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COVID-19 disproportionately affects racial and ethnic minority populations, but comparatively few epidemiologic studies have been performed on children as compared to adults.To characterise factors associated with SARS-CoV-2 infections amongst children from Chicago, Illinois, USA.A test-negative case-control study of children tested for SARS-CoV-2 (0-18 years) at three medical centres of the Rush University System for Health between 12 March and 7 December 2020 was conducted. Of 8462 children, 1,302 tested positive by real-time PCR or rapid (NAAT) testing. Infection with SARS-CoV-2 was analysed as the outcome variable; effects of predictors were assessed by logistic regression analysis. A Paediatric Risk Score Index with a concordance index of 72% of accuracy was created to predict SARS-CoV-2 infection.The median age of cases was 13 years. On multivariable analysis, factors associated with SARS-CoV-2 infection were being Hispanic/Latinx (odds ratio [OR] 2.45, 95% CI 1.99, 3.03); Black/African-American (OR 1.31, 95% CI 1.03, 1.66); overweight/obese (OR 1.27, 95% CI 1.02, 1.58); older age, 10-14 years (OR 1.70, 95% CI 1.39, 2.08), 15-18 years (OR 2.06, 95% CI 1.71, 2.47); from households with income$50,000 (OR 1.36, 95% CI 1.17, 1.60); or residing in predominantly minority neighbourhoods (OR 1.45, 95% CI 1.17, 1.80). Infections were higher during the second "fall" wave (5 October 2020 onward) compared with the first "spring" wave (OR 2.30, 95% CI 2.01, 2.63). Within Chicago, racial/ethnic minority neighbourhoods had striking positivity rates, as high as 39% in majority Hispanic/Latinx West Lawn neighbourhood. In suburban Chicago, highest positivity rates (20%-28%) were in zip codes within Hispanic/Latinx communities.Infection with SARS-CoV-2 is more likely amongst children of Hispanic/Latinx ethnicity, Black/African-American race, aged 10-18 years, who are overweight/obese, from lower income households, and from minority neighbourhoods. Future studies should focus on the prevention of COVID-19 infection in children of highest risk.

Executive summaryTesting of asymptomatic patients for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) (ie, “asymptomatic screening) to attempt to reduce the risk of nosocomial transmission has been extensive and resource intensive, and such testing is of unclear benefit when added to other layers of infection prevention mitigation controls. In addition, the logistic challenges and costs related to screening program implementation, data noting the lack of substantial aerosol generation with elective controlled intubation, extubation, and other procedures, and the adverse patient and facility consequences of asymptomatic screening call into question the utility of this infection prevention intervention. Consequently, the Society for Healthcare Epidemiology of America (SHEA) recommends against routine universal use of asymptomatic screening for SARS-CoV-2 in healthcare facilities. Specifically, preprocedure asymptomatic screening is unlikely to provide incremental benefit in preventing SARS-CoV-2 transmission in the procedural and perioperative environment when other infection prevention strategies are in place, and it should not be considered a requirement for all patients. Admission screening may be beneficial during times of increased virus transmission in some settings where other layers of controls are limited (eg, behavioral health, congregate care, or shared patient rooms), but widespread routine use of admission asymptomatic screening is not recommended over strengthening other infection prevention controls. In this commentary, we outline the challenges surrounding the use of asymptomatic screening, including logistics and costs of implementing a screening program, and adverse patient and facility consequences. We review data pertaining to the lack of substantial aerosol generation during elective controlled intubation, extubation, and other procedures, and we provide guidance for when asymptomatic screening for SARS-CoV-2 may be considered in a limited scope.

Background Black Americans have been disproportionately impacted by COVID-19, with systemic inequities contributing to increased incidence and mortality. In Chicago, access to COVID-19 testing was scarce in many predominantly Black neighborhoods early in the pandemic, exacerbating inequities. We aimed to assess uptake and yield of a COVID-19 testing campaign to increase access in high-risk, underserved Chicago communities. Methods The Alive Church Network (ACN) is a community-driven coalition of Black pastors and public health researchers developed to address health inequities in Chicago. For this initiative, ACN implemented two strategies to improve access to COVID-19 testing in underserved neighborhoods: 1) church-based testing, with nurses and community health workers (CHWs) stationed in churches to perform PCR testing for community members and church staff (Dec 2020-Dec 2021) and 2) community site testing, with nurses and CHWs deployed to 8 local sites (e.g., Salvation Army) to conduct weekly PCR testing for employees and clients (May 2021-Mar 2022). We assessed characteristics of individuals undergoing testing; symptom and exposure history; and COVID-19 positivity. In addition, we compared positivity for ACN sites with Chicago citywide positivity over time. Results A total of 3420 tests were performed for 1703 individuals. Of those tested, 931 (54.7%) were tested at churches and 772 (45.3%) were tested at community partner sites. Those presenting to churches were older (mean 44.8 vs. 39.1 years), more likely to be female (56.5% vs. 48.5%), and more likely to have a chronic medical condition (37.1% vs. 22.5%, Table). Prevalence of COVID-19 symptoms and exposure history were similar for those presenting to church and community sites (Table). Overall, ACN test positivity was similar to Chicago citywide positivity; however, ACN test positivity was much higher during the Omicron surge (24% vs. 11%, Figure). Characteristics of individuals tested for COVID-19 at church and community sites COVID-19 test positivity, ACN sites vs. Chicago citywide Conclusion The ACN testing campaign increased access to COVID-19 testing in underserved neighborhoods in Chicago and had high yield during the Omicron surge. Church-based testing was successful for reaching older, medically vulnerable individuals. Ensuring widespread access to testing is essential for health equity and to reduce COVID-19 morbidity and mortality. Disclosures All Authors: No reported disclosures.

