Showing papers by "Evan J. Anderson published in 2018"

Procalcitonin Accurately Identifies Hospitalized Children With Low Risk of Bacterial Community-Acquired Pneumonia.

Abstract: 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.

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

Abstract: 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.

Pneumococcal Community-Acquired Pneumonia Detected by Serotype-Specific Urinary Antigen Detection Assays

Abstract: Background Streptococcus pneumoniae is considered the leading bacterial cause of pneumonia in adults. Yet, it was not commonly detected by traditional culture-based and conventional urinary testing in a recent multicenter etiology study of adults hospitalized with community-acquired pneumonia (CAP). We used novel serotype-specific urinary antigen detection (SSUAD) assays to determine whether pneumococcal cases were missed by traditional testing. Methods We studied adult patients hospitalized with CAP at 5 hospitals in Chicago and Nashville (2010-2012) and enrolled in the Etiology of Pneumonia in the Community (EPIC) study. Traditional diagnostic testing included blood and sputum cultures and conventional urine antigen detection (ie, BinaxNOW). We applied SSUAD assays that target serotypes included in the 13-valent pneumococcal conjugate vaccine (PCV13) to stored residual urine specimens. Results Among 1736 patients with SSUAD and ≥1 traditional pneumococcal test performed, we identified 169 (9.7%) cases of pneumococcal CAP. Traditional tests identified 93 (5.4%) and SSUAD identified 76 (4.4%) additional cases. Among 14 PCV13-serotype cases identified by culture, SSUAD correctly identified the same serotype in all of them. Cases identified by SSUAD vs traditional tests were similar in most demographic and clinical characteristics, although disease severity and procalcitonin concentration were highest among those with positive blood cultures. The proportion of pneumonia cases caused by serotypes exclusively covered by PCV13 was not significantly different between the first and second July-June study periods (6.4% vs 4.0%). Conclusions Although restricted to the detection of only 13 serotypes, SSUAD testing substantially increased the detection of pneumococcal pneumonia among adults hospitalized with CAP.

Neonatal and Pediatric Candidemia: Results From Population-Based Active Laboratory Surveillance in Four US Locations, 2009-2015.

Abstract: Introduction Candida is a leading cause of healthcare-associated bloodstream infections in the United States. Infants and children have unique risk factors for candidemia, and the Candida species distribution in this group is different that among adults; however, candidemia epidemiology in this population has not been described recently. Methods We conducted active population-based candidemia surveillance in 4 US metropolitan areas between 2009 and 2015. We calculated incidences among neonates (0-30 days old), infants (0-364 days old), and noninfant children (1-19 years old), documented their clinical features and antifungal drug resistance. Results We identified 307 pediatric candidemia cases. Incidence trends varied according to site, but overall, the incidence in neonates decreased from 31.5 cases/100000 births in 2009 to 10.7 to 11.8 cases/100000 births between 2012 and 2015, the incidence in infants decreased from 52.1 cases/100000 in 2009 to 15.7 to 17.5 between 2012 and 2015, and the incidence in noninfant children decreased steadily from 1.8 cases/100000 in 2009 to 0.8 in 2014. Common underlying conditions were prematurity in neonates (78%), surgery in nonneonate infants (38%), and malignancy in noninfant children (28%). Most neonate cases were caused by C albicans (67%), whereas non-C. albicans species accounted for 60% of cases in nonneonate infants and noninfant children. Fluconazole and echinocandin resistance rates were low overall. Thirty-day crude mortality was 13%. Conclusions The incidence of candidemia among neonates and infants declined after 2009 but remained stable from 2012 to 2015. Antifungal drug resistance is uncommon. Reasons for the lack of recent declines in neonatal and infant candidemia deserve further exploration. In this article, we describe the epidemiology of candidemia in children in the United States and on the basis of data collected as part of US Centers for Disease Control and Prevention active population-based surveillance. Trends in incidence, clinical characteristics, species distribution, and resistance rates are presented.

