Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 56
Filter
Add more filters

Publication year range
1.
J Med Internet Res ; 24(12): e42332, 2022 12 01.
Article in English | MEDLINE | ID: mdl-36269222

ABSTRACT

BACKGROUND: Virtual reality (VR) devices are increasingly used in health care settings. The use among patients has the potential to unintentionally transmit pathogens between patients and hospital staff. No standard operating procedure for disinfection exists to ensure safe use between patients. OBJECTIVE: This study aims to determine the efficacy of disinfectants on VR devices in order to ensure safe use in health care settings. METHODS: Three types of bacteria were inoculated onto porous and nonporous surfaces of 2 VR devices: the Meta Oculus Quest and Meta Oculus Quest 2. Disinfection was performed using either isopropyl alcohol or alcohol-free quaternary ammonium wipes. A quantitative culture was used to assess the adequacy of disinfection. A survey was separately sent out to VR device technicians at other pediatric health care institutes to compare the methods of disinfection and how they were established. RESULTS: Both products achieved adequate disinfection of the treated surfaces; however, a greater log-kill was achieved on nonporous surfaces than on the porous surfaces. Alcohol performed better than quaternary ammonium on porous surfaces. The survey respondents reported a wide variability in disinfection processes with only 1 person reporting an established standard operating procedure. CONCLUSIONS: Disinfection can be achieved through the use of either isopropyl alcohol or quaternary ammonium products. Porous surfaces showed lesser log-kill rates than the nonporous surfaces, indicating that the use of an added barrier may be of benefit and should be a point of future research. Given the variability in the disinfection process across health care systems, a standard operating procedure is proposed.


Subject(s)
Ammonium Compounds , Virtual Reality , Child , Humans , Disinfection/methods , 2-Propanol , Ethanol , Surveys and Questionnaires , Delivery of Health Care
2.
Appl Environ Microbiol ; 84(8)2018 04 15.
Article in English | MEDLINE | ID: mdl-29439992

ABSTRACT

Hot-air hand dryers in multiple men's and women's bathrooms in three basic science research areas in an academic health center were screened for their deposition on plates of (i) total bacteria, some of which were identified, and (ii) a kanamycin-resistant Bacillus subtilis strain, PS533, spores of which are produced in large amounts in one basic science research laboratory. Plates exposed to hand dryer air for 30 s averaged 18 to 60 colonies/plate; but interior hand dryer nozzle surfaces had minimal bacterial levels, plates exposed to bathroom air for 2 min with hand dryers off averaged ≤1 colony, and plates exposed to bathroom air moved by a small fan for 20 min had averages of 15 and 12 colonies/plate in two buildings tested. Retrofitting hand dryers with HEPA filters reduced bacterial deposition by hand dryers ∼4-fold, and potential human pathogens were recovered from plates exposed to hand dryer air whether or not a HEPA filter was present and from bathroom air moved by a small fan. Spore-forming colonies, identified as B. subtilis PS533, averaged ∼2.5 to 5% of bacteria deposited by hand dryers throughout the basic research areas examined regardless of distance from the spore-forming laboratory, and these were almost certainly deposited as spores. Comparable results were obtained when bathroom air was sampled for spores. These results indicate that many kinds of bacteria, including potential pathogens and spores, can be deposited on hands exposed to bathroom hand dryers and that spores could be dispersed throughout buildings and deposited on hands by hand dryers.IMPORTANCE While there is evidence that bathroom hand dryers can disperse bacteria from hands or deposit bacteria on surfaces, including recently washed hands, there is less information on (i) the organisms dispersed by hand dryers, (ii) whether hand dryers provide a reservoir of bacteria or simply blow large amounts of bacterially contaminated air, and (iii) whether bacterial spores are deposited on surfaces by hand dryers. Consequently, this study has implications for the control of opportunistic bacterial pathogens and spores in public environments including health care settings. Within a large building, potentially pathogenic bacteria, including bacterial spores, may travel between rooms, and subsequent bacterial/spore deposition by hand dryers is a possible mechanism for spread of infectious bacteria, including spores of potential pathogens if present.


