Association of Radiology Findings with Etiology of Community Acquired Pneumonia among Children.

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.

Early Intravenous Magnesium Sulfate Administration in the Emergency Department for Severe Asthma Exacerbations.

BACKGROUND: Severe asthma exacerbations in pediatric patients occur frequently and can require pediatric intensive care unit (PICU) admission. OBJECTIVE: To determine if early administration of intravenous magnesium sulfate (IVMg) to pediatric patients experiencing severe asthma exacerbations, defined as a respiratory clinical score (RCS) of 9 to 12, resulted in fewer PICU admissions. METHODS: Retrospective chart review of pediatric patients aged from 2 to 17 years presenting with a severe asthma exacerbation to a single tertiary care pediatric emergency department. Univariable and multivariable logistic regression analyses were used to determine if admission to the PICU was associated with early IVMg treatment, within 60 minutes of registration. RESULTS: A total of 1911 patients were included in the study, of which 1541 received IVMg. The average time to IVMg was 79 minutes, with 35% of the patients receiving it within 60 minutes of arrival. Two hundred forty-eight (13%) were admitted to the PICU, 641 (34%) were admitted to the general inpatient floor, and 1022 (53%) were discharged home. Factors associated with increased odds ratio (OR) of PICU admission were: early IVMg (OR, 1.63; 95% CI: 1.16-2.28), arrival mode to the emergency department via ambulance (OR, 2.23; 95% CI: 1.45-3.43), history of PICU admission for asthma (OR, 1.73; 95% CI: 1.22-2.44), and diagnosis of status asthmaticus (OR, 8.88; 95% CI: 3.49-30.07). Calculated OR of PICU admission subcategorized by RCS for early IVMg patients, after controlling for PICU risk factors, are as follows: RCS 9 (reference), RCS 10 (OR, 2.52; 95% CI: 0.89-2.23), RCS 11 (OR, 2.19; 95% CI: 1.3-3.70), and RCS 12 (OR, 4.12; 95% CI: 2.13-7.95). CONCLUSIONS: Early administration of IVMg to pediatric patients experiencing severe asthma exacerbations does not result in fewer PICU admissions.

How Broad Should Gram-Negative Coverage Be for Febrile Parenteral Nutrition Dependent Short Bowel Syndrome Patients?

ABSTRACT: Broader spectrum Gram-negative antibiotics are commonly utilized empirically for central line-associated bloodstream infections (CLABSI) in febrile short bowel syndrome (SBS) patients receiving home parenteral nutrition compared to those used empirically for inpatient-acquired CLABSI. This analysis reports 57 CLABSI in 22 patients with SBS admitted from the community and 78 inpatient-acquired CLABSI in 76 patients over a 5-year period. Proportional Gram-negative CLABSI was similar between the SBS and inpatient-acquired cohorts (43.8% vs42.3%, respectively, P  = 0.78). 1.8% and 10.3% (P = 0.125) of Gram-negative CLABSI were non-susceptible to ceftriaxone and 0% and 3.8% (P = 0.52) were non-susceptible to ceftazidime in the SBS and inpatient-acquired cohorts, respectively. In the SBS cohort, home ethanol lock therapy and prior culture results impacted Gramnegative pathogen distribution. Broader empiric Gram-negative coverage for CLABSI among SBS patients compared to inpatients is unnecessary. Third-generation cephalosporins represent appropriate empiric Gramnegative agents for febrile SBS patients presenting from the community to our institution.

Parainfluenza Virus Types 1-3 Infections Among Children and Adults Hospitalized With Community-acquired Pneumonia.

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 8 US 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 < .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 nonbacterial pneumonia, whereas children with bacterial pneumonia exhibited increased severity (odds ratio, 8.42; 95% confidence interval, 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.

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 8 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 codetections with other pathogen types, we compared features of HMPV-associated pneumonia with other viral, atypical, and bacterial pneumonia and modeled the severity (mild, moderate, and 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 codetected 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 codetections in children (n = 1778), compared to HMPV (reference), bacterial pneumonia exhibited increased severity (odds ratio [OR], 3.66; 95% confidence interval [CI], 1.43-9.40), respiratory syncytial virus (RSV; OR, 0.76; 95% CI, .59-.99) and atypical (OR, 0.39; 95% CI, .19-.81) infections exhibited decreased severity, and other viral pneumonia exhibited similar severity (OR, 0.88; 95% CI, .55-1.39). In adults (n = 2145), bacterial (OR, 3.74; 95% CI, 1.87-7.47) and RSV pneumonia (OR, 1.82; 95% CI, 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 was otherwise as or more severe than other common pathogens.

