Replacing rifampicin with minocycline increases the activity of the treatment regimen for Mycobacterium avium complex pulmonary disease in a dynamic hollow-fibre system.

Mycobacterium avium complex bacteria cause chronic pulmonary disease (MAC-PD) in susceptible patients [1]. The recommended treatment regimen (rifampicin, ethambutol and azithromycin) achieves 65% cure rates but with considerable toxicity and drug-drug interactions [2,3]. Minocycline proved active in monotherapy experiments using the hollow-fibre model [4].

A loading dose of clofazimine to rapidly achieve steady-state-like concentrations in patients with nontuberculous mycobacterial disease.

Objectives: Clofazimine is a promising drug for the treatment of nontuberculous mycobacterial (NTM) diseases. Accumulation of clofazimine to reach steady-state plasma concentrations takes months. A loading dose may reduce the time to steady-state-like concentrations.

Patients at risk of nontuberculous mycobacterial pulmonary disease who need testing evaluated using a modified Delphi process by European experts.

Background: Identifying patients at risk of nontuberculous mycobacterial pulmonary disease (NTM-PD) is challenging. Delays in NTM-PD identification and management are associated with declining lung function and increased morbidity and mortality.

Study Design And Methods: European NTM-PD experts (n=12) participated in a three-round modified Delphi process to score symptoms and comorbidities potentially associated with NTM-PD as reasons to test for nontuberculous mycobacteria.

Clinical Significance, Species Distribution, and Temporal Trends of Nontuberculous Mycobacteria, Denmark, 1991-2022.

Nontuberculous mycobacteria (NTM) are emerging as notable causative agents of opportunistic infections. To examine clinical significance, species distribution, and temporal trends of NTM in Denmark, we performed a nationwide register-based study of all unique persons with NTM isolated in the country during 1991-2022. We categorized patients as having definite disease, possible disease, or isolation by using a previously validated method.

Incidence and clinical significance of non-tuberculous mycobacteria among migrants in Denmark: A nationwide register-based cohort study from 1991 through 2021.

Background: There is limited knowledge about non-tuberculous mycobacteria (NTM) infections in migrants. We aimed to assess the incidence and clinical significance of NTM among migrants in Denmark.

Method: Nationwide register-based cohort study of migrants with a positive NTM culture in Denmark from 1991 through 2021, stratified by patient demographics, disease localisation, species, and clinical significance.

Real-World Patients' Diagnosis-to-Treatment Journey with Nontuberculous Mycobacterial Pulmonary Disease: A Cross-Sectional Survey.

Introduction: The incidence and prevalence of nontuberculous mycobacterial pulmonary disease (NTM-PD) are increasing globally. Approximately 80% of NTM-PD cases in Japan and five countries within Europe (Eur5; France, Germany, Italy, Spain, and the UK) are caused by Mycobacterium avium complex (MAC). This study describes the clinical decision-making process associated with the management of patients with NTM-PD in Japan and the Eur5.

Rifampicin has no role in treatment of complex pulmonary disease and bactericidal sterilising drugs are needed: a viewpoint.

https://bit.ly/3PUGvbV

Impact of the COVID-19 pandemic on the real-world diagnostic infrastructure for tuberculosis-An ESGMYC collaborative study.

We determined the impact of the COVID-19 pandemic on mycobacterial diagnostic services. 40 laboratories from 22 countries completed an online questionnaire covering the redeployment of the laboratory infrastructure and/or staff for SARS-CoV-2 testing, staff shortages and supply chain disruptions. 28 laboratories reported monthly numbers of samples processed for mycobacterial investigations and monthly numbers of M.

ddPCR enables rapid detection of bloodstream infections in patients on home parenteral nutrition: A prospective cohort study.

Introduction: Chronic intestinal failure patients (CIF) require a central venous access device (CVAD) to administer parenteral nutrition. Most serious complication related to a CVAD is a central line-associated bloodstream infection (CLABSI). The golden standard to diagnose a CLABSI are blood cultures, however, they may require 1-5 days before getting a result.

Dual β-lactam therapy to improve treatment outcome in Mycobacterium abscessus disease.

Background: Antibiotic treatment of Mycobacterium abscessus disease is toxic and poorly effective and lacks a firm evidence base. Dual β-lactam and β-lactam/β-lactamase inhibitor combinations may be interesting leads to improve treatment outcomes.

Objectives: To summarize the current preclinical studies on dual β-lactam and β-lactam/β-lactamase inhibitor combinations against M.

Why do we use 100 mg of clofazimine in TB and NTM treatment?

Current tuberculosis and non-tuberculous mycobacterial disease guidelines recommend the use of clofazimine in a 100 mg once-daily dose. The rationale behind this exact dose is not provided. I performed a literature review to determine the reasoning behind the current dosing regimen.

Clinical presentation, management, and outcome of suspected central nervous system infections in Indonesia: a prospective cohort study.

Background: Little is known about the etiology, clinical presentation, management, and outcome of central nervous system (CNS) infections in Indonesia, a country with a high burden of infectious diseases and a rising prevalence of HIV.