Subject(s)
Air Microbiology , Bacteria/isolation & purification , Hand Disinfection/methods , Hand/microbiology , Spores, Bacterial/isolation & purification , Toilet Facilities , Bacillus subtilis/isolation & purification , Humans , Mexico
3.
Curr Opin Pediatr ; 27(1): 124-31, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25565574

ABSTRACT

PURPOSE OF REVIEW: The prevalence of multidrug-resistant (MDR) infections caused by Gram-negative rods (GNRs) such as Escherichia coli and Klebsiella pneumoniae is increasing in large part because of the production of extended-spectrum ß-lactamases (ESBLs) that confer resistance to third-generation cephalosporins such as ceftriaxone. This review examines the clinical implication of changes in the epidemiology, diagnostic tools, and reporting criteria for ESBL-GNRs. RECENT FINDINGS: Pediatric ESBL-GNR infections, once associated only with hospitals, are increasing in the community. The most common risk factor for ESBL-GNR infection is previous antibiotic use. Evidence also exists for prolonged fecal carriage after discharge from neonatal ICUs, leading to community transmission with close contact of known carriers. Controversial changes in the laboratory criteria for GNR cephalosporin resistance have also contributed to the increased numbers of reported MDR-GNR infections. Newer diagnostic tools will enable more rapid identification of MDR-GNR infections, leading to earlier implementation of appropriate therapy. SUMMARY: ESBL-GNR infections are no longer limited to ICUs and are now being identified in children presenting from the community. Appropriate antibiotic prescribing practices are critical to limit the spread of ESBL-GNRs, and pediatricians must prepare to identify and treat these challenging infections.


Subject(s)
Community-Acquired Infections/microbiology , Drug Resistance, Multiple/immunology , Escherichia coli Infections/microbiology , Gram-Negative Bacterial Infections/microbiology , Klebsiella Infections/microbiology , beta-Lactamases/metabolism , Anti-Bacterial Agents , Child , Child, Preschool , Community-Acquired Infections/drug therapy , Community-Acquired Infections/epidemiology , Cross Infection , Escherichia coli/pathogenicity , Escherichia coli Infections/drug therapy , Escherichia coli Infections/immunology , Gram-Negative Bacterial Infections/epidemiology , Humans , Infant , Klebsiella Infections/drug therapy , Klebsiella Infections/immunology , Klebsiella pneumoniae/pathogenicity , Microbial Sensitivity Tests , Prevalence , beta-Lactam Resistance/immunology
4.
J Immunol ; 190(10): 5196-206, 2013 May 15.
Article in English | MEDLINE | ID: mdl-23606537

ABSTRACT

We have previously reported that TLR4 signaling is increased in LPS-stimulated cystic fibrosis (CF) macrophages (MΦs), contributing to the robust production of proinflammatory cytokines. The heme oxygenase-1 (HO-1)/CO pathway modulates cellular redox status, inflammatory responses, and cell survival. The HO-1 enzyme, together with the scaffold protein caveolin 1 (CAV-1), also acts as a negative regulator of TLR4 signaling in MΦs. In this study, we demonstrate that in LPS-challenged CF MΦs, HO-1 does not compartmentalize normally to the cell surface and instead accumulates intracellularly. The abnormal HO-1 localization in CF MΦs in response to LPS is due to decreased CAV-1 expression, which is controlled by the cellular oxidative state, and is required for HO-1 delivery to the cell surface. Overexpression of HO-1 or stimulating the pathway with CO-releasing molecules enhances CAV-1 expression in CF MΦs, suggesting a positive-feed forward loop between HO-1/CO induction and CAV-1 expression. These manipulations re-established HO-1 and CAV-1 cell surface localization in CF MΦs. Consistent with restoration of HO-1/CAV-1-negative regulation of TLR4 signaling, genetic or pharmacological (CO-releasing molecule 2) induced enhancement of this pathway decreased the inflammatory response of CF MΦs and CF mice treated with LPS. In conclusion, our results demonstrate that the counterregulatory HO-1/CO pathway, which is critical in balancing and limiting the inflammatory response, is defective in CF MΦs through a CAV-1-dependent mechanism, exacerbating the CF MΦ response to LPS. This pathway could be a potential target for therapeutic intervention for CF lung disease.