Analysis of Community-Acquired Urinary Tract Infection Treatment in Pediatric Patients Requiring Hospitalization: Opportunity for Use of Narrower Spectrum Antibiotics.

Background: The most narrow-spectrum antibiotic possible should be used for empiric and definitive treatment of pediatric urinary tract infections (UTIs). Objectives: The objectives of this study were to determine an appropriate narrow-spectrum antibiotic for empiric UTI treatment, factors differentiating empiric first-generation cephalosporin (FGC) versus third-generation cephalosporin (TGC) coverage, and factors associated with unnecessarily broad-spectrum definitive antibiotic treatment. Methods: This was a retrospective chart review of children admitted from 2013 to 2015 who were diagnosed with a UTI and received treatment. Multivariable logistic regression assessed independent factors associated with our outcomes. Results: Of 568 diagnosed UTIs, 88.6% received empiric TGC treatment. Empiric coverage among cultured organisms was only 5.4% lower in FGC versus TGC. Adolescent age group (odds ratio [OR] = 8.83, 95% confidence interval [CI] = 1.47-53.11), uncircumcised males (OR = 4.52, 95% CI = 1.27-16.08), Hispanic ethnicity (OR = 4.37, 95% CI = 1.14-16.82), and hospitalization within the preceding 3 months (OR = 4.73, 95% CI = 1.38-16.23) were associated with FGC nonsusceptibility among TGC susceptible Enterobacteriaceae pathogens. De-escalation occurred in 55.8% of diagnosed UTIs eligible for de-escalation at discharge. Urine white blood cell (WBC) count >5 (OR = 2.89, 95% CI = 1.14-7.21), serum WBC count (OR = 1.04, 95% CI = 1.01-1.07), and having only one narrow-spectrum treatment option (OR = 5.1, 95% CI = 2.43-10.66) were associated with unnecessarily broad-spectrum definitive treatment. Conclusion and Relevance: FGC would be an appropriate narrow-spectrum empiric agent for UTIs at our institution. The factors associated with FGC nonsusceptibility can further stratify empiric treatment decisions. The factors associated with unnecessarily broad-spectrum definitive treatment illustrate areas for educational efforts and future research regarding UTI treatment.

Mycoplasma pneumoniae Among Children Hospitalized With Community-acquired Pneumonia.

Background: The epidemiology of Mycoplasma pneumoniae (Mp) among US children (<18 years) hospitalized with community-acquired pneumonia (CAP) is poorly understood. Methods: In the Etiology of Pneumonia in the Community 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: One hundred and eighty two (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 4% (6/169) isolates. Of 178 (98%) Mp PCR-positive children tested for copathogens, 50 (28%) had ≥1 copathogen detected. Variables significantly associated with higher odds of Mp detection included age (10-17 years: adjusted odds ratio [aOR], 10.7 [95% confidence interval {CI}, 5.4-21.1] and 5-9 years: aOR, 6.4 [95% CI, 3.4-12.1] vs 2-4 years), outpatient antibiotics ≤5 days preadmission (aOR, 2.3 [95% CI, 1.5-3.5]), and copathogen detection (aOR, 2.1 [95% CI, 1.3-3.3]). Clinical characteristics were non-specific. Conclusions: Usually considered as a mild respiratory infection, Mp was the most commonly detected bacteria among children aged ≥5 years hospitalized with CAP, one-quarter of whom had codetections. Although associated with clinically nonspecific symptoms, there was a need for intensive care in some cases. Mycoplasma pneumoniae should be included in the differential diagnosis for school-aged children hospitalized with CAP.

Etiology and Impact of Coinfections in Children Hospitalized With Community-Acquired Pneumonia.

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.

Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults.

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.).

Community-acquired pneumonia requiring hospitalization among U.S. children.

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.).

A Randomized Trial Comparing Metered Dose Inhalers and Breath Actuated Nebulizers.

