribed in 21 patients for a median duration of 13 months (range, 2-84 months), led to minor adverse effects.Conclusion: L-amB induction treatment improves survival in patients with PVE-C. Medical treatment followed by long-term maintenance fluconazole may be the best treatment option for frail patients