Subject(s)
Caveolin 1/metabolism , Cystic Fibrosis Transmembrane Conductance Regulator/metabolism , Heme Oxygenase-1/metabolism , Macrophages/immunology , Macrophages/metabolism , Adolescent , Adult , Animals , Caveolin 1/biosynthesis , Cells, Cultured , Child , Child, Preschool , Cystic Fibrosis/immunology , Cystic Fibrosis/metabolism , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Cystic Fibrosis Transmembrane Conductance Regulator/immunology , Female , Heme Oxygenase-1/biosynthesis , Humans , Inflammation/immunology , Lipopolysaccharides/immunology , Lung Diseases/immunology , Lung Diseases/metabolism , Male , Membrane Proteins/biosynthesis , Membrane Proteins/metabolism , Mice , Mice, Knockout , Nasal Polyps , Reactive Oxygen Species/metabolism , Signal Transduction , Toll-Like Receptor 4/metabolism , Young Adult
5.
Proc Natl Acad Sci U S A ; 108(13): 5354-9, 2011 Mar 29.
Article in English | MEDLINE | ID: mdl-21402903

ABSTRACT

Although commensal bacteria are crucial in maintaining immune homeostasis of the intestine, the role of commensal bacteria in immune responses at other mucosal surfaces remains less clear. Here, we show that commensal microbiota composition critically regulates the generation of virus-specific CD4 and CD8 T cells and antibody responses following respiratory influenza virus infection. By using various antibiotic treatments, we found that neomycin-sensitive bacteria are associated with the induction of productive immune responses in the lung. Local or distal injection of Toll-like receptor (TLR) ligands could rescue the immune impairment in the antibiotic-treated mice. Intact microbiota provided signals leading to the expression of mRNA for pro-IL-1ß and pro-IL-18 at steady state. Following influenza virus infection, inflammasome activation led to migration of dendritic cells (DCs) from the lung to the draining lymph node and T-cell priming. Our results reveal the importance of commensal microbiota in regulating immunity in the respiratory mucosa through the proper activation of inflammasomes.


Subject(s)
Adaptive Immunity/immunology , Influenza A virus/immunology , Metagenome , Respiratory Tract Infections/immunology , Respiratory Tract Infections/microbiology , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacteria/drug effects , Bacteria/immunology , Bacteria/pathogenicity , Dendritic Cells/immunology , Homeostasis , Host-Pathogen Interactions , Humans , Inflammasomes , Interleukin-18/genetics , Interleukin-18/immunology , Interleukin-1beta/genetics , Interleukin-1beta/immunology , Mice , Mice, Inbred C57BL , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/virology , Toll-Like Receptors/immunology
6.
Infect Dis Clin North Am ; 38(1): 149-162, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38280761

ABSTRACT

Patients with cystic fibrosis (CF) often develop respiratory tract infections with pathogenic multidrug-resistant organisms (MDROs) such as methicillin-resistant Staphylococcus aureus, and a variety of gram-negative organisms that include Pseudomonas aeruginosa, Burkholderia sp., Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and nontuberculous mycobacteria (NTM). Despite the introduction of new therapies to address underlying cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction, MDRO infections remain a problem and novel antimicrobial interventions are still needed. Therapeutic approaches include improving the efficacy of existing drugs by adjusting the dose based on differences in CF patient pharmacokinetics/pharmacodynamics, the development of inhaled formulations to reduce systemic adverse events, and the use of newer beta-lactam/beta-lactamase combinations. Alternative innovative therapeutic approaches include the use of gallium and bacteriophages to treat MDRO pulmonary infections including those with extreme antibiotic resistance. However, additional clinical trials are required to determine the optimal dosing and efficacy of these different strategies and to identify patients with CF most likely to benefit from these new treatment options.


Subject(s)
Anti-Infective Agents , Cystic Fibrosis , Methicillin-Resistant Staphylococcus aureus , Respiratory Tract Infections , Stenotrophomonas maltophilia , Humans , Cystic Fibrosis/complications , Cystic Fibrosis/drug therapy , Cystic Fibrosis/microbiology , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/microbiology , Anti-Infective Agents/therapeutic use , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use
7.
Article in English | MEDLINE | ID: mdl-38889196

ABSTRACT

Sepsis is a leading cause of pediatric mortality and timely antibiotic administration has been shown to improve outcomes. In this retrospective review of a single center sepsis dataset, we identified younger age and female sex as more likely to have delays in antibiotics.

8.
Article in English | MEDLINE | ID: mdl-38774120

ABSTRACT

COVID-19 vaccine uptake in healthcare personnel (HCP) is poor. A cross-sectional survey study of behavioral health HCP was performed. Commonly identified reasons for vaccination were protecting others and oneself. Reasons against were a lack of perceived protection, dosing intervals, and side effects. Assessing vaccination attitudes can assist in uptake strategy.

