Natural Clostridioides difficile Toxin Immunization in Colonized Infants.

BACKGROUND: Clostridioides (Clostridium) difficile colonization is common among infants. Serological sequelae of infant C. difficile colonization are poorly understood. METHODS: In this prospective cohort study of healthy infants, stools serially collected between ages 1-2 and 9-12 months were tested for non-toxigenic and toxigenic C. difficile (TCD). Cultured isolates underwent whole-genome sequencing. Serum collected at 9-12 months underwent measurement of IgA, IgG, and IgM against TCD toxins A and B and neutralizing antibody (NAb) titers against toxin B. For comparison, antitoxin IgG and NAb were measured in cord blood from 50 mothers unrelated to study infants. RESULTS: Among 32 infants, 16 (50%) were colonized with TCD; 12 were first colonized >1 month before serology measurements. A variety of sequence types were identified, and there was evidence of putative in-home (enrolled siblings) and outpatient clinic transmission. Infants first colonized with TCD >1 month prior had significantly greater serum antitoxin IgA and IgG against toxins A (P = .02 for both) and B (P = .009 and .008, respectively) compared with non-TCD-colonized infants, and greater IgG compared with unrelated cord blood (P = .005). Five of 12 (42%) colonized infants had detectable NAb titers compared with zero non-TCD-colonized infants (P = .02). Breastfeeding was not associated with differences in serological measurements. CONCLUSIONS: TCD colonization is associated with a humoral immune response against toxins A and B, with evidence of toxin B neutralization in vitro. The extent and duration of protection against CDI later in life afforded by natural C. difficile immunization events require further investigation.

Epidemic Adolescent Binge Drinking at Lollapalooza, A Music Festival in Chicago.

OBJECTIVES: Lollapalooza (LP) is an annual 3-day outdoor music festival in Chicago. Underage drinking and drug use are believed to be common, but the burden on emergency departments (EDs) has not been documented. We assessed the burden on health care resources associated with this music festival. METHODS: We performed a retrospective chart review of adolescent (aged 11-20 years) ED visits during LP weekend and 4 summer comparison weekends at Lurie Children's Hospital in Chicago, Ill, in 2014 (n = 356). We then analyzed adolescent alcohol- and drug-related hospital visits to all Chicago hospitals for each weekend in 2014 0 using Illinois hospital discharge data. RESULTS: Adolescents accounted for a greater proportion of our ED visits during LP weekend than comparison weekends (25% vs 19%, P < 0.02). Lollapalooza weekend patients were more likely female (P = 0.025), older (P = 0.0067), more often unsupervised (P < 0.0001), and less likely to live in the city (P < 0.001) than adolescents seen during comparison weekends. Thirty-one underage adolescents who attended LP were treated in our ED; 84% were intoxicated (blood alcohol content, 88-328 mg/dL). Citywide there was an 11-fold increase in adolescent alcohol-related hospital visits during LP weekend compared with an average weekend. Drug intoxication was much less common. CONCLUSIONS: Adolescents seen in our ED the weekend of LP were older, more often female, frequently unsupervised, and less likely to be city residents than those seen during comparison weekends. Those who attended LP had high rates of alcohol intoxication. This surge of intoxicated adolescent patients affected numerous EDs in the city.

Group A Streptococcus pharyngitis in Children: New Perspectives on Rapid Diagnostic Testing and Antimicrobial Stewardship.

The most common cause of bacterial pharyngitis is Group A Streptococcus (GAS). Accurate diagnosis of GAS pharyngitis is crucial to identify children who would benefit from antibiotic treatment. Rapid diagnosis has the potential to reduce antibiotic overuse. Current national guidelines differ in their recommendations for GAS testing. While rapid antigen detection tests (RADTs) are widely used, their sensitivity is considered too low for stand-alone testing by several expert bodies. Newer molecular tests using nucleic acid amplification show higher accuracy and fast results, but their cost, complexity, and very high sensitivity may limit widespread adoption. This review provides up-to-date evidence regarding rapid diagnostic testing and antimicrobial stewardship in children with sore throat. We discuss discrepancies across GAS testing guidelines at the international level, patient selection for testing for GAS, rapid test accuracy, and the potential role of rapid GAS tests to promote antibiotic stewardship, with emphasis on emerging rapid molecular tests.