Objective:To develop a pediatric research agenda focused on pediatric healthcare-associated infections and antimicrobial stewardship topics that will yield the highest impact on child health.Participants:The study included 26 geographically diverse adult and pediatric infectious diseases clinicians with expertise in healthcare-associated infection prevention and/or antimicrobial stewardship (topic identification and ranking of priorities), as well as members of the Division of Healthcare Quality and Promotion at the Centers for Disease Control and Prevention (topic identification).Methods:Using a modified Delphi approach, expert recommendations were generated through an iterative process for identifying pediatric research priorities in healthcare associated infection prevention and antimicrobial stewardship. The multistep, 7-month process included a literature review, interactive teleconferences, web-based surveys, and 2 in-person meetings.Results:A final list of 12 high-priority research topics were generated in the 2 domains. High-priority healthcare-associated infection topics included judicious testing for Clostridioides difficile infection, chlorhexidine (CHG) bathing, measuring and preventing hospital-onset bloodstream infection rates, surgical site infection prevention, surveillance and prevention of multidrug resistant gram-negative rod infections. Antimicrobial stewardship topics included β-lactam allergy de-labeling, judicious use of perioperative antibiotics, intravenous to oral conversion of antimicrobial therapy, developing a patient-level “harm index” for antibiotic exposure, and benchmarking and or peer comparison of antibiotic use for common inpatient conditions.Conclusions:We identified 6 healthcare-associated infection topics and 6 antimicrobial stewardship topics as potentially high-impact targets for pediatric research.

BACKGROUND Extended-spectrum β-lactamase (ESBL)-producing Enterobacterales-(Ent) infections are increasing in pediatrics. Before CTX-M ESBL emerged, the most common infection-associated ESBL genes were TEM and SHV-type ESBLs. We sought to define the current epidemiology of Ent infections in children due to blaTEM and blaSHV (TEM-SHV-Ent). METHODS A retrospective case-control analysis of children with TEM-SHV-Ent infections at 3 Chicago-area hospitals was performed. Cases had extended-spectrum-cephalosporin (ESC)-resistant infections due to blaTEM or blaSHV. DNA analysis assessed β-lactamase (bla) genes, multilocus sequence types, and E. coli phylogenetic grouping. Controls had ESC-susceptible Ent infections, matched 3:1 to cases by age, source, and hospital. Clinical-epidemiologic infection predictors were assessed. RESULTS Of 356 ESC-R-Ent isolates from children (median 4.3 years), 38 (10.7%) were positive solely for blaTEM-ESBL (26%) or blaSHV-ESBL genes (74%). Predominant organisms were Klebsiella (34.2%) and E. coli (31.6%); 67% of E. coli were phylogroup B2. Multilocus sequence types revealed multiple strains, 58% resistant to ≥3 antibiotic classes. On multivariable analysis, children with TEM-SHV-Ent infections more often had recent inpatient care (OR, 8.2), yet were diagnosed mostly as outpatients (OR, 25.6) and less in Neonatal Intensive Care Units (OR, 0.036) than controls. TEM-SHV-Ent patients had more gastrointestinal (OR, 23.7) and renal comorbidities (OR, 4.2). Differences in demographics, antibiotic exposure, and foreign bodies were not found. CONCLUSION TEM-SHV-Ent are commonly linked to inpatient exposures in children with chronic conditions but most often present in outpatient settings. Clinicians should be aware of the potential increased risk for TEM-SHV-Ent infections in outpatients with gastrointestinal and renal comorbidities and histories of prolonged hospital stays.

Background Fluoroquinolones are uncommonly prescribed in children, yet pediatric multidrug resistant (MDR) enterobacteriaceae (Ent) infections often reveal fluoroquinolone resistance (FQR). We sought to define the molecular epidemiology of FQR and MDR-Ent in children. Methods A case-control analysis of children with MDR-Ent infections at 3 Chicago hospitals was performed. Cases were children with third-generation cephalosporin-resistant and/or carbapenem-resistant Ent infections. Polymerase chain reaction and DNA analysis assessed bla and plasmid-mediated FQR (PMFQR) genes. Controls were children with third-generation cephalosporin, fluoroquinolone, and carbapenem-susceptible Ent infections matched by age, source and hospital. We assessed clinical-epidemiologic predictors of PMFQR Ent infection. Results Of 169 third-generation cephalosporin-resistant and/or carbapenem-resistant Ent isolates from children (median age, 4.8 years), 85 were FQR; 56 (66%) contained PMFQR genes. The predominant organism was Escherichia coli, and most common bla gene blaCTX-M-1 group. In FQR isolates, PMFQR gene mutations included aac6'1bcr, oqxA/B, qepA and qnrA/B/D/S in 83%, 15%, 13% and 11% of isolates, respectively. FQR E. coli was often associated with phylogroup B2, ST43/ST131. On multivariable analysis, PMFQR Ent infections occurred mostly in outpatients (odds ratio, 33.1) of non-black-white-Hispanic race (odds ratio, 6.5). Residents of Southwest Chicago were >5 times more likely to have PMFQR Ent infections than those in the reference region, while residence in Central Chicago was associated with a 97% decreased risk. Other demographic, comorbidity, invasive-device, antibiotic use or healthcare differences were not found. Conclusions The strong association of infection with MDR organisms showing FQR with patient residence rather than with traditional risk factors suggests that the community environment is a major contributor to spread of these pathogens in children.

Infectious diseases outbreaks are a cause of significant morbidity and mortality among hospitalized patients. Infants admitted to the neonatal intensive care unit (NICU) are particularly vulnerable to infectious complications during hospitalization. Thus, rapid recognition of and response to outbreaks in the NICU is essential. At Rush University Medical Center, whole-genome sequencing (WGS) has been utilized since early 2016 as an adjunctive method for outbreak investigations. The use of WGS and potential lessons learned are illustrated for 3 different NICU outbreak investigations involving methicillin-resistant Staphylococcus aureus (MRSA), group B Streptococcus (GBS), and Serratia marcescens. WGS has contributed to the understanding of the epidemiology of outbreaks in our NICU, and it has also provided further insight in settings of unusual diseases or when lower-resolution typing methods have been inadequate. WGS has emerged as the new gold standard for evaluating strain relatedness. As barriers to implementation are overcome, WGS has the potential to transform outbreak investigation in healthcare settings.

