Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-30 (of 34 Records) |
Query Trace: McCullers JA[original query] |
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Association of radiology findings with etiology of community acquired pneumonia among children
Arnold SR , Jain S , Dansie D , Kan H , Williams DJ , Ampofo K , Anderson EJ , Grijalva CG , Bramley AM , Pavia AT , Edwards KM , Nolan VG , McCullers JA , Kaufman RA . J Pediatr 2023 261 113333 OBJECTIVE: To evaluate the association between consolidation on chest radiograph and typical bacterial etiology of childhood community acquired pneumonia (CAP) in the Etiology of Pneumonia in the Community study. STUDY DESIGN: Hospitalized children <18 years of age with CAP enrolled in the Etiology of Pneumonia in the Community study at 3 children's hospitals between January 2010 and June 2012 were included. Testing of blood and respiratory specimens used multiple modalities to identify typical and atypical bacterial, or viral infection. Study radiologists classified chest radiographs (consolidation, other infiltrates [interstitial and/or alveolar], pleural effusion) using modified World Health Organization pneumonia criteria. Infiltrate patterns were compared according to etiology of CAP. RESULTS: Among 2212 children, there were 1302 (59%) with consolidation with or without other infiltrates, 910 (41%) with other infiltrates, and 296 (13%) with pleural effusion. In 1795 children, at least 1 pathogen was detected. Among these patients, consolidation (74%) was the most frequently observed pattern (74% in typical bacterial CAP, 58% in atypical bacterial CAP, and 54% in viral CAP). Positive and negative predictive values of consolidation for typical bacterial CAP were 12% (95% CI 10%-15%) and 96% (95% CI 95%-97%) respectively. In a multivariable model, typical bacterial CAP was associated with pleural effusion (OR 7.3, 95% CI 4.7-11.2) and white blood cell ≥15 000/mL (OR 3.2, 95% CI 2.2-4.9), and absence of wheeze (OR 0.5, 95% CI 0.3-0.8) or viral detection (OR 0.2, 95% CI 0.1-0.4). CONCLUSIONS: Consolidation predicted typical bacterial CAP poorly, but its absence made typical bacterial CAP unlikely. Pleural effusion was the best predictor of typical bacterial infection, but too uncommon to aid etiology prediction. |
Red blood cell distribution width and pediatric community-acquired pneumonia disease severity
Lee J , Zhu Y , Williams DJ , Self WH , Arnold SR , McCullers JA , Ampofo K , Pavia AT , Anderson EJ , Jain S , Edwards KM , Grijalva CG . Hosp Pediatr 2022 12 (9) 798-805 BACKGROUND AND OBJECTIVES: No standardized risk assessment tool exists for community-acquired pneumonia (CAP) in children. This study aims to investigate the association between red blood cell distribution width (RDW) and pediatric CAP. METHODS: Data prospectively collected by the Etiology of Pneumonia in the Community study (2010-2012) was used. Study population was pediatric patients admitted to tertiary care hospitals in Nashville and Memphis, Tennessee with clinically and radiographically confirmed CAP. The earliest measured RDW value on admission was used, in quintiles and also as a continuous variable. Outcomes analyzed were: severe CAP (requiring ICU, mechanical ventilation, vasopressor support, or death) or moderate CAP (hospital admission only). Analysis used multivariable logistic regression and restricted cubic splines modeling. RESULTS: In 1459 eligible children, the median age was 29 months (interquartile range: 12-73), median RDW was 13.3% (interquartile range: 12.5-14.3), and 289 patients (19.8%) developed severe disease. In comparison with the lowest RDW quintile (Q1), the adjusted odds ratio (95% CI) for severe CAP in subsequent quintiles were, Q2: 1.20 (0.72-1.99); Q3: 1.28 (0.76-2.14); Q4: 1.69 (1.01-2.82); Q5: 1.25 (0.73-2.13). Consistently, RDW restricted cubic splines demonstrated an independent, nonlinear, positive association with CAP severity (P = .027), with rapid increases in the risk of severe CAP with RDW values up to 15%. CONCLUSIONS: Higher presenting RDW was associated with an increased risk of severe CAP in hospitalized children. Widely available and inexpensive, RDW can serve as an objective data point to help with clinical assessments. |
Parainfluenza virus types 1-3 infections among children and adults hospitalized with community-acquired pneumonia
Howard LM , Edwards KM , Zhu Y , Williams DJ , Self WH , Jain S , Ampofo K , Pavia AT , Arnold SR , McCullers JA , Anderson EJ , Wunderink RG , Grijalva CG . Clin Infect Dis 2020 73 (11) e4433-e4443 BACKGROUND: Parainfluenza virus (PIV) is a leading cause of lower respiratory tract infections. Although there are several distinct PIV serotypes, few studies have compared the clinical characteristics and severity of infection among the individual PIV serotypes and between PIV and other pathogens in patients with community-acquired pneumonia. METHODS: We conducted active population-based surveillance for radiographically confirmed community-acquired pneumonia hospitalizations among children and adults in eight United States hospitals with systematic collection of clinical data and respiratory, blood, and serological specimens for pathogen detection. We compared clinical features of PIV-associated pneumonia among individual serotypes 1, 2, and 3 and among all PIV infections with other viral, atypical, and bacterial pneumonias. We also compared in-hospital disease severity among groups employing an ordinal scale (mild, moderate, severe) using multivariable proportional odds regression. RESULTS: PIV was more commonly detected in children (155/2354 [6.6%]) than in adults (66/2297 [2.9%]) (p<0.001). Other pathogens were commonly co-detected among PIV cases (110/221 [50%]). Clinical features of PIV-1, PIV-2, and PIV-3 infections were similar to one another in both children and adults with pneumonia. In multivariable analysis, children with PIV-associated pneumonia exhibited similar severity to children with other non-bacterial pneumonia; whereas children with bacterial pneumonia, exhibited increased severity (OR 8.42 [95% CI 1.88, 37.80]). In adults, PIV-associated pneumonia exhibited similar severity to other pneumonia pathogens. CONCLUSIONS: Clinical features did not distinguish among infection with individual PIV serotypes in patients hospitalized with community acquired pneumonia. However, in children, PIV pneumonia was less severe than bacterial pneumonia. |
Clinical features of human metapneumovirus-associated community-acquired pneumonia hospitalizations