BACKGROUND: Despite little evidence for its effectiveness, the breath-actuated nebulizer (BAN) is the default albuterol delivery method in our pediatric emergency department. OBJECTIVE: We compared the clinical efficacy of BAN and the metered-dose inhaler (MDI) in treating subjects patients 2 to 17 years of age who presented with mild to moderate asthma exacerbations. METHODS: This is a randomized, nonblinded, noninferiority study conducted at a single pediatric tertiary care emergency department. Subjects presenting with a Pediatric Asthma Score ranging from 5 to 11 received albuterol by BAN or MDI via standard weight-based and symptom severity dosing protocols. Aerosolized ipratropium (via BAN) and intravenous magnesium sulfate were given when clinically indicated. The primary outcome was patient disposition. The noninferiority margin for the primary outcome was an admission rate difference ≤10%. Analyses were adjusted for confounders that were significant at p ≤ 0.10. RESULTS: We enrolled 890 subjects between October 2014 and April 2015. BAN and MDI groups were comparable for age, gender, and race but not for pretreatment symptom severity; 51% in the MDI group had a Pediatric Asthma Score of moderate severity (8-11) vs. 63% in the BAN group (p < 0.003). Unadjusted admission rates were 11.9% for MDI and 12.8% for BAN, for an unadjusted risk difference of -0.9% (95% confidence interval -5% to 3%). After adjusting for baseline confounder severity, the risk difference was 2% (95% confidence interval -4% to 7%), which met the criteria for noninferiority. CONCLUSIONS: Albuterol therapy by MDI is noninferior to BAN for the treatment of mild to moderate asthma exacerbations in children 2 to 17 years of age.

Human Bocavirus Capsid Messenger RNA Detection in Children With Pneumonia.

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.

Rhinovirus Viremia in Patients Hospitalized With Community-Acquired Pneumonia.

Background: Rhinoviruses (RVs) are ubiquitous respiratory pathogens that often cause mild or subclinical infections. Molecular detection of RVs 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 reverse-transcription polymerase chain reaction. Rhinovirus species and type were determined by partial genome sequencing. Results: Overall, 57 of 570 (10%) RV-positive patients were viremic, and all were children aged <10 years (n = 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 codetected 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 1 out of 7 RV-infected children aged <10 years hospitalized with CAP were viremic. In contrast with other RV species, RV-C infections were highly associated with viremia and were usually the only respiratory pathogen identified, suggesting that RV-C viremia may be an important diagnostic indicator in pediatric pneumonia.

Relationship Between Body Mass Index and Outcomes Among Hospitalized Patients With Community-Acquired Pneumonia.

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 Centers for Disease Control and Prevention 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; 95% CI, 1.4-3.2), and odds of mechanical ventilation were higher in children with obesity (aOR, 2.7; 95% CI, 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; 95% CI, 1.1-2.4), and odds of mechanical ventilation were lowest in adults who were overweight (aOR, 0.5; 95% CI, .3-.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.

Improved Detection of Respiratory Pathogens by Use of High-Quality Sputum with TaqMan Array Card Technology.

New diagnostic platforms often use nasopharyngeal or oropharyngeal (NP/OP) swabs for pathogen detection for patients hospitalized with community-acquired pneumonia (CAP). We applied multipathogen testing to high-quality sputum specimens to determine if more pathogens can be identified relative to NP/OP swabs. Children (<18 years old) and adults hospitalized with CAP were enrolled over 2.5 years through the Etiology of Pneumonia in the Community (EPIC) study. NP/OP specimens with matching high-quality sputum (defined as ≤10 epithelial cells/low-power field [lpf] and ≥25 white blood cells/lpf or a quality score [q-score] definition of 2+) were tested by TaqMan array card (TAC), a multipathogen real-time PCR detection platform. Among 236 patients with matched specimens, a higher proportion of sputum specimens had ≥1 pathogen detected compared with NP/OP specimens in children (93% versus 68%; P < 0.0001) and adults (88% versus 61%; P < 0.0001); for each pathogen targeted, crossing threshold (CT) values were earlier in sputum. Both bacterial (361 versus 294) and viral detections (245 versus 140) were more common in sputum versus NP/OP specimens, respectively, in both children and adults. When available, high-quality sputum may be useful for testing in hospitalized CAP patients.

Serology Enhances Molecular Diagnosis of Respiratory Virus Infections Other than Influenza in Children and Adults Hospitalized with Community-Acquired Pneumonia.

Both molecular and serological assays have been used previously to determine the etiology of community-acquired pneumonia (CAP). However, the extent to which these methods are correlated and the added diagnostic value of serology for respiratory viruses other than influenza virus have not been fully evaluated. Using data from patients enrolled in the Centers for Disease Control and Prevention (CDC) Etiology of Pneumonia in the Community (EPIC) study, we compared real-time reverse transcription-PCR (RT-PCR) and serology for the diagnosis of respiratory syncytial virus (RSV), human metapneumovirus (HMPV), parainfluenza virus 1 to 3 (PIV1, PIV2, and PIV3), and adenovirus (AdV) infections. Of 5,126 patients enrolled, RT-PCR and serology test results were available for 2,023, including 1,087 children below the age of 18 years and 936 adults. For RSV, 287 (14.2%) patients were positive by RT-PCR and 234 (11.6%) were positive by serology; for HMPV, 172 (8.5%) tested positive by RT-PCR and 147 (7.3%) by serology; for the PIVs, 94 (4.6%) tested positive by RT-PCR and 92 (4.6%) by serology; and for AdV, 111 (5.5%) tested positive by RT-PCR and 62 (3.1%) by serology. RT-PCR provided the highest number of 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%). The method concordance estimated by Cohen's kappa coefficient (κ) ranged from good (for RSV; κ = 0.73) to fair (for AdV; κ = 0.27). Heterotypic seroresponses observed between PIVs and persistent low-level AdV shedding may account for the 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 respiratory viruses other than influenza virus to CAP.