A male individual aged 18 years with no significant past medical history presented with fever, headache, dry cough, and chest pain. On clinical examination, he had tachycardia and hypotension needing intravenous fluid resuscitation and inotropic support. A chest radiograph revealed streaky lung opacities, and he was treated with antibiotics for suspected community-acquired pneumonia complicated by septic shock. Significant elevation of cardiac enzymes was noted, and there was a continued need for inotropes to maintain normotension. He also developed intermittent bradycardia, with serial electrocardiograms showing first-degree atrioventricular block, low-voltage QRS complexes, and ST-T wave changes and telemetry demonstrating junctional and ventricular escape rhythm. A complete workup for sepsis and acute myocarditis were performed to find the etiologic agent. Intravenous immunoglobulins were started to treat myocarditis, with eventual clinical improvement. He was eventually diagnosed with an unusual etiology for his illness. He was noted to still have intermittent ventricular escape rhythm on electrocardiograms on follow-up 2 weeks after discharge but continues to remain asymptomatic and in good health.

Treatment of multidrug-resistant Gram-negative bacterial pathogens represents a critical clinical need. Here, we report a novel γ-lactam pyrazolidinone that targets penicillin-binding proteins (PBPs) and incorporates a siderophore moiety to facilitate uptake into the periplasm. The MIC values of γ-lactam YU253434, 1, are reported along with the finding that 1 is resistant to hydrolysis by all four classes of β-lactamases. The druglike characteristics and mouse PK data are described along with the X-ray crystal structure of 1 binding to its target PBP3.

ObjectiveTo assess variability in antimicrobial use and associations with infection testing in pediatric ventilator-associated events (VAEs).DesignDescriptive retrospective cohort with nested case-control study.SettingPediatric intensive care units (PICUs), cardiac intensive care units (CICUs), and neonatal intensive care units (NICUs) in 6 US hospitals.PatientsChildren≤18 years ventilated for≥1 calendar day.MethodsWe identified patients with pediatric ventilator-associated conditions (VACs), pediatric VACs with antimicrobial use for≥4 days (AVACs), and possible ventilator-associated pneumonia (PVAP, defined as pediatric AVAC with a positive respiratory diagnostic test) according to previously proposed criteria.ResultsAmong 9,025 ventilated children, we identified 192 VAC cases, 43 in CICUs, 70 in PICUs, and 79 in NICUs. AVAC criteria were met in 79 VAC cases (41%) (58% CICU; 51% PICU; and 23% NICU), and varied by hospital (CICU, 20–67%; PICU, 0–70%; and NICU, 0–43%). Type and duration of AVAC antimicrobials varied by ICU type. AVAC cases in CICUs and PICUs received broad-spectrum antimicrobials more often than those in NICUs. Among AVAC cases, 39% had respiratory infection diagnostic testing performed; PVAP was identified in 15 VAC cases. Also, among AVAC cases, 73% had no associated positive respiratory or nonrespiratory diagnostic test.ConclusionsAntimicrobial use is common in pediatric VAC, with variability in spectrum and duration of antimicrobials within hospitals and across ICU types, while PVAP is uncommon. Prolonged antimicrobial use despite low rates of PVAP or positive laboratory testing for infection suggests that AVAC may provide a lever for antimicrobial stewardship programs to improve utilization.

Community-acquired multidrug resistant Enterobacteriaceae (MDR-Ent) infections continue to increase in the United States. In prior studies, we identified neighboring regions in Chicago, Illinois, where children have 5 to 6 times greater odds of MDR-Ent infections. To prevent community spread of MDR-Ent, we need to identify the MDR-Ent reservoirs. A pilot study of 4 Chicago waterways for MDR-Ent and associated antibiotic resistance genes (ARGs) was conducted. Three waterways (A1 to A3) are labeled safe for “incidental contact recreation” (e.g., kayaking), and A4 is a nonrecreational waterway that carries nondisinfected water. Surface water samples were collected and processed for standard bacterial culture and shotgun metagenomic sequencing. Generally, A3 and A4 (neighboring waterways which are not hydraulically connected) were strikingly similar in bacterial taxa, ARG profiles, and abundances of corresponding clades and genera within the Enterobacteriaceae. Additionally, total ARG abundances recovered from the full microbial community were strongly correlated between A3 and A4 (R(2) = 0.97). Escherichia coli numbers (per 100 ml water) were highest in A4 (783 most probable number [MPN]) and A3 (200 MPN) relative to A2 (84 MPN) and A1 (32 MPN). We found concerning ARGs in Enterobacteriaceae such as MCR-1 (colistin), Qnr and OqxA/B (quinolones), CTX-M, OXA and ACT/MIR (beta-lactams), and AAC (aminoglycosides). We found significant correlations in microbial community composition between nearby waterways that are not hydraulically connected, suggesting cross-seeding and the potential for mobility of ARGs. Enterobacteriaceae and ARG profiles support the hypothesized concerns that recreational waterways are a potential source of community-acquired MDR-Ent.

Antimicrobial resistance is a global public health threat and a danger that continues to escalate. These menacing bacteria are having an impact on all populations; however, until recently, the increasing trend in drug-resistant infections in infants and children has gone relatively unrecognized. This article highlights the current clinical and molecular data regarding infection with antibiotic-resistant bacteria in children, with an emphasis on transmissible resistance and spread via horizontal gene transfer.

Carbapenem-resistant Enterobacteriaceae (CRE) are a serious public health threat. Infections due to these organisms are associated with significant morbidity and mortality. Mechanisms of drug resistance in gram-negative bacteria (GNB) are numerous; β-lactamase genes carried on mobile genetic elements are a key mechanism for the rapid spread of antibiotic-resistant GNB worldwide. Transmissible carbapenem-resistance in Enterobacteriaceae has been recognized for the last 2 decades, but global dissemination of carbapenemase-producing Enterobacteriaceae (CPE) is a more recent problem that, once initiated, has been occurring at an alarming pace. In this article, we discuss the evolution of CRE, with a focus on the epidemiology of the CPE pandemic; review risk factors for colonization and infection with the most common transmissible CPE worldwide, Klebsiella pneumoniae carbapenemase–producing K. pneumoniae; and present strategies used to halt the striking spread of these deadly pathogens.

