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

Objective: Mycobacterium avium complex bacteria cause chronic pulmonary disease (MAC-PD) in susceptible patients. 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.

Elderly patients with tuberculosis in a low-incidence country - Clinical characteristics, inflammation and outcome.

Background: Susceptibility to respiratory infections increases with age. Diagnosing and treating tuberculosis in the elderly comes with the challenges of fewer specific symptoms and possibly more side effects of treatment. Much is unknown when it comes to tuberculosis in the elderly, especially in relation to inflammation, which may impact mortality.

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

https://bit.ly/3PUGvbV

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.

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.

Real-world treatment patterns in patients with nontuberculous mycobacterial lung disease in the Netherlands based on medication dispensing data.

Purpose: Real-world data on antibiotic management of nontuberculous mycobacterial lung disease (NTM-LD) is limited for many countries. This study aimed to evaluate real-world treatment practices of NTM-LD in the Netherlands using medication dispensing data.

Methods: A retrospective longitudinal real-world study was conducted using IQVIA's Dutch pharmaceutical dispensing database.

MGIT Enriched Shotgun Metagenomics for Routine Identification of Nontuberculous Mycobacteria: a Route to Personalized Health Care.

Currently, nontuberculous mycobacteria (NTM) are identified using small genomic regions, and species-level identification is often not possible. We introduce a next-generation sequencing (NGS) workflow that identifies mycobacteria to (sub)species level on the basis of the whole genome extracted from enriched shotgun metagenomic data. This technique is used to study the association between genotypes and clinical manifestations to pave the way to more personalized health care.

Amikacin Liposomal Inhalation Suspension in the Treatment of Lung Infection: A French Observational Experience.

Background: infections remain difficult to manage in both cystic fibrosis (CF) and non-CF patients and reported clinical outcomes are largely unsatisfactory. Clinical trial data are limited and no approved therapies are currently available for the management of lung diseases. As an alternative, cohort studies may provide insightful information into the management of pulmonary disease.

Interleukin-1 receptor antagonist anakinra as treatment for paradoxical responses in HIV-negative tuberculosis patients: A case series.

Background: Paradoxical inflammatory responses can occur during microbiologically successful antituberculous therapy. Optimal treatment is unknown, but corticosteroids are used most often. It is likely that interleukin-1 (IL-1) plays a central role in the development of these paradoxical responses, and if corticosteroids fail or are undesirable because of adverse effects, anti-IL-1 therapy may therefore be a rational choice.

Professionals' Treatment Preferences in the Prodromal Phase of Parkinson's Disease: A Discrete Choice Experiment.

Background: In Parkinson's disease (PD), several disease-modifying treatments are being tested in (pre-)clinical trials. To successfully implement such treatments, it is important to have insight into factors influencing the professionals' decision to start disease-modifying treatments in persons who are in the prodromal stage of PD.

Objective: We aim to identify factors that professionals deem important in deciding to a start disease-modifying treatment in the prodromal stage of PD.

Treatment of severe complex pulmonary disease with adjunctive amikacin and clofazimine standard regimen alone: a retrospective study.

https://bit.ly/30dxdRj.

RNA Sequencing Elucidates Drug-Specific Mechanisms of Antibiotic Tolerance and Resistance in Mycobacterium abscessus.

Mycobacterium abscessus is an opportunistic pathogen notorious for its resistance to most classes of antibiotics and low cure rates. M. abscessus carries an array of mostly unexplored defense mechanisms.

Prediction of Moxifloxacin Concentrations in Tuberculosis Patient Populations by Physiologically Based Pharmacokinetic Modeling.

Moxifloxacin has an important role in the treatment of tuberculosis (TB). Unfortunately, coadministration with the cornerstone TB drug rifampicin results in suboptimal plasma exposure. We aimed to gain insight into the moxifloxacin pharmacokinetics and the interaction with rifampicin.

Standard therapy of Mycobacterium avium complex pulmonary disease shows limited efficacy in an open source hollow fibre system that simulates human plasma and epithelial lining fluid pharmacokinetics.

Objectives: Mycobacterium avium complex (MAC) bacteria can cause chronic pulmonary disease (PD). Current treatment regimens of azithromycin, ethambutol and rifampicin have culture conversion rates of around 65%. Dynamic, preclinical models to assess the efficacy of treatment regimens are important to guide clinical trial development.

The role of amikacin in the treatment of nontuberculous mycobacterial disease.

: Guidelines recommend the use of amikacin in the treatment of nontuberculous mycobacterial (NTM) disease. The authors have evaluated the evidence for the position of amikacin in NTM disease treatment.: The authors performed a literature search for original research on amikacin in NTM disease, including its mechanism of action, emergence of resistance, pre-clinical and clinical investigations.

The epidemiology of nontuberculous mycobacterial pulmonary disease in the Netherlands.

Background: Nontuberculous mycobacteria (NTM) are emerging opportunistic pathogens of humans. Because NTM pulmonary disease (PD) is not a notifiable disease in Europe, the epidemiology of NTM-PD is not well known. However, the prevalence of NTM-PD is thought to be increasing, particularly in countries where tuberculosis rates have decreased.

Imatinib in patients with severe COVID-19: a randomised, double-blind, placebo-controlled, clinical trial.

Background: The major complication of COVID-19 is hypoxaemic respiratory failure from capillary leak and alveolar oedema. Experimental and early clinical data suggest that the tyrosine-kinase inhibitor imatinib reverses pulmonary capillary leak.

Methods: This randomised, double-blind, placebo-controlled, clinical trial was done at 13 academic and non-academic teaching hospitals in the Netherlands.