Howard LM , Edwards KM , Zhu Y , Grijalva CG , Self WH , Jain S , Ampofo K , Pavia AT , Arnold SR , McCullers JA , Anderson EJ , Wunderink RG , Williams DJ . Clin Infect Dis 2020 72 (1) 108-117 BACKGROUND: Human metapneumovirus (HMPV) is a leading cause of respiratory tract infections. Few studies have compared the clinical characteristics and severity of HMPV-associated pneumonia with other pathogens. METHODS: Active population-based surveillance was previously conducted for radiographically-confirmed community-acquired pneumonia hospitalizations among children and adults in eight United States hospitals. Clinical data and specimens for pathogen detection were systematically collected. We described clinical features of all HMPV-associated pneumonia, and after excluding co-detections with other pathogen types, we compared features of HMPV-associated pneumonia with other viral, atypical, and bacterial pneumonia and modeled severity (mild, moderate, severe) and length of stay using multivariable proportional odds regression. RESULTS: HMPV was detected in 298/2358 (12.6%) children and 88/2320 (3.8%) adults hospitalized with pneumonia and was commonly co-detected with other pathogens (125/298 [42%] children and 21/88 [24%] adults). Fever and cough were the most common presenting symptoms of HMPV-associated pneumonia and were also common symptoms of other pathogens. After excluding co-detections, in children (n=1778), compared to HMPV (reference), bacterial pneumonia exhibited increased severity (OR 3.66 [95% CI 1.43-9.40]), RSV (0.76 [0.59-0.99]) and atypical (0.39 [0.19-0.81]) infections exhibited decreased severity, and other viral pneumonia exhibited similar severity (0.88 [0.55-1.39]). In adults (n=2145), bacterial (3.74 [1.87-7.47]) and RSV pneumonia (1.82 [1.32-2.50]) were more severe than HMPV (reference), but all other pathogens had similar severity. CONCLUSIONS: Clinical features did not reliably distinguish HMPV-associated pneumonia from other pathogens. HMPV-associated pneumonia was less severe than bacterial and adult RSV pneumonia but otherwise as or more severe than other common pathogens. |
Prevalence, risk factors, and outcomes of bacteremic pneumonia in children
Fritz CQ , Edwards KM , Self WH , Grijalva CG , Zhu Y , Arnold SR , McCullers JA , Ampofo K , Pavia AT , Wunderink RG , Anderson EJ , Bramley AM , Jain S , Williams DJ . Pediatrics 2019 144 (1) BACKGROUND: Previous studies examining bacteremia in hospitalized children with pneumonia are limited by incomplete culture data. We sought to determine characteristics of children with bacteremic pneumonia using data from a large prospective study with systematic blood culturing. METHODS: Children <18 years hospitalized with pneumonia and enrolled in the multicenter Etiology of Pneumonia in the Community study between January 2010 and June 2012 were eligible. Bivariate comparisons were used to identify factors associated with bacteremia. Associations between bacteremia and clinical outcomes were assessed by using Cox proportional hazards regression for length of stay and logistic regression for ICU admission and invasive mechanical ventilation or shock. RESULTS: Blood cultures were obtained in 2143 (91%) of 2358 children; 46 (2.2%) had bacteremia. The most common pathogens were Streptococcus pneumoniae (n = 23, 50%), Staphylococcus aureus (n = 6, 13%), and Streptococcus pyogenes (n = 4, 9%). Characteristics associated with bacteremia included male sex, parapneumonic effusion, lack of chest indrawing or wheezing, and no previous receipt of antibiotics. Children with bacteremia had longer lengths of stay (median: 5.8 vs 2.8 days; adjusted hazard ratio: 0.79 [0.73-0.86]) and increased odds of ICU admission (43% vs 21%; adjusted odds ratio: 5.21 [3.82-6.84]) and invasive mechanical ventilation or shock (30% vs 8%; adjusted odds ratio: 5.28 [2.41-11.57]). CONCLUSIONS: Bacteremia was uncommonly detected in this large multicenter cohort of children hospitalized with community-acquired pneumonia but was associated with severe disease. S pneumoniae was detected most often. Blood culture was of low yield in general but may have greater use in those with parapneumonic effusion and ICU admission. |
Prevalence of Staphylococcus aureus and use of antistaphylococcal therapy in children hospitalized with pneumonia
Frush JM , Zhu Y , Edwards KM , Grijalva CG , Thomsen IP , Self WH , Jain S , Anderson EJ , Ampofo K , Pavia AT , Arnold SR , McCullers JA , Williams DJ . J Hosp Med 2018 13 (12) 848-852 Within a cohort of >2,000 children hospitalized with community-acquired pneumonia, staphylococcal pneumonia was rare (1%) but associated with adverse in-hospital outcomes. Despite this low prevalence, use of antistaphylococcal antibiotics was common (24%). Efforts are needed to minimize overuse of antistaphylococcal antibiotics while also ensuring adequate treatment for pathogen-specific diseases. |
Use of multiple imputation to estimate the proportion of respiratory virus detections among patients hospitalized with community-acquired pneumonia
Bozio CH , Flanders WD , Finelli L , Bramley AM , Reed C , Gandhi NR , Vidal JE , Erdman D , Levine MZ , Lindstrom S , Ampofo K , Arnold SR , Self WH , Williams DJ , Grijalva CG , Anderson EJ , McCullers JA , Edwards KM , Pavia AT , Wunderink RG , Jain S . Open Forum Infect Dis 2018 5 (4) ofy061 Background: Real-time polymerase chain reaction (PCR) on respiratory specimens and serology on paired blood specimens are used to determine the etiology of respiratory illnesses for research studies. However, convalescent serology is often not collected. We used multiple imputation to assign values for missing serology results to estimate virus-specific prevalence among pediatric and adult community-acquired pneumonia hospitalizations using data from an active population-based surveillance study. Methods: Presence of adenoviruses, human metapneumovirus, influenza viruses, parainfluenza virus types 1-3, and respiratory syncytial virus was defined by positive PCR on nasopharyngeal/oropharyngeal specimens or a 4-fold rise in paired serology. We performed multiple imputation by developing a multivariable regression model for each virus using data from patients with available serology results. We calculated absolute and relative differences in the proportion of each virus detected comparing the imputed to observed (nonimputed) results. Results: Among 2222 children and 2259 adults, 98.8% and 99.5% had nasopharyngeal/oropharyngeal specimens and 43.2% and 37.5% had paired serum specimens, respectively. Imputed results increased viral etiology assignments by an absolute difference of 1.6%-4.4% and 0.8%-2.8% in children and adults, respectively; relative differences were 1.1-3.0 times higher. Conclusions: Multiple imputation can be used when serology results are missing, to refine virus-specific prevalence estimates, and these will likely increase estimates. |
Mycoplasma pneumoniae among children hospitalized with community-acquired pneumonia