9.
Infect Control Hosp Epidemiol ; 44(2): 230-233, 2023 02.
Article in English | MEDLINE | ID: mdl-35387702

ABSTRACT

OBJECTIVE: Optimizing needleless connector hub disinfection practice is a key strategy in central-line-associated bloodstream infection (CLABSI) prevention. In this mixed-methods evaluation, 3 products with varying scrub times were tested for experimental disinfection followed by a qualitative nursing assessment of each. METHODS: Needleless connectors were inoculated with varying concentrations of Staphylococcus epidermidis, Pseudomonas aeruginosa, and Staphylococcus aureus followed by disinfection with a 70% isopropyl alcohol (IPA) wipe (a 15-second scrub time and a 15-second dry time), a 70% IPA cap (a 10-second scrub time and a 5-second dry time), or a 3.15% chlorhexidine gluconate with 70% IPA (CHG/IPA) wipe (a 5-second scrub time and a 5-second dry time). Cultures of needleless connectors were obtained after disinfection to quantify bacterial reduction. This was followed by surveying a convenience sample of nursing staff with intensive care unit assignments at an academic tertiary hospital on use of each product. RESULTS: All products reduced overall bacterial burden when compared to sterile water controls, however the IPA and CHG/IPA wipes were superior to the IPA caps when product efficacy was compared. Nursing staff noted improved compliance with CHG/IPA wipes compared with the IPA wipes and the IPA caps, with many preferring the lesser scrub and dry times required for disinfection. CONCLUSION: Achieving adequate bacterial disinfection of needleless connectors while maximizing healthcare staff compliance with scrub and dry times may be best achieved with a combination CHG/IPA wipe.


Subject(s)
Cross Infection , Disinfectants , Humans , Disinfectants/pharmacology , Cross Infection/prevention & control , Disinfection/methods , Chlorhexidine/pharmacology , Catheters, Indwelling/microbiology , 2-Propanol/pharmacology
10.
Pediatrics ; 151(2)2023 02 01.
Article in English | MEDLINE | ID: mdl-36625072

ABSTRACT

BACKGROUND AND OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) is prevalent in most NICUs, with a high rate of skin colonization and subsequent invasive infections among hospitalized neonates. The effectiveness of interventions designed to reduce MRSA infection in the NICU during the coronavirus disease 2019 (COVID-19) pandemic has not been characterized. METHODS: Using the Institute for Healthcare Improvement's Model for Improvement, we implemented several process-based infection prevention strategies to reduce invasive MRSA infections at our level IV NICU over 24 months. The outcome measure of invasive MRSA infections was tracked monthly utilizing control charts. Process measures focused on environmental disinfection and hospital personnel hygiene were also tracked monthly. The COVID-19 pandemic was an unexpected variable during the implementation of our project. The pandemic led to restricted visitation and heightened staff awareness of the importance of hand hygiene and proper use of personal protective equipment, as well as supply chain shortages, which may have influenced our outcome measure. RESULTS: Invasive MRSA infections were reduced from 0.131 to 0 per 1000 patient days during the initiative. This positive shift was sustained for 30 months, along with a delayed decrease in MRSA colonization rates. Several policy and practice changes regarding personnel hygiene and environmental cleaning likely contributed to this reduction. CONCLUSIONS: Implementation of a multidisciplinary quality improvement initiative aimed at infection prevention strategies led to a significant decrease in invasive MRSA infections in the setting of the COVID-19 pandemic.


Subject(s)
COVID-19 , Cross Infection , Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Infant, Newborn , Humans , Cross Infection/prevention & control , Cross Infection/epidemiology , Intensive Care Units, Neonatal , Staphylococcal Infections/epidemiology , Staphylococcal Infections/prevention & control , Pandemics/prevention & control , Infection Control , COVID-19/prevention & control
11.
Antimicrob Agents Chemother ; 56(1): 582-3, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22064529

ABSTRACT

The Etest glycopeptide resistance detection identified two potential heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) isolates from a screen of 288 methicillin-resistant Staphylococcus aureus (MRSA) isolates from patients at a Connecticut Veterans Hospital. However, the two isolates did not meet the criteria for hVISA by the population analysis profile-area under the curve analysis, arguing against routine screening for hVISA in this low prevalence population.


