Sandra R. Arnold

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.).

Relationship Between Maternal and Neonatal Staphylococcus aureus Colonization

OBJECTIVE: The study aimed to assess whether maternal colonization with Staphylococcus aureus during pregnancy or at delivery was associated with infant staphylococcal colonization. METHODS: For this prospective cohort study, women were enrolled at 34 to 37 weeks of gestation between 2007 and 2009. Nasal and vaginal swabs for culture were obtained at enrollment; nasal swabs were obtained from women and their infants at delivery and 2- and 4-month postbirth visits. Logistic regression was used to determine whether maternal colonization affected infant colonization. RESULTS: Overall, 476 and 471 mother-infant dyads had complete data for analysis at enrollment and delivery, respectively. Maternal methicillin-resistant S aureus (MRSA) colonization occurred in 10% to 17% of mothers, with the highest prevalence at enrollment. Infant MRSA colonization peaked at 2 months of age, with 20.9% of infants colonized. Maternal staphylococcal colonization at enrollment increased the odds of infant staphylococcal colonization at birth (odds ratio; 95% confidence interval: 4.8; 2.4–9.5), hospital discharge (2.6; 1.3–5.0), at 2 months of life (2.7; 1.6–4.3), and at 4 months of life (2.0; 1.1–3.5). Similar results were observed for maternal staphylococcal colonization at delivery. Fifty maternal-infant dyads had concurrent MRSA colonization: 76% shared isolates of the same pulsed-field type, and 30% shared USA300 isolates. Only 2 infants developed staphylococcal disease. CONCLUSIONS: S aureus colonization (including MRSA) was extremely common in this cohort of maternal-infant pairs. Infants born to mothers with staphylococcal colonization were more likely to be colonized, and early postnatal acquisition appeared to be the primary mechanism.

Association Between Hospitalization With Community-Acquired Laboratory-Confirmed Influenza Pneumonia and Prior Receipt of Influenza Vaccination

IMPORTANCE Few studies have evaluated the relationship between influenza vaccination and pneumonia, a serious complication of influenza infection. OBJECTIVE To assess the association between influenza vaccination status and hospitalization for community-acquired laboratory-confirmed influenza pneumonia. DESIGN, SETTING, AND PARTICIPANTS The Etiology of Pneumonia in the Community (EPIC) study was a prospective observational multicenter study of hospitalizations for community-acquired pneumonia conducted from January 2010 through June 2012 at 4 US sites. In this case-control study, we used EPIC data from patients 6 months or older with laboratory-confirmed influenza infection and verified vaccination status during the influenza seasons and excluded patients with recent hospitalization, from chronic care residential facilities, and with severe immunosuppression. Logistic regression was used to calculate odds ratios, comparing the odds of vaccination between influenza-positive (case) and influenza-negative (control) patients with pneumonia, controlling for demographics, comorbidities, season, study site, and timing of disease onset. Vaccine effectiveness was estimated as (1 - adjusted odds ratio) × 100%. EXPOSURE Influenza vaccination, verified through record review. MAIN OUTCOMES AND MEASURES Influenza pneumonia, confirmed by real-time reverse-transcription polymerase chain reaction performed on nasal/oropharyngeal swabs. RESULTS Overall, 2767 patients hospitalized for pneumonia were eligible for the study; 162 (5.9%) had laboratory-confirmed influenza. Twenty-eight of 162 cases (17%) with influenza-associated pneumonia and 766 of 2605 controls (29%) with influenza-negative pneumonia had been vaccinated. The adjusted odds ratio of prior influenza vaccination between cases and controls was 0.43 (95% CI, 0.28-0.68; estimated vaccine effectiveness, 56.7%; 95% CI, 31.9%-72.5%). CONCLUSIONS AND RELEVANCE Among children and adults hospitalized with community-acquired pneumonia, those with laboratory-confirmed influenza-associated pneumonia, compared with those with pneumonia not associated with influenza, had lower odds of having received influenza vaccination.

Impact of Just-in-Time and Just-in-Place Simulation on Intern Success With Infant Lumbar Puncture.