Performance of a Molecular Test for Group A Streptococcus Pharyngitis.

We performed a prospective study to determine if the pretest probability of a positive loop-mediated isothermal amplification test is greater when there are more signs and symptoms of GAS pharyngitis. Patients were enrolled if a clinician obtained a GAS RADT. The McIsaac score was calculated. The prevalence of positive LAMP and RADT results increased as the McIsaac score increased. The calculated sensitivity of LAMP was superior to RADT.

Practicing What We Preach: An Effort to Improve Safe Sleep of Hospitalized Infants.

Introduction: To prevent sudden unexpected infant death, pediatric providers recommend the ABCs of infant sleep: Alone, on the Back, and in an empty Crib. This study's objective was to document sleep practices of infants admitted to a large children's hospital, examine adherence to American Academy of Pediatrics safe sleep guidelines, and develop interventions to improve guideline adherence. Methods: We conducted a pre/post quality improvement study at a single quaternary care medical center from 2015 to 2019. Infants 0 to younger than 12 months were observed in their sleeping environment pre- and post-implementation of multiple hospital-wide interventions to improve the sleep safety of hospitalized infants. Results: Only 1.3% of 221 infants observed preintervention met all ABCs of safe sleep; 10.6% of 237 infants met the ABCs of safe sleep postintervention. Significant improvements in the post-intervention cohort included sleeping in a crib (94% versus 80% preintervention; P < 0.001), avoidance of co-sleeping (3% versus 15% preintervention; P < 0.001), absence of supplies in the crib (58% versus 15% preintervention; P < 0.001), and presence of an empty crib (13% versus 2% preintervention; P < 0.001). Conclusions: Most infants hospitalized at our institution do not sleep in a safe environment. However, the implementation of a care bundle led to improvements in the sleep environment in the hospital. Further research is necessary to continue improving in-hospital safe sleep and to assess whether these practices impact the home sleep environment.

Standardization of Epidemiological Surveillance of Group A Streptococcal Pharyngitis.

Pharyngitis, more commonly known as sore throat, is caused by viral and/or bacterial infections. Group A Streptococcus (Strep A) is the most common bacterial cause of pharyngitis. Strep A pharyngitis is an acute, self-limiting disease but if undertreated can lead to suppurative complications, nonsuppurative poststreptococcal immune-mediated diseases, and toxigenic presentations. We present a standardized surveillance protocol, including case definitions for pharyngitis and Strep A pharyngitis, as well as case classifications that can be used to differentiate between suspected, probable, and confirmed cases. We discuss the current tests used to detect Strep A among persons with pharyngitis, including throat culture and point-of-care tests. The type of surveillance methodology depends on the resources available and the objectives of surveillance. Active surveillance and laboratory confirmation is the preferred method for case detection. Participant eligibility, the surveillance population and additional considerations for surveillance of pharyngitis are addressed, including baseline sampling, community engagement, frequency of screening and season. Finally, we discuss the core elements of case report forms for pharyngitis and provide guidance for the recording of severity and pain associated with the course of an episode.

Natural history of burnout, stress, and fatigue in a pediatric resident cohort over three years.

