In vitro susceptibility of 147 international clinical Mycobacterium abscessus isolates to epetraborole and comparators by broth microdilution.

Background: Mycobacterium abscessus is a highly drug-resistant non-tuberculous mycobacterium (NTM) for which treatment is limited by the lack of active oral antimycobacterials and frequent adverse reactions. Epetraborole is a novel oral, boron-containing antimicrobial that inhibits bacterial leucyl-tRNA synthetase, an essential enzyme in protein synthesis, and has been shown to have anti-M. abscessus activity in preclinical studies.

Durlobactam in combination with β-lactams to combat .

() presents significant clinical challenges. This study evaluated the synergistic effects of a β-lactam and β-lactamase inhibitor combination against and explored the underlying mechanisms. Synergy was assessed through MIC tests and time-kill studies, and binding affinities of nine β-lactams and BLIs to eight target receptors (L,D-transpeptidases [LDT] 1-5, D,D-carboxypeptidase, penicillin-binding protein [PBP] B, and PBP-lipo) were assessed using mass spectrometry and kinetic studies.

Nontuberculous Mycobacterial Pulmonary Disease: Patients, Principles, and Prospects.

Nontuberculous mycobacterial pulmonary disease (NTM-PD) is increasing in incidence globally and challenging to manage. The 2020 multisociety treatment guideline and the 2022 consensus recommendations provide comprehensive evidence-based guides to manage pulmonary diseases caused by the most common NTM. However, with >190 different NTM species that may require different multidrug regimens for treatment, the breadth and complexity of NTM-PD remain daunting for both patients and clinicians.

Target regimen profiles for tuberculosis treatment.

Simpler, shorter, safer and more effective treatments for tuberculosis that are easily accessible to all people with tuberculosis are desperately needed. In 2016, the World Health Organization (WHO) developed target regimen profiles for the treatment of tuberculosis to make drug developers aware of both the important features of treatment regimens, and patient and programmatic needs at the country level. In view of recent ground-breaking advances in tuberculosis treatment, WHO has revised and updated these regimen profiles.

Brensocatib in non-cystic fibrosis bronchiectasis: ASPEN protocol and baseline characteristics.

Introduction: Brensocatib is an investigational, oral, reversible inhibitor of dipeptidyl peptidase-1 shown to prolong time to first exacerbation in adults with bronchiectasis. Outlined here are the clinical trial design, and baseline characteristics and treatment patterns of adult patients enrolled in the phase 3 ASPEN trial (NCT04594369).

Methods: The ASPEN trial is a global study enrolling patients with a clinical history consistent with bronchiectasis (cough, chronic sputum production and/or recurrent respiratory infections), diagnosis confirmed radiologically and ≥2 exacerbations in the prior 12 months.

: the canary in the coal mine?

() is a species of nontuberculous mycobacteria (NTM) that rarely causes infection. It has previously been labeled the most common NTM contaminant. Bronchiectasis is a disease characterized by abnormal airway dilation leading to chronic cough, sputum production and pulmonary infections.

Synergistic effects of sulopenem in combination with cefuroxime or durlobactam against .

Unlabelled: () affects patients with immunosuppression or underlying structural lung diseases such as cystic fibrosis (CF). Additionally, poses clinical challenges due to its resistance to multiple antibiotics. Herein, we investigated the synergistic effect of dual β-lactams [sulopenem and cefuroxime (CXM)] or the combination of sulopenem and CXM with β-lactamase inhibitors [BLIs-avibactam (AVI) or durlobactam (DUR)].

Preclinical murine models for the testing of antimicrobials against Mycobacterium abscessus pulmonary infections: Current practices and recommendations.

Mycobacterium abscessus, a rapidly growing nontuberculous mycobacterium, is increasingly recognized as an important pathogen of the human lung, disproportionally affecting people with cystic fibrosis (CF) and other susceptible individuals with non-CF bronchiectasis and compromised immune functions. M. abscessus infections are extremely difficult to treat due to intrinsic resistance to many antibiotics, including most anti-tuberculous drugs.

Notes from the Field: Potential Outbreak of Extrapulmonary Mycobacterium abscessus subspecies massiliense Infections from Stem Cell Treatment Clinics in Mexico - Arizona and Colorado, 2022.

Mycobacterium abscessus is an intrinsically drug-resistant, rapidly growing, nontuberculous mycobacterium; extrapulmonary infections have been reported in association with medical tourism (1). During November-December 2022, two Colorado hospitals (hospitals A and B) treated patient A, a Colorado woman aged 30-39 years, for M. abscessus meningitis.

activity of cefoxitin, imipenem, meropenem, and ceftaroline in combination with vaborbactam against .

(MAB) infections pose a growing public health threat. Here, we assessed the activity of the boronic acid-based β-lactamase inhibitor, vaborbactam, with different β-lactams against 100 clinical MAB isolates. Enhanced activity was observed with meropenem and ceftaroline with vaborbactam (1- and >4-fold MIC/ reduction).