Background:Candida auris and carbapenemase-producing organisms (CPO) are multidrug-resistant organisms that can colonize people for prolonged periods and can cause invasive infections and spread in healthcare settings, particularly in high-acuity long-term care facilities. Point-prevalence surveys (PPSs) conducted in long-term acute-care hospitals in the Chicago region identified median prevalence of colonization to be 31% for C. auris and 24% for CPO. Prevalence of C. auris colonization has not been described in pediatric populations in the United States, and limited data exist on CPO colonization in children outside intensive care units. The Chicago Department of Public Health (CDPH) conducted a PPS to assess C. auris and CPO colonization in a pediatric hospital serving high-acuity patients with extended lengths of stay (LOS). Methods: CDPH conducted a PPS in August 2019 in a pediatric hospital with extended LOS to screen for C. auris and CPO colonization. Medical devices (ie, gastrostomy tubes, tracheostomies, mechanical ventilators, and central venous catheters [CVC]) and LOS were documented. Screening specimens consisted of composite bilateral axillae and groin swabs for C. auris and rectal swabs for CPO testing. The Wisconsin State Laboratory of Hygiene tested all specimens. Real-time polymerase chain reaction (PCR) assays were used to detect C. auris DNA and carbapenemase genes: blaKPC, blaNDM, blaVIM, blaOXA-48, and blaIMP (Xpert Carba-R Assay, Cepheid, Sunnyvale, CA). All axillae and groin swabs were processed by PCR and culture to identify C. auris. For CPO, culture was only performed on PCR-positive specimens. Results: Of the 29 patients hospitalized, 26 (90%) had gastrostomy tubes, 24 (83%) had tracheostomies, 20 (69%) required mechanical ventilation, and 3 (10%) had CVCs. Also, 25 (86%) were screened for C. auris and CPO; 4 (14%) lacked parental consent and were not swabbed. Two rectal specimens were unsatisfactory, producing invalid CPO test results. Median LOS was 35 days (range, 1–300 days). No patients were positive for C. auris. From CPO screening, blaOXA-48 was detected in 1 patient sample, yielding a CPO prevalence of 3.4% (1 of 29). No organism was recovered from the blaOXA-48 positive specimen. Conclusions: This is the first documented screening of C. auris colonization in a pediatric hospital with extended LOS. Despite a high prevalence of C. auris and CPOs in adult healthcare settings of similar acuity in the region, C. auris was not identified and CPOs were rare at this pediatric facility. Additional evaluations in pediatric hospitals should be conducted to further understand C. auris and CPO prevalence in this population.Funding: NoneDisclosures: None

OBJECTIVEAdult ventilator-associated event (VAE) definitions include ventilator-associated conditions (VAC) and subcategories for infection-related ventilator-associated complications (IVAC) and possible ventilator-associated pneumonia (PVAP). We explored these definitions for children.DESIGNRetrospective cohortSETTINGPediatric, cardiac, or neonatal intensive care units (ICUs) in 6 US hospitalsPATIENTSPatients ≤18 years old ventilated for ≥1 dayMETHODSWe identified patients with pediatric VAC based on previously proposed criteria. We applied adult temperature, white blood cell count, antibiotic, and culture criteria for IVAC and PVAP to these patients. We matched pediatric VAC patients with controls and evaluated associations with adverse outcomes using Cox proportional hazards models.RESULTSIn total, 233 pediatric VACs (12,167 ventilation episodes) were identified. In the cardiac ICU (CICU), 62.5% of VACs met adult IVAC criteria; in the pediatric ICU (PICU), 54.2% of VACs met adult IVAC criteria; and in the neonatal ICU (NICU), 20.2% of VACs met adult IVAC criteria. Most patients had abnormal white blood cell counts and temperatures; we therefore recommend simplifying surveillance by focusing on “pediatric VAC with antimicrobial use” (pediatric AVAC). Pediatric AVAC with a positive respiratory diagnostic test (“pediatric PVAP”) occurred in 8.9% of VACs in the CICU, 13.3% of VACs in the PICU, and 4.3% of VACs in the NICU. Hospital mortality was increased, and hospital and ICU length of stay and duration of ventilation were prolonged among all pediatric VAE subsets compared with controls.CONCLUSIONSWe propose pediatric AVAC for surveillance related to antimicrobial use, with pediatric PVAP as a subset of AVAC. Studies on generalizability and responsiveness of these metrics to quality improvement initiatives are needed, as are studies to determine whether lower pediatric VAE rates are associated with improvements in other outcomes.Infect Control Hosp Epidemiol 2017;38:327–333

BackgroundThe pandemic of extended-spectrum-beta-lactamase (ESBL)-producing-Enterobacteriaceae (Ent) is strongly linked to the dissemination of CTX-M-type-ESBL-Ent. We sought to define the epidemiology of infections in children due to an emerging resistance type, CTX-M-9-group-producing-Ent (CTX-M-9-grp-Ent).MethodsA multi-centered case-control analysis of Chicago children with CTX-M-9-grp-Ent infections was performed. Cases were defined as children possessing extended-spectrum-cephalosporin-resistant (ESC-R) infections. PCR and DNA analysis assessed beta-lactamase (bla) genes, multi-locus sequence types (MLST) and phylogenetic grouping of E. coli. Controls were children with ESC-susceptible (ESC-S)-Ent infections matched 3:1 by age, source, and hospital. The clinical-epidemiologic predictors of CTX-M-9-grp-Ent infection were assessed.ResultsOf 356 ESC-R-Ent isolates from children (median age 4.1 years), CTX-M-9-group was the solely detected bla gene in 44(12.4%). The predominant species was E. coli (91%) of virulent phylogroups D(60%) and B2(40%). MLST revealed multiple strain types. On multivariable analysis, CTX-M-9-grp-Ent occurred more often in E. coli (OR 7.0), children of non-black-white-Hispanic race (OR 6.5), and outpatients (OR 4.5) which was a very unexpected finding for infections due to antibiotic-resistant bacteria. Residents of South Chicago were 6.7 times more likely to have CTX-M-9-grp-Ent infections than those in the reference region (West), while residence in Northwestern Chicago was associated with an 81% decreased risk. Other demographic, comorbidity, invasive-device, and antibiotic use differences were not found.ConclusionsCTX-M-9-grp-Ent infection is strikingly associated with patient residence and is occurring in children without traditional in-patient exposure risk factors. This suggests that among children, the community environment may be a key contributor in the spread of these resistant pathogens.