Kutty PK , Jain S , Taylor TH , Bramley AM , Diaz MH , Ampofo K , Arnold SR , Williams DJ , Edwards KM , McCullers JA , Pavia AT , Winchell JM , Schrag SJ , Hicks LA . Clin Infect Dis 2018 68 (1) 5-12 Background: The burden and epidemiology of Mycoplasma pneumoniae (Mp) among U.S. children (<18 years) hospitalized with community-acquired pneumonia (CAP) are poorly understood. Methods: In the Etiology of Pneumonia in the Community (EPIC) study, we prospectively enrolled 2254 children hospitalized with radiographically-confirmed pneumonia from January 2010-June 2012 and tested nasopharyngeal/oropharyngeal swabs for Mp using real-time polymerase chain reaction (PCR). Clinical and epidemiological features of Mp-PCR-positive and -negative children were compared using logistic regression. Macrolide susceptibility was assessed by genotyping isolates. Results: In the EPIC study, 182(8%) children were Mp-PCR-positive (median age: 7 years); 12% required intensive care and 26% had pleural effusion. No in-hospital deaths occurred. Macrolide resistance was found in 6/169(4%) isolates. Of 178(98%) Mp-PCR-positive children tested for co-pathogens, 50(28%) had >/=1 co-pathogen detected. Variables significantly associated with higher odds of Mp detection included age {10-17 years [adjusted odds ratio (aOR): 7.9 (95% confidence interval (CI): 4.5-13.6)] and 5-9 years [aOR: 4.8 (CI: 2.9-7.8)] vs. 2-4 years}, outpatient antibiotics </=5 days pre-admission [aOR: 2.3 (CI: 1.5-3.4)], and co-pathogen detection [aOR: 2.1 (CI: 1.3-3.1)]. Clinical characteristics often seen included hilar lymphadenopathy, rales, headache, sore throat, and decreased breath sounds. Conclusions: Usually considered as a mild respiratory infection, M. pneumoniae was the most commonly detected bacteria among children >/=5 years hospitalized with CAP; one-quarter of whom had co-detections. Although associated with clinically non-specific symptoms, there was a need for intensive care support in some cases. M. pneumoniae should be included in the differential diagnosis for school-aged children hospitalized with CAP. |
Virulent PB1-F2 residues: effects on fitness of H1N1 influenza A virus in mice and changes during evolution of human influenza A viruses
Alymova IV , McCullers JA , Kamal RP , Vogel P , Green AM , Gansebom S , York IA . Sci Rep 2018 8 (1) 7474 Specific residues of influenza A virus (IAV) PB1-F2 proteins may enhance inflammation or cytotoxicity. In a series of studies, we evaluated the function of these virulence-associated residues in the context of different IAV subtypes in mice. Here, we demonstrate that, as with the previously assessed pandemic 1968 (H3N2) IAV, PB1-F2 inflammatory residues increase the virulence of H1N1 IAV, suggesting that this effect might be a universal feature. Combining both inflammatory and cytotoxic residues in PB1-F2 enhanced virulence further, compared to either motif alone. Residues from these virulent motifs have been present in natural isolates from human seasonal IAV of all subtypes, but there has been a trend toward a gradual reduction in the number of virulent residues over time. However, human IAV of swine and avian origin tend to have more virulent residues than do the human-adapted seasonal strains, raising the possibility that donation of PB1 segments from these zoonotic viruses may increase the severity of some seasonal human strains. Our data suggest the value of surveillance of virulent residues in both human and animal IAV to predict the severity of influenza season. |
The etiology and impact of co-infections 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 . J Infect Dis 2017 218 (2) 179-188 Background: Recognition that co-infections 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 demographics, clinical characteristics, and outcomes between groups with viruses alone, bacteria alone, or co-infections. We also assessed the frequency of selected pairings of co-detected pathogens and their clinical characteristics. Results: 576 (26%) of the children studied had a co-infection. Children with only virus detection were younger and more likely to be black and have co-morbidities such as asthma compared to those with bacteria alone. Children with virus-bacteria co-infections had a higher frequency of leukocytosis, consolidation on chest X-ray, increased length of stay, and more frequent parapneumonic effusions, intensive care unit admission, and need for mechanical ventilation when compared to viruses alone. Virus-virus co-infections 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: Co-infections occurred in 26% of children hospitalized for CAP. Children with bacterial infections, alone or complicated by a virus, have worse outcomes than children infected with a virus alone. |
Effectiveness of beta-Lactam monotherapy vs macrolide combination therapy for children hospitalized with pneumonia
Williams DJ , Edwards KM , Self WH , Zhu Y , Arnold SR , McCullers JA , Ampofo K , Pavia AT , Anderson EJ , Hicks LA , Bramley AM , Jain S , Grijalva CG . JAMA Pediatr 2017 171 (12) 1184-1191 Importance: beta-Lactam monotherapy and beta-lactam plus macrolide combination therapy are both common empirical treatment strategies for children hospitalized with pneumonia, but few studies have evaluated the effectiveness of these 2 treatment approaches. Objective: To compare the effectiveness of beta-lactam monotherapy vs beta-lactam plus macrolide combination therapy among a cohort of children hospitalized with pneumonia. Design, Setting, and Participants: We analyzed data from the Etiology of Pneumonia in the Community Study, a multicenter, prospective, population-based study of community-acquired pneumonia hospitalizations conducted from January 1, 2010, to June 30, 2012, in 3 children's hospitals in Nashville, Tennessee; Memphis, Tennessee; and Salt Lake City, Utah. The study included all children (up to 18 years of age) who were hospitalized with radiographically confirmed pneumonia and who received beta-lactam monotherapy or beta-lactam plus macrolide combination therapy. Data analysis was completed in April 2017. Main Outcomes and Measures: We defined the referent as beta-lactam monotherapy, including exclusive use of an oral or parenteral second- or third-generation cephalosporin, penicillin, ampicillin, ampicillin-sulbactam, amoxicillin, or amoxicillin-clavulanate. Use of a beta-lactam plus an oral or parenteral macrolide (azithromycin or clarithromycin) served as the comparison group. We modeled the association between these groups and patients' length of stay using multivariable Cox proportional hazards regression. Covariates included demographic, clinical, and radiographic variables. We further evaluated length of stay in a cohort matched by propensity to receive combination therapy. Logistic regression was used to evaluate secondary outcomes in the unmatched cohort, including intensive care admission, rehospitalizations, and self-reported recovery at follow-up. Results: Our study included 1418 children (693 girls and 725 boys) with a median age of 27 months (interquartile range, 12-69 months). This cohort was 60.1% of the 2358 children enrolled in the Etiology of Pneumonia in the Community Study with radiographically confirmed pneumonia in the study period; 1019 (71.9%) received beta-lactam monotherapy and 399 (28.1%) received beta-lactam plus macrolide combination therapy. In the unmatched cohort, there was no statistically significant difference in length of hospital stay between children receiving beta-lactam monotherapy and combination therapy (median, 55 vs 59 hours; adjusted hazard ratio, 0.87; 95% CI, 0.74-1.01). The propensity-matched cohort (n = 560, 39.5%) showed similar results. There were also no significant differences between treatment groups for the secondary outcomes. Conclusions and Relevance: Empirical macrolide combination therapy conferred no benefit over beta-lactam monotherapy for children hospitalized with community-acquired pneumonia. The results of this study elicit questions about the routine empirical use of macrolide combination therapy in this population. |
Rhinovirus Viremia in Patients Hospitalized with Community Acquired Pneumonia.