BACKGROUND: Burnout is known to be high amongst physician trainees. Factors such as stress, fatigue, social environment, and resilience could affect burnout. Cross-sectional data describe burnout in pediatric residents, but the trajectory of burnout in a cohort of residents followed longitudinally through the full course of residency training has not been reported. We prospectively examined the prevalence and trajectory of burnout, stress, fatigue, social connectedness, and resilience in a pediatric resident cohort from orientation through three years of residency. The cohort (N = 33) was surveyed six times between 2015-2018 using the Abbreviated Maslach Burnout Inventory (AMBI), Perceived Stress Scale (PSS), Epworth Sleepiness Scale (ESS), Social Connectedness Scale-Revised (SCS-R), and Connor-Davidson Resilience Scale (CD-RISC10). Data were analyzed using repeated measures mixed effects models. Significant change from baseline was considered to be adjusted p < 0.05. Response rate was >50% at each timepoint; 69% of trainees completed surveys ≥4 times. Scores were significantly worse than baseline in all surveys, at every timepoint, with the exception of AMBI-PA (personal accomplishment) at the PGY1/PGY2 transition and SCS-R and CD-RISC10 at the end of training. The most significant changes from baseline occurred mid-PGY1 to mid-PGY2. At least 65% of residents demonstrated worse scores than baseline on 36/40 (90%) follow-up surveys. Furthermore, ≥65% met criteria for emotional exhaustion and moderate stress at every timepoint. SCS-R was the only survey measure to improve at residency completion compared to baseline. CONCLUSION: Within 6 months of starting residency this pediatric resident cohort became burned out, stressed, fatigued, less socially connected, and less resilient. Burnout is only one factor that indicates impaired resident well-being. To fully address this, a comprehensive examination of how residents are trained is needed to identify effective interventions. ABBREVIATIONS: MBI - Maslach Burnout Inventory; AMBI - Abbreviated Maslach Burnout Inventory; AMBI-EE - Emotional Exhaustion; AMBI-D - Depersonalization; AMBI-PA - Personal Accomplishment; AMBI-SAT - Satisfaction with Medicine; LCH - Ann & Robert H. Lurie Children's Hospital of Chicago/Lurie Children's Hospital; P/CN - Pediatrics/Child Neurology; PSS - Perceived Stress Scale; ESS - Epworth Sleepiness Scale; CD-RISC10 - Resilience; SCS-R - Social Connectedness Scale Revised; PGY - Post-Graduate Year.

Seven-year surveillance of north american pediatric group a streptococcal pharyngitis isolates.

BACKGROUND: Pharyngeal group A streptococcal (GAS) emm type surveillance enhances understanding of the epidemiology of pharyngitis and invasive GAS disease and formulation of multivalent type-specific vaccines. In addition, such surveillance provides pre-GAS vaccine baseline data. We assessed geographic and temporal trends in GAS emm-type distribution among pediatric pharyngeal isolates collected systematically in the United States and Canada from 2000 to 2007. METHODS: We collected approximately 100 acute GAS pharyngitis isolates from each of 13 widely scattered sites (10 in the United States and 3 in Canada) annually for 7 seasons (2000-2007) from 3- to 18-year-old children. We assessed emm type and subtype by DNA sequencing and analyzed temporal and geographic trends. RESULTS: A total of 7040 US and 1434 Canadian GAS isolates were studied. The 6 most prevalent emm types (in descending order) were 1, 12, 28, 4, 3, and 2 in the United States and 12, 1, 28, 4, 3, 2, and 77 in Canada, constituting 70%-71% of isolates in each country; 10 emm types constituted 87%-89% total. Fifty-six emm types were identified in the United States, including 8 new types, and 33 types in Canada. Although a few types predominated nationally, marked variability among individual sites and at individual sites from year to year was observed. US-Canadian differences in type distribution were apparent. Twenty percent of isolates represented emm subtypes that differed slightly from reference types; 110 new subtypes were identified. An experimental 26-valent M protein vaccine covers 85% of pharyngitis isolates. CONCLUSIONS: Although overall US and Canadian emm type distribution was consistent and relatively few types dominated nationally, striking intersite and temporal variations within individual sites in prevalent emm types of GAS occurred. These results have important implications for the development and formulation of type-specific GAS vaccines.

Highly Sensitive Molecular Assay for Group A Streptococci Over-identifies Carriers and May Impact Outpatient Antimicrobial Stewardship.