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.

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.

Community-Acquired Pneumonia Hospitalization among Children with Neurologic Disorders.

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.

Reduction of Broad-Spectrum Antimicrobial Use in a Tertiary Children's Hospital Post Antimicrobial Stewardship Program Guideline Implementation.

OBJECTIVES: The core strategies recommended for antimicrobial stewardship programs, formulary restriction with preauthorization and prospective audit and feedback, can be difficult to implement with limited resources; therefore, we took an approach of guideline development and education with the goal of reducing overall antibiotic use and unwarranted use of broad-spectrum antimicrobials. DESIGN: Retrospective chart review before and after intervention. SETTING: Le Bonheur Children's Hospital pediatric, neonatal, and cardiac ICUs. PATIENTS: All patients in our pediatric, neonatal, and cardiac ICUs within the time frame of the study. INTERVENTIONS: Baseline review in our ICUs revealed excessive use of broad-spectrum antibiotics and inconsistency in managing common pediatric infections. Guidelines were developed and implemented using cycles of education, retrospective review, and feedback. Purchasing and antibiotic use data were obtained to assess changes before and after guideline implementation. Unit-specific days of therapy were measured using periodic chart audit. Segmented regression analysis was used to assess changes in purchasing and broad-spectrum antibiotic days of therapy. The change in median monthly purchases was assessed using 2-tail Student t test. MEASUREMENTS AND MAIN RESULTS: Hospital-wide targeted broad-spectrum antibiotic days of therapy/1,000 patient-days during the preimplementation year averaged 105 per month and decreased 33% to 70 per month during the postimplementation year. The overall antibiotic days of therapy decreased 41%, 21%, and 18%, and targeted broad-spectrum antibiotic days of therapy decreased by 99%, 75%, and 61% in the cardiac, pediatric, and neonatal ICUs, respectively, after guideline implementation. Yearly purchases of our most common broad-spectrum antibiotics decreased 62% from $230,059 to $86,887 after guideline implementation. Median monthly purchases of these drugs before implementation were $19,389 and $11,043 after implementation (p < 0.001). CONCLUSIONS: Guideline implementation was successful in reducing targeted broad-spectrum antibiotic use and acquisition cost. Programs with very limited resources may find similar implementation of guidelines effective to provide initial success, so that putting into practice one of the more resource intensive core strategies, such as prospective audit and feedback, may be feasible.

Distinguishing Benign Mediastinal Masses from Malignancy in a Histoplasmosis-Endemic Region.

OBJECTIVE: To describe the characteristics of benign and malignant mediastinal masses, which may predict their etiology and facilitate the safe and timely management of patients, especially those residing in histoplasmosis-endemic regions. STUDY DESIGN: We conducted a retrospective review of the health records of 131 patients aged <19 years who were referred to 2 tertiary care children's hospitals between 2005 and 2010 for evaluation of mediastinal masses. RESULTS: Most patients (79%) had benign masses, including 98 with confirmed or suspected histoplasmosis. Overall, compared with patients with malignant masses, patients with benign masses were younger and more likely to be African American, to complain of cough, and to have pulmonary nodules by chest computed tomography. In addition, patients with malignant disease were more likely to complain of malaise and to have neck swelling, abnormal extrathoracic lymphadenopathy, lymphopenia, anterior mediastinal involvement, and/or pleural effusion. Positive histoplasmosis serologic tests were specific but insensitive for a benign etiology. No single clinical, laboratory, or radiologic feature was sufficiently sensitive and specific for distinguishing between benign and malignant masses; however, the presence of lymphopenia, anterior mediastinal involvement, or enlarged cervical lymph nodes on computed tomography had a sensitivity of 93%, specificity of 95%, positive predictive value of 86%, and negative predictive value of 97% for cancer. Sixty-four patients (49%) underwent invasive testing, including 37 (36%) of those with benign masses. CONCLUSION: Patients in this series who had involvement of the anterior mediastinum, lymphopenia, or enlarged cervical lymph nodes had a high likelihood of cancer. Expectant management of patients lacking these characteristics may be safe and reduce unnecessary invasive testing.