Methods: We included adult patients with suspected CNS infections at two referral hospitals in a prospective cohort between April 2019 and December 2021. Clinical, laboratory, and radiological assessments were standardized.

Challenging the gold standard: the limitations of molecular assays for detection of heteroresistance.

Objectives: Heteroresistant infections are defined as infections in which a mixture of drug-resistant and drug-susceptible populations are present. In (), heteroresistance poses a challenge in diagnosis and has been linked with poor treatment outcomes. We compared the analytical sensitivity of molecular methods, such as GeneXpert and whole genome sequencing (WGS) in detecting heteroresistance when compared with the 'gold standard' phenotypic assay: the agar proportion method (APM).

Clofazimine as a substitute for rifampicin improves efficacy of pulmonary disease treatment in the hollow-fiber model.

complex pulmonary disease is treated with an azithromycin, ethambutol, and rifampicin regimen, with limited efficacy. The role of rifampicin is controversial due to inactivity, adverse effects, and drug interactions. Here, we evaluated the efficacy of clofazimine as a substitute for rifampicin in an intracellular hollow-fiber infection model.

complex pulmonary disease patients with limited treatment options.

https://bit.ly/3QwLQ8T.

Safety and Efficacy of Clofazimine as an Alternative for Rifampicin in Mycobacterium avium Complex Pulmonary Disease Treatment: Outcomes of a Randomized Trial.

Background: Results of retrospective studies have suggested clofazimine as an alternative for rifampicin in the treatment of Mycobacterium avium complex pulmonary disease (MAC-PD).

Research Question: Is a treatment regimen consisting of clofazimine-ethambutol-macrolide noninferior to the standard treatment regimen (rifampicin-ethambutol-macrolide) in the treatment of MAC-PD?

Study Design And Methods: In this single-center, nonanonymized clinical trial, adult patients with MAC-PD were randomly assigned in a 1:1 ratio to receive rifampicin or clofazimine as adjuncts to an ethambutol-macrolide regimen. The primary outcome was sputum culture conversion following 6 months of treatment.

Successful addition of topical antibiotic treatment after surgery in treatment-refractory nontuberculous mycobacterial skin and soft tissue infections.

Treatment of skin and soft tissue infections with nontuberculous mycobacteria sometimes fails despite repeated debridements and long-term systemic antibiotic therapy. These treatment-refractory infections can cause significant morbidity and pose a treatment challenge. Following surgery, we treated three patients with negative pressure wound therapy with the instillation and dwell time of topical antibiotics, in addition to systemic antibiotic treatment.

The role of rifampicin within the treatment of pulmonary disease.

Rifampicin is recommended for the treatment of complex pulmonary disease alongside azithromycin and ethambutol. We evaluated the azithromycin-ethambutol backbone with and without rifampicin in an intracellular hollow fiber model and performed RNA sequencing to study the differences in adaptation. In an hollow fiber experiment, we simulated epithelial lining fluid pharmacokinetic profiles of the recommended 3-drug (rifampicin, ethambutol, and azithromycin) or a 2-drug (ethambutol and azithromycin) treatment.

Non-tuberculous mycobacteria disease pre-lung transplantation: A systematic review of the treatment regimens and duration pre- and post-transplant.

Background: There is lack of consensus on non-tuberculous mycobacteria pulmonary disease (NTM-PD) treatment regimen and duration in patient listed for lung transplantation (LTx). We conducted a systematic review on treatment regimen and duration pre- and directly post-LTx, for patients with known NTM-PD pre-LTx. Additionally, we searched for risk factors for NTM disease development post-LTx and for mortality.

Monotherapy: Key cause of macrolide-resistant Mycobacterium avium complex disease.

Background: Macrolide-resistant Mycobacterium avium complex (MAC) disease is very difficult to cure. Macrolide-resistance emerges in patients and is largely preventable by appropriate screening and treatment practices.

Methods: Patients with macrolide-resistant MAC isolates between March 2019 and March 2022 were retrieved from the mycobacteriology reference laboratory database at Radboudumc, Nijmegen, the Netherlands.

The potential role of drug transporters and amikacin modifying enzymes in M. avium.

Objectives: Mycobacterium avium (M. avium) complex bacteria cause opportunistic infections in humans. Treatment yields cure rates of 60% and consists of a macrolide, a rifamycin, and ethambutol, and in severe cases, amikacin.

Risk Factors for Nontuberculous Mycobacterial Pulmonary Disease: A Systematic Literature Review and Meta-Analysis.

Background: Nontuberculous mycobacterial pulmonary disease (NTM-PD) is widely underdiagnosed, and certain patient groups, such as those with underlying respiratory diseases, are at increased risk of developing the disease. Understanding patients at risk is essential to allow for prompt testing and diagnosis and appropriate management to prevent disease progression.

Research Question: What are the risk factors for NTM-PD that should prompt a physician to consider NTM testing and diagnosis?

Study Design And Methods: Electronic searches of PubMed and EMBASE were conducted in July 2021 for the period 2011-2021.