Lu X , Schneider E , Jain S , Bramley AM , Hymas W , Stockmann C , Ampofo K , Arnold SR , Williams DJ , Self WH , Patel A , Chappell JD , Grijalva CG , Anderson EJ , Wunderink RG , McCullers JA , Edwards KM , Pavia AT , Erdman DD . J Infect Dis 2017 216 (9) 1104-1111 Background: Rhinoviruses (RVs) are ubiquitous respiratory pathogens that often cause mild or subclinical infections. Molecular detection of RV from the upper respiratory tract can be prolonged, complicating etiologic association in persons with severe lower respiratory tract infections. Little is known about RV viremia and its value as a diagnostic indicator in persons hospitalized with community-acquired pneumonia (CAP). Methods: Sera from RV-positive children and adults hospitalized with CAP were tested for RV by real-time RT-PCR. RV species and type were determined by partial genome sequencing. Results: Overall, 57/570 (10%) RV-positive patients were viremic and all were children <10 years old [57/375 (15.2%)]. Although RV-A was the most common RV species detected from respiratory specimens (48.8%), almost all viremias were RV-C (98.2%). Viremic patients had fewer co-detected pathogens and were more likely to have chest retractions, wheezing and a history of underlying asthma/reactive airway disease than patients without viremia. Conclusions: More than one out of seven RV-infected children <10 years old hospitalized with CAP were viremic. In contrast with other RV species, RV-C infections were highly associated with viremia and more often the only respiratory pathogen identified, suggesting that RV-C viremia may be an important diagnostic indicator in pediatric pneumonia. |
Human Bocavirus Capsid Messenger RNA Detection in Children With Pneumonia.
Schlaberg R , Ampofo K , Tardif KD , Stockmann C , Simmon KE , Hymas W , Flygare S , Kennedy B , Blaschke A , Eilbeck K , Yandell M , McCullers JA , Williams DJ , Edwards K , Arnold SR , Bramley A , Jain S , Pavia AT . J Infect Dis 2017 216 (6) 688-696 Background: The role of human bocavirus (HBoV) in respiratory illness is uncertain. HBoV genomic DNA is frequently detected in both ill and healthy children. We hypothesized that spliced viral capsid messenger RNA (mRNA) produced during active replication might be a better marker for acute infection. Methods: As part of the Etiology of Pneumonia in the Community (EPIC) study, children aged <18 years who were hospitalized with community-acquired pneumonia (CAP) and children asymptomatic at the time of elective outpatient surgery (controls) were enrolled. Nasopharyngeal/oropharyngeal specimens were tested for HBoV mRNA and genomic DNA by quantitative polymerase chain reaction. Results: HBoV DNA was detected in 10.4% of 1295 patients with CAP and 7.5% of 721 controls (odds ratio [OR], 1.4 [95% confidence interval {CI}, 1.0-2.0]); HBoV mRNA was detected in 2.1% and 0.4%, respectively (OR, 5.1 [95% CI, 1.6-26]). When adjusted for age, enrollment month, and detection of other respiratory viruses, HBoV mRNA detection (adjusted OR, 7.6 [95% CI, 1.5-38.4]) but not DNA (adjusted OR, 1.2 [95% CI, .6-2.4]) was associated with CAP. Among children with no other pathogens detected, HBoV mRNA (OR, 9.6 [95% CI, 1.9-82]) was strongly associated with CAP. Conclusions: Detection of HBoV mRNA but not DNA was associated with CAP, supporting a pathogenic role for HBoV in CAP. HBoV mRNA could be a useful target for diagnostic testing. |
Low retinol-binding protein and vitamin D levels are associated with severe outcomes in children hospitalized with lower respiratory tract infection and respiratory syncytial virus or human metapneumovirus detection
Hurwitz JL , Jones BG , Penkert RR , Gansebom S , Sun Y , Tang L , Bramley AM , Jain S , McCullers JA , Arnold SR . J Pediatr 2017 187 323-327 Retinol binding protein and vitamin D were measured in children aged <5 years hospitalized with lower respiratory tract infection and respiratory syncytial virus and/or human metapneumovirus detections. Low vitamin levels were observed in 50% of the children and were associated with significantly elevated risk of the need for intensive care unit admission and invasive mechanical ventilation. |
Relationship between body mass index and outcomes among hospitalized patients with community-acquired pneumonia
Bramley AM , Reed C , Finelli L , Self WH , Ampofo K , Arnold SR , Williams DJ , Grijalva CG , Anderson EJ , Stockmann C , Trabue C , Fakhran S , Balk R , McCullers JA , Pavia AT , Edwards KM , Wunderink RG , Jain S . J Infect Dis 2017 215 (12) 1873-1882 Background: The effect of body mass index (BMI) on community-acquired pneumonia (CAP) severity is unclear. Methods: We investigated the relationship between BMI and CAP outcomes [hospital length of stay (LOS), intensive care unit (ICU) admission, and invasive mechanical ventilation] in hospitalized CAP patients from the CDC Etiology of Pneumonia in the Community (EPIC) study, adjusting for age, demographics, underlying conditions, and smoking status (adults only). Results: Compared with normal weight children, odds of ICU admission were higher in children who were overweight (adjusted odds ratio [aOR] 1.7, 95% confidence interval [CI] 1.1-2.8) or obese (aOR 2.1, 1.4-3.2) and odds of mechanical ventilation were higher in children with obesity (aOR 2.7, 1.3-5.6). When stratified by asthma (presence/absence), these findings remained significant only in children with asthma. Compared with normal weight adults, odds of LOS >3 days were higher in adults who were underweight (aOR, 1.6, 1.1-2.4), and odds of mechanical ventilation were lowest in adults who were overweight (aOR, 0.5, 0.3-0.9). Conclusions: Children who were overweight or obese, particularly those with asthma, had higher odds of ICU admission or mechanical ventilation. In contrast, adults who were underweight had longer LOS. These results underscore the complex relationship between BMI and CAP outcomes. |
Influence of antibiotics on the detection of bacteria by culture-based and culture-independent diagnostic tests in patients hospitalized with community-acquired pneumonia
