Publications by authors named "Andrew T Pavia"

147 Publications

Pneumonia Severity in Children: Utility of Procalcitonin in Risk Stratification.

Hosp Pediatr 2021 Mar 12;11(3):215-222. Epub 2021 Feb 12.

Vanderbilt University Medical Center, Nashville, Tennessee.

Objectives: To determine if serum procalcitonin, an indicator of bacterial etiology in pneumonia in all ages and a predictor of severe pneumonia in adults, is associated with disease severity in children with community-acquired pneumonia.

Methods: We prospectively enrolled children 2 months to <18 years with clinical and radiographic pneumonia at 2 children's hospitals (2014-2019). Procalcitonin samples were obtained at presentation. An ordinal outcome scale of pneumonia severity was defined: very severe (intubation, shock, or death), severe (intensive care admission without very severe features and/or high-flow nasal cannula), moderate (hospitalization without severe or very severe features), and mild (discharge). Hospital length of stay (LOS) was also examined. Ordinal logistic regression was used to model associations between procalcitonin and outcomes. We estimated adjusted odds ratios (aORs) for a variety of cut points of procalcitonin ranging from 0.25 to 3.5 ng/mL.

Results: The study included 488 children with pneumonia; 30 (6%) were classified as very severe, 106 (22%) as severe, 327 (67%) as moderate, and 25 (5%) as mild. Median procalcitonin in the very severe group was 5.06 (interquartile range [IQR] 0.90-16.83), 0.38 (IQR 0.11-2.11) in the severe group, 0.29 (IQR 0.09-1.90) in the moderate group, and 0.21 (IQR 0.12-1.2) in the mild group. Increasing procalcitonin was associated with increasing severity (range of aORs: 1.03-1.25) and increased LOS (range of aORs: 1.04-1.36). All comparisons were statistically significant.

Conclusions: Higher procalcitonin was associated with increased severity and LOS. Procalcitonin may be useful in helping clinicians evaluate pneumonia severity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1542/hpeds.2020-001842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898232PMC
March 2021

A modular approach to integrating multiple data sources into real-time clinical prediction for pediatric diarrhea.

Elife 2021 Feb 2;10. Epub 2021 Feb 2.

Division of Infectious Diseases, Department of Internal Medicine, University of Utah, Salt Lake City, United States.

Traditional clinical prediction models focus on parameters of the individual patient. For infectious diseases, sources external to the patient, including characteristics of prior patients and seasonal factors, may improve predictive performance. We describe the development of a predictive model that integrates multiple sources of data in a principled statistical framework using a post-test odds formulation. Our method enables electronic real-time updating and flexibility, such that components can be included or excluded according to data availability. We apply this method to the prediction of etiology of pediatric diarrhea, where 'pre-test' epidemiologic data may be highly informative. Diarrhea has a high burden in low-resource settings, and antibiotics are often over-prescribed. We demonstrate that our integrative method outperforms traditional prediction in accurately identifying cases with a viral etiology, and show that its clinical application, especially when used with an additional diagnostic test, could result in a 61% reduction in inappropriately prescribed antibiotics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7554/eLife.63009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853717PMC
February 2021

Clinical predictors for etiology of acute diarrhea in children in resource-limited settings.

PLoS Negl Trop Dis 2020 10 9;14(10):e0008677. Epub 2020 Oct 9.

Division of Infectious Diseases, Department of Internal Medicine, University of Utah, Salt Lake City, UT, United States of America.

Background: Diarrhea is one of the leading causes of childhood morbidity and mortality in lower- and middle-income countries. In such settings, access to laboratory diagnostics are often limited, and decisions for use of antimicrobials often empiric. Clinical predictors are a potential non-laboratory method to more accurately assess diarrheal etiology, the knowledge of which could improve management of pediatric diarrhea.