Background:Fluoroquinolones (FQs) are uncommonly prescribed in children, yet pediatric multidrug-resistant (MDR)-Enterobacteriaceae (Ent) infections often reveal FQ resistance (FQR). We sought to define the molecular epidemiology of FQR and MDR-Ent in children.Methods:A case-control analysis of children with MDR-Ent infections at 3 Chicago hospitals was performed. Cases were children with third-generation-cephalosporin-resistant (3GCR) and/or carbapenem-resistant (CR)-Ent infections. PCR and DNA analysis assessed bla and plasmid-mediated FQR (PMFQR) genes. Controls were children with 3GC and carbapenem susceptible-Ent infections matched by age, source and hospital. We assessed clinical-epidemiologic predictors of PMFQR Ent infection.Results:Of 169 3GCR and/or CR Ent isolates from children (median age 4.8 years), 85 were FQR; 56 (66%) contained PMFQR genes. The predominant organism was E. coli and most common bla gene blaCTX-M-1 group. In FQR isolates, PMFQR gene mutations included aac6’1b-cr, oqxA/B, qepA, and qnrA/B/D/S in 83%, 15%, 13% and 11% of isolates, respectively. FQR E. coli was often associated with phylogroup B2, ST43/ST131. On multivariable analysis, PMFQR Ent infections occurred mostly in outpatients (OR 33.1) of non-black-white-Hispanic race (OR 6.5). Residents of Southwest Chicago were >5 times more likely to have PMFQR-Ent infections than those in the reference region, while residence in Central Chicago was associated with a 97% decreased risk. Other demographic, comorbidity, invasive-device, antibiotic use, or healthcare differences were not found.Conclusions:The strong association of infection with MDROs showing FQR with patient residence rather than with traditional risk factors suggests that the community environment is a major contributor to spread of these pathogens in children.

BACKGROUND: Acinetobacter baumannii is a common cause of healthcare-associated infections. Carbapenem-resistant (CR) A baumannii is a significant threat globally. We used a large reference laboratory database to study the epidemiology of A baumannii in children in the United States. METHODS: Antimicrobial susceptibility data from The Surveillance Network were used to phenotypically identify antibiotic resistance in A baumannii isolates in children 1–17 years of age between January 1999 and July 2012. Logistic regression analysis was used to calculate trends in the prevalence of antibiotic resistance in A baumannii. Isolates from infants (

A newly proposed surveillance definition for ventilator-associated conditions among neonatal and pediatric patients has been associated with increased morbidity and mortality among ventilated patients in cardiac ICU, neonatal ICU, and PICU. This study aimed to identify potential risk factors associated with pediatric ventilator-associated conditions.Retrospective cohort.Six U.S. hospitals PATIENTS:: Children less than or equal to 18 years old ventilated for greater than or equal to 1 day.None.We identified children with pediatric ventilator-associated conditions and matched them to children without ventilator-associated conditions. Medical records were reviewed for comorbidities and acute care factors. We used bivariate and multivariate conditional logistic regression models to identify factors associated with ventilator-associated conditions. We studied 192 pairs of ventilator-associated conditions cases and matched controls (113 in the PICU and cardiac ICU combined; 79 in the neonatal ICU). In the PICU/cardiac ICU, potential risk factors for ventilator-associated conditions included neuromuscular blockade (odds ratio, 2.29; 95% CI, 1.08-4.87), positive fluid balance (highest quartile compared with the lowest, odds ratio, 7.76; 95% CI, 2.10-28.6), and blood product use (odds ratio, 1.52; 95% CI, 0.70-3.28). Weaning from sedation (i.e., decreasing sedation) or interruption of sedation may be protective (odds ratio, 0.44; 95% CI, 0.18-1.11). In the neonatal ICU, potential risk factors included blood product use (odds ratio, 2.99; 95% CI, 1.02-8.78), neuromuscular blockade use (odds ratio, 3.96; 95% CI, 0.93-16.9), and recent surgical procedures (odds ratio, 2.19; 95% CI, 0.77-6.28). Weaning or interrupting sedation was protective (odds ratio, 0.07; 95% CI, 0.01-0.79).In mechanically ventilated neonates and children, we identified several possible risk factors associated with ventilator-associated conditions. Next steps include studying propensity-matched cohorts and prospectively testing whether changes in sedation management, transfusion thresholds, and fluid management can decrease pediatric ventilator-associated conditions rates and improve patient outcomes.

Molecular typing using repetitive sequenced-based PCR (rep-PCR) and hsp60 sequencing were applied to a collection of diverse Enterobacter cloacae complex isolates. To determine the most practical method for reference laboratories, we analyzed 71 E. cloacae complex isolates from sporadic and outbreak occurrences originating from 4 geographic areas. While rep-PCR was more discriminating, hsp60 sequencing provided a broader and a more objective geographical tracking method similar to multilocus sequence typing (MLST). In addition, we suggest that MLST may have higher discriminative power compared to hsp60 sequencing, although rep-PCR remains the most discriminative method for local outbreak investigations. In addition, rep-PCR can be an effective and inexpensive method for local outbreak investigation.

654 Virulence Volume 4 issue 7 Staphylococcus aureus infects millions worldwide. Methicillin-sensitive and methicillin-resistant S. aureus (MSSA and MRSA) isolates may closely share virulence determinants through related clonal complexes. The purpose of this pilot study was to assess the epidemiology of S. aureus colonization in pregnant women in a community-acquired MRSA endemic area at the time of group B streptococcus screening. Of 107 women, 23 were colonized with MSSA, none with MRSA. Virulence factors Panton–Valentine leukocidin and ACME arcA were found in 75% and 6% of isolates, respectively. Mothers of infants with longer lengths of stay were 1.5 times more likely to be S. aureus colonized (P = 0.07). Postpartum infections occurred in 13%. The impact of colonization on maternal health should continue to be studied. Staphylococcus aureus (S. aureus) is a common bacterial pathogen encountered by primary care providers and subspecialists alike. S. aureus frequently colonizes the anterior nares but also the skin, nails, pharynx, axilla, perineum, and vagina. Reported rates of S. aureus vaginal colonization during pregnancy range from 4% to 22%. The overall prevalence of community-acquired MRSA (CA-MRSA) infection in Chicago, Illinois has increased over A prospective cohort pilot study of the clinical and molecular epidemiology of Staphylococcus aureus in pregnant women at the time of group B streptococcal screening in a large urban medical center in Chicago, IL USA

Reports of invasive disease caused by non-toxigenic Corynebacterium diphtheriae are increasing; however, medical management has not been extensively studied. We describe what we believe is the first documented case of penicillin and cephalosporin-resistant C diphtheriae endocarditis in a child successfully treated with vancomycin, meropenem, and valvular replacement surgery.