Harris AM , Bramley AM , Jain S , Arnold SR , Ampofo K , Self WH , Williams DJ , Anderson EJ , Grijalva CG , McCullers JA , Pavia AT , Wunderink RG , Edwards KM , Winchell JM , Hicks LA . Open Forum Infect Dis 2017 4 (1) ofx014 BACKGROUND: Specimens collected after antibiotic exposure may reduce culture-based bacterial detections. The impact on culture-independent diagnostic tests is unclear. We assessed the effect of antibiotic exposure on both of these test results among patients hospitalized with community-acquired pneumonia (CAP). METHODS: Culture-based bacterial testing included blood cultures and high-quality sputum or endotracheal tube (ET) aspirates; culture-independent testing included urinary antigen testing (adults) for Streptococcus pneumoniae and Legionella pneumophila and polymerase chain reaction (PCR) on nasopharyngeal and oropharyngeal (NP/OP) swabs for Mycoplasma pneumoniae and Chlamydia pneumoniae. The proportion of bacterial detections was compared between specimens collected before and after either any antibiotic exposure (prehospital and/or inpatient) or only prehospital antibiotics and increasing time after initiation of inpatient antibiotics. RESULTS: Of 4678 CAP patients, 4383 (94%) received antibiotics: 3712 (85%) only inpatient, 642 (15%) both inpatient and prehospital, and 29 (<1%) only prehospital. There were more bacterial detections in specimens collected before antibiotics for blood cultures (5.2% vs 2.6%; P < .01) and sputum/ET cultures (50.0% vs 26.8%; P < .01) but not urine antigen (7.0% vs 5.7%; P = .53) or NP/OP PCR (6.7% vs 5.4%; P = .31). For all diagnostic testing, bacterial detections declined with increasing time between inpatient antibiotic administration and specimen collection. CONCLUSIONS: Bacteria were less frequently detected in culture-based tests collected after antibiotics and in culture-independent tests that had longer intervals between antibiotic exposure and specimen collection. Bacterial yield could improve if specimens were collected promptly, preferably before antibiotics, providing data for improved antibiotic selection. |
Oseltamivir use among children and adults hospitalized with community-acquired pneumonia
Oboho IK , Bramley A , Finelli L , Fry A , Ampofo K , Arnold SR , Self WH , Williams DJ , Mark Courtney D , Zhu Y , Anderson EJ , Grijalva CG , McCullers JA , Wunderink RG , Pavia AT , Edwards KM , Jain S . Open Forum Infect Dis 2017 4 (1) ofw254 Background. Data on oseltamivir treatment among hospitalized community-acquired pneumonia (CAP) patients are limited. Methods. Patients hospitalized with CAP at 6 hospitals during the 2010-2012 influenza seasons were included. We assessed factors associated with oseltamivir treatment using logistic regression. Results. Oseltamivir treatment was provided to 89 of 1627 (5%) children (< 18 years) and 143 of 1051 (14%) adults. Among those with positive clinician-ordered influenza tests, 39 of 61 (64%) children and 37 of 48 (77%) adults received oseltamivir. Among children, oseltamivir treatment was associated with hospital A (adjusted odds ratio [aOR], 2.76; 95% confidence interval [CI], 1.36-4.88), clinician-ordered testing performed (aOR, 2.44; 95% CI, 1.47-5.19), intensive care unit (ICU) admission (aOR, 2.09; 95% CI, 1.27-3.45), and age ≥2 years (aOR, 1.43; 95% CI, 1.16-1.76). Among adults, oseltamivir treatment was associated with clinician- ordered testing performed (aOR, 8.38; 95% CI, 4.64-15.12), hospitals D and E (aOR, 3.46-5.11; 95% CI, 1.75-11.01), Hispanic ethnicity (aOR, 2.06; 95% CI, 1.18-3.59), and ICU admission (aOR, 2.05; 95% CI, 1.34-3.13). Conclusions. Among patients hospitalized with CAP during influenza season, oseltamivir treatment was moderate overall and associated with clinician-ordered testing, severe illness, and specific hospitals. Increased clinician education is needed to include influenza in the differential diagnosis for hospitalized CAP patients and to test and treat patients empirically if influenza is suspected. |
Procalcitonin accurately identifies hospitalized children with low risk of bacterial community-acquired pneumonia
Stockmann C , Ampofo K , Killpack J , Williams DJ , Edwards KM , Grijalva CG , Arnold SR , McCullers JA , Anderson EJ , Wunderink RG , Self WH , Bramley A , Jain S , Pavia AT , Blaschke AJ . J Pediatric Infect Dis Soc 2017 7 (1) 46-53 BACKGROUND: Lower procalcitonin (PCT) concentrations are associated with reduced risk of bacterial community-acquired pneumonia (CAP) in adults, but data in children are limited. METHODS: We analyzed serum PCT concentrations from children hospitalized with radiographically confirmed CAP enrolled in the Centers for Disease Control and Prevention's Etiology of Pneumonia in the Community (EPIC) Study. Blood and respiratory specimens were tested using multiple pathogen detection methods for typical bacteria (eg, Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus), atypical bacteria (Mycoplasma pneumoniae and Chlamydophila pneumoniae), and respiratory viruses. Multivariable regression was used to assess associations between PCT concentrations and etiology and severity. RESULTS: Among 532 children (median age, 2.4 years; interquartile range [IQR], 1.0-6.3), patients with typical bacteria had higher PCT concentrations (+/-viruses; n = 54; median, 6.10; IQR, 0.84-22.79 ng/mL) than those with atypical bacteria (+/-viruses; n = 82; median, 0.10; IQR, 0.06-0.39 ng/mL), viral pathogens only (n = 349; median, 0.33; IQR, 0.12-1.35 ng/mL), or no pathogen detected (n = 47; median, 0.44; IQR, 0.10-1.83 ng/mL) (P < .001 for all). No child with PCT <0.1 ng/mL had typical bacteria detected. Procalcitonin <0.25 ng/mL featured a 96% negative predictive value (95% confidence interval [CI], 93-99), 85% sensitivity (95% CI, 76-95), and 45% specificity (95% CI, 40-50) in identifying children without typical bacterial CAP. CONCLUSIONS: Lower PCT concentrations in children hospitalized with CAP were associated with a reduced risk of typical bacterial detection and may help identify children who would not benefit from antibiotic treatment. |
Glycosylation changes in the globular head of H3N2 influenza hemagglutinin modulate receptor binding without affecting virus virulence
Alymova IV , York IA , Air GM , Cipollo JF , Gulati S , Baranovich T , Kumar A , Zeng H , Gansebom S , McCullers JA . Sci Rep 2016 6 36216 Since the emergence of human H3N2 influenza A viruses in the pandemic of 1968, these viruses have become established as strains of moderate severity. A decline in virulence has been accompanied by glycan accumulation on the hemagglutinin globular head, and hemagglutinin receptor binding has changed from recognition of a broad spectrum of glycan receptors to a narrower spectrum. The relationship between increased glycosylation, binding changes, and reduction in H3N2 virulence is not clear. We evaluated the effect of hemagglutinin glycosylation on receptor binding and virulence of engineered H3N2 viruses. We demonstrate that low-binding virus is as virulent as higher binding counterparts, suggesting that H3N2 infection does not require either recognition of a wide variety of, or high avidity binding to, receptors. Among the few glycans recognized with low-binding virus, there were two structures that were bound by the vast majority of H3N2 viruses isolated between 1968 and 2012. We suggest that these two structures support physiologically relevant binding of H3N2 hemagglutinin and that this physiologically relevant binding has not changed since the 1968 pandemic. Therefore binding changes did not contribute to reduced severity of seasonal H3N2 viruses. This work will help direct the search for factors enhancing influenza virulence. |
Serology Enhances Molecular Diagnosis of Respiratory Virus Infections Other than Influenza in Children and Adults Hospitalized with Community-Acquired Pneumonia.