Methods: We used clinical and quantitative molecular etiologic data from the Global Enteric Multicenter Study (GEMS), a prospective, case-control study, to develop predictive models for the etiology of diarrhea. Using random forests, we screened the available variables and then assessed the performance of predictions from random forest regression models and logistic regression models using 5-fold cross-validation.

Results: We identified 1049 cases where a virus was the only etiology, and developed predictive models against 2317 cases where the etiology was known but non-viral (bacterial, protozoal, or mixed). Variables predictive of a viral etiology included lower age, a dry and cold season, increased height-for-age z-score (HAZ), lack of bloody diarrhea, and presence of vomiting. Cross-validation suggests an AUC of 0.825 can be achieved with a parsimonious model of 5 variables, achieving a specificity of 0.85, a sensitivity of 0.59, a NPV of 0.82 and a PPV of 0.64.

Conclusion: Predictors of the etiology of pediatric diarrhea can be used by providers in low-resource settings to inform clinical decision-making. The use of non-laboratory methods to diagnose viral causes of diarrhea could be a step towards reducing inappropriate antibiotic prescription worldwide.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pntd.0008677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588112PMC
October 2020

Clinical and molecular epidemiology of invasive Staphylococcus aureus infection in Utah children; continued dominance of MSSA over MRSA.

PLoS One 2020 18;15(9):e0238991. Epub 2020 Sep 18.

Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Utah, Salt Lake City, Utah, United States of America.

Background: Invasive Staphylococcus aureus infections are a common cause of morbidity and mortality in children. In the early 2000's the proportion of infections due the methicillin-resistant S. aureus (MRSA) increased rapidly. We described the clinical and molecular epidemiology of invasive S. aureus disease in a pediatric population.

Methods: We prospectively identified children in Utah with invasive S. aureus infections. Medical records were reviewed to determine diagnosis and clinical characteristics. Isolates were genotyped using multi-locus sequence typing. The presence of genes encoding the Panton-Valentine leukocidin (PVL) was determined using polymerase chain reaction.

Results: Over a 4-year period between January 2009 and December 2012, we identified 357 children, hospitalized at Primary Children's Hospital, with invasive S. aureus infections and isolates available for the study. Methicillin-susceptible S. aureus (MSSA) caused 79% of disease, while MRSA caused only 21% of disease. Mortality associated with invasive S. aureus infection was 3.6%. The most common diagnoses were osteoarticular infections (38%) followed by central line associated blood stream infections (19%) and pneumonia (12%). We identified 41 multi-locus sequence types. The majority of isolates belonged to 6 predominant clonal complexes (CC5, CC8, CC15, CC30, CC45, CC59). PVL was present in a minority (16%) of isolates, of which most were ST8 MRSA.

Conclusions: MSSA was the primary cause of invasive S. aureus infections at our institution throughout the study period. A limited number of predominant strains accounted for the majority of invasive disease. The classic virulence factor PVL was uncommon in MSSA isolates. Further study is needed to improve our understanding of S. aureus virulence and disease pathogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238991PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500648PMC
October 2020

Parainfluenza Virus Types 1-3 Infections Among Children and Adults Hospitalized with Community-Acquired Pneumonia.

Clin Infect Dis 2020 Jul 18. Epub 2020 Jul 18.

Department of Health Policy, Vanderbilt University Medical Center, Nashville, TN.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciaa973DOI Listing
July 2020

Oral Step-Down Therapy With Levofloxacin for Febrile Neutropenia in Children With Cancer.

J Pediatric Infect Dis Soc 2021 Feb;10(1):27-33

Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA.

Background: Although febrile neutropenia (FN) is a frequent complication in children with cancer receiving chemotherapy, there remains significant variability in selection of route (intravenous [IV] vs oral) and length of therapy. We implemented a guideline with a goal to change practice from using IV antibiotics after hospital discharge to the use of step-down oral therapy with levofloxacin for most children with FN until absolute neutrophil count > 500. The objectives of this study were to determine the impact of this guideline on home IV antibiotic use, and to evaluate the safety of implementation of this guideline.

