Neutrophil Extracellular Traps: An Emerging Therapeutic Target to Improve Infectious Disease Outcomes.

Neutrophils possess a diverse repertoire of pathogen clearance mechanisms, one of which is the formation of neutrophil extracellular traps (NETs). NETs are complexes of histone proteins and DNA coated with proteolytic enzymes that are released extracellularly to entrap pathogens and aid in their clearance, in a process known as NETosis. Intravascular NETosis may drive a massive inflammatory response that has been shown to contribute to morbidity and mortality in many infectious diseases, including malaria, dengue fever, influenza, bacterial sepsis, and severe acute respiratory syndrome coronavirus 2 infection.

Pediatric COVID-19 Health Disparities and Vaccine Equity.

While most children with coronavirus 2019 (COVID-19) experience mild illness, some are vulnerable to severe disease and develop long-term complications. Children with disabilities, those from lower-income homes, and those from racial and ethnic minority groups are more likely to be hospitalized and to have poor outcomes following an infection. For many of these same children, a wide range of social, economic, and environmental disadvantages have made it more difficult for them to access COVID-19 vaccines.

Potent Activity of Ertapenem Plus Cefazolin Within Staphylococcal Biofilms: A Contributing Factor in the Treatment of Methicillin-Susceptible Endocarditis.

Background: Besides antistaphylococcal beta-lactams and source control, there are limited validated antimicrobial salvage options in patients with prolonged methicillin-susceptible (MSSA) bacteremia, including infective endocarditis (IE).

Methods: MSSA IE cases treated with ertapenem (ETP) plus cefazolin (CZ) were compared with matched IE cases treated with standard beta-lactam monotherapy. The bactericidal activity of ETP plus CZ was also compared with nafcillin (NAF), CZ, and ETP alone using an in vitro MSSA biofilm model.

Azithromycin: An Underappreciated Quinolone-Sparing Oral Treatment for Infections.

Outpatient treatment of infections is challenged by increasing rates of resistance to fluoroquinolones, the only class of antibiotics which offers an established oral route of administration against this organism. Azithromycin does not demonstrate activity against when evaluated under standard methods of susceptibility testing with bacteriologic media. However, growing evidence shows that azithromycin is very active against when using physiologic media that recapitulate the in vivo milieu and is supported by animal models of infection and various clinical settings, including cystic fibrosis.

Impact of Clopidogrel on Clinical Outcomes in Patients with Staphylococcus aureus Bacteremia: a National Retrospective Cohort Study.

Activated platelets have known antimicrobial activity against Staphylococcus aureus. Accelerated clearance of platelets induced by S. aureus can result in thrombocytopenia and increased mortality in patients.

SARS-CoV-2 acquisition and immune pathogenesis among school-aged learners in four diverse schools.

Background: Understanding SARS-CoV-2 infection in children is necessary to reopen schools safely.

Methods: We measured SARS-CoV-2 infection in 320 learners [10.5 ± 2.

Ticagrelor Increases Platelet-Mediated Staphylococcus aureus Killing, Resulting in Clearance of Bacteremia.

Platelets are a critical immune defense against Staphylococcus aureus bloodstream infections. Staphylococcus aureus α-toxin is a virulence factor that decreases platelet viability and accelerates platelet clearance. It has been shown that ticagrelor blocks α-toxin-mediated platelet injury and resulting thrombocytopenia, protecting mice in a lethal S.

SARS-CoV-2 Acquisition and Immune Pathogenesis Among School-Aged Learners in Four Diverse Schools.

Background: Understanding SARS-CoV-2 infection in children is necessary to reopen schools safely.

Methods: We measured SARS-CoV-2 infection in 320 learners [10.5 ± 2.

SARS-CoV-2 vaccine testing and trials in the pediatric population: biologic, ethical, research, and implementation challenges.

As the nation implements SARS-CoV-2 vaccination in adults at an unprecedented scale, it is now essential to focus on the prospect of SARS-CoV-2 vaccinations in pediatric populations. To date, no children younger than 12 years have been enrolled in clinical trials. Key challenges and knowledge gaps that must be addressed include (1) rationale for vaccines in children, (2) possible effects of immune maturation during childhood, (3) ethical concerns, (4) unique needs of children with developmental disorders and chronic conditions, (5) health inequities, and (6) vaccine hesitancy.

Granadaene Photobleaching Reduces the Virulence and Increases Antimicrobial Susceptibility of Streptococcus agalactiae.

Streptococcus agalactiae, also known as Group B Streptococcus (GBS), is increasingly recognized as a major cause of soft tissue and invasive diseases in the elderly and diabetic populations. Antibiotics like penicillin are used with great frequency to treat these infections, although antimicrobial resistance is increasing among GBS strains and underlines a need for alternative methods not reliant on traditional antibiotics. GBS granadaene pigment is related to the hemolysin/cytolysin of GBS, which is critical for the pathogenesis of GBS diseases.