Zhang Y , Sakthivel SK , Bramley A , Jain S , Haynes A , Chappell JD , Hymas W , Lenny N , Patel A , Qi C , Ampofo K , Arnold SR , Self WH , Williams DJ , Hillyard D , Anderson EJ , Grijalva CG , Zhu Y , Wunderink RG , Edwards KM , Pavia AT , McCullers JA , Erdman DD . J Clin Microbiol 2016 55 (1) 79-89 Both molecular and serological assays have been used previously to determine the etiology of community-acquired pneumonia (CAP). However, the correlation of these methods and added diagnostic value of serology has not been fully evaluated. Using data from patients enrolled in the Centers for Disease Control and Prevention Etiology of Pneumonia in the Community (EPIC) study, we compared real-time RT-PCR and serology for diagnosis of respiratory syncytial virus (RSV), human metapneumovirus (HMPV), parainfluenza viruses 1-3 (PIV) and adenovirus (AdV) infections. Of 5126 patients enrolled, RT-PCR and serology test results were available for 2023, including 1087 children <18 years of age and 936 adults. For RSV, 287 (14.2%) patients were positive by RT-PCR and 234 (11.6%) were positive by serology; HMPV, 172 (8.5%) tested positive by RT-PCR and 147 (7.3%) by serology; PIVs, 94 (4.6%) tested positive by RT-PCR and 92 (4.6%) by serology; and AdV, 111 (5.5%) positive by RT-PCR and 62 (3.1%) by serology. RT-PCR provided the most positive detections overall, but serology increased diagnostic yield for RSV (by 11.8%), HMPV (by 25.0%), AdV (by 32.4%), and PIV (by 48.9%). Method concordance estimated by Cohen's kappa (kappa) coefficient ranged from good (RSV, 0.73 kappa) to fair (AdV, 0.27 kappa). Heterotypic seroresponses observed between PIV and persistent low-level AdV shedding may account for higher method discordance observed with each of these viruses. Serology can be a helpful adjunct to RT-PCR for research-based assessment of the etiologic contribution of non-influenza respiratory viruses to CAP. |
Predicting severe pneumonia outcomes in children
Williams DJ , Zhu Y , Grijalva CG , Self WH , Harrell FE Jr , Reed C , Stockmann C , Arnold SR , Ampofo KK , Anderson EJ , Bramley AM , Wunderink RG , McCullers JA , Pavia AT , Jain S , Edwards KM . Pediatrics 2016 138 (4) BACKGROUND: Substantial morbidity and excessive care variation are seen with pediatric pneumonia. Accurate risk-stratification tools to guide clinical decision-making are needed. METHODS: We developed risk models to predict severe pneumonia outcomes in children (<18 years) by using data from the Etiology of Pneumonia in the Community Study, a prospective study of community-acquired pneumonia hospitalizations conducted in 3 US cities from January 2010 to June 2012. In-hospital outcomes were organized into an ordinal severity scale encompassing severe (mechanical ventilation, shock, or death), moderate (intensive care admission only), and mild (non-intensive care hospitalization) outcomes. Twenty predictors, including patient, laboratory, and radiographic characteristics at presentation, were evaluated in 3 models: a full model included all 20 predictors, a reduced model included 10 predictors based on expert consensus, and an electronic health record (EHR) model included 9 predictors typically available as structured data within comprehensive EHRs. Ordinal regression was used for model development. Predictive accuracy was estimated by using discrimination (concordance index). RESULTS: Among the 2319 included children, 21% had a moderate or severe outcome (14% moderate, 7% severe). Each of the models accurately identified risk for moderate or severe pneumonia (concordance index across models 0.78-0.81). Age, vital signs, chest indrawing, and radiologic infiltrate pattern were the strongest predictors of severity. The reduced and EHR models retained most of the strongest predictors and performed as well as the full model. CONCLUSIONS: We created 3 risk models that accurately estimate risk for severe pneumonia in children. Their use holds the potential to improve care and outcomes. |
Association of sputum microbiota profiles with severity of community-acquired pneumonia in children.
Pettigrew MM , Gent JF , Kong Y , Wade M , Gansebom S , Bramley AM , Jain S , Arnold SL , McCullers JA . BMC Infect Dis 2016 16 317 BACKGROUND: Competitive interactions among bacteria in the respiratory tract microbiota influence which species can colonize and potentially contribute to pathogenesis of community-acquired pneumonia (CAP). However, understanding of the role of respiratory tract microbiota in the clinical course of pediatric CAP is limited. METHODS: We sought to compare microbiota profiles in induced sputum and nasopharyngeal/oropharyngeal (NP/OP) samples from children and to identify microbiota profiles associated with CAP severity. We used 16S ribosomal RNA sequencing and several measures of microbiota profiles, including principal component analysis (PCA), to describe the respiratory microbiota in 383 children, 6 months to <18 years, hospitalized with CAP. We examined associations between induced sputum and NP/OP microbiota profiles and CAP severity (hospital length of stay and intensive care unit admission) using logistic regression. RESULTS: Relative abundance of bacterial taxa differed in induced sputum and NP/OP samples. In children 6 months to < 5 years, the sputum PCA factor with high relative abundance of Actinomyces, Veillonella, Rothia, and Lactobacillales was associated with decreased odds of length of stay ≥ 4 days [adjusted odds ratio (aOR) 0.69; 95 % confidence interval (CI) 0.48-0.99]. The sputum factor with high relative abundance of Haemophilus and Pasteurellaceae was associated with increased odds of intensive care unit admission [aOR 1.52; 95 % CI 1.02-2.26]. In children 5 to < 18 years, the sputum factor with high relative abundance of Porphyromonadaceae, Bacteriodales, Lactobacillales, and Prevotella was associated with increased odds of length of stay ≥ 4 days [aOR 1.52; 95 % CI 1.02-2.26]. Taxa in NP/OP samples were not associated with CAP severity. CONCLUSION: Certain taxa in the respiratory microbiota, which were detected in induced sputum samples, are associated with the clinical course of CAP. |
Identification of Bacterial and Viral Codetections With Mycoplasma pneumoniae Using the TaqMan Array Card in Patients Hospitalized With Community-Acquired Pneumonia.
