Child Pedestrian Safety.

The field of pedestrian safety has advanced with new evidence related to pediatric pedestrian education, the risks of distracted walking, the benefits of design and programming in safe routes to school, and the emergence of the "Vision Zero" strategy to eliminate all traffic fatalities and severe injuries while increasing safe, healthy, equitable mobility for all. This statement is a revision of the 2009 American Academy of Pediatrics policy statement "Pedestrian Safety" and is accompanied by a technical report (www.pediatrics.org/cgi/doi/10.1542/peds.2023-062508) providing additional detail to support recommendations. This statement is intended to assist practicing pediatricians to offer evidence-based advice to families about the benefits of active transportation and the specific risks and safety precautions to consider for child pedestrians at different ages. For community pediatricians and the American Academy of Pediatrics, the statement provides an overview of specific programs and policies that, if implemented, could foster independent mobility for children while increasing pediatric pedestrian safety. This statement identifies trends in public health and urban design relevant to pedestrian safety.

Epidemiology and Prevention of Child Pedestrian Injury.

This report supports policy recommendations in the accompanying policy statement "Child Pedestrian Safety" (www.pediatrics.org/cgi/doi/10.1542/peds.2023-62506). It reviews trends in public health and urban design relevant to pedestrian safety and provides information to assist practicing pediatricians discussing the benefits of active transportation and the specific risks and safety precautions to consider for child pedestrians at different ages. The report offers the evidence base for which programs and policies that, if implemented, could foster independent mobility for children while increasing pediatric pedestrian safety. Since the previous policy statement was published in 2009, the field of pedestrian safety has advanced with new evidence related to pediatric pedestrian education, the risks of distracted walking, the benefits of design and programming in safe routes to school, and the emergence of the "Vision Zero" public health and safety initiatives to prevent all serious and fatal transportation injuries.

Colonization with Escherichia coli ST131-H30R (H30R) Corresponds with Increased Serum Anti-O25 IgG Levels and Decreased TNFα and IL-10 Responsiveness to H30R.

An exceptional gut-colonizing ability may underlie the dramatic epidemiological success of the multidrug-resistant H30R subclone of Escherichia coli sequence type 131 (O25b:K+:H4). In order to inform the development of colonization-preventing measures, we studied systemic immune correlates of H30R intestinal colonization. Human volunteers' fecal samples were screened for H30R by selective culture and PCR. Subjects were assessed by enzyme immunoassay for serum levels of anti-O25 IgG (representing H30R) and anti-O6 IgG (representing non-H30 E. coli generally), initially and for up to 14 months. Whole blood was tested for the antigen-stimulated release of IFNγ, TNFα, IL-4, IL-10, and IL-17 after incubation with E. coli strains JJ1886 (H30R; O25b:K+:H4) or CFT073 (non-H30; O6:K2:H1). Three main findings were obtained. First, H30R-colonized subjects had significantly higher anti-O25 IgG levels than controls, but similar anti-O6 IgG levels, suggesting an IgG response to H30R colonization. Second, anti-O25 and anti-O6 IgG levels were stable over time. Third, H30R-colonized subjects exhibited a lower TNFα and IL-10 release than controls in response to strain JJ1886 (H30R) relative to strain CFT073 (non-H30R), consistent with TNFα hypo-responsiveness to H30R possibly predisposing to H30R colonization. Thus, H30R-colonized hosts exhibit a sustained serum anti-O25 IgG response and an underlying deficit in TNFα responsiveness to H30R that could potentially be addressed for colonization prevention.

Prevalence and characteristics of multidrug-resistant Escherichia coli sequence type ST131 at two academic centers in Boston and Minneapolis, USA.

