Search

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.

Background Fluoroquinolones (FQs) are not commonly prescribed in children, yet the increasing incidence of multidrug resistant (MDR) Ent infections in this population often reveals FQ resistance. We sought to define the role of FQ resistance in the epidemiology of MDR Ent in children, with an overall goal to devise treatment and prevention strategies. Methods A case-control study of children (0-18 years) at 3 Chicago hospitals was performed. Cases had infections by FQ susceptible, 3rd generation cephalosporin-resistant (3GCR) and/or carbapenem-resistant (CR) Ent harboring a non or low level expressed PMFQR gene (PMFQS Ent). Controls had FQR infections due to 3GCR and/or CR Ent with expressed PMFQR genes (PMFQR Ent). We sought bla genes by PCR or DNA (BD Max Check-Points assay®) and PMFQR genes by PCR. We performed Rep-PCR, MLST, and E. coli phylogenetic grouping. Demographics; comorbidities; and device, antibiotic, and healthcare exposures were evaluated. Predictors of infection were assessed. Results Of 170 G3CR and/or CR Ent isolates, 85 (50%) were FQS; 23 (27%) had PMFQR genes (PMFQS cases). 85 (50%) were FQR; 53 (62%) had PMFQR genes (PMFQR controls). The median age for children with PMFQS Ent and PMFQR Ent were 4.3 and 6.2 years, respectively (p=NS). Of 23 PMFQS Ent, 53% were Klebsiella and of 53 PMFQR Ent, 76% were E. coli. The most common bla and PMFQR genes in PMFQS Ent were blaSHV ESBL (44%); oqxB (57%) and aac-6’1b-cr (52%) and in PMFQR Ent were blaCTX-M-1 group (76%); aac-6’1b-cr (91%) and oqxA (17%). Multivariable regression analysis showed children with PMFQS Ent infections were more likely to have hospital onset infection (OR 5.7, 95% CI 1.6-22) and isolates with multiple bla genes (OR 3.8, 95% CI 1.1-14.5). The presence of invasive devices mediated the effects of healthcare setting in the final model. Differences in demographics, comorbidities, or antibiotic use were not found. Conclusion Paradoxically, PMFQS Ent infections were often hospital onset and PMFQR Ent infections were community onset. PMFQS Ent commonly co-harbored multiple bla and PMFQR genes, affecting therapeutic options and suggesting need for contact precautions. Control of PMFQS Ent infections in children will require validating sources and risk factors. Disclosures Robert A. Bonomo, MD, entasis (Research Grant or Support)Merck (Grant/Research Support)NIH (Grant/Research Support)VA Merit Award (Grant/Research Support)VenatoRx (Grant/Research Support)

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.

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

BACKGROUND: Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae (KPC-CRE) are multidrug-resistant organisms (MDRO) causing morbidity and mortality worldwide. KPC-CRE prevalence is increasing in pediatric populations, though multi-centered data are lacking. Identifying risk factors for KPC-CRE infection in children and classifying genotypes is a priority in this vulnerable population. METHODS: A case-case-control study of patients (0–22 years) at 3 tertiary-care Chicago-area medical centers, 2008–2015, was conducted. Case group 1 children possessed KPC-CRE infections; case group 2 harbored carbapenem-susceptible Enterobacteriaceae (CSE) infections; control had negative cultures. Case-control matching was 1:1:3 by age, infection site, and hospital. Statistical and molecular analyses were performed. RESULTS: Eighteen KPC-CRE infections were identified; median patient age was 16.5 years. Of 4 available KPC-CRE, two were unrelated, non-ST258 KP strains harboring bla(KPC-2), one was a ST258 KP harboring bla(KPC-3), and the last was an E. coli containing bla(KPC-2). KPC-CRE and CSE-infected patients had more MDRO infections, long-term care facility admissions, and lengths of stay (LOS) >7 days before culture. KPC-CRE and CSE patients had more gastrointestinal (GI) comorbidities (ORs 28.0 and 6.4) and ≥3 comorbidities (ORs 15.4 and 3.5) compared to controls; KPC-CRE patients had significantly more pulmonary and neurologic comorbidities (both ORs 4.4) or GI and pulmonary devices (ORs 11.4 and 6.1). Compared to controls, CSE patients had more prior fluoroquinolone use (OR 7.4); KPC-CRE patients had more carbapenem or aminoglycoside use (ORs 10.0 and 8.0). Race, gender, LOS, and mortality differences were insignificant. CONCLUSIONS: Pediatric patients with KPC-CRE infection suffer from high multi-system disease/device burdens and exposures to carbapenems and aminoglycosides. Different from adult reports, non-ST258 KP strains were more common, and LOS and mortality rates were similar in all groups. Pediatric CRE control in should focus on modifiable risk factors including antibiotic and device utilization.