Ceftriaxone is a third-generation cephalosporin with broad-spectrum activity against both Gram-positive and Gram-negative bacteria. Despite its effectiveness, its use for the treatment of infections in neonatal patients has been limited because of concern about its potential toxicity.Our aim was to review the literature for an association between ceftriaxone and cardiopulmonary events, hyperbilirubinemia, and pseudolithiasis among neonates.We searched PubMed and EMBASE and included studies that evaluated ceftriaxone safety in neonates. Study bias was evaluated in the following domains: exposure measurement, outcome measurement, attrition, generalizability, confounding, statistical analysis, and reporting.We included nine studies regarding ceftriaxone side effects, primarily spontaneous reports, published case reports, and small case series. Reports of bilirubin displacement attributed to ceftriaxone included increases in serum bilirubin necessitating antibiotic change in a subset of infants after administration of ceftriaxone. One study described self-resolving biliary sludge after ceftriaxone administration in six of 80 infants. Cardiopulmonary adverse events included a report of eight cardiopulmonary events related to concomitant ceftriaxone-calcium infusion, including seven infant deaths. Additional cardiopulmonary events reported included perinatal asphyxia, pulmonary hypertension, and thrombocytosis. However, the available literature had small sample sizes, poor external validity, and inconsistent outcome ascertainment methods, which made it impossible to estimate the magnitude of risk.Concomitant administration of intravenous ceftriaxone and calcium-containing solutions should be avoided in neonates. However, further controlled studies are needed to assess whether bilirubin displacement associated with the use of ceftriaxone is clinically relevant, particularly in healthy term and near-term neonates with mild hyperbilirubinemia.

We report the first case of a child in the United States infected with an organism producing a Verona Integron-Encoded Metallo-β-Lactamase. This child succumbed to a ventilator-associated pneumonia caused by a Klebsiella pneumoniae producing this resistance mechanism.

Antibiotic resistance among gram-negative bacteria has reached critical levels. The rise of carbapenem resistance in Enterobacteriaceae carrying additional resistance genes to multiple antibiotic classes has created a generation of organisms nearly resistant to all available therapy. Carbapenem-resistant Enterobacteriaceae (CRE) infections are known to be associated with significant morbidity and mortality, and these pathogens have now made their way to the most vulnerable populations, including children. This review provides a brief overview of CRE, with a focus on CRE infections in children, and highlights available data on the epidemiology, clinical characteristics, carbapenemase types, risk factors, treatment, and outcomes of these multi-drug resistant infections in the pediatric population.

Macrolide resistance (MR) in group A Streptococcus (GAS) has been well documented in several countries and has become clinically significant since the large increases in macrolide usage during the 1970s. Macrolides are recommended as an alternative therapy for GAS pharyngitis, the most common cause of bacterial pharyngitis. Macrolide resistance has been associated with certain emm types, a sequence-based typing system of the hypervariable region of the GAS M-protein gene. Clinical failure of macrolide treatment of GAS infections can be associated with complications including acute rheumatic fever and rheumatic heart disease, the leading cause of acquired heart disease in children worldwide. Here we report 2 pediatric cases of MR and/or treatment failure in the treatment of GAS pharyngitis with the subsequent development of acute rheumatic fever. We also review the literature on worldwide MR rates, molecular classifications, and emm types, primarily associated with GAS pharyngeal isolates between the years of 2000 and 2010. The use of macrolides in the management of GAS pharyngitis should be limited to patients with significant penicillin allergy.

Background There is an increasing incidence of extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae infections in children. However, most studies focus only on CTX-M-1 group (CTX-M-15). We sought to define the epidemiology of the CTX-M-9 group (CTX-M-9) producing Enterobacteriaceae infections in children to devise more effective treatment and prevention strategies. Methods A case–control study of children (0–21 y), cared for by 3 Chicago area hospitals during 2011–16, was performed. Cases were 44 children diagnosed with third-generation cephalosporin (3GC) resistant and/or carbapenem-resistant (CR) Enterobacteriaceae infections who had CTX-M-9 genes accounting for β-lactam resistance. PCR amplification, DNA sequencing, and DNA microarray analysis (Check-Points®) assessed for bla genes. MLST, rep-PCR and phylogenetic analysis were also performed. Controls were 135 children with 3GC and carbapenem susceptible Enterobacteriaceae infections matched by age range and hospital. Demographics; comorbidities; device, antibiotic, and healthcare exposures; and the impact of location of patient residence were evaluated. Race categories were white, black, Hispanic, and other. Stratified analysis and multivariable logistic regression were used to explore associations between predictors and CTX-M-9 infection. Data were analyzed in SAS 9.4. Results The median age of cases was 4.1 years. The predominant organism (39/44, 89%) was E. coli of virulent phylogroups B2 (41%) and D (59%). MLST analysis revealed that this collection of strains was polyclonal. On multivariable analysis, children with CTX-M-9 Enterobacteriaceae infections were more likely to be diagnosed in an outpatient clinic (OR 4.5), have E. coli infection (OR 7.0), and be of race “other” (OR 7.6) vs. controls. Residents of South Chicago were 6.7 times more likely to have a CTX-M-9 Enterobacteriaceae infection than controls; while residence in Northwest Chicago was associated with a 81% decreased risk. Significant differences in other demographics, comorbidities, invasive devices, antibiotic use, or recent healthcare were not found. Conclusion We observed striking regional differences in occurrence of CTX-M-9 producing Enterobacteriaceae, suggesting that environmental influences and plasmid transfer may contribute to acquisition. It is worrisome that a large number of ESBL Enterobacteriaceae strains bearing CTX-M ESBLs circulate in the community among children. Disclosures All authors: No reported disclosures.