BACKGROUND: Escherichia coli sequence type (ST) ST131, with its emergent resistance-associated H30Rx, H30R1, and C1-M27 clonal subsets, accounts for the greatest share of extraintestinal E. coli infections and most extended-spectrum ß-lactamase (ESBL)-producing E. coli. METHODS: We characterized and compared consecutive E. coli urine isolates from two geographically distinct medical centers in Minneapolis, Minnesota (n = 172) and Boston, Massachusetts (n = 143) for ESBL phenotype, CTX-M-type ESBL genes, phylogenetic groups, selected ST131 subclones, and 40 extraintestinal virulence genes. RESULTS: Whereas the Boston vs. Minneapolis isolates had a similar prevalence of phylogenetic groups (mainly B2: 79% vs 73%), ST131 (34% vs 28%), H30 (28% vs 21%), and H30Rx (6% vs 5%), the emerging C1-M27 subclone occurred uniquely among Boston (6%) isolates. ESBL production was more prevalent among Boston isolates (15% vs 8%) and among ST131 isolates. Identified ESBL genes included blaCTX-M-27 (Boston only) and blaCTX-M-15. Ciprofloxacin resistance was ST131-associated and similarly prevalent across centers. Boston isolates had higher virulence gene scores. CONCLUSIONS: Despite numerous similarities to Minneapolis isolates, Boston ST131 isolates demonstrated more prevalent ESBL production, higher virulence gene scores, and, uniquely, the C1-M27 subclone and blaCTX-M-27. Broader surveillance is needed to define the prevalence of ST131's globally successful C1-M27 subclone across the U.S.

Novel Multiplex PCR Method and Genome Sequence-Based Analog for High-Resolution Subclonal Assignment and Characterization of Escherichia coli Sequence Type 131 Isolates.

Escherichia coli sequence type 131 (ST131) is a pandemic, multidrug-resistant extraintestinal pathogen. The multiple distinctive ST131 subclones differ for rfb and fliC alleles (O and H antigens), fimH allele (type-1 fimbriae adhesin), resistance phenotype and genotype, clinical correlates, and host predilection. Current PCR assays for detecting ST131 and its main subclones offer limited sub-ST characterization. Here we combined 22 novel and 14 published primers for a multiplex PCR assay to detect and extensively characterize ST131 isolates. The primers target mdh36, gyrB47, trpA72, sbmA, plsB, nupC, rmuC, kefC, ybbW, the O16 and O25b rfb variants, five fimH alleles (fimH22, fimH27, fimH30, fimH35, and fimH41), two fliC alleles (H4 and H5), a (subclone-specific) fluoroquinolone resistance-associated parC allele, and a (subclone-specific) prophage marker. The resulting amplicons resolve 15 molecular subsets within ST131, including 3 within clade A (H41 subclone), 5 within clade B (H22 subclone), and 7 within clade C (H30 subclone), which includes subclones C0 (H30S: 2 subsets), C1 and C1-M27 (H30R1: 2 subsets), and C2 (H30Rx: 3 subsets). Validation in three laboratories showed that this assay provides a rapid, accurate, and portable method for rapidly detecting and characterizing E. coli ST131 and its key subsets. Additionally, for users with whole genome sequencing (WGS) capability, we developed a command-line executable called ST131Typer, an in silico version of the extended multiplex PCR assay. Its accuracy was 87.8%, with most issues due to incomplete or fragmented input genome assemblies. These two novel assays should facilitate detailed ST131 subtyping using either endpoint PCR or WGS. IMPORTANCE These novel assays provide greater subclonal resolution and characterization of E. coli ST131 isolates than do the available comparable PCR assays, plus offer a novel sequence-based alternative to PCR. They may prove useful for molecular epidemiological studies, surveillance, and, potentially, clinical management.

Bacteriophage Cocktail and Microcin-Producing Probiotic Escherichia coli Protect Mice Against Gut Colonization With Multidrug-Resistant Escherichia coli Sequence Type 131.

Non-antibiotic measures are needed to reduce the rate of infections due to multidrug-resistant organisms (MDROs), including by eliminating the commensal reservoir that underlies such strains' dissemination and leads to recurrent infections. Here, we tested a cocktail of pre-selected bacteriophages and an engineered microcin C7-producing probiotic Escherichia coli Nissle-1917 strain for their ability to reduce gut colonization by an E. coli strain from sequence type 131 (ST131)-H30R, which is the major clonal group of MDROs among extraintestinal clinical E. coli isolates. Although the bacteriophage cocktail was highly effective against ST131-H30R strains both in vitro and in a murine model of subcutaneous sepsis, it was only weakly and transiently effective against gut colonization by the target ST131-H30R strain (0.5 log10 decrease on d + 1: p < 0.001; no significant effect on d + 4 and beyond). The probiotic strain, while also highly active against ST131-H30R in vitro, was ineffective against ST131-H30R gut colonization despite its abundant presence in feces. Nonetheless, despite failing as decolonizing agents when administered separately, when co-administered the bacteriophage cocktail and probiotic strain exhibited striking synergy against ST131-H30R gut colonization. This combinatory effect was most pronounced on d + 1 (3.3 log10 target strain decrease: p < 0.001), and persisted until d + 7 (0.5 log10 decrease; p < 0.02.). Although by d + 10 the ST131-H30R load was fully restored, these findings provide proof of concept for combined bacteriophage-plus-probiotic administration to reduce or, possibly, to prevent gut colonization with MDROs in high-risk individuals.