Methods: We performed a quasi-experimental, pre-post study of discharge FN treatment at a stand-alone children's hospital in patients without bacteremia discharged between January 2013 and October 2018. In January 2015, a multidisciplinary team created a guideline to switch most children with FN to oral levofloxacin, which was formally implemented as of September 2017. Discharges during the postintervention period (after September 2017) were compared to discharges in the preintervention period (between January 2013 and December 2014).

Results: In adjusted multivariable regression analyses, the postimplementation period was associated with a decrease in home IV antibiotics (adjusted risk ratio [aRR], 0.07 [95% confidence interval {CI}, .03-.13]) and fewer IV antibiotic initiations within 24 hours of a new healthcare encounter up to 7 days after discharge (aRR, 0.39 [95% CI, .17-.93]) compared to the preintervention time period.

Conclusions: Step-down oral levofloxacin for children with FN who are afebrile with an ANC ≤ 500 at discharge is feasible and resulted in similar clinical outcomes compared to home IV antibiotics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jpids/piaa015DOI Listing
February 2021

Clinical Features of Human Metapneumovirus-Associated Community-acquired Pneumonia Hospitalizations.

Clin Infect Dis 2021 01;72(1):108-117

Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciaa088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823075PMC
January 2021

Reply to Verweij et al.

Clin Infect Dis 2020 01;70(2):350-351

Division of Pediatric Infectious Diseases, University of Utah, Salt Lake City.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciz568DOI Listing
January 2020

Clinical and Molecular Epidemiology of Invasive Haemophilus influenzae Serotype a Infections in Utah Children.

J Pediatric Infect Dis Soc 2020 Dec;9(6):650-655

Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah, USA.

Background: Following widespread use of the Haemophilus influenzae serotype b (Hib) vaccine, H. influenzae serotype a (Hia) has emerged as an important pathogen in children in some regions. We describe the clinical features and molecular epidemiology of invasive Hia disease in children in Utah over an 11-year period.

Methods: We identified cases of invasive Hia disease, defined as detection of Hia from a normally sterile site, in children aged <18 years from Utah between 2007 and 2017. Medical records were reviewed to determine demographic characteristics and clinical outcomes. Available Hia isolates were genotyped using multilocus sequence typing, and phylogenetic division was determined using sodC polymerase chain reaction. Presence of the putative virulence-associated IS1016-bexA duplication-deletion was evaluated.

Results: We identified 51 children with invasive Hia. The average annual incidence was 1.7 cases per 100 000 children aged <5 years; 4.8 cases per 100 000 children aged <1 year. The median age was 11.3 months. The most common clinical presentation was meningitis (53%), followed by pneumonia (14%) and septic arthritis (14%). Twenty-two children (43%) required admission to an intensive care unit; 1 died. Sequence type (ST) 62, phylogenetic division II isolates caused 75% (21/28) of disease. No isolates contained the virulence-associated IS1016-bexA duplication-deletion.

Conclusions: Hia is a significant cause of severe invasive bacterial infection in Utah. The majority of infections were caused by ST62 isolates, a phylogenetic division II Hia type that lacks the IS1016-bexA duplication-deletion. Hia ST62 has not been commonly reported elsewhere, suggesting a unique molecular epidemiology in our population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jpids/piz088DOI Listing
December 2020

Response to Apewokin and Onyishi.

Clin Infect Dis 2020 06;70(12):2749-2750

Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciz839DOI Listing
June 2020

Prevalence, Risk Factors, and Outcomes of Bacteremic Pneumonia in Children.

Pediatrics 2019 07;144(1)

Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tennessee.

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 ( = 23, 50%), ( = 6, 13%), and ( = 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. 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1542/peds.2018-3090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615516PMC
July 2019

Economic Burden of Home Antimicrobial Therapy: OPAT Versus Oral Therapy.