Protecting the Community Through Child Vaccination

Abstract: The direct impact of vaccines on children is well described, but the major public health impact of indirect protection provided to the community by vaccines is underappreciated. Community protection occurs when vaccinated persons block the chain of transmission, protecting undervaccinated or unvaccinated susceptible community members by preventing exposure and limiting the spread of the pathogen through the community. Substantial declines in disease incidence have occurred shortly after implementing new childhood vaccines, including declines among vaccine-ineligible children, adolescents, and adults. Protection of susceptible community members depends on maintaining high vaccination rates. Improved recognition of community protection will strengthen childhood vaccination strategies that will protect our communities into the future.

Risk scoring tool to predict respiratory syncytial virus hospitalisation in premature infants.

Abstract: Background The objective was to develop a risk scoring tool which predicts respiratory syncytial virus hospitalisation (RSVH) in moderate-late preterm infants (32-35 weeks' gestational age) in the Northern Hemisphere. Methods Risk factors for RSVH were pooled from six observational studies of infants born 32 weeks and 0 days to 35 weeks and 6 days without comorbidity from 2000 to 2014. Of 13 475 infants, 484 had RSVH in the first year of life. Logistic regression was used to identify the most predictive risk factors, based on area under the receiver operating characteristic curve (AUROC). The model was validated internally by 100-fold bootstrapping and externally with data from a seventh observational study. The model coefficients were converted into rounded multipliers, stratified into risk groups, and number needed to treat (NNT) calculated. Results The risk factors identified in the model included (i) proximity of birth to the RSV season; (ii) second-hand smoke exposure; and (iii) siblings and/or daycare. The AUROC was 0.773 (sensitivity: 68.9%; specificity: 73.0%). The mean AUROC from internal bootstrapping was 0.773. For external validation with data from Ireland, the AUROC was 0.707 using Irish coefficients and 0.681 using source model coefficients. Cut-off scores for RSVH were ≤19 for low- (1.0%), 20-45 for moderate- (3.3%), and 50-56 (9.5%) for high-risk infants. The high-risk group captured 62.0% of RSVHs within 23.6% of the total population (NNT 15.3). Conclusions This risk scoring tool has good predictive accuracy and can improve targeting for RSVH prevention in moderate-late preterm infants.

Prevalence of Staphylococcus aureus and Use of Antistaphylococcal Therapy in Children Hospitalized with Pneumonia

Abstract: 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.

Trends in rotavirus from 2001 to 2015 in two paediatric hospitals in Atlanta, Georgia.

Abstract: We compared rotavirus detection patterns before (2001-2006) and after (2008-2015) rotavirus vaccine introduction. We also compared rotavirus detection patterns in odd (2009, 2011, 2013, 2015) and even (2008, 2010, 2012, 2014) years post-vaccine separately. Results of stool rotavirus antigen testing from inpatient, outpatient and emergency department encounters from July 2000 to July 2015 at two paediatric hospital laboratories in Atlanta, Georgia were reviewed. Post-vaccine, rotavirus detection declined (30.2% vs. 13.7% (overall 54.6% decline, P <0.001)), occurred more frequently outside the rotavirus season (19.8% vs. 3.5%; P < 0.001), and was more common among older children (26 vs. 13 median months of age; P < 0.001). During odd years post-vaccine, rotavirus detection was significantly higher than even years (20.2% vs. 6.4%; P < 0.001). Rotavirus detection declined substantially and developed a biennial pattern in the post-vaccine era. The intensity and temporality of rotavirus detection in odd years post-vaccine resembled that observed pre-vaccine, although considerably reduced in magnitude.

Use of Multiple Imputation to Estimate the Proportion of Respiratory Virus Detections Among Patients Hospitalized With Community-Acquired Pneumonia.

Abstract: 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.

746. Characteristics of Respiratory Syncytial Virus (RSV) Infection Among Hospitalized Adults, United States, 2014–2017

Abstract: Background Respiratory syncytial virus (RSV) vaccines are in clinical development for older adults. We described RSV infections among adults requiring hospitalization and risk factors for severe outcomes using a population-based platform, the Influenza Hospitalization Surveillance Network (FluSurv-NET).