Intestinal Persistence of Colonizing Escherichia coli Strains, Especially ST131-H30, in Relation to Bacterial and Host Factors.

BACKGROUND: Superior gut colonization may underlie the pandemic emergence of the resistance-associated H30 subclone of Escherichia coli sequence type 131 (ST131-H30). Little is known about the associated host and bacterial characteristics, or the comparative persistence of non-ST131 intestinal E. coli. METHODS: Generic and fluoroquinolone-resistant E. coli isolates from volunteers' serial fecal samples underwent clonal analysis and extensive polymerase chain reaction (PCR)-based characterization (phylogroup, selected sequence types, virulence genes). Kaplan-Meier survival analysis and Cox proportional hazards survival analysis using penalized regression (a machine-learning method) were used to identify correlates of strain persistence. RESULTS: Screening of 2005 subjects at the Minneapolis VA Medical Center identified 222 subjects (117 veterans, 105 human and animal household members) for longitudinal fecal surveillance. Analysis of their 585 unique-by-subject fecal E. coli strains identified multiple epidemiological, ecological, and bacterial correlates of strain persistence. ST131-H30, a strong univariable correlate of persistence, was superseded in multivariable analysis by outpatient status, fluoroquinolone resistance, and diverse (predominantly iron uptake-related) virulence genes. CONCLUSIONS: ST131-H30 exhibits exceptional intestinal persistence, possibly due to a combination of fluoroquinolone resistance and virulence factors, which may be primarily colonization factors. This identifies both likely contributors to the ST131-H30 pandemic and potential targets for interventions against it.

Molecular Characteristics, Ecology, and Zoonotic Potential of Escherichia coli Strains That Cause Hemorrhagic Pneumonia in Animals.

Hemorrhagic pneumonia (HP) is a rare but highly lethal disease, mainly of dogs and cats, caused by hemolytic Escherichia coli strains that contain cnf1 (encoding cytotoxic necrotizing factor 1). After encountering fatal HP in two dogs, we used contemporary molecular methods, including multilocus sequence typing and whole-genome sequencing, to compare the corresponding case isolates with published HP clinical isolates and newly obtained fecal E. coli isolates from 20 humans and animals in the index HP case household. We also compared the aggregated HP clinical isolates, which represented 13 discrete strains, by pulsotype with a large, private pulsotype library of diverse-source E. coli. The HP clinical isolates represented a narrow range of phylogenetic group B2 lineages (mainly sequence types 12 and 127), O types (mainly O4 and O6), and H types (mainly H5 and H31), but diverse fimH alleles (type-1 fimbriae adhesin). Their extensive, highly conserved virulence genotypes, which qualified as extraintestinal pathogenic E. coli (ExPEC), encoded diverse adhesins, toxins, iron uptake systems, and protectins. Household surveillance identified multiple HP-like fecal strains, plus abundant between-host strain sharing, including of the household's index HP strain. The pulsotype library search identified, for five HP clinical strains, same-pulsotype human and animal fecal and clinical (predominantly urine) isolates, from diverse locales and time periods. Thus, E. coli strains that cause HP derive from a narrow range of ExPEC lineages within phylogroup B2, contain multiple virulence genes other than cnf1, are shared extensively between hosts, and likely function in nature mainly as intestinal colonizers and uropathogens. IMPORTANCE This study clarifies the clonal background and extensive virulence genotypes of the E. coli strains that cause hemorrhagic pneumonia in domestic animals (mainly dogs and cats), shows that such strains circulate among animals and humans, identifies a substantial intestinal colonization component to their lifestyle, and extends their known clinical manifestations to include bacteremia and urinary tract infection. The findings place these strains better into context vis-à-vis current understandings of E. coli phylogeny, ecology, and pathogenesis; identify questions for future research; and may prove relevant for surveillance and prevention efforts.