BACKGROUND: Timely, accurate diagnosis of group A streptococci (GAS) pharyngitis prevents acute rheumatic fever and limits antibiotic overuse. The illumigene group A Streptococcus assay (Meridian Bioscience, Cincinnati, OH) is a molecular test for GAS pharyngitis with high sensitivity and specificity. We sought to determine whether the illumigene test is more likely than throat culture to be positive in patients without pharyngeal symptoms and explore the limits of detection of the test. METHODS: Patients 3-17 years of age were eligible if they had no history of pharyngitis or use of antibiotics within the previous 2 weeks; there were no upper respiratory infection symptoms, sore throat or fever and no signs of infection. Culture and illumigene were performed on duplicate throat swabs. Excess lysate from a subset of illumigene tests was evaluated by real-time polymerase chain reaction. Institutional Review Board approval was obtained. RESULTS: We enrolled 385 patients from February 2016 to October 2017; mean age was 10 yr; 51% were male. Most visits were for health supervision (69%). Significantly more illumigene tests (78/385, 20.3%) than throat cultures (48/385, 12.5%) were positive (χ; P =0.0035). Illumigene was "indeterminate" for 3 patients, leaving 382 pairs of swabs for analysis. Results were discordant for 32 of 382 pairs (8.4%); 31 of 32 (97%) were illumigene-positive/culture-negative (McNemar test; P < 0.000001). Real-time polymerase chain reaction was negative in 4 of 13 (31%) tested illumigene-positive lysates; the paired culture had been negative in all four. The limit of detection for the illumigene test was 55 colony forming units/mL. CONCLUSIONS: The illumigene test is significantly more likely than throat culture to yield positive results in patients without GAS pharyngitis. Failure to appropriately select patients for testing may negatively impact antimicrobial stewardship efforts without benefit to patients.

Caution Needed: Molecular Diagnosis of Pediatric Group A Streptococcal Pharyngitis.

Among throat swabs processed in the microbiology laboratory as back-up for negative rapid antigen detection test results, we found a significant increase in the proportion that tested positive for group A streptococci after changing from throat culture to a molecular test.For group A streptococcus testing, our hospital laboratory replaced throat cultures with a stand-alone molecular diagnostic test that takes no more than 1 hour to perform. The prevalence of positive laboratory test results increased significantly (P < .0001) after the change to molecular testing, probably because of the extreme sensitivity of the molecular test.

Macrolide resistance and emm type distribution of invasive pediatric group A streptococcal isolates: three-year prospective surveillance from a children's hospital.

OBJECTIVE: Macrolide-resistant group A streptococci (GAS) have been suggested to have more invasive potential. An M protein-based GAS vaccine is currently in development. We sought to define the GAS emm types and macrolide resistance rates among pediatric invasive GAS isolates collected prospectively during a recent 40-month period at our children's hospital. PATIENTS AND METHODS: We prospectively identified and collected GAS isolates from patients with invasive GAS disease (isolates from normally sterile sites). Susceptibility assays for erythromycin and clindamycin were performed by E-test. emm typing was performed by the Centers for Disease Control and Prevention. Clinical characteristics of patients were identified by chart review. RESULTS: A total of 37 patient isolates were identified, of which 35 isolates were able to be characterized. Four patients had underlying illness. No macrolide resistance was detected among the isolates. The most common emm types causing invasive disease were emm 1.0 (43%) and emm 12.0 (11.1%). CONCLUSIONS: In this group of 35 invasive GAS isolates, no cases of macrolide resistance were found. emm type 1 accounted for the highest percentage of invasive disease, followed by emm type 12. The type-specific GAS M protein-based vaccine currently in development includes the emm types of 33 of 35 (94%) of the invasive emm types in this series.

Differences in SpeB protease activity among group A streptococci associated with superficial, invasive, and autoimmune disease.

The secreted cysteine proteinase SpeB is an important virulence factor of group A streptococci (GAS), whereby SpeB activity varies widely among strains. To establish the degree to which SpeB activity correlates with disease, GAS organisms were recovered from patients with pharyngitis, impetigo, invasive disease or acute rheumatic fever (ARF), and selected for analysis using rigorous sampling criteria; >300 GAS isolates were tested for SpeB activity by casein digestion assays, and each GAS isolate was scored as a SpeB-producer or non-producer. Highly significant statistical differences (p < 0.01) in SpeB production are observed between GAS recovered from patients with ARF (41.5% SpeB-non-producers) compared to pharyngitis (20.5%), invasive disease (16.7%), and impetigo (5.5%). SpeB activity differences between pharyngitis and impetigo isolates are also significant, whereas pharyngitis versus invasive isolates show no significant difference. The disproportionately greater number of SpeB-non-producers among ARF-associated isolates may indicate an altered transcriptional program for many rheumatogenic strains and/or a protective role for SpeB in GAS-triggered autoimmunity.