Nontuberculous Mycobacterial Infections in Pediatric Solid Organ Transplant and Hematopoietic Cell Transplant Recipients.

The diagnosis of nontuberculous mycobacterial infections is challenging in pediatric solid organ transplant and hematopoietic cell transplant recipients due to the absence of specific clinical manifestations, limitations of sampling, prolonged times for culture and identification, and difficulty discerning colonization from clinical disease. Treatment is dependent on the nontuberculous mycobacterial species, disease type, and pattern of drug resistance. Treatment of nontuberculous mycobacterial infections involves prolonged durations of therapy using multiple medications, which are limited by toxicities and drug-drug interactions.

Treatment of Mycobacterium avium Complex Pulmonary Disease: When Should I Treat and What Therapy Should I Start?

Treatment of M avium pulmonary disease requires a three-drug, macrolide-based regimen that is administered for 12 months beyond culture conversion. The regimen can be administered 3 days a week in non-cavitary, nodular bronchiectatic disease but should be given daily when cavitary disease is present. For treatment refractory disease, amikacin liposome inhalation suspension is added to the regimen.

In vitro susceptibility patterns for slowly growing non-tuberculous mycobacteria in the USA from 2018 to 2022.

Background: Treatment of slowly growing non-tuberculous mycobacteria (SGM) is challenging. In vitro antimicrobial susceptibility testing (AST) is needed to optimize a multidrug regimen but requires weeks to result. Aggregated AST patterns, or an antibiogram, of SGM would be helpful to providers.

Prospective evaluation of nontuberculous mycobacteria disease in cystic fibrosis: The design of the PREDICT study.

Background: Nontuberculous mycobacteria (NTM) are an important cause of airway infections in people with cystic fibrosis (pwCF). Isolation of NTM from respiratory specimens of pwCF do not mandate treatment in the absence of clinical and radiologic features of NTM pulmonary disease (NTM-PD), as some pwCF clear the infection without treatment and others do not appear to progress to NTM-PD despite persistent infection. An evidence-based protocol to standardize diagnosis of NTM-PD is needed to systematically identify pwCF who may benefit from treatment.

Mycobacterium abscessus Meningitis Associated with Stem Cell Treatment During Medical Tourism.

Mycobacterium abscessus infections have been reported as adverse events related to medical tourism. We report M. abscessus meningitis in a patient who traveled from Colorado, USA, to Mexico to receive intrathecal stem cell injections as treatment for multiple sclerosis.

Long-term Safety and Tolerability of Omadacycline for the Treatment of Infections.

Background: is a virulent human pathogen. Treatment is complex and often poorly tolerated with suboptimal rates of eradication, highlighting the need for improved therapeutics. This study reports clinical experience with omadacycline for treatment of infections at five large nontuberculous mycobacterial (NTM) disease clinics across the United States to better understand long-term safety and tolerability.

Towards development of evidence to inform recommendations for the evaluation and management of bronchiectasis.

Bronchiectasis (BE) is a chronic condition characterized by airway dilation as a consequence of a variety of pathogenic processes. It is often associated with persistent airway infection and an inflammatory response resulting in cough productive of purulent sputum, which has an adverse impact on quality of life. The prevalence of BE is increasing worldwide.

Molecular Epidemiologic Investigation of Subspecies Lung Infections at an Adult Cystic Fibrosis Program.

Outbreaks of nontuberculous mycobacteria (NTM) among people with cystic fibrosis (pwCF) have been reported at CF centers with conflicting conclusions. The occurrence of NTM at the UVMC (University of Vermont Medical Center) adult CF program was investigated. Use the HALT NTM (Healthcare-associated Links in Transmission of NTM) toolkit to investigate the healthcare-associated transmission and/or acquisition of NTM among pwCF having genetically similar NTM isolates.

In vitro susceptibility patterns for rapidly growing nontuberculous mycobacteria in the United States.

Antimicrobial susceptibility testing for rapidly growing mycobacteria (RGM) is uncommon or only performed in large reference laboratories. Here we developed a cumulative antibiogram for 14 RGM using the largest sample size to date (N = 3860). All RGM showed 82% to 100% susceptibility to amikacin.

Nontuberculous Mycobacterial Infections in Cystic Fibrosis.

Nontuberculous mycobacteria (NTM) are important pathogens, with a longitudinal prevalence of up to 20% within the cystic fibrosis (CF) population. Diagnosis of NTM pulmonary disease in people with CF (pwCF) is challenging, as a majority have NTM infection that is transient or indolent, without evidence of clinical consequence. In addition, the radiographic and clinical manifestations of chronic coinfections with typical CF pathogens can overlap those of NTM, making diagnosis difficult.