Subject(s)
Methicillin-Resistant Staphylococcus aureus/genetics , Staphylococcal Infections/drug therapy , Vancomycin Resistance , Vancomycin/administration & dosage , Aged , Anti-Bacterial Agents/administration & dosage , Area Under Curve , Bacterial Typing Techniques , Connecticut/epidemiology , False Positive Reactions , Humans , Male , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Microbial Sensitivity Tests , Prevalence , Staphylococcal Infections/epidemiology , Staphylococcal Infections/microbiology , Veterans
12.
Clin Chest Med ; 43(4): 667-676, 2022 12.
Article in English | MEDLINE | ID: mdl-36344073

ABSTRACT

Patients with cystic fibrosis (CF) often develop respiratory tract infections with pathogenic multidrug-resistant organisms (MDROs) such as methicillin-resistant Staphylococcus aureus, and a variety of gram-negative organisms that include Pseudomonas aeruginosa, Burkholderia sp., Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and nontuberculous mycobacteria (NTM). Despite the introduction of new therapies to address underlying cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction, MDRO infections remain a problem and novel antimicrobial interventions are still needed. Therapeutic approaches include improving the efficacy of existing drugs by adjusting the dose based on differences in CF patient pharmacokinetics/pharmacodynamics, the development of inhaled formulations to reduce systemic adverse events, and the use of newer beta-lactam/beta-lactamase combinations. Alternative innovative therapeutic approaches include the use of gallium and bacteriophages to treat MDRO pulmonary infections including those with extreme antibiotic resistance. However, additional clinical trials are required to determine the optimal dosing and efficacy of these different strategies and to identify patients with CF most likely to benefit from these new treatment options.


Subject(s)
Cystic Fibrosis , Methicillin-Resistant Staphylococcus aureus , Pseudomonas Infections , Respiratory Tract Infections , Stenotrophomonas maltophilia , Humans , Cystic Fibrosis/complications , Cystic Fibrosis/drug therapy , Pseudomonas aeruginosa , Respiratory Tract Infections/drug therapy , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Pseudomonas Infections/drug therapy
13.
Trop Med Infect Dis ; 7(2)2022 Feb 14.
Article in English | MEDLINE | ID: mdl-35202221

ABSTRACT

Pediatric patients with untreated tuberculosis infection (TBI), also called latent TBI, are at risk of progression to active TB disease. The primary aim of this study was to identify factors associated with higher rates of missed appointments and failure to complete therapy for pediatric patients with TBI. A secondary aim was to determine the impact of the COVID-19 pandemic and the rise of telehealth on TBI missed appointment rates. We first performed a retrospective chart review of 129 pediatric patients referred to the free Yale Pediatric Winchester Chest Tuberculosis Clinic from 2016-2019. Associations between demographic/clinical variables and missed appointments/failure to complete therapy were analyzed using univariate and bivariate chi-square tests. Language, lack of primary provider, and distance to clinic were the main contributors to missed appointments and poor treatment adherence. There was an association between the number of missed appointments and failure to complete treatment (p = 0.050). A second cohort of 29 patients was analyzed from January-December 2021 when telehealth was offered for follow-up appointments. Of these follow-up visits, 54% were conducted via telehealth, and the clinic's missed appointment rate dropped significantly from 16.9% to 5.8% during this time frame (p = 0.037). These data demonstrate that telehealth is accepted as an alternative by patients for follow-up TBI visits.