Hosp Pediatr 2019 04;9(4):234-240

Infectious Disease, Department of Pediatrics, School of Medicine and

Background: There is increasing evidence that outpatient parenteral antimicrobial therapy (OPAT) is overused for children and that outcomes with oral therapy are equivalent. Our objective was to compare economic burden between OPAT and oral therapy, accounting for direct and indirect costs and caregiver quality of life (QoL).

Methods: We conducted a prospective cohort study of caregivers for children after hospitalization who were treated with prolonged antimicrobial therapy. We collected data about missed work and school and time spent administering therapy. Caregivers completed the Pediatric Quality of Life Inventory to assess QoL. Clinical information included length of stay, treatment indication, and type of therapy (OPAT versus oral therapy). Direct medical costs were obtained by using a microcosting system and accounted for medication, supplies, and home-nursing visits. The primary cost outcome was the mean daily cost of therapy. Multivariable models were developed to adjust for potential confounders.

Results: Two hundred and twelve caregivers completed surveys: 123 (58%) for oral therapy and 89 (42%) for OPAT. Caregivers administering OPAT reported more missed work, missed school for their children, time with daily medication administration (90 vs 6 minutes; < .01) and lower QoL scores (77.8 vs 68.9) than caregivers administering oral therapy. The mean daily cost was $65 (95% confidence interval: $51-$78) for OPAT and $7 (95% confidence interval: $4-$9) for oral therapy. Relative differences in cost and QoL between groups did not change after model adjustment.

Conclusions: The overall burden of OPAT is substantially higher than that of oral therapy, including higher direct and indirect costs and greater impact on caregiver QoL. These findings strongly support efforts to use oral therapy in place of OPAT when clinically appropriate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1542/hpeds.2018-0193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434972PMC
April 2019

Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenzaa.

Clin Infect Dis 2019 03;68(6):e1-e47

Division of Pediatric Infectious Diseases, University of Utah, Salt Lake City.

These clinical practice guidelines are an update of the guidelines published by the Infectious Diseases Society of America (IDSA) in 2009, prior to the 2009 H1N1 influenza pandemic. This document addresses new information regarding diagnostic testing, treatment and chemoprophylaxis with antiviral medications, and issues related to institutional outbreak management for seasonal influenza. It is intended for use by primary care clinicians, obstetricians, emergency medicine providers, hospitalists, laboratorians, and infectious disease specialists, as well as other clinicians managing patients with suspected or laboratory-confirmed influenza. The guidelines consider the care of children and adults, including special populations such as pregnant and postpartum women and immunocompromised patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciy866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6653685PMC
March 2019

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

J Hosp Med 2018 12 31;13(12):848-852. Epub 2018 Oct 31.

Division of Hospital Medicine, Monroe Carell Jr. Children's Hospital and the Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12788/jhm.3093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321763PMC
December 2018

Shortened IV Antibiotic Course for Uncomplicated, Late-Onset Group B Streptococcal Bacteremia.

Pediatrics 2018 11 11;142(5). Epub 2018 Oct 11.

Divisions of Hospital Medicine and.

: media-1vid110.1542/5804909691001PEDS-VA_2018-0345 BACKGROUND: Guidelines recommend a prolonged course (10 days) of intravenous (IV) antibiotic therapy for infants with uncomplicated, late-onset group B (GBS) bacteremia. Our objective was to determine the frequency with which shorter IV antibiotic courses are used and to compare rates of GBS disease recurrence between prolonged and shortened IV antibiotic courses.

Methods: We performed a multicenter retrospective cohort study of infants aged 7 days to 4 months who were admitted to children's hospitals in the Pediatric Health Information System database from 2000 to 2015 with GBS bacteremia. The exposure was shortened IV antibiotic therapy, defined as discharge from the index GBS visit after a length of stay of ≤8 days without a peripherally inserted central catheter charge. The primary outcome was readmission for GBS bacteremia, meningitis, or osteomyelitis in the first year of life. Outcomes were analyzed by using propensity-adjusted, inverse probability-weighted regression models.