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 (

Infection rates have increased in all age groups and settings nationally., The prevalence of carbapenem-resistant Enterobacteriaceae (CRE) infections is increasing in the United States. However, few studies have addressed their epidemiology in children. To phenotypically identify CRE isolates cultured from patients 1–17 years of age, we used antimicrobial susceptibilities of Enterobacteriaceae reported to 300 laboratories participating in The Surveillance Network–USA database during January 1999–July 2012. Of 316,253 isolates analyzed, 266 (0.08%) were identified as CRE. CRE infection rate increases were highest for Enterobacter species, blood culture isolates, and isolates from intensive care units, increasing from 0.0% in 1999–2000 to 5.2%, 4.5%, and 3.2%, respectively, in 2011–2012. CRE occurrence in children is increasing but remains low and is less common than that for extended-spectrum β-lactamase–producing Enterobacteriaceae. The molecular characterization of CRE isolates from children and clinical epidemiology of infection are essential for development of effective prevention strategies.

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.

Background AmpC producing Ent are an important cause of multidrug-resistant (MDR) infections in pediatrics. Since most AmpC Ent studies have been conducted in adults, we characterized the molecular epidemiology of AmpC Ent strains with transmissible resistance and identified factors associated with AmpC Ent infections in children. Methods A case–control study of children (0–18 years) at 4 Chicago hospitals during 2011–18 was performed. Cases were 44 children with infections due to Ent harboring an AmpC as detected by DNA microarray (Check-Points®). PCR, DNA sequencing, MLST, and phylogenetic analyses were performed. Controls (ctrls) were 132 children with expanded-spectrum cephalosporin-susceptible Ent infections matched by age and hospital. Demographics; residence; comorbidities; device, antibiotic, and healthcare exposures were evaluated. Predictors of AmpC Ent infection were assessed by logistic regression. Results The median age of AmpC Ent patients was 3.0 years; 50% were male. Of blaAmpC genes, 68% were blaACT/MIR-type and 25% blaCMY-type. Predominant organisms were Enterobacter cloacae (59%) and Escherichia coli (32%); 27% of AmpC E. cloacae belonged to ST114 and 62% co-harbored a blaESBL gene, predominately blaSHV (94%). Most AmpC E. coli strains were unrelated; 71% carried blaCMY, 64% belonged to phylogroups B2/D, and 50% co-harbored blaCTX-M. On bivariate analysis vs. ctrls, AmpC Ent infections were more likely to be respiratory (39% vs. 18%, P < 0.01) and less likely to be urinary tract (41% vs. 67%, P < 0.01) or community-acquired (14% vs. 33%, P < 0.02). By multivariable analysis, children with AmpC Ent infections were more likely to be nonwhite, non-black, non-Hispanic (OR 4.7, CI 1.4–16.1) and have infections due to Enterobacter (OR 7.7, CI 3.5–17). Differences in gender, healthcare location, residential neighborhood, antibiotic exposures, comorbidities, devices or outcomes were not found. Conclusion AmpC Ent infections often had healthcare onset, were due to Enterobacter, and occurred in nonwhite, non-black, non-Hispanic children. AmpC Ent commonly co-harbored blaSHV and blaCTX-M ESBL genes which affects therapeutic options and suggests the need for contact precautions. Control of AmpC Ent infections in children will require validating sources and risk factors. Disclosures All authors: No reported disclosures.

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.

Background Pseudomonas aeruginosa is a common cause of healthcare-associated infection. Multidrug-resistant (MDR) (>3 classes) and carbapenem-resistant (CR) P aeruginosa are significant threats globally. We used a large reference-laboratory database to study the epidemiology of P aeruginosa in children in the United States. Methods Antimicrobial susceptibility data from the Surveillance Network were used to phenotypically identify MDR and CR P aeruginosa isolates in children aged 1 to 17 years between January 1999 and July 2012. Logistic regression analysis was used to calculate trends in the prevalence of MDR and CR P aeruginosa. Isolates from infants (

Metallo-β-lactamase-producing Enterobacteriaceae are emerging in the U.S. and are becoming a significant threat. Unfortunately, there is little recognition of the increasing reports of these organisms in U.S. children, a vulnerable population that may suffer severe long-term consequences., Metallo-β-lactamases (MBLs) are emerging as the most notable resistance determinants in Enterobacteriaceae. In many cases, the genes encoding MBLs are part of complex, mobile genetic elements that carry other resistance determinants. In the United States, there are increasing reports of MBL-producing Enterobacteriaceae, with New Delhi MBLs (NDMs) accounting for the majority of transmissible MBL infections. Many infections caused by NDM-producing bacteria are associated with international travel and medical tourism. However, little recognition of the introduction of MBL-producing Enterobacteriaceae into the pediatric community has followed. Reports suggest that this occurred as early as 2002. Here, we reflect on the unwelcome emergence of MBL-producing Enterobacteriaceae in US children and the available clinical and molecular data associated with spread. Since 2002, there have been disturbing reports that include the most readily transmissible MBLs, blaIMP, blaVIM, and blaNDM types. In the majority of children with available data, a history of foreign travel is absent.