BACKGROUND AND OBJECTIVE: Simulation-based skill trainings are common; however, optimal instructional designs that improve outcomes are not well specified. We explored the impact of just-in-time and just-in-place training (JIPT) on interns’ infant lumbar puncture (LP) success. METHODS: This prospective study enrolled pediatric and emergency medicine interns from 2009 to 2012 at 34 centers. Two distinct instructional design strategies were compared. Cohort A (2009–2010) completed simulation-based training at commencement of internship, receiving individually coached practice on the LP simulator until achieving a predefined mastery performance standard. Cohort B (2010–2012) had the same training plus JIPT sessions immediately before their first clinical LP. Main outcome was LP success, defined as obtaining fluid with first needle insertion and <1000 red blood cells per high-power field. Process measures included use of analgesia, early stylet removal, and overall attempts. RESULTS: A total of 436 first infant LPs were analyzed. The LP success rate in cohort A was 35% (13/37), compared with 38% (152/399) in cohort B (95% confidence interval for difference [CI diff], −15% to +18%). Cohort B exhibited greater analgesia use (68% vs 19%; 95% CI diff, 33% to 59%), early stylet removal (69% vs 54%; 95% CI diff, 0% to 32%), and lower mean number of attempts (1.4 ± 0.6 vs 2.1 ± 1.6, P < .01) compared with cohort A. CONCLUSIONS: Across multiple institutions, intern success rates with infant LP are poor. Despite improving process measures, adding JIPT to training bundles did not improve success rate. More research is needed on optimal instructional design strategies for infant LP.

Antibiotic choice for children hospitalized with pneumonia and adherence to national guidelines

INTRODUCTION: The 2011 national guidelines for the management of childhood community-acquired pneumonia (CAP) recommended narrow-spectrum antibiotics (eg, ampicillin) for most children hospitalized with CAP. We assessed the impact of these guidelines on antibiotic prescribing at 3 children’s hospitals. METHODS: Children hospitalized with clinical and radiographic CAP were enrolled from January 1, 2010, through June 30, 2012, at 3 hospitals in Tennessee and Utah as part of the Centers for Disease Control and Prevention Etiology of Pneumonia in the Community study. Antibiotic selection was determined by the treating provider. The impact of the guidelines and hospital-level implementation efforts was determined by assessing the monthly percentage of enrolled children receiving third-generation cephalosporins or penicillin/ampicillin. Segmented linear regression was used to compare observed antibiotic selection in the postguideline period with expected antibiotic use projected from preguideline months. RESULTS: Overall, 2121 children were included. During the preguideline period, 52.8% (interquartile range 47.8–56.6) of children with CAP received third-generation cephalosporins, whereas 2.7% (2.1, 7.0) received penicillin/ampicillin. By 9 months postguidelines, third-generation cephalosporin use declined (absolute difference −12.4% [95% confidence interval −19.8% to −5.1%]), whereas penicillin/ampicillin use increased (absolute difference 11.3% [4.3%–18.3%]). The most substantial changes were noted at those institutions that implemented guideline-related dissemination activities. CONCLUSIONS: After publication of national guidelines, third-generation cephalosporin use declined and penicillin/ampicillin use increased among children hospitalized with CAP. Changes were more apparent among those institutions that proactively disseminated the guidelines, suggesting that targeted, hospital-based efforts are important for timely implementation of guideline recommendations.

Secondhand Smoke Exposure and Illness Severity among Children Hospitalized with Pneumonia