14.
Microbiol Spectr ; 10(1): e0253521, 2022 02 23.
Article in English | MEDLINE | ID: mdl-35107362

ABSTRACT

Patients with chronic respiratory diseases use home nebulizers that are often contaminated with pathogenic microbes to deliver aerosolized medications. The conditions under which these microbes leave the surface as bioaerosols during nebulization are not well characterized. The objectives of this study were to (i) determine whether different pathogens detach and disperse from the nebulizer surface during aerosolization and (ii) measure the effects of relative humidity and drying times on bacterial surface detachment and aerosolization. Bacteria were cultured from bioaerosols after Pari LC Plus albuterol nebulization using two different sources, as follows: (i) previously used nebulizers donated by anonymous patients with cystic fibrosis (CF) and (ii) nebulizers inoculated with bacteria isolated from the lungs of CF patients. Fractionated bioaerosols were collected with a Next-Generation Impactor. For a subset of bacteria, surface adherence during rewetting was measured with fluorescence microscopy. Bacteria dispersed from the surface of used CF patient nebulizers during albuterol nebulization. Eighty percent (16/20) of clinical isolates inoculated on the nebulizer in the laboratory formed bioaerosols. Detachment from the plastic surface into the chamber solution predicted bioaerosol production. Increased relative humidity and decreased drying times after inoculation favored bacterial dispersion on aerosols during nebulized therapy. Pathogenic bacteria contaminating nebulizer surfaces detached from the surface as bioaerosols during nebulized therapies, especially under environmental conditions when contaminated nebulizers were dried or stored at high relative humidity. This finding emphasizes the need for appropriate nebulizer cleaning, disinfection, and complete drying during storage and informs environmental conditions that favor bacterial surface detachment during nebulization. IMPORTANCE Studies from around the world have demonstrated that many patients use contaminated nebulizers to deliver medication into their lungs. While it is known that using contaminated medications in a nebulizer can lead to a lung infection, whether bacteria on the surface of a contaminated nebulizer detach as bioaerosols capable of reaching the lung has not been studied. This work demonstrates that a subset of clinical bacteria enter solution from the surface during nebulization and are aerosolized. Environmental conditions of high relative humidity during storage favor dispersion from the surface. We also provide results of an in vitro assay conducted to monitor bacterial surface detachment during multiple cycles of rewetting that correlate with the results of nebulizer/bacterial surface interactions. These studies demonstrate for the first time that pathogenic bacteria on the nebulizer surface pose a risk of bacterial inhalation to patients who use contaminated nebulizers.


Subject(s)
Bacteria/isolation & purification , Cystic Fibrosis/therapy , Equipment Contamination/statistics & numerical data , Nebulizers and Vaporizers/microbiology , Aerosols/chemistry , Bacteria/classification , Bacteria/genetics , Bacteria/growth & development , Bacterial Adhesion , Humans
15.
Exp Mol Med ; 54(5): 639-652, 2022 05.
Article in English | MEDLINE | ID: mdl-35581352

ABSTRACT

Overwhelming neutrophilic inflammation is a leading cause of lung damage in many pulmonary diseases, including cystic fibrosis (CF). The heme oxygenase-1 (HO-1)/carbon monoxide (CO) pathway mediates the resolution of inflammation and is defective in CF-affected macrophages (MΦs). Here, we provide evidence that systemic administration of PP-007, a CO releasing/O2 transfer agent, induces the expression of HO-1 in a myeloid differentiation factor 88 (MyD88) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)-dependent manner. It also rescues the reduced HO-1 levels in CF-affected cells induced in response to lipopolysaccharides (LPS) or Pseudomonas aeruginosa (PA). Treatment of CF and muco-obstructive lung disease mouse models with a single clinically relevant dose of PP-007 leads to effective resolution of lung neutrophilia and to decreased levels of proinflammatory cytokines in response to LPS. Using HO-1 conditional knockout mice, we show that the beneficial effect of PP-007 is due to the priming of circulating monocytes trafficking to the lungs in response to infection to express high levels of HO-1. Finally, we show that PP-007 does not compromise the clearance of PA in the setting of chronic airway infection. Overall, we reveal the mechanism of action of PP-007 responsible for the immunomodulatory function observed in clinical trials for a wide range of diseases and demonstrate the potential use of PP-007 in controlling neutrophilic pulmonary inflammation by promoting the expression of HO-1 in monocytes/macrophages.


Subject(s)
Cystic Fibrosis , Pneumonia , Animals , Cystic Fibrosis/complications , Cystic Fibrosis/metabolism , Cystic Fibrosis/pathology , Heme Oxygenase-1 , Inflammation/metabolism , Lipopolysaccharides/metabolism , Lung/pathology , Mice , Monocytes/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Pneumonia/pathology
16.
Cell Rep ; 41(11): 111797, 2022 12 13.
Article in English | MEDLINE | ID: mdl-36516754

ABSTRACT

Persistent neutrophil-dominated lung inflammation contributes to lung damage in cystic fibrosis (CF). However, the mechanisms that drive persistent lung neutrophilia and tissue deterioration in CF are not well characterized. Starting from the observation that, in patients with CF, c-c motif chemokine receptor 2 (CCR2)+ monocytes/macrophages are abundant in the lungs, we investigate the interplay between monocytes/macrophages and neutrophils in perpetuating lung tissue damage in CF. Here we show that CCR2+ monocytes in murine CF lungs drive pathogenic transforming growth factor ß (TGF-ß) signaling and sustain a pro-inflammatory environment by facilitating neutrophil recruitment. Targeting CCR2 to lower the numbers of monocytes in CF lungs ameliorates neutrophil inflammation and pathogenic TGF-ß signaling and prevents lung tissue damage. This study identifies CCR2+ monocytes as a neglected contributor to the pathogenesis of CF lung disease and as a therapeutic target for patients with CF, for whom lung hyperinflammation and tissue damage remain an issue despite recent advances in CF transmembrane conductance regulator (CFTR)-specific therapeutic agents.