Photo-Disassembly of Membrane Microdomains Revives Conventional Antibiotics against MRSA.

Confronted with the rapid evolution and dissemination of antibiotic resistance, there is an urgent need to develop alternative treatment strategies for drug-resistant pathogens. Here, an unconventional approach is presented to restore the susceptibility of methicillin-resistant (MRSA) to a broad spectrum of conventional antibiotics via photo-disassembly of functional membrane microdomains. The photo-disassembly of microdomains is based on effective photolysis of staphyloxanthin, the golden carotenoid pigment that gives its name.

Azithromycin Exerts Bactericidal Activity and Enhances Innate Immune Mediated Killing of MDR .

Azithromycin (AZM), the most commonly prescribed antibiotic in the United States, is thought to have no activity against multidrug-resistant Gram-negative pathogens such as (AX) per standard minimum inhibitory concentration testing in cation-adjusted Mueller Hinton Broth. Here we provide the first report of AZM bactericidal activity against carbapenem-resistant isolates of AX, with a multifold decrease in minimum inhibitory concentration across 12 clinical isolates when examined under physiologic testing conditions that better recapitulate the in vivo human environment. This pharmaceutical activity, evident in eukaryotic tissue culture media, is associated with enhanced AZM intracellular penetration and synergistic killing with human whole blood, serum, and neutrophils.

Cefazolin and Ertapenem Salvage Therapy Rapidly Clears Persistent Methicillin-Susceptible Staphylococcus aureus Bacteremia.

Cefazolin and ertapenem combination therapy was used successfully to salvage 11 cases (6 endocarditis) of persistent methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, including immediate clearance (≤24 hours) in 8 cases. While in vitro synergy was modest, cefazolin plus ertapenem exhibited synergistic action in a rat model of MSSA endocarditis. The combination of cefazolin and ertapenem provides potent in vivo activity against MSSA beyond what is predicted in vitro and warrants further clinical study in the treatment of refractory MSSA bacteremia and endocarditis.

Association of Enterovirus D68 with Acute Flaccid Myelitis, Philadelphia, Pennsylvania, USA, 2009-2018.

Acute flaccid myelitis (AFM) is a polio-like disease that results in paralysis in previously healthy persons. Although the definitive cause of AFM remains unconfirmed, enterovirus D68 (EV-D68) is suspected based on 2014 data demonstrating an increase in AFM cases concomitant with an EV-D68 outbreak. We examined the prevalence in children and the molecular evolution of EV-D68 for 2009-2018 in Philadelphia, Pennsylvania, USA.

Avibactam Sensitizes Carbapenem-Resistant NDM-1-Producing Klebsiella pneumoniae to Innate Immune Clearance.

Infections caused by New Delhi metallo-β-lactamase (NDM)-producing strains of multidrug-resistant Klebsiella pneumoniae are a global public health threat lacking reliable therapies. NDM is impervious to all existing β-lactamase inhibitor (BLI) drugs, including the non-β-lactam BLI avibactam (AVI). Though lacking direct activity against NDMs, AVI can interact with penicillin-binding protein 2 in a manner that may influence cell wall dynamics.

Long-term follow-up of IPEX syndrome patients after different therapeutic strategies: An international multicenter retrospective study.

Background: Immunodysregulation polyendocrinopathy enteropathy x-linked (IPEX) syndrome is a monogenic autoimmune disease caused by FOXP3 mutations. Because it is a rare disease, the natural history and response to treatments, including allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppression (IS), have not been thoroughly examined.

Objective: This analysis sought to evaluate disease onset, progression, and long-term outcome of the 2 main treatments in long-term IPEX survivors.

The neural substrate of gesture recognition.

Previous studies have linked action recognition with a particular pool of neurons located in the ventral premotor cortex, the posterior parietal cortex and the superior temporal sulcus (the mirror neuron system). However, it is still unclear if transitive and intransitive gestures share the same neural substrates during action-recognition processes. In the present study, we used event-related functional magnetic resonance imaging (fMRI) to assess the cortical areas active during recognition of pantomimed transitive actions, intransitive gestures, and meaningless control actions.

Recognition of point-light biological motion: mu rhythms and mirror neuron activity.

Changes in power in the mu frequency band (8-13Hz) of the electroencephalogram (EEG) is thought to indirectly reflect the activity of mirror neurons in premotor cortex. Activation of these neurons by self-performed, observed or imagined motor actions is assumed to produce asynchronous firing and a reduction in mu rhythm oscillation (referred to as mu suppression) in sensorimotor cortex. A recent fMRI study by Saygin et al.