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].

Advances in tuberculosis biomarkers: unravelling risk factors, active disease and treatment success.

Tuberculosis (TB) is a major global health threat and demands improved diagnostic and treatment monitoring methods. Conventional diagnostics, such as sputum smear microscopy and culture, are limited by slow results and low sensitivity, particularly in certain patient groups. Recent advances in biomarker research offer promising solutions in three key areas: risk of disease, diagnosis of active disease and monitoring of treatment response.

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.

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.

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.

Unraveling antibiotic resistance mechanisms in Mycobacterium abscessus: the potential role of efflux pumps.

Objectives: Mycobacterium abscessus is an opportunistic respiratory pathogen in patients with underlying lung disease. It is infamously known for its low treatment success rates because of its resistance to multiple classes of antibiotics. Further insight into M.

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.

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.

Genome-wide analysis in unravels a high level of genetic homoplasy associated with cefotaxime resistance.

Cefotaxime (CTX) is a third-generation cephalosporin (3GC) commonly used to treat infections caused by . Two genetic mechanisms have been associated with 3GC resistance in . The first is the conjugative transfer of a plasmid harbouring antibiotic-resistance genes.

Epidemiology of nontuberculous mycobacterial pulmonary disease in Europe and Japan by Delphi estimation.

Background: Nontuberculous mycobacterial pulmonary disease (NTM-PD) is an emerging opportunistic infection, but basic epidemiological data are lacking in most regions. We have investigated epidemiology and diagnostic and treatment practices in five EU countries (United Kingdom, Spain, Italy, France, Germany; EU5) and Japan.

Study Design: and methods: Annual prevalence in each country was established using a 2-round Delphi method in combination with a regional prevalence-estimation model that incorporated data obtained from a blinded physician screening survey (3154 physicians) and a real-world NTM-PD treating-physician/patient-chart observational study (619 physicians - 1429 patient charts).

Thioridazine Is an Efflux Pump Inhibitor in Mycobacterium avium Complex but of Limited Clinical Relevance.

Treatment of complex pulmonary disease (MAC-PD) is challenging partly due to high efflux pump expression. Thioridazine might block these efflux pumps. We explore the efficacy of thioridazine against isolates using MICs, time-kill combination assays, macrophage infection assays, and efflux assays.

The differential effect of clarithromycin and azithromycin on induction of macrolide resistance in .

Antibiotic resistance in renders treatment poorly effective. Despite -gene-mediated macrolide resistance, treatment with azithromycin or clarithromycin is recommended. It is contested whether macrolides differ in ) induction.

Minocycline Has No Clear Role in the Treatment of Mycobacterium abscessus Disease.

causes a difficult-to-treat pulmonary disease (MAb-PD). After initial intravenous treatment, minocycline is recommended in the oral continuation phase of treatment. We determined the MICs, synergy, and time-kill kinetics of minocycline against With MICs of 8 to 512 mg/liter, rapid emergence of tolerance in time-kill assays, and no synergy with other drugs used to treat MAb-PD, minocycline appears ineffective against These data question its role as a MAb-PD treatment modality.

Molecular Markers for Sensitive Detection of Asexual Stage Parasites and their Application in a Malaria Clinical Trial.

parasite life stages respond differently to antimalarial drugs. Sensitive stage-specific molecular assays may help to examine parasite dynamics at microscopically detectable and submicroscopic parasite densities in epidemiological and clinical studies. In this study, we compared the performance of skeleton-binding protein 1 (SBP1), ring-infected erythrocyte surface antigen, Hyp8, ring-exported protein 1 (REX1), and PHISTb mRNA for detecting ring-stage trophozoite-specific transcripts using quantitative reverse transcriptase polymerase chain reaction.

The shape of the iceberg: quantification of submicroscopic Plasmodium falciparum and Plasmodium vivax parasitaemia and gametocytaemia in five low endemic settings in Ethiopia.

Background: The widespread presence of low-density asymptomatic infections with concurrent gametocytes may be a stumbling block for malaria elimination. This study investigated the asymptomatic reservoir of Plasmodium falciparum and Plasmodium vivax infections in schoolchildren from five settings in northwest Ethiopia.

Methods: Two cross-sectional surveys were conducted in June and November 2015, enrolling 551 students from five schools and 294 students from three schools, respectively.