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Assessing Acinetobacter baumannii Virulence and Persistence in a Murine Model of Lung Infection.
Palmer LD, Green ER, Sheldon JR, Skaar EP
(2019) Methods Mol Biol 1946: 289-305
MeSH Terms: Acinetobacter Infections, Acinetobacter baumannii, Acute Disease, Animals, Bacterial Load, Biopsy, Disease Models, Animal, Flow Cytometry, Immunity, Immunohistochemistry, Mice, Pneumonia, Bacterial, Virulence
Show Abstract · Added April 2, 2019
Acinetobacter baumannii is a Gram-negative opportunistic pathogen and a leading cause of ventilator-associated pneumonia. Murine models of A. baumannii lung infection allow researchers to experimentally assess A. baumannii virulence and host response. Intranasal administration of A. baumannii models acute lung infection. This chapter describes the methods to test A. baumannii virulence in a murine model of lung infection, including assessing the competitive index of a bacterial mutant and the associated inflammatory responses.
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13 MeSH Terms
In-Hospital Deaths Among Adults With Community-Acquired Pneumonia.
Waterer GW, Self WH, Courtney DM, Grijalva CG, Balk RA, Girard TD, Fakhran SS, Trabue C, McNabb P, Anderson EJ, Williams DJ, Bramley AM, Jain S, Edwards KM, Wunderink RG
(2018) Chest 154: 628-635
MeSH Terms: Adult, Aged, Aged, 80 and over, Cause of Death, Community-Acquired Infections, Female, Hospital Mortality, Humans, Male, Middle Aged, Pneumonia, Prospective Studies, Risk Factors, United States
Show Abstract · Added July 27, 2018
BACKGROUND - Adults hospitalized with community-acquired pneumonia (CAP) are at high risk for short-term mortality. However, it is unclear whether improvements in in-hospital pneumonia care could substantially lower this risk. We extensively reviewed all in-hospital deaths in a large prospective CAP study to assess the cause of each death and assess the extent of potentially preventable mortality.
METHODS - We enrolled adults hospitalized with CAP at five tertiary-care hospitals in the United States. Five physician investigators reviewed the medical record and study database for each patient who died to identify the cause of death, the contribution of CAP to death, and any preventable factors potentially contributing to death.
RESULTS - Among 2,320 enrolled patients, 52 (2.2%) died during initial hospitalization. Among these 52 patients, 33 (63.4%) were ≥ 65 years old, and 32 (61.5%) had ≥ two chronic comorbidities. CAP was judged to be the direct cause of death in 27 patients (51.9%). Ten patients (19.2%) had do-not-resuscitate orders prior to admission. Four patients were identified in whom a lapse in quality of care potentially contributed to death; preexisting end-of-life limitations were present in two of these patients. Two patients seeking full medical care experienced a lapse in in-hospital quality of pneumonia care that potentially contributed to death.
CONCLUSIONS - In this study of adults with CAP at tertiary-care hospitals with a low mortality rate, most in-hospital deaths did not appear to be preventable with improvements in in-hospital pneumonia care. Preexisting end-of-life limitations in care, advanced age, and high comorbidity burden were common among those who died.
Copyright © 2018 American College of Chest Physicians. All rights reserved.
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14 MeSH Terms
Response.
Self WH, Upchurch CP, Wunderink RG, Waterer GW, Grijalva CG, Edwards KM
(2018) Chest 153: 763-764
MeSH Terms: Community-Acquired Infections, Humans, Pneumonia, Radiography, Tomography, X-Ray Computed
Added July 27, 2018
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5 MeSH Terms
Long-Term Cognitive Impairment after Hospitalization for Community-Acquired Pneumonia: a Prospective Cohort Study.
Girard TD, Self WH, Edwards KM, Grijalva CG, Zhu Y, Williams DJ, Jain S, Jackson JC
(2018) J Gen Intern Med 33: 929-935
MeSH Terms: Adult, Aged, Aged, 80 and over, Cognitive Dysfunction, Cohort Studies, Community-Acquired Infections, Female, Follow-Up Studies, Hospitalization, Humans, Male, Middle Aged, Pneumonia, Prospective Studies, Surveys and Questionnaires, Time Factors, Young Adult
Show Abstract · Added July 27, 2018
BACKGROUND - Recent studies suggest older patients hospitalized for community-acquired pneumonia are at risk for new-onset cognitive impairment. The characteristics of long-term cognitive impairment after pneumonia, however, have not been elucidated.