Results: Of 775 infants who were diagnosed with uncomplicated, late-onset GBS bacteremia, 612 (79%) received a prolonged IV course of antibiotic therapy, and 163 (21%) received a shortened course. Rates of treatment with shortened IV courses varied by hospital (range: 0%-67%; SD: 20%). Three patients (1.8%) in the shortened IV duration group experienced GBS recurrence, compared with 14 patients (2.3%) in the prolonged IV duration group (adjusted absolute risk difference: -0.2%; 95% confidence interval: -3.0% to 2.5%).

Conclusions: Shortened IV antibiotic courses are prescribed among infants with uncomplicated, late-onset GBS bacteremia, with low rates of disease recurrence and treatment failure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1542/peds.2018-0345DOI Listing
November 2018

Transmission of rhinovirus in the Utah BIG-LoVE families: Consequences of age and household structure.

PLoS One 2018 25;13(7):e0199388. Epub 2018 Jul 25.

Health Sciences Center, Texas A&M University, College Station, TX, United States of America.

Background: Common cold viruses create significant health and financial burdens, and understanding key loci of transmission would help focus control strategies. This study (1) examines factors that influence when individuals transition from a negative to positive test (acquisition) or a positive to negative test (loss) of rhinovirus (HRV) and other respiratory tract viruses in 26 households followed weekly for one year, (2) investigates evidence for intrahousehold and interhousehold transmission and the characteristics of individuals implicated in transmission, and (3) builds data-based simulation models to identify factors that most strongly affect patterns of prevalence.

Methods: We detected HRV, coronavirus, paramyxovirus, influenza and bocavirus with the FilmArray polymerase chain reaction (PCR) platform (BioFire Diagnostics, LLC). We used logistic regression to find covariates affecting acquisition or loss of HRV including demographic characteristics of individuals, their household, their current infection status, and prevalence within their household and across the population. We apply generalized linear mixed models to test robustness of results.

Results: Acquisition of HRV was less probable in older individuals and those infected with a coronavirus, and higher with a higher proportion of other household members infected. Loss of HRV is reduced with a higher proportion of other household members infected. Within households, only children and symptomatic individuals show evidence for transmission, while between households only a higher number of infected older children (ages 5-19) increases the probability of acquisition. Coronaviruses, paramyxoviruses and bocavirus also show evidence of intrahousehold transmission. Simulations show that age-dependent susceptibility and transmission have the largest effects on mean HRV prevalence.

Conclusions: Children are most likely to acquire and most likely to transmit HRV both within and between households, with infectiousness concentrated in symptomatic children. Simulations predict that the spread of HRV and other respiratory tract viruses can be reduced but not eliminated by practices within the home.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0199388PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6059387PMC
January 2019

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

Open Forum Infect Dis 2018 Apr 16;5(4):ofy061. Epub 2018 Mar 16.

Centers for Disease Control and Prevention, Atlanta, Georgia.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ofid/ofy061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5890478PMC
April 2018

Impact of Implementing Antibiotic Stewardship Programs in 15 Small Hospitals: A Cluster-Randomized Intervention.

Clin Infect Dis 2018 08;67(4):525-532

Division of Pediatric Infectious Diseases, University of Utah School of Medicine, Salt Lake City.

Background: Studies on the implementation of antibiotic stewardship programs (ASPs) in small hospitals are limited. Accreditation organizations now require all hospitals to have ASPs.