OBJECTIVETo determine the prevalence and acquisition of extended-spectrum β-lactamases (ESBLs), plasmid-mediated AmpCs (pAmpCs), and carbapenemases (“MDR Enterobacteriaceae”) colonizing children admitted to a pediatric intensive care unit (PICU).DESIGNProspective study.SETTING40-bed PICU.METHODSAdmission and weekly thereafter rectal surveillance swabs were collected on all pediatric patients during a 6-month study period. Routine phenotypic identification and antibiotic susceptibility testing were performed. Enterobacteriaceae displaying characteristic resistance profiles underwent further molecular characterization to identify genetic determinants of resistance likely to be transmitted on mobile genetic elements and to evaluate relatedness of strains including DNA microarray, multilocus sequence typing, repetitive sequence-based PCR, and hsp60 sequencing typing.RESULTSEvaluating 854 swabs from unique children, the overall prevalence of colonization with an MDR Enterobacteriaceae upon admission to the PICU based on β-lactamase gene identification was 4.3% (n=37), including 2.8% ESBLs (n=24), 1.3% pAmpCs (n=11), and 0.2% carbapenemases (n=2). Among 157 pediatric patients contributing 603 subsequent weekly swabs, 6 children (3.8%) acquired an incident MDR Enterobacteriaceae during their PICU stay. One child acquired a pAmpC (E. coli containing blaDHA) related to an isolate from another patient.CONCLUSIONSApproximately 4% of children admitted to a PICU were colonized with MDR Enterobacteriaceae (based on β-lactamase gene identification) and an additional 4% of children who remained in the PICU for at least 1 week acquired 1 of these organisms during their PICU stay. The acquired MDR Enterobacteriaceae were relatively heterogeneous, suggesting that a single source was not responsible for the introduction of these resistance mechanisms into the PICU setting.Infect Control Hosp Epidemiol 2016;37:535–543

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.

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.

Background In theory, active surveillance of methicillin-resistant Staphylococcus aureus (MRSA) reduces MRSA spread by identifying all MRSA-colonized patients and placing them under contact precautions. In October 2007, Illinois mandated active MRSA surveillance in all intensive care units, including neonatal intensive care units (NICUs) and pediatric intensive care units (PICUs). We evaluated MRSA trends in a large metropolitan region in the wake of this law. Methods Chicago hospitals with a NICU or PICU were recruited for 8 single-day point prevalence surveys that occurred twice-yearly between June 2008 and July 2011 and then yearly in 2012 to 2013. Samples from all patients were cultured for MRSA (nose and umbilicus for neonates, nose and groin for pediatric patients). Hospital-reported admission MRSA-screening results also were obtained. Point prevalence cultures were screened for MRSA by using broth enrichment, chromogenic agar, and standard confirmatory methods. Results All eligible hospitals (N = 10) participated (10 NICUs, 6 PICUs). Hospital-reported adherence to state-mandated MRSA screening at admission was high (95% for NICUs, 94% for PICUs). From serial point prevalence surveys, overall MRSA prevalences in the NICUs and PICUs were 4.2% (89 of 2101) and 5.7% (36 of 632), respectively. MRSA colonization prevalences were unchanged in the NICUs (year-over-year risk ratio [RR], 0.93 [95% confidence interval (CI), 0.78-1.12]; P = .45) and trended toward an increase in the PICUs (RR, 1.25 [95% CI, 0.72-2.12]; P = .053). We estimated that 81% and 40% of MRSA-positive patients in the NICUs and PICUs, respectively, had newly acquired MRSA. Conclusions In a region with mandated active MRSA surveillance, we found ongoing unchanged rates of MRSA colonization and acquisition among NICU and PICU patients.

A 4-month-old boy with past medical history of eczema presented with fever and cough; a chest radiograph showed lung consolidation, and he was initially treated with amoxicillin for presumed community-acquired pneumonia. After several days, his fever persisted. He was also profoundly anemic. Antibiotic coverage was broadened because of the concern for resistant organisms; he began to improve and was discharged from the hospital. However, at 5 months of age, his fever returned, and he continued to demonstrate lung consolidation on chest radiograph. Additionally, he had lost weight and continued to be anemic. Splenic cysts were noted on abdominal ultrasound. He was diagnosed with an unusual etiology for his pneumonia and improved with the appropriate therapy. An underlying immunodeficiency was suspected, but initial testing was nondiagnostic. At 12 months of age, he presented with another infection, and the final diagnosis was made.

Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae present an ever-growing burden in the hospital and community settings, across all ages and demographics. Infections due to ESBL-containing pathogens continue to be associated with significant morbidity and mortality worldwide. With widespread empiric broad-spectrum β-lactam use creating selective pressure, and the resultant emergence of stable, rapidly proliferating ESBL-producing clones with continued horizontal gene transfer across genera, addressing this issue remains imperative. Although well characterized in adults, the epidemiology, risk factors, outcomes, therapies, and control measures for ESBL-producing bacteria are less appreciated in children. This analysis provides a brief summary of ESBL-producing Enterobacteriaceae in children, with a focus on recent clinical and molecular data regarding colonization and infection in nonoutbreak settings.