OBJECTIVE - To characterize long-term cognitive impairment among adults of all ages hospitalized for community-acquired pneumonia.
DESIGN - Prospective cohort study.
PARTICIPANTS - Adults without severe preexisting cognitive impairment who were hospitalized with community-acquired pneumonia.
MAIN MEASURES - At enrollment, we estimated baseline cognitive function with the Short Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). At 2- and 12-month follow-up, we assessed cognition using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and tests of executive function, diagnosing cognitive impairment when results were ≥ 1.5 standard deviations below published age-adjusted means for the general population. We also identified subtypes of mild cognitive impairment using standard definitions.
KEY RESULTS - We assessed 58 (73%) of 80 patients who survived to 2-month follow-up and 57 (77%) of 74 who survived to 12-month follow-up. The median [range] age of survivors tested was 57 [19-97] years. Only 8 (12%) had evidence of mild cognitive impairment at baseline according to the Short IQCODE, but 21 (38%) at 2 months and 17 (30%) at 12 months had mild cognitive impairment per the RBANS. Moderate-to-severe cognitive impairment was common among adults ≥ 65 years [4/13 (31%) and 5/13 (38%) at 2 and 12 months, respectively] but also affected many of those < 65 years [10/43 (23%) and 8/43 (19%) at 2 and 12 months, respectively]. Deficits were most often noted in visuospatial function, attention, and memory.
CONCLUSIONS - A year after hospitalization for community-acquired pneumonia, moderate-to-severe impairment in multiple cognitive domains affected one-third of patients ≥ 65 years old and 20% of younger patients, and another third of survivors had mild cognitive impairment.
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17 MeSH Terms
Procalcitonin as a Marker of Etiology in Adults Hospitalized With Community-Acquired Pneumonia.
Self WH, Wunderink RG, Jain S, Edwards KM, Grijalva CG, Etiology of Pneumonia in the Community (EPIC) Study Investigators
(2018) Clin Infect Dis 66: 1640-1641
MeSH Terms: Adult, Community-Acquired Infections, Humans, Pneumonia, Procalcitonin
Added July 27, 2018
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5 MeSH Terms
Pneumococcal Community-Acquired Pneumonia Detected by Serotype-Specific Urinary Antigen Detection Assays.
Wunderink RG, Self WH, Anderson EJ, Balk R, Fakhran S, Courtney DM, Qi C, Williams DJ, Zhu Y, Whitney CG, Moore MR, Bramley A, Jain S, Edwards KM, Grijalva CG
(2018) Clin Infect Dis 66: 1504-1510
MeSH Terms: Adult, Aged, Antigens, Bacterial, Community-Acquired Infections, Diagnostic Tests, Routine, Female, Humans, Male, Middle Aged, Pneumococcal Infections, Pneumonia, Bacterial, Serogroup, Urinalysis
Show Abstract · Added July 27, 2018
Background - Streptococcus pneumoniae is considered the leading bacterial cause of pneumonia in adults. Yet, it was not commonly detected by traditional culture-based and conventional urinary testing in a recent multicenter etiology study of adults hospitalized with community-acquired pneumonia (CAP). We used novel serotype-specific urinary antigen detection (SSUAD) assays to determine whether pneumococcal cases were missed by traditional testing.
Methods - We studied adult patients hospitalized with CAP at 5 hospitals in Chicago and Nashville (2010-2012) and enrolled in the Etiology of Pneumonia in the Community (EPIC) study. Traditional diagnostic testing included blood and sputum cultures and conventional urine antigen detection (ie, BinaxNOW). We applied SSUAD assays that target serotypes included in the 13-valent pneumococcal conjugate vaccine (PCV13) to stored residual urine specimens.
Results - Among 1736 patients with SSUAD and ≥1 traditional pneumococcal test performed, we identified 169 (9.7%) cases of pneumococcal CAP. Traditional tests identified 93 (5.4%) and SSUAD identified 76 (4.4%) additional cases. Among 14 PCV13-serotype cases identified by culture, SSUAD correctly identified the same serotype in all of them. Cases identified by SSUAD vs traditional tests were similar in most demographic and clinical characteristics, although disease severity and procalcitonin concentration were highest among those with positive blood cultures. The proportion of pneumonia cases caused by serotypes exclusively covered by PCV13 was not significantly different between the first and second July-June study periods (6.4% vs 4.0%).