Methods: The objective of this cluster-randomized intervention was to assess the effectiveness of implementing ASPs in Intermountain Healthcare's 15 small hospitals. Each hospital was randomized to 1 of 3 ASPs of escalating intensity. Program 1 hospitals were provided basic antibiotic stewardship education and tools, access to an infectious disease hotline, and antibiotic utilization data. Program 2 hospitals received those interventions plus advanced education, audit and feedback for select antibiotics, and locally controlled antibiotic restrictions. Program 3 hospitals received program 2 interventions plus audit and feedback on the majority of antibiotics, and an infectious diseases-trained clinician approved restricted antibiotics and reviewed microbiology results. Changes in total and broad-spectrum antibiotic use within programs (intervention versus baseline) and the difference between programs in the magnitude of change in antibiotic use (eg, program 3 vs 1) were evaluated with mixed models.

Results: Program 3 hospitals showed reductions in total (rate ratio, 0.89; confidence interval, .80-.99) and broad-spectrum (0.76; .63-.91) antibiotic use when the intervention period was compared with the baseline period. Program 1 and 2 hospitals did not experience a reduction in antibiotic use. Comparison of the magnitude of effects between programs showed a similar trend favoring program 3, but this was not statistically significant.

Conclusions: Only the most intensive ASP intervention was associated with reduction in total and broad-spectrum antibiotic use when compared with baseline.

Clinical Trials Registration: NCT03245879.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciy155DOI Listing
August 2018

Mycoplasma pneumoniae Among Children Hospitalized With Community-acquired Pneumonia.

Clin Infect Dis 2019 01;68(1):5-12

Centers for Disease Control and Prevention, Atlanta, Georgia.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciy419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6552676PMC
January 2019

Outpatient Parenteral Antimicrobial Therapy in Young Infants.

J Pediatric Infect Dis Soc 2018 May;7(2):e40-e42

Division of Infectious Disease, Department of Pediatrics, University of Utah, Salt Lake City.

We examined clinical outcomes for 53 young infants (<3 months of age) treated with outpatient parenteral antimicrobial therapy after discharge from a freestanding children's hospital. None of the patients experienced treatment failure or disease progression; 9% of them experienced a catheter-related complication, but this percentage is not different than that for older children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jpids/piy002DOI Listing
May 2018

Reply to Mercuro et al.

Clin Infect Dis 2018 09;67(8):1307-1308

Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciy275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6160600PMC
September 2018

Is Parotitis One More Complication of Influenza? The Ongoing Challenge of Determining Causal Associations.

Authors:
Andrew T Pavia

Clin Infect Dis 2018 08;67(4):502-503

Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Utah, Salt Lake City.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciy140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070059PMC
August 2018

Opportunities to Improve Fluoroquinolone Prescribing in the United States for Adult Ambulatory Care Visits.

Clin Infect Dis 2018 06;67(1):134-136

Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia.

The Food and Drug Administration warned against fluoroquinolone use for conditions with effective alternative agents. An estimated 5.1% of adult ambulatory fluoroquinolone prescriptions were for conditions that did not require antibiotics, and 19.9% were for conditions where fluoroquinolones are not recommended first-line therapy. Unnecessary fluoroquinolone use should be reduced.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciy035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005119PMC
June 2018

Rhinovirus in Febrile Infants and Risk of Bacterial Infection.

Pediatrics 2018 02 17;141(2). Epub 2018 Jan 17.

Departments of Pediatrics.

Background: Febrile infants with viral respiratory infections have a reduced risk of bacterial infection compared with virus-negative infants. The risk of concomitant bacterial infection in febrile infants positive for human rhinovirus (HRV) by polymerase chain reaction (PCR) is unknown.

Methods: Infants 1-90 days old managed using the care process model for well-appearing febrile infants and with respiratory viral testing by PCR (RVPCR) in the emergency department or inpatient setting of 22 hospitals in the Intermountain Healthcare system from 2007-2016 were identified. Relative risk (RR) of bacterial infection was calculated for infants with HRV, non-HRV viruses, or no virus detected.