OBJECTIVE To assess the relationship between secondhand smoke (SHS) exposure and disease severity among children hospitalized with community-acquired pneumonia (CAP). STUDY DESIGN Children hospitalized with clinical and radiographic CAP were enrolled between January 1, 2010, and June 30, 2012 at 3 hospitals in Tennessee and Utah as part of the Centers for Disease Control and Preventions Etiology of Pneumonia in the Community study. Household SHS exposure was defined based on the number of smokers in the childs home. Outcomes included hospital length of stay, intensive care unit admission, and mechanical ventilation. Proportional hazards and logistic regression models were used to assess associations between SHS exposure and outcomes. All models were adjusted for age, sex, race/ethnicity, household education level, government insurance, comorbidities, enrollment site, year, and season. RESULTS Of the 2219 children included in the study, SHS exposure was reported in 785 (35.4%), including 325 (14.8%) with ≥2 smokers in the home. Compared with nonexposed children, the children exposed to ≥2 smokers had longer length of stay (median, 70.4 hours vs 64.4 hours; adjusted hazard ratio, 0.85; 95% CI, 0.75-0.97) and were more likely to receive intensive care (25.2% vs 20.9%; aOR, 1.44; 95% CI, 1.05-1.96), but not mechanical ventilation. Outcomes in children exposed to only 1 household smoker were similar to those in nonexposed children. CONCLUSION Children hospitalized with CAP from households with ≥2 smokers had a longer length of stay and were more likely to require intensive care compared with children from households with no smokers, suggesting that they experienced greater pneumonia severity.

Molecular Detection and Characterization of Mycoplasma pneumoniae Among Patients Hospitalized With Community-Acquired Pneumonia in the United States

We report molecular characteristics of M. pneumoniae in respiratory specimens from children and adults hospitalized with CAP. The P1 type 1 genotype and MLVA type 4/5/7/2 predominated, but proportions of types differed between children and adults. Macrolide resistance was rare.

Vancomycin Dosing Practices, Trough Concentrations, and Predicted Area Under the Curve in Children With Suspected Invasive Staphylococcal Infections

Reply to Letter to the Editor—We appreciate the comments from Dr Frymoyer concerning the most appropriate pediatric equation for calculating glomerular filtration rate (GFR) and agree that each method has limitations. Although the original Schwartz equation [1] may overestimate GFR when the newer method for measuring creatinine is used, there are several reasons why we chose to use the original equationinsteadoftherevisedSchwartz equation [2]. First, the newer equation was developed from the Chronic Kidney Disease in Children cohort and has not been widely studied in children without kidney disease. Sch wartz and colleagues [2] concluded that additional studies in healthy children with a higher GFR are needed before recommending the widespread use of this equation in all children. Also, data from 2 recent studies suggest that the newer equation may underestimate GFR in children with mild kidney disease [3] and in children with normal renal function [4]. Therefore, our institution has not implemented the revised Schwartz equation into routine clinical practice due to the limited data supporting its applicability in children without kidney dysfunction. Finally, Schwartz [5] also suggested that equations used to estimate GFR should correct for differences in body habitus, sex, puberty, infancy, and prematurity. Because our patient cohort included children ages 2 months to 18 years with normal baseline renal function, we chose to use the original Schwartz equation that accounts for differences in age and sex [6]. We agree that the difference in equations used to estimate GFR likely contributes to thedifference inpredictedarea under the curve (AUC) reported in the modeling study by Frymoyer and colleagues [7] and our retrospective study [8]. In addition, we excluded patients with any type of renal dysfunction, so we would expect to observe a faster vancomycin clearance compared with a general pediatric population kinetics study. Our estimate for vancomycin clearance of 0.15 L/h/kg is within the range of reported values for vancomycin clearance in children (0.103–0.157 L/h/kg) that Frymoyer and colleagues [7] used in their original modeling study. These differences in estimated GFR and predicted AUC reaffirm the conclusions by Schwartz and colleagues [5] that more studies are needed in order to generate a widely applicable equation to estimate GFR in pediatric patients. Therefore, we do not believe there is currently a standard method of calculating GFR, and the method chosen should not only be based on the process used for measuring serum creatinine but also be based on the patient population being assessed, as we attempted to do in our study.

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

ABSTRACT 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 Cohens 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.

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

Importance &bgr;-Lactam monotherapy and &bgr;-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 &bgr;-lactam monotherapy vs &bgr;-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 &bgr;-lactam monotherapy or &bgr;-lactam plus macrolide combination therapy. Data analysis was completed in April 2017. Main Outcomes and Measures We defined the referent as &bgr;-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 &bgr;-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 &bgr;-lactam monotherapy and 399 (28.1%) received &bgr;-lactam plus macrolide combination therapy. In the unmatched cohort, there was no statistically significant difference in length of hospital stay between children receiving &bgr;-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 &bgr;-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.