Conclusions - Although restricted to the detection of only 13 serotypes, SSUAD testing substantially increased the detection of pneumococcal pneumonia among adults hospitalized with CAP.
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13 MeSH Terms
Increased non-AIDS mortality among persons with AIDS-defining events after antiretroviral therapy initiation.
Pettit AC, Giganti MJ, Ingle SM, May MT, Shepherd BE, Gill MJ, Fätkenheuer G, Abgrall S, Saag MS, Del Amo J, Justice AC, Miro JM, Cavasinni M, Dabis F, Monforte AD, Reiss P, Guest J, Moore D, Shepherd L, Obel N, Crane HM, Smith C, Teira R, Zangerle R, Sterne JA, Sterling TR, Antiretroviral Therapy Cohort Collaboration (ART-CC) investigators
(2018) J Int AIDS Soc 21:
MeSH Terms: Acquired Immunodeficiency Syndrome, Adult, Anti-HIV Agents, Cohort Studies, Female, Humans, Lymphoma, Non-Hodgkin, Male, Middle Aged, Pneumonia, Pneumocystis, Tuberculosis
Show Abstract · Added March 14, 2018
INTRODUCTION - HIV-1 infection leads to chronic inflammation and to an increased risk of non-AIDS mortality. Our objective was to determine whether AIDS-defining events (ADEs) were associated with increased overall and cause-specific non-AIDS related mortality after antiretroviral therapy (ART) initiation.
METHODS - We included HIV treatment-naïve adults from the Antiretroviral Therapy Cohort Collaboration (ART-CC) who initiated ART from 1996 to 2014. Causes of death were assigned using the Coding Causes of Death in HIV (CoDe) protocol. The adjusted hazard ratio (aHR) for overall and cause-specific non-AIDS mortality among those with an ADE (all ADEs, tuberculosis (TB), Pneumocystis jiroveci pneumonia (PJP), and non-Hodgkin's lymphoma (NHL)) compared to those without an ADE was estimated using a marginal structural model.
RESULTS - The adjusted hazard of overall non-AIDS mortality was higher among those with any ADE compared to those without any ADE (aHR 2.21, 95% confidence interval (CI) 2.00 to 2.43). The adjusted hazard of each of the cause-specific non-AIDS related deaths were higher among those with any ADE compared to those without, except metabolic deaths (malignancy aHR 2.59 (95% CI 2.13 to 3.14), accident/suicide/overdose aHR 1.37 (95% CI 1.05 to 1.79), cardiovascular aHR 1.95 (95% CI 1.54 to 2.48), infection aHR (95% CI 1.68 to 2.81), hepatic aHR 2.09 (95% CI 1.61 to 2.72), respiratory aHR 4.28 (95% CI 2.67 to 6.88), renal aHR 5.81 (95% CI 2.69 to 12.56) and central nervous aHR 1.53 (95% CI 1.18 to 5.44)). The risk of overall and cause-specific non-AIDS mortality differed depending on the specific ADE of interest (TB, PJP, NHL).
CONCLUSIONS - In this large multi-centre cohort collaboration with standardized assignment of causes of death, non-AIDS mortality was twice as high among patients with an ADE compared to without an ADE. However, non-AIDS related mortality after an ADE depended on the ADE of interest. Although there may be unmeasured confounders, these findings suggest that a common pathway may be independently driving both ADEs and NADE mortality. While prevention of ADEs may reduce subsequent death due to NADEs following ART initiation, modification of risk factors for NADE mortality remains important after ADE survival.
© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.
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11 MeSH Terms
Bacterial-derived Neutrophilic Inflammation Drives Lung Remodeling in a Mouse Model of Chronic Obstructive Pulmonary Disease.