Results: Of 10 964 febrile infants identified, 4037 (37%) had RVPCR. Of these, 2212 (55%) were positive for a respiratory virus; 1392 (35%) for HRV alone. Bacterial infection was identified in 9.5%. Febrile infants with HRV detected were more likely to have bacterial infection than those with non-HRV viruses (7.8% vs 3.7%; < .001; RR 2.12 [95% CI 1.43-3.15]). Risk of urinary tract infection was not significantly different for HRV-positive infants at any age, nor was risk of invasive bacterial infection (IBI; bacteremia and/or meningitis) meaningfully different for infants 1-28 day olds. Infants 29-90 days old with HRV had a decreased likelihood of IBI (RR 0.52 [95% CI 0.34-0.80]).

Conclusions: HRV is common in febrile infants. Detection did not alter risk of concomitant urinary tract infection at any age or risk of IBI in infants 1-28 days old. HRV detection may be relevant in considering risk of IBI for infants 29-90 days of age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1542/peds.2017-2384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5810600PMC
February 2018

Geographic Variability in Diagnosis and Antibiotic Prescribing for Acute Respiratory Tract Infections.

Infect Dis Ther 2018 Mar 22;7(1):171-174. Epub 2017 Dec 22.

Centers for Disease Control and Prevention, Atlanta, GA, USA.

Introduction: Antibiotic prescribing rates vary substantially across regions in the USA. Whether these differences are driven primarily by a greater tendency to treat certain infections (i.e., overtreatment) in certain regions or differences in the tendency to diagnose certain infections (i.e., overdiagnosis) is poorly understood.

Methods: We examined data from 2012 to 2013 using the National Ambulatory Medical Care Survey, which is a nationally representative sample of visits to office-based physicians. For each of nine geographic regions, we examined the relationship between the visit rate/1000 population for respiratory diagnoses for which antibiotics were prescribed to the visit rate/1000 population for selected respiratory diagnoses where antibiotic therapy may be warranted.

Results: The visit rate for all respiratory conditions resulting in an antibiotic prescription was lowest (109/1000 population) in the Pacific Region and highest (176/1000, 95% CI 138-213) in the East South Central Region. The diagnosis rate for selected respiratory conditions where antibiotic therapy may be warranted was also lowest (119/1000, 95% CI 91-147) in the Pacific Region and highest (189/1000, 95% CI 153-225) in the East South Central Region.

Conclusion: Antibiotic prescribing rates for respiratory conditions vary by region and are strongly associated with the rate with which selected respiratory conditions are diagnosed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40121-017-0181-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840100PMC
March 2018

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

J Infect Dis 2018 06;218(2):179-188

Department of Pediatrics, University of Tennessee Health Science Center, Memphis.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/infdis/jix641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108488PMC
June 2018

Effectiveness of β-Lactam Monotherapy vs Macrolide Combination Therapy for Children Hospitalized With Pneumonia.

JAMA Pediatr 2017 12;171(12):1184-1191

Department of Health Policy, Vanderbilt University Medical Center, Nashville, Tennessee.

Importance: β-Lactam monotherapy and β-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 β-lactam monotherapy vs β-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 β-lactam monotherapy or β-lactam plus macrolide combination therapy. Data analysis was completed in April 2017.

Main Outcomes And Measures: We defined the referent as β-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 β-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 β-lactam monotherapy and 399 (28.1%) received β-lactam plus macrolide combination therapy. In the unmatched cohort, there was no statistically significant difference in length of hospital stay between children receiving β-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 β-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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamapediatrics.2017.3225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6583650PMC
December 2017

Rhinovirus Viremia in Patients Hospitalized With Community-Acquired Pneumonia.

J Infect Dis 2017 11;216(9):1104-1111

Centers for Disease Control and Prevention.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/infdis/jix455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5724377PMC
November 2017

Human Bocavirus Capsid Messenger RNA Detection in Children With Pneumonia.

J Infect Dis 2017 09;216(6):688-696

Departments of Pediatrics.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/infdis/jix352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5853397PMC
September 2017