Diaz MH , Cross KE , Benitez AJ , Hicks LA , Kutty P , Bramley AM , Chappell JD , Hymas W , Patel A , Qi C , Williams DJ , Arnold SR , Ampofo K , Self WH , Grijalva CG , Anderson EJ , McCullers JA , Pavia AT , Wunderink RG , Edwards KM , Jain S , Winchell JM . Open Forum Infect Dis 2016 3 (2) ofw071 Mycoplasma pneumoniae was detected in a number of patients with community-acquired pneumonia in a recent prospective study. To assess whether other pathogens were also detected in these patients, TaqMan Array Cards were used to test 216 M pneumoniae-positive respiratory specimens for 25 additional viral and bacterial respiratory pathogens. It is interesting to note that 1 or more codetections, predominantly bacterial, were identified in approximately 60% of specimens, with codetections being more common in children. |
Community-acquired pneumonia hospitalization among children with neurologic disorders
Millman AJ , Finelli L , Bramley AM , Peacock G , Williams DJ , Arnold SR , Grijalva CG , Anderson EJ , McCullers JA , Ampofo K , Pavia AT , Edwards KM , Jain S . J Pediatr 2016 173 188-195 e4 OBJECTIVE: To describe and compare the clinical characteristics, outcomes, and etiology of pneumonia among children hospitalized with community-acquired pneumonia (CAP) with neurologic disorders, non-neurologic underlying conditions, and no underlying conditions. STUDY DESIGN: Children <18 years old hospitalized with clinical and radiographic CAP were enrolled at 3 US children's hospitals. Neurologic disorders included cerebral palsy, developmental delay, Down syndrome, epilepsy, non-Down syndrome chromosomal abnormalities, and spinal cord abnormalities. We compared the epidemiology, etiology, and clinical outcomes of CAP in children with neurologic disorders with those with non-neurologic underlying conditions, and those with no underlying conditions using bivariate, age-stratified, and multivariate logistic regression analyses. RESULTS: From January 2010-June 2012, 2358 children with radiographically confirmed CAP were enrolled; 280 (11.9%) had a neurologic disorder (52.1% of these individuals also had non-neurologic underlying conditions), 934 (39.6%) had non-neurologic underlying conditions only, and 1144 (48.5%) had no underlying conditions. Children with neurologic disorders were older and more likely to require intensive care unit (ICU) admission than children with non-neurologic underlying conditions and children with no underlying conditions; similar proportions were mechanically ventilated. In age-stratified analysis, children with neurologic disorders were less likely to have a pathogen detected than children with non-neurologic underlying conditions. In multivariate analysis, having a neurologic disorder was associated with ICU admission for children ≥2 years of age. CONCLUSIONS: Children with neurologic disorders hospitalized with CAP were less likely to have a pathogen detected and more likely to be admitted to the ICU than children without neurologic disorders. |
Glycosylation analysis of engineered H3N2 influenza A virus hemagglutinins with sequentially added historically relevant glycosylation sites
An Y , McCullers JA , Alymova I , Parsons LM , Cipollo JF . J Proteome Res 2015 14 (9) 3957-69 The influenza virus surface glycoprotein hemagglutinin (HA) is the major target of host neutralizing antibodies. The oligosaccharides of HA can contribute to HA's antigenic characteristics. After a leap to humans from a zoonotic host, influenza can gain N-glycosylation sequons over time as part of its fitness strategy. This glycosylation expansion has not been studied at the structural level. Here we examine HA N-glycosylation of H3N2 virus strains that we have engineered to closely mimic glycosylation sites gained between 1968 through 2002 starting with pandemic A/Hong Kong/1/68 (H3N2: HK68). HAs studied include HK68 and engineered forms with 1, 2, and 4 added sites. We have used: nano-LC-MS(E) for glycopeptide composition, sequence and site occupancy analysis, and MALDI-TOF MS permethylation profiling for characterization of released glycans. Our study reveals that 1) the majority of N-sequons are occupied at ≥90%, 2) the class and complexity of the glycans varies by region over the landscape of the proteins, 3) Asn 165 and Asn 246, which are associated with interactions between HA and SP-D lung collectin, are exclusively high mannose type. Based on this study and previous reports we provide structural insight as to how the immune system responses may differ depending on HA glycosylation. |
Molecular Detection and Characterization of Mycoplasma pneumoniae Among Patients Hospitalized With Community-Acquired Pneumonia in the United States.
Diaz MH , Benitez AJ , Cross KE , Hicks LA , Kutty P , Bramley AM , Chappell JD , Hymas W , Patel A , Qi C , Williams DJ , Arnold SR , Ampofo K , Self WH , Grijalva CG , Anderson EJ , McCullers JA , Pavia AT , Wunderink RG , Edwards KM , Jain S , Winchell JM . Open Forum Infect Dis 2015 2 (3) ofv106 BACKGROUND: Mycoplasma pneumoniae is a common cause of community-acquired pneumonia (CAP). The molecular characteristics of M pneumoniae detected in patients hospitalized with CAP in the United States are poorly described. METHODS: We performed molecular characterization of M pneumoniae in nasopharyngeal/oropharyngeal swabs from children and adults hospitalized with CAP in the Centers for Disease Control and Prevention Etiology of Pneumonia in the Community (EPIC) study, including P1 typing, multilocus variable-number tandem-repeat analysis (MLVA), and macrolide susceptibility genotyping. RESULTS: Of 216 M pneumoniae polymerase chain reaction-positive specimens, 40 (18.5%) were obtained from adults and 176 (81.5%) from children. P1 type distribution differed between adults (64% type 1 and 36% type 2) and children (84% type 1, 13% type 2, and 3% variant) (P < .05) and among sites (P < .01). Significant differences in the proportions of MLVA types 4/5/7/2 and 3/5/6/2 were also observed by age group (P < .01) and site (P < .01). A macrolide-resistant genotype was identified in 7 (3.5%) specimens, 5 of which were from patients who had recently received macrolide therapy. No significant differences in clinical characteristics were identified among patients with various strain types or between macrolide-resistant and -sensitive M pneumoniae infections. CONCLUSIONS: The P1 type 1 genotype and MLVA type 4/5/7/2 predominated, but there were differences between children and adults and among sites. Macrolide resistance was rare. Differences in strain types did not appear to be associated with differences in clinical outcomes. Whole genome sequencing of M pneumoniae may help identify better ways to characterize strains. |
Secondhand smoke exposure and illness severity among children hospitalized with pneumonia
Ahn A , Edwards KM , Grijalva CG , Self WH , Zhu Y , Chappell JD , Arnold SR , McCullers JA , Ampofo K , Pavia AT , Bramley AM , Jain S , Williams DJ . J Pediatr 2015 167 (4) 869-874 e1 OBJECTIVE: To assess the relationship between secondhand smoke (SHS) exposure and disease severity among children hospitalized with community-acquired pneumonia (CAP). STUDY DESIGN: Children hospitalized with clinical and radiographic CAP were enrolled between January 1, 2010, and June 30, 2012 at 3 hospitals in Tennessee and Utah as part of the Centers for Disease Control and Prevention's Etiology of Pneumonia in the Community study. Household SHS exposure was defined based on the number of smokers in the child's home. Outcomes included hospital length of stay, intensive care unit admission, and mechanical ventilation. Proportional hazards and logistic regression models were used to assess associations between SHS exposure and outcomes. All models were adjusted for age, sex, race/ethnicity, household education level, government insurance, comorbidities, enrollment site, year, and season. RESULTS: Of the 2219 children included in the study, SHS exposure was reported in 785 (35.4%), including 325 (14.8%) with ≥2 smokers in the home. Compared with nonexposed children, the children exposed to ≥2 smokers had longer length of stay (median, 70.4 hours vs 64.4 hours; adjusted hazard ratio, 0.85; 95% CI, 0.75-0.97) and were more likely to receive intensive care (25.2% vs 20.9%; aOR, 1.44; 95% CI, 1.05-1.96), but not mechanical ventilation. Outcomes in children exposed to only 1 household smoker were similar to those in nonexposed children. CONCLUSION: Children hospitalized with CAP from households with ≥2 smokers had a longer length of stay and were more likely to require intensive care compared with children from households with no smokers, suggesting that they experienced greater pneumonia severity. |
