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.

Application of the hollow fibre infection model (HFIM) in antimicrobial development: a systematic review and recommendations of reporting.

Objectives: This systematic review focuses on the use of the in vitro hollow fibre infection model (HFIM) for microbial culture. We summarize the direction of the field to date and propose best-practice principles for reporting of the applications.

Methods: Searches in six databases (MEDLINE®, EMBASE®, PubMed®, BIOSIS®, SCOPUS® and Cochrane®) up to January 2020 identified 129 studies meeting our inclusion criteria.

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.

Norepinephrine Dysregulates the Immune Response and Compromises Host Defense during Sepsis.

Sepsis is characterized by a dysregulated immune response to infection. Norepinephrine, the cornerstone vasopressor used in septic shock, may contribute to immune dysregulation and impact host defense. To investigate effects of norepinephrine and the alternative vasopressor vasopressin on the immune response and host defense.

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.

A Dutch Case Report of Successful Treatment of Chronic Relapsing Urinary Tract Infection with Bacteriophages in a Renal Transplant Patient.

We report a case of a 58-year-old renal transplant patient who developed a recurrent urinary tract infection with an extended-spectrum β-lactamase (ESBL)-positive strain in the first month posttransplant. Even though it tested susceptible to carbapenems and despite repeated meropenem treatment, his infection recurred. The infection eventually evolved into epididymitis that was successfully treated with meropenem and bacteriophages.

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.

Minocycline treatment for pulmonary Mycobacterium avium complex disease based on pharmacokinetics/pharmacodynamics and Bayesian framework mathematical models.

Objectives: Our aim was to identify the pharmacokinetic/pharmacodynamic parameters of minocycline in the hollow-fibre system (HFS) model of pulmonary Mycobacterium avium complex (MAC) and to identify the optimal clinical dose.

Methods: Minocycline MICs for 55 MAC clinical isolates from the Netherlands were determined. We also co-incubated primary isolated macrophages infected with MAC with minocycline.

Implementation of Semiautomated Antimicrobial Susceptibility Interpretation Hardware for Nontuberculous Mycobacteria May Overestimate Susceptibility.

Nontuberculous mycobacteria (NTM) cause severe opportunistic infections and have a rising incidence in most settings. Rising diagnostic need must be met by national reference laboratories, which rely on Clinical and Laboratory Standards Institute (CLSI) guideline-approved manual readout of microtiter plates for antimicrobial susceptibility testing (AST) to determine antibiotic minimum inhibitory concentrations (MICs). Interpretation of these plates leads to different outcomes between laboratories.

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.

Optimal RNA isolation method and primer design to detect gene knockdown by qPCR when validating Drosophila transgenic RNAi lines.

Objective: RNA interference is employed extensively in Drosophila research to study gene function within a specific cell-type or tissue. Thousands of transgenic Drosophila lines have been generated to express double stranded RNA for gene knockdown; however, no standardized method exists for quantifying their knockdown efficiency. Since antibodies are not available for many proteins, quantitative real-time PCR is often used.