The impact of BCG dose and revaccination on trained immunity.

The innate immune system can display heterologous memory-like responses termed trained immunity after stimulation by certain vaccinations or infections. In this randomized, placebo-controlled trial, we investigated the modulation of Bacille Calmette-Guérin (BCG)-induced trained immunity by BCG revaccination or high-dose BCG administration, in comparison to a standard dose. We show that monocytes from all groups of BCG-vaccinated individuals exerted increased TNFα production after ex-vivo stimulation with various unrelated pathogens.

An Perspective on What Individual Antimicrobials Add to Mycobacterium avium Complex Therapies.

For Mycobacterium avium complex pulmonary disease (MAC-PD), current treatment regimens yield low cure rates. To obtain an evidence-based combination therapy, we assessed the activity of six drugs, namely, clarithromycin (CLR), rifampin (RIF), ethambutol (EMB), amikacin (AMK), clofazimine (CLO), and minocycline (MIN), alone and in combination, against Mycobacterium avium and studied the contributions of individual antibiotics to efficacy. The MICs of all antibiotics against M.

The Benzimidazole SPR719 Shows Promising Concentration-Dependent Activity and Synergy against Nontuberculous Mycobacteria.

Nontuberculous mycobacterial pulmonary disease (NTM-PD) is emerging worldwide. Currently recommended multidrug treatment regimens yield poor outcomes, and new drugs and regimens are direly needed. SPR719, the active moiety of SPR720, is a new benzimidazole antibiotic with limited data on antimycobacterial activity.

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.

Inhaled tigecycline is effective against Mycobacterium abscessus in vitro and in vivo.

Background: Mycobacterium abscessus causes chronic pulmonary infections. Owing to its resistance to most classes of antibiotics, treatment is complex and cure rates are only 45%. Tigecycline is active against M.

Is there a role for tedizolid in the treatment of non-tuberculous mycobacterial disease?

Background: Pulmonary infections caused by non-tuberculous mycobacteria (NTM) are hard to treat and have low cure rates despite intensive multidrug therapy.

Objectives: To assess the feasibility of tedizolid, a new oxazolidinone, for the treatment of Mycobacterium avium and Mycobacterium abscessus.

Methods: We determined MICs of tedizolid for 113 isolates of NTM.

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.

Auranofin Activity Exposes Thioredoxin Reductase as a Viable Drug Target in .

Nontuberculous mycobacteria (NTM) are highly drug-resistant, opportunistic pathogens that can cause pulmonary disease. The outcomes of the currently recommended treatment regimens are poor, especially for New or repurposed drugs are direly needed. Auranofin, a gold-based antirheumatic agent, was investigated for Here, we test auranofin against NTM and We tested the susceptibility of 63 NTM isolates to auranofin using broth microdilution.

Stable pantothenamide bioisosteres: novel antibiotics for Gram-positive bacteria.

The emergence of multidrug resistant bacteria has prioritized the development of new antibiotics. N-substituted pantothenamides, analogs of the natural compound pantetheine, were reported to target bacterial coenzyme A biosynthesis, but these compounds have never reached the clinic due to their instability in biological fluids. Plasma-stable pantothenamide analogs could overcome these issues.

Clofazimine inhalation suspension for the aerosol treatment of pulmonary nontuberculous mycobacterial infections.

Background: Nontuberculous mycobacteria are recognized as a concern for cystic fibrosis (CF) patients due to increasing disease prevalence and the potential for detrimental effects on pulmonary function and mortality. Current standard of care involves prolonged systemic antibiotics, which often leads to severe side effects and poor treatment outcomes. In this study, we investigated the tolerability and efficacy of a novel inhaled therapeutic in various mouse models of NTM disease.

A bedaquiline/clofazimine combination regimen might add activity to the treatment of clinically relevant non-tuberculous mycobacteria.

Background: Non-tuberculous mycobacteria (NTM) infections are hard to treat. New antimicrobial drugs and smarter combination regimens are needed.

Objectives: Our aim was to determine the in vitro activity of bedaquiline against NTM and assess its synergy with established antimycobacterials.

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.

Mycobacterium avium complex bacteria remain viable in sputum during storage and refrigeration.

Diagnostic mycobacteriology often involves shipping of samples to centralized laboratories. Using two quantitative culture techniques, we show that 7 days storage of sputum samples at room temperature or 4 °C does not affect the number of viable Mycobacterium avium complex bacteria. Storage at room temperature increases the chance of contamination.