To identify a pediatric ventilator-associated condition definition for use in neonates and children by exploring whether potential ventilator-associated condition definitions identify patients with worse outcomes.Retrospective cohort study and a matched cohort analysis.Pediatric, cardiac, and neonatal ICUs in five U.S. hospitals.Children 18 years old or younger ventilated for at least 1 day.None.We evaluated the evidence of worsening oxygenation via a range of thresholds for increases in daily minimum fraction of inspired oxygen (by 0.20, 0.25, and 0.30) and daily minimum mean airway pressure (by 4, 5, 6, and 7 cm H2O). We required worsening oxygenation be sustained for at least 2 days after at least 2 days of stability. We matched patients with a ventilator-associated condition to those without and used Cox proportional hazard models with frailties to examine associations with hospital mortality, hospital and ICU length of stay, and duration of ventilation. The cohort included 8,862 children with 10,209 hospitalizations and 77,751 ventilator days. For the fraction of inspired oxygen 0.25/mean airway pressure 4 definition (i.e., increase in minimum daily fraction of inspired oxygen by 0.25 or mean airway pressure by 4), rates ranged from 2.9 to 3.2 per 1,000 ventilator days depending on ICU type; the fraction of inspired oxygen 0.30/mean airway pressure 7 definition yielded ventilator-associated condition rates of 1.1-1.3 per 1,000 ventilator days. All definitions were significantly associated with greater risk of hospital death, with hazard ratios ranging from 1.6 (95% CI, 0.7-3.4) to 6.8 (2.9-16.0), depending on thresholds and ICU type. Each definition was associated with prolonged hospitalization, time in ICU, and duration of ventilation, among survivors. The advisory board of the study proposed using the fraction of inspired oxygen 0.25/mean airway pressure 4 thresholds to identify pediatric ventilator-associated conditions in ICUs.Pediatric patients with ventilator-associated conditions are at substantially higher risk for mortality and morbidity across ICUs, regardless of thresholds used. Next steps include identification of risk factors, etiologies, and preventative measures for pediatric ventilator-associated conditions.

Molecular typing using repetitive sequenced-based PCR (rep-PCR) and hsp60 sequencing were applied to a collection of diverse Enterobacter cloacae complex isolates. To determine the most practical method for reference laboratories, we analyzed 71 E. cloacae complex isolates from sporadic and outbreak occurrences originating from 4 geographic areas. While rep-PCR was more discriminating, hsp60 sequencing provided a broader and a more objective geographical tracking method similar to multilocus sequence typing (MLST). In addition, we suggest that MLST may have higher discriminative power compared to hsp60 sequencing, although rep-PCR remains the most discriminative method for local outbreak investigations. In addition, rep-PCR can be an effective and inexpensive method for local outbreak investigation.

Background ESBL Ent infections are increasingly prevalent in the pediatric population; however, most ESBL Ent studies have focused on adults and/or CTX-M-type strains. We sought to characterize the molecular epidemiology of ESBL Ent strains and to identify factors associated with TEM- and SHV-type ESBL Ent (TEMSHV Ent) infections in children. Methods A case–control study of children (0–18 years) cared for by 3 Chicago hospitals during 2011–2016 was performed. Cases were 38 children with infections due to Ent harboring a lone TEM- or SHV-type ESBL as detected by DNA microarray (Check-Points®). PCR, DNA sequencing, Rep-PCR, plasmid typing, and phylogenetic grouping were also performed. Controls (ctrls) were 137 children with third-generation cephalosporin susceptible Ent infections matched by age and hospital. Demographics; patient residence; comorbidities; device, antibiotic, and healthcare exposures were evaluated. Bivariate and multivariable logistic regression analyses explored associations between predictors and TEMSHV Ent infection. Results Of 38 TEMSHV Ent infections, 74% were SHV-type and 26% TEM-type. The median age of TEMSHV Ent patients was 4.3 (0–17.9) years. Predominant organisms were Klebsiella spp. (34.2%) and E. coli (31.6%); 67% of E. coli were phylogroup B2. Most strains were unrelated; 47% were MDRO. On bivariate analysis, TEMSHV Ent patients were more likely to be male (53% vs. 34%, P = 0.04), have longer LOS after infection (35d vs. 14d, P < 0.001) but no difference in mortality, and have less UTIs (53% vs. 75%, P = 0.01) than ctrls. On multivariable analysis, children with TEMSHV Ent infections more often had recent inpatient care (OR 8.2), yet were diagnosed more frequently as outpatients (OR 25.6) and less often in NICUs (OR 0.036) than ctrls. TEMSHV Ent patients had more gastrointestinal (GI) (OR 23.7) and renal comorbidities (OR 4.2) vs. ctrls. Differences in race, gender, residential neighborhood, antibiotic exposure, and foreign bodies were not significant after controlling for other factors. Conclusion In children, factors associated with TEMSHV Ent infections include recent inpatient care and GI and renal comorbidities. Infections are associated with longer LOS but not greater mortality. Control of TEMSHV Ent infections in children should focus on validating and responding to these risk factors. Disclosures M. K. Hayden, Sage, Inc: Sage is contributing product to healthcare facilities participating in a regional collaborative on which I am a co-investigator. Neither I nor my hospital receive product., Sage is contributing product to healthcare facilities participating in a regional collaborative on which I am a co-investigator. Neither I nor my hospital receive product.; Clorox, Inc.: I have received funding from Clorox for an investigator-initiated clinical trial., Research support; CDC: Grant Investigator, Research grant; OpGen: receipt of in kind laboratory services, Research support; R. A. Bonomo, Merck: Grant Investigator and Investigator, Consulting fee and Research support; Allergan: Grant Investigator, Research support; Wockhardt: Grant Investigator, Research support; Glaxo Smith Kline: Grant Investigator, Research support; Astra Zeneca: Grant Investigator, Research support; Actavis: Speaker’s Bureau, Speaker honorarium