354. Evidence of Aspergillosis Among Patients With Influenza-Associated Hospitalizations—United States, 2005–2017

Abstract: Abstract Background Invasive aspergillosis primarily affects immunosuppressed persons, but it has also been observed in immunocompetent patients with severe influenza. Several case series suggest that severe influenza infection might be an under-recognized risk factor for aspergillosis. We examined the frequency of aspergillosis-related hospital discharge codes in a national surveillance database of influenza hospitalizations. Methods We analyzed laboratory-confirmed influenza-associated hospitalizations reported during 2005–2017 to Centers for Disease Control and Prevention (CDC)’s Influenza Hospitalization Surveillance Network (FluSurv-NET), which includes children and adults in 13 states. We obtained data on underlying conditions and clinical course through medical chart abstraction. We defined invasive aspergillosis cases as influenza hospitalizations with ≥1 of the following the International Classification of Diseases (ICD) 9th or 10th Clinical Modification discharge diagnosis codes: 117.3 (aspergillosis), 484.6 (pneumonia in aspergillosis), B44.0 (invasive pulmonary aspergillosis), B44.2 (tonsillar aspergillosis), and B44.7 (disseminated aspergillosis). Results Among 92,671 influenza hospitalizations, we identified 94 cases (0.1%) that had invasive aspergillosis codes. Characteristics of patients were: 60% male (56/94), 72% white race (60/83), and median age 58 years [interquartile range (IQR) 41–67]. Influenza A accounted for 80% (75/94) of cases. Seventy-nine percent (74/94) received antiviral therapy. Underlying conditions included 63% (59/94) immunocompromising condition, 51% (48/94) chronic lung disease, 22% (21/94) renal disease, and 15% (14/94) asthma. Forty-eight percent of patients (45/94) required intensive care. At the time of discharge, 60% (56/94) were diagnosed with pneumonia and 14% (13/94) died. Conclusion Over one-third of patients with invasive aspergillosis did not have a documented immunosuppressive condition. ICD codes are likely an imperfect way to identify invasive aspergillosis, and further studies are needed to characterize risk factors and verify diagnoses for aspergillosis among patients with severe influenza. Disclosures E. J. Anderson, NovaVax: Grant Investigator, Research grant. Pfizer: Grant Investigator, Research grant. AbbVie: Consultant, Consulting fee. MedImmune: Investigator, Research support. PaxVax: Investigator, Research support. Micron: Investigator, Research support. K. Talbot, sanofi pasteur: Investigator, Research support. Gilead: Investigator, Research support. MedImmune: Investigator, Research support. Seqirus: Scientific Advisor, Consulting fee. MedImmune: Scientific Advisor, Consulting fee.

2494. Influenza B Hospitalizations Are Associated With Mortality in Children, FluSurv-NET, 2011–2017

Abstract: Abstract Background Influenza B viruses (B) co-circulate with influenza A viruses (A) and contribute to influenza-associated hospitalizations each season. We used data from the Influenza Hospitalization Surveillance Network (FluSurv-NET) to determine the association between B virus hospitalizations and mortality among children. Methods We included data from children aged 0–17 years, residing in a FluSurv-NET catchment area, and hospitalized with laboratory-confirmed influenza during 2011–2012 through 2016–2017. We abstracted data on underlying conditions, clinical course and outcomes from medical charts. After excluding cases with unknown influenza type or with A/B coinfection, we compared characteristics of children hospitalized with A vs. B using univariate analyses and multivariable logistic regression, to determine the independent association between virus type and in-hospital mortality. Results Among 7671 children hospitalized with influenza, 5607 (73%) had A and 2064 (27%) had B. The proportion of B hospitalizations varied by season from 11% during 2013–2014 to 42% during 2012–2013. Among children with B, median age was 4 years (interquartile range 1–8 years), 58% were male and 36% were non-Hispanic white. In univariate analysis, children with B were more likely to be older, have cardiovascular and neurologic disease, to be vaccinated (38 vs. 32%), and to be hospitalized ≥2 days after illness onset, and were less likely to have asthma and receive antivirals (71 vs. 79%) compared with those with A (P < 0.05). There were no differences in the proportion with ≥1 underlying condition (59% both groups). Patients with B vs. A were no more likely to require intensive care (19 vs. 20%; p 0.34) or receive mechanical ventilation (6 vs. 5%; p 0.13); however, patients with B were more likely to die in-hospital (1 vs. 0.4%; P < 0.01). The unadjusted odds of in-hospital mortality for children with B vs. A was 2.3 (95% confidence interval (CI) 1.3–4.1), which remained elevated at 2.0 (95% CI 1.1–3.7) after adjusting for age, season and underlying conditions. Conclusion Influenza B virus infections were associated with severe outcomes among hospitalized children. Although death was uncommon, children with B had twice the odds of dying in-hospital compared with those with A virus infection. Disclosures E. J. Anderson, NovaVax: Grant Investigator, Research grant. Pfizer: Grant Investigator, Research grant. AbbVie: Consultant, Consulting fee. MedImmune: Investigator, Research support. PaxVax: Investigator, Research support. Micron: Investigator, Research support. H. K. Talbot, Sanofi Pasteur: Investigator, Research grant. Gilead: Investigator, Research grant. MedImmune: Investigator, Research grant. Vaxinnate: Safety Board, none. Seqirus: Safety Board, none.