Richmond BW, Du RH, Han W, Benjamin JT, van der Meer R, Gleaves L, Guo M, McKissack A, Zhang Y, Cheng DS, Polosukhin VV, Blackwell TS
(2018) Am J Respir Cell Mol Biol 58: 736-744
MeSH Terms: Airway Remodeling, Aminopyridines, Animals, Bacillus, Benzamides, Cyclopropanes, Disease Models, Animal, Mice, Inbred C57BL, Mice, Mutant Strains, Neutrophils, Pneumonia, Bacterial, Pulmonary Disease, Chronic Obstructive, Pulmonary Emphysema, Receptors, Cell Surface
Show Abstract · Added March 21, 2018
Loss of secretory IgA is common in the small airways of patients with chronic obstructive pulmonary disease and may contribute to disease pathogenesis. Using mice that lack secretory IgA in the airways due to genetic deficiency of polymeric Ig receptor (pIgR mice), we investigated the role of neutrophils in driving the fibrotic small airway wall remodeling and emphysema that develops spontaneously in these mice. By flow cytometry, we found an increase in the percentage of neutrophils among CD45 cells in the lungs, as well as an increase in total neutrophils, in pIgR mice compared with wild-type controls. This increase in neutrophils in pIgR mice was associated with elastin degradation in the alveolar compartment and around small airways, along with increased collagen deposition in small airway walls. Neutrophil depletion using anti-Ly6G antibodies or treatment with broad-spectrum antibiotics inhibited development of both emphysema and small airway remodeling, suggesting that airway bacteria provide the stimulus for deleterious neutrophilic inflammation in this model. Exogenous bacterial challenge using lysates prepared from pathogenic and nonpathogenic bacteria worsened neutrophilic inflammation and lung remodeling in pIgR mice. This phenotype was abrogated by antiinflammatory therapy with roflumilast. Together, these studies support the concept that disruption of the mucosal immune barrier in small airways contributes to chronic obstructive pulmonary disease progression by allowing bacteria to stimulate chronic neutrophilic inflammation, which, in turn, drives progressive airway wall fibrosis and emphysematous changes in the lung parenchyma.
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14 MeSH Terms
Etiology and Impact of Coinfections in Children Hospitalized With Community-Acquired Pneumonia.
Nolan VG, Arnold SR, Bramley AM, Ampofo K, Williams DJ, Grijalva CG, Self WH, Anderson EJ, Wunderink RG, Edwards KM, Pavia AT, Jain S, McCullers JA
(2018) J Infect Dis 218: 179-188
MeSH Terms: Adolescent, Bacteria, Child, Child, Preschool, Cohort Studies, Coinfection, Community-Acquired Infections, Female, Hospitalization, Humans, Infant, Infant, Newborn, Male, Pneumonia, Treatment Outcome, Viruses
Show Abstract · Added July 27, 2018
Background - Recognition that coinfections are common in children with community-acquired pneumonia (CAP) is increasing, but gaps remain in our understanding of their frequency and importance.
Methods - We analyzed data from 2219 children hospitalized with CAP and compared demographic and clinical characteristics and outcomes between groups with viruses alone, bacteria alone, or coinfections. We also assessed the frequency of selected pairings of codetected pathogens and their clinical characteristics.
Results - A total of 576 children (26%) had a coinfection. Children with only virus detected were younger, more likely to be black, and more likely to have comorbidities such as asthma, compared with children infected with typical bacteria alone. Children with virus-bacterium coinfections had a higher frequency of leukocytosis, consolidation on chest radiography, parapneumonic effusions, intensive care unit admission, and need for mechanical ventilation and an increased length of stay, compared with children infected with viruses alone. Virus-virus coinfections were generally comparable to single-virus infections, with the exception of the need for oxygen supplementation, which was higher during the first 24 hours of hospitalization in some virus-virus pairings.
Conclusions - Coinfections occurred in 26% of children hospitalized for CAP. Children with typical bacterial infections, alone or complicated by a viral infection, have worse outcomes than children infected with a virus alone.
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16 MeSH Terms
An Unusual Source of Sepsis in Two Previously Healthy Children.
Frazier SB, Katz S, Wood JB, Cassat JE
(2018) Clin Pediatr (Phila) 57: 1120-1122
MeSH Terms: Anti-Bacterial Agents, Bacteremia, Child, Combined Modality Therapy, Disease Progression, Emergency Service, Hospital, Fluid Therapy, Follow-Up Studies, Humans, Infant, Male, Pneumonia, Bacterial, Pyelonephritis, Risk Assessment, Sampling Studies, Severity of Illness Index, Streptococcal Infections, Treatment Outcome
Added April 3, 2018
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18 MeSH Terms