Subject(s)
Cystic Fibrosis , Pneumonia , Humans , Mice , Animals , Cystic Fibrosis/pathology , Monocytes/metabolism , Cystic Fibrosis Transmembrane Conductance Regulator , Pneumonia/pathology , Lung/pathology , Inflammation/pathology , Receptors, Chemokine/metabolism , Macrophages/metabolism , Transforming Growth Factor beta/metabolism
17.
JAMA Netw Open ; 5(1): e2141227, 2022 01 04.
Article in English | MEDLINE | ID: mdl-35084484

ABSTRACT

Importance: It is not known how effective child masking is in childcare settings in preventing the transmission of SARS-CoV-2. This question is critical to inform health policy and safe childcare practices. Objective: To assess the association between masking children 2 years and older and subsequent childcare closure because of COVID-19. Design, Setting, and Participants: A prospective, 1-year, longitudinal electronic survey study of 6654 childcare professionals at home- and center-based childcare programs in all 50 states was conducted at baseline (May 22 to June 8, 2020) and follow-up (May 26 to June 23, 2021). Using a generalized linear model (log-binomial model) with robust SEs, this study evaluated the association between childcare program closure because of a confirmed or suspected COVID-19 case in either children or staff during the study period and child masking in both early adoption (endorsed at baseline) and continued masking (endorsed at baseline and follow-up), while controlling for physical distancing, other risk mitigation strategies, and program and community characteristics. Exposures: Child masking in childcare programs as reported by childcare professionals at baseline and both baseline and follow-up. Main Outcomes and Measures: Childcare program closure because of a suspected or confirmed COVID-19 case in either children or staff as reported in the May 26 to June 23, 2021, end survey. Results: This survey study of 6654 childcare professionals (mean [SD] age, 46.9 [11.3] years; 750 [11.3%] were African American, 57 [0.9%] American Indian/Alaska Native, 158 [2.4%] Asian, 860 [12.9%] Hispanic, 135 [2.0%] multiracial [anyone who selected >1 race on the survey], 18 [0.3%] Native Hawaiian/Pacific Islander, and 5020 [75.4%] White) found that early adoption (baseline) of child masking was associated with a 13% lower risk of childcare program closure because of a COVID-19 case (adjusted relative risk, 0.87; 95% CI, 0.77-0.99), and continued masking for 1 year was associated with a 14% lower risk (adjusted relative risk, 0.86; 95% CI, 0.74-1.00). Conclusions and Relevance: This survey study of childcare professionals suggests that masking young children is associated with fewer childcare program closures, enabling in-person education. This finding has important public health policy implications for families that rely on childcare to sustain employment.


Subject(s)
COVID-19/prevention & control , Child Care/statistics & numerical data , Child Care/standards , Child Day Care Centers/statistics & numerical data , Child Day Care Centers/standards , Masks/statistics & numerical data , Masks/standards , Adult , COVID-19/epidemiology , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Longitudinal Studies , Male , Middle Aged , Prospective Studies , SARS-CoV-2 , United States/epidemiology
18.
Mol Microbiol ; 75(1): 76-91, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19943895

ABSTRACT

Oxidative stress is one of the main challenges bacteria must cope with during infection. Here, we identify a new oxidative stress sensing and response ospR (oxidative stress response and pigment production Regulator) gene in Pseudomonas aeruginosa. Deletion of ospR leads to a significant induction in H(2)O(2) resistance. This effect is mediated by de-repression of PA2826, which lies immediately upstream of ospR and encodes a glutathione peroxidase. Constitutive expression of ospR alters pigment production and beta-lactam resistance in P. aeruginosa via a PA2826-independent manner. We further discovered that OspR regulates additional genes involved in quorum sensing and tyrosine metabolism. These regulatory effects are redox-mediated as addition of H(2)O(2) or cumene hydroperoxide leads to the dissociation of OspR from promoter DNA. A conserved Cys residue, Cys-24, plays the major role of oxidative stress sensing in OspR. The serine substitution mutant of Cys-24 is less susceptible to oxidation in vitro and exhibits altered pigmentation and beta-lactam resistance. Lastly, we show that an ospR null mutant strain displays a greater capacity for dissemination than wild-type MPAO1 strain in a murine model of acute pneumonia. Thus, OspR is a global regulator that senses oxidative stress and regulates multiple pathways to enhance the survival of P. aeruginosa inside host.