2280. Antibiotic Exposure Does Not Impact Serological Responses to Rotavirus Vaccination

Abstract: Abstract Background Antibiotic exposure around the time of rotavirus (RV) immunization has been suggested to diminish immune responses, but data are sparse. Methods We retrospectively analyzed data from a randomized RV vaccine study (NCT01266850) outlined in the Table. Concomitant antibiotic use, defined as receipt of an antibiotic 14 days before or 7 days after RV immunization, was recorded. The primary outcome was RV-specific IgA seroresponse (IgA ≥20 U/mL) by ELISA obtained 1 month after the last dose of RV vaccine and geometric mean titer (GMT) to strain WC3 (RV5 backbone) or strain 89–12 (RV1 backbone). Only subjects who received all scheduled vaccine doses and phlebotomy were included. Data were assessed for homogeneity across vaccine schedule groups, stratified by antibiotic exposure. We examined differences in seroresponse adjusting for treatment group, gender, race, ethnicity, and study site using logistic regression models. Results Of the 1384 immunized children, 1174 (85%) met inclusion criteria.Table: Treatment Allocation and Effect of Antibiotic Exposure on Seroresponses Groups 1 2 3 4 5 Immunization Schedule Rotateq® (RV5) 3 doses N = 206 RV5, RV1, RV1 N = 207 RV5, RV5, RV1N = 194 Rotarix® (RV1) 2 dosesN = 287 RV1, RV5, RV5N = 280 Seroresponse: Antibiotic Exposed 21/25 (84%) 20/20 (100%) 18/22 (82%) 13/15 (87%) 32/32 (100%) Seroresponse: Antibiotic Not-Exposed 167/181 (92%) 168/187 (90%) 158/172 (92%) 209/272 (77%) 238/248 (96%) Nearly 10% (n = 114) of participants were antibiotic exposed; group 4 had the least antibiotic exposure (P = 0.05). No differences in GMT or seroresponses were observed to either WC3 or 89–12 (figure) by antibiotic exposure. In the multivariable logistic regression model, there were no significant differences for gender, race, ethnicity, site, or antibiotic exposure (P-value ≥0.5 for IgA seroresponse). The only observed difference in seroresponses was by RV vaccine group (P < 0.0001). Conclusion Antibiotic administration around the time of RV vaccine did not diminish RV-specific IgA seroresponses observed 1 month after the last RV vaccine dose.Figure: Proportion mounting IgA seroresponse to rotavirus immunization, stratified by antibiotic exposure status Disclosures E. J. Anderson, NovaVax: Grant Investigator, Research grant. Pfizer: Grant Investigator, Research grant. AbbVie: Consultant, Consulting fee. MedImmune: Investigator, Research support. PaxVax: Investigator, Research support. Micron: Investigator, Research support. C. B. Creech, Pfizer: Grant Investigator, Research grant. Novartis: Grant Investigator, Research grant. A. L. Shane, International Scientific Association of Probiotics and Prebiotics: Member, Reimbursement of travel and lodging for attendance and presentations at international scientific meetings 2016 and prior and support for attendance at meeting at FDA in 2017 to discuss probiotic and prebiotic research. K. Edwards, Novartis: Grant Investigator, Research grant. Novartis: Scientific Advisor, Consulting fee.