Pseudomonas aeruginosa is a Gram-negative pathogen commonly associated with nosocomial infections such as hospital-acquired pneumonia. It uses a type III secretion system to deliver effector proteins directly into the cytosol of host cells. Type III secretion in P. aeruginosa has been linked to severe disease and worse clinical outcomes in animal and human studies. The majority of P. aeruginosa strains secrete ExoS, a bifunctional toxin with GTPase-activating protein and ADP-ribosyltransferase activities. Numerous in vitro studies have investigated the targets and cellular effects of ExoS, linking both its enzymatic activities with inhibition of bacterial internalization. However, little is known about how this toxin facilitates the progression of infection in vivo. In this study, we used a mouse model to investigate the role of ExoS in inhibiting phagocytosis during pneumonia. We first confirmed previous findings that the ADP-ribosyltransferase activity of ExoS, but not the GTPase-activating protein activity, was responsible for bacterial persistence and decreased host survival in this model. We then used two distinct assays to demonstrate that ExoS inhibited phagocytosis during pneumonia. In contrast to the findings of several in vitro studies, this in vivo inhibition was also dependent on the ADP-ribosyltransferase activity, but not the GTPase-activating protein activity, of ExoS. These results demonstrate for the first time the antiphagocytic function of ExoS in the context of an actual infection and indicate that blocking the ADP-ribosyltransferase activity of ExoS may have potential therapeutic benefit., IMPORTANCE Pseudomonas aeruginosa is a major cause of hospital-acquired infections. To cause severe disease, this bacterium uses a type III secretion system that delivers four effector proteins, ExoS, ExoT, ExoU, and ExoY, into host cells. The majority of P. aeruginosa strains secrete ExoS, a bifunctional toxin with GTPase-activating protein and ADP-ribosyltransferase activities. In cell culture models, both enzymatic activities have been associated with decreased bacterial internalization. However, our study is the first to examine a role for ExoS in blocking phagocytosis in an animal model. We report that ExoS does inhibit phagocytosis during pneumonia. The ADP-ribosyltransferase activity, but not the GTPase-activating protein activity, of ExoS is necessary for this effect. Our findings highlight the ability of P. aeruginosa to manipulate the inflammatory response during pneumonia to facilitate bacterial survival.

We describe the first pediatric case of Gemella bergeriae endocarditis in a 15-year-old boy with tetralogy of Fallot and pulmonary atresia who presented with weight loss, chills, and cold intolerance. Blood cultures revealed Gram-positive cocci that failed to type with Lancefield group antiserum. The identification of the organism was confirmed by 16S rRNA gene sequencing.

Background. Extended-spectrum β-lactamase (ESBL)–producing Enterobacteriaceae infections are an emerging problem in children. We sought to identify risk factors and describe outcomes associated with pediatric ESBL-producing bacterial infections at 2 hospitals in Chicago, IL from 2008 to 2011. Methods. A case–case–control study of children aged 0–17 years was conducted. Cases of Escherichia coli, Klebsiella, and Proteus spp. ESBL-producing bacterial infections (n = 30) were compared to uninfected controls and in parallel, cases of non-ESBL–producing bacterial infections (n = 30) were compared to uninfected controls (n = 60). We then qualitatively compared these results. Results. Median age of cases was 1.06 years; 62% of isolates were from urine, and 60% were E. coli .B y multivariable analysis, ESBL cases were 5.7 and 3.3 times more likely to have gastrointestinal (P = .001; 95% confidence interval [CI] 1.9–17.0) and neurologic (P = .001; 95% CI 1.1–3.7) comorbidities, respectively, than controls; non-ESBL cases were also more likely to have gastrointestinal comorbidities than controls (P= .014; odds ratio 3.6; 95% CI 1.2–10.1). Study period prevalence remained stable (1.7%). Most (60%) infections occurred in the intensive care unit; however, 30% of children presented in the outpatient setting. Seventy-seven percent of isolates were multidrug resistant (ie, resistant to 3 antibiotic classes). Recurrence of infection occurred in 17% of ESBL cases. Crude mortality rates (7%) did not differ between cases and controls. Conclusions. The incidence of pediatric infection due to ESBL-positive Enterobacteriaceae was stable at 2 large tertiary-care medical centers over a 4-year period. Multidrug resistance in pediatric ESBL isolates is common. Risk factors for infection due to ESBL-producing bacteria include neurologic medical conditions.

Enterobacteriaceae infections resistant to extended-spectrum β-lactams are an emerging problem in children. We used a large database of clinical isolates to describe the national epidemiology of extended-spectrum β-lactamase (ESBL)-producing and third-generation cephalosporin-resistant (G3CR) Enterobacteriaceae.Antimicrobial susceptibilities of Klebsiella pneumoniae, Escherichia coli, and Proteus mirabilis reported to ∼300 laboratories participating in The Surveillance Network (TSN) between January 1999 and December 2011 were used to phenotypically identify G3CR and ESBL isolates cultured from patients18 years. Bi-annual trends in the prevalence of each phenotype were stratified by species, patient location, culture site, age, and region. Children of age 0-1 years were excluded from analysis as data were only available from 2010 onwards.Out of 368,398 pediatric isolates, 1.97% (7255) were identified as G3CR, and 0.47% (1734) as ESBL producers. The prevalence of both phenotypes increased, respectively, from 1.39% and 0.28% in 1999-2001 to 3% and 0.92% in 2010-2011. Trends were significant across all demographic and age groups, including outpatients, with the highest proportion of isolates in the 1-5-year-old age group. The majority of G3CR and ESBL isolates were E. coli (67.8% and 65.2%, respectively). Among ESBLs, resistance to ≥3 antibiotic classes was 74%. The lower regional prevalence of ESBL-producing bacteria in the upper Midwest relative to the rest of the country is consistent with recent local data.Rates of G3CR and ESBL infections in children are increasing in both inpatient and ambulatory settings nationally. The identification of host factors and exposures leading to infection in children is essential.

Enterovirus is a known cause of central nervous system infection in the neonatal population and typically has a benign course; however, neurologic complications have been reported. We describe what we believe to be the first documented case of enteroviral meningoencephalitis complicated by central diabetes insipidus in a neonate.