Community-acquired pneumonia requiring hospitalization among U.S. adults
Jain S , Self WH , Wunderink RG , Fakhran S , Balk R , Bramley AM , Reed C , Grijalva CG , Anderson EJ , Courtney DM , Chappell JD , Qi C , Hart EM , Carroll F , Trabue C , Donnelly HK , Williams DJ , Zhu Y , Arnold SR , Ampofo K , Waterer GW , Levine M , Lindstrom S , Winchell JM , Katz JM , Erdman D , Schneider E , Hicks LA , McCullers JA , Pavia AT , Edwards KM , Finelli L . N Engl J Med 2015 373 (5) 415-27 BACKGROUND: Community-acquired pneumonia is a leading infectious cause of hospitalization and death among U.S. adults. Incidence estimates of pneumonia confirmed radiographically and with the use of current laboratory diagnostic tests are needed. METHODS: We conducted active population-based surveillance for community-acquired pneumonia requiring hospitalization among adults 18 years of age or older in five hospitals in Chicago and Nashville. Patients with recent hospitalization or severe immunosuppression were excluded. Blood, urine, and respiratory specimens were systematically collected for culture, serologic testing, antigen detection, and molecular diagnostic testing. Study radiologists independently reviewed chest radiographs. We calculated population-based incidence rates of community-acquired pneumonia requiring hospitalization according to age and pathogen. RESULTS: From January 2010 through June 2012, we enrolled 2488 of 3634 eligible adults (68%). Among 2320 adults with radiographic evidence of pneumonia (93%), the median age of the patients was 57 years (interquartile range, 46 to 71); 498 patients (21%) required intensive care, and 52 (2%) died. Among 2259 patients who had radiographic evidence of pneumonia and specimens available for both bacterial and viral testing, a pathogen was detected in 853 (38%): one or more viruses in 530 (23%), bacteria in 247 (11%), bacterial and viral pathogens in 59 (3%), and a fungal or mycobacterial pathogen in 17 (1%). The most common pathogens were human rhinovirus (in 9% of patients), influenza virus (in 6%), and Streptococcus pneumoniae (in 5%). The annual incidence of pneumonia was 24.8 cases (95% confidence interval, 23.5 to 26.1) per 10,000 adults, with the highest rates among adults 65 to 79 years of age (63.0 cases per 10,000 adults) and those 80 years of age or older (164.3 cases per 10,000 adults). For each pathogen, the incidence increased with age. CONCLUSIONS: The incidence of community-acquired pneumonia requiring hospitalization was highest among the oldest adults. Despite current diagnostic tests, no pathogen was detected in the majority of patients. Respiratory viruses were detected more frequently than bacteria. (Funded by the Influenza Division of the National Center for Immunizations and Respiratory Diseases.). |
Antibiotic choice for children hospitalized with pneumonia and adherence to national guidelines
Williams DJ , Edwards KM , Self WH , Zhu Y , Ampofo K , Pavia AT , Hersh AL , Arnold SR , McCullers JA , Hicks LA , Bramley AM , Jain S , Grijalva CG . Pediatrics 2015 136 (1) 44-52 INTRODUCTION: The 2011 national guidelines for the management of childhood community-acquired pneumonia (CAP) recommended narrow-spectrum antibiotics (eg, ampicillin) for most children hospitalized with CAP. We assessed the impact of these guidelines on antibiotic prescribing at 3 children's hospitals. METHODS: Children hospitalized with clinical and radiographic CAP were enrolled from January 1, 2010, through June 30, 2012, at 3 hospitals in Tennessee and Utah as part of the Centers for Disease Control and Prevention Etiology of Pneumonia in the Community study. Antibiotic selection was determined by the treating provider. The impact of the guidelines and hospital-level implementation efforts was determined by assessing the monthly percentage of enrolled children receiving third-generation cephalosporins or penicillin/ampicillin. Segmented linear regression was used to compare observed antibiotic selection in the postguideline period with expected antibiotic use projected from preguideline months. RESULTS: Overall, 2121 children were included. During the preguideline period, 52.8% (interquartile range 47.8-56.6) of children with CAP received third-generation cephalosporins, whereas 2.7% (2.1, 7.0) received penicillin/ampicillin. By 9 months postguidelines, third-generation cephalosporin use declined (absolute difference -12.4% [95% confidence interval -19.8% to -5.1%]), whereas penicillin/ampicillin use increased (absolute difference 11.3% [4.3%-18.3%]). The most substantial changes were noted at those institutions that implemented guideline-related dissemination activities. CONCLUSIONS: After publication of national guidelines, third-generation cephalosporin use declined and penicillin/ampicillin use increased among children hospitalized with CAP. Changes were more apparent among those institutions that proactively disseminated the guidelines, suggesting that targeted, hospital-based efforts are important for timely implementation of guideline recommendations. |
Community-acquired pneumonia requiring hospitalization among U.S. children
Jain S , Williams DJ , Arnold SR , Ampofo K , Bramley AM , Reed C , Stockmann C , Anderson EJ , Grijalva CG , Self WH , Zhu Y , Patel A , Hymas W , Chappell JD , Kaufman RA , Kan JH , Dansie D , Lenny N , Hillyard DR , Haynes LM , Levine M , Lindstrom S , Winchell JM , Katz JM , Erdman D , Schneider E , Hicks LA , Wunderink RG , Edwards KM , Pavia AT , McCullers JA , Finelli L . N Engl J Med 2015 372 (9) 835-45 BACKGROUND: Incidence estimates of hospitalizations for community-acquired pneumonia among children in the United States that are based on prospective data collection are limited. Updated estimates of pneumonia that has been confirmed radiographically and with the use of current laboratory diagnostic tests are needed. METHODS: We conducted active population-based surveillance for community-acquired pneumonia requiring hospitalization among children younger than 18 years of age in three hospitals in Memphis, Nashville, and Salt Lake City. We excluded children with recent hospitalization or severe immunosuppression. Blood and respiratory specimens were systematically collected for pathogen detection with the use of multiple methods. Chest radiographs were reviewed independently by study radiologists. RESULTS: From January 2010 through June 2012, we enrolled 2638 of 3803 eligible children (69%), 2358 of whom (89%) had radiographic evidence of pneumonia. The median age of the children was 2 years (interquartile range, 1 to 6); 497 of 2358 children (21%) required intensive care, and 3 (<1%) died. Among 2222 children with radiographic evidence of pneumonia and with specimens available for bacterial and viral testing, a viral or bacterial pathogen was detected in 1802 (81%), one or more viruses in 1472 (66%), bacteria in 175 (8%), and both bacterial and viral pathogens in 155 (7%). The annual incidence of pneumonia was 15.7 cases per 10,000 children (95% confidence interval [CI], 14.9 to 16.5), with the highest rate among children younger than 2 years of age (62.2 cases per 10,000 children; 95% CI, 57.6 to 67.1). Respiratory syncytial virus was more common among children younger than 5 years of age than among older children (37% vs. 8%), as were adenovirus (15% vs. 3%) and human metapneumovirus (15% vs. 8%). Mycoplasma pneumoniae was more common among children 5 years of age or older than among younger children (19% vs. 3%). CONCLUSIONS: The burden of hospitalization for children with community-acquired pneumonia was highest among the very young, with respiratory viruses the most commonly detected causes of pneumonia. (Funded by the Influenza Division of the National Center for Immunization and Respiratory Diseases.). |
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