Subject(s)
Gene Expression Regulation, Bacterial , Pseudomonas aeruginosa/physiology , Repressor Proteins/physiology , Stress, Physiological , Amino Acid Substitution/genetics , Animals , Anti-Bacterial Agents/pharmacology , Female , Gene Deletion , Glutathione Peroxidase/metabolism , Hydrogen Peroxide/toxicity , Mice , Mice, Inbred C57BL , Models, Biological , Mutagenesis, Site-Directed , Oxidative Stress , Pigments, Biological/biosynthesis , Pneumonia/microbiology , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/metabolism , Pseudomonas aeruginosa/pathogenicity , Quorum Sensing , Repressor Proteins/genetics , Signal Transduction , Tyrosine/metabolism , Virulence , beta-Lactam Resistance , beta-Lactams/pharmacology
19.
Yale J Biol Med ; 84(3): 321-4, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21966051

ABSTRACT

A 26-year-old male intravenous drug user (IDU) presented twice within 6 months with relapsed polymicrobial infective endocarditis (IE) due to Eikenella corrodens and Streptococcus constellatus after completing two courses of appropriate antimicrobial therapy. This report points to relapsing endocarditis as a clinical entity that warrants attention in IDUs when E. corrodens or S. constellatus are causative agents of IE.


Subject(s)
Coinfection/microbiology , Eikenella corrodens/pathogenicity , Endocarditis, Bacterial/microbiology , Gram-Negative Bacterial Infections/drug therapy , Streptococcal Infections/drug therapy , Streptococcus constellatus/pathogenicity , Adult , Ceftriaxone/pharmacology , Eikenella corrodens/isolation & purification , Gram-Negative Bacterial Infections/microbiology , Humans , Male , Metronidazole/pharmacology , Oxacillin/pharmacology , Recurrence , Streptococcal Infections/microbiology , Streptococcus constellatus/isolation & purification , Substance-Related Disorders
20.
Pediatr Infect Dis J ; 40(3): 175-181, 2021 03 01.
Article in English | MEDLINE | ID: mdl-33399431

ABSTRACT

BACKGROUND: The objective was to evaluate patterns of pediatric coronavirus disease 2019 testing in a large health system throughout the pandemic, before and after school reopening. METHODS: This was a cross-sectional time-series study of clinical virology results from children tested for severe acute respiratory syndrome coronavirus 2 in Southern Connecticut and areas of New York and Rhode Island. Data collected include demographics, hospital admission, changes in percent positive tests over time, detection intervals in persistently positive children and cycle threshold values. The setting was the Yale New Haven Health System has 6 hospitals at 4 Connecticut locations, 1 hospital in Rhode Island and ambulatory locations in Connecticut, Rhode Island and New York. Participants included twenty-three-thousand one-hundred thirty-seven children ≤ 18 years of age, tested for coronavirus disease 2019 at an ambulatory testing site, the emergency department or on an inpatient unit within the Yale New Haven Health System. RESULTS: Among all tests, 3.2% were positive. Older children consistently made up the larger portion of positive pediatric cases, regardless of community prevalence. Increased pediatric cases later in the pandemic when prevalence in adults was relatively low correlates with a higher number of tests performed in children and not with an increased positivity rate. No significant changes in trends of positivity were detected after the reopening of schools. Symptomatic and asymptomatic children had similar cycle threshold values regardless of age, and a subset of children demonstrated persistent viral detection, some for as long as 6 weeks. CONCLUSION: An increase in pediatric cases documented in the late summer was predominately due to increased access to testing for children. The percent positivity in children did not change in the first 3 weeks after school opened. A subset of children has detectable severe acute respiratory syndrome coronavirus 2 RNA in the upper respiratory tract for weeks after the initial infection.


Subject(s)
COVID-19/epidemiology , Pandemics , SARS-CoV-2/isolation & purification , Adolescent , COVID-19/virology , COVID-19 Testing , Child , Child, Preschool , Connecticut/epidemiology , Cross-Sectional Studies , Demography , Female , Hospitalization , Humans , Inpatients , Male , New York/epidemiology , Prevalence , Rhode Island/epidemiology , SARS-CoV-2/genetics
SELECTION OF CITATIONS
SEARCH DETAIL