Global molecular epidemiology of carbapenem-resistant Escherichia coli (2002-2017).

The emergence of carbapenem-resistant (CR) Escherichia coli obliges an assessment of such strains' molecular epidemiology. Accordingly, we characterized in detail a globally distributed collection of CR E. coli isolates, then explored for associations between geographical origin and bacterial traits, and between different bacterial traits. We used established PCR-based assays and broth microdilution MIC determinations to characterize 343 global CR (i.e., non-susceptible to ≥ 1 carbapenem) extraintestinal E. coli isolates (2002-2017) for diverse molecular traits-including phylogroups, sequence types (STs), beta-lactamase genes, and 51 virulence genes-and susceptibility to 12 relevant antimicrobial agents. The study population was tremendously diverse according to all assessed variables. Nonetheless, certain geographically aligned, unifying themes emerged. These included an association of an Asia/West Pacific origin with non-B2/D/F phylogroups and STs, lower molecularly inferred virulence, more extensive resistance, and specific resistance genes (notably, metallo-beta-lactamases). Likewise, U.S. isolates from the central region, vs. other regions, were more virulent-appearing and more often from phylogroup B2 and ST131, but less extensively resistant and more often carbapenemase-gene negative. The global CR E. coli population is highly diverse according to multiple characteristics and varies significantly by geographical region. This predictably will pose challenges for prevention and management, and obliges ongoing surveillance.

Bringing Physical Exam Skills Back from the Dead.

Physical examination education begins early for medical learners. A hindrance to physical exam competency is lack of exposure to pathology in standardized patient settings. This research focuses on improving medical education through the utilization of cadavers that have undergone a soft-embalming technique: the Thiel method. Three scenarios were created in four Thiel cadavers: anterior cruciate ligament (ACL) tear, posterior cruciate ligament (PCL) tear, and sham incision. Students were asked to diagnose ACL tears using the Lachman exam. A total of 54 learners participated in the study. Post-surveys indicated most learners: (1) prefer to use standardized patients (SPs) and soft-embalmed cadavers in their physical examination courses, (2) increased their confidence in performing the Lachman exam on real patients, and (3) enhanced their Lachman technique. SPs ultimately cannot volitionally reproduce the physical exam findings of ACL deficiency. Consequently, learners cannot accurately identify positive versus negative examination findings. Thiel-embalmed cadavers are a valuable resource for physical examination education. (Journal of Surgical Orthopaedic Advances 30(2):112-115, 2021).

Activity of plazomicin against carbapenem-intermediate or -resistant Escherichia coli isolates from the United States and international sites in relation to clonal background, resistance genes, co-resistance, and region.

BACKGROUND: Emerging carbapenem resistance in Escherichia coli, including sequence type 131 (ST131), threatens therapeutic efficacy. Plazomicin (PLZ), a semisynthetic aminoglycoside approved by the FDA in 2018, overcomes the most common aminoglycoside resistance mechanisms and maintains activity against many carbapenem-intermediate or -resistant (CIR) E. coli strains. OBJECTIVES: To assess plazomicin susceptibility among CIR E. coli in relation to region and multiple bacterial characteristics. METHODS: We determined broth microdilution MICs for plazomicin and 11 comparators against 343 CIR clinical E. coli isolates, then compared susceptibility results by bacterial characteristics and region. The collection comprised 203 US isolates (2002-17) and 141 isolates from 17 countries in Europe, Latin America, and the Asia-West Pacific region (2003-17). Isolates were characterized for phylogenetic group, resistance-associated sequence types (STs) and subsets thereof, and relevant ß-lactamase-encoding genes. RESULTS: Plazomicin exhibited the highest percentage susceptible (89%) after tigecycline (99%). The percentage susceptible to plazomicin varied significantly by phylogroup (63%, group B1; versus >93%, others) and ST131 subclone (92%, H30Rx; versus 87%-89%, H30R1 and non-H30), but not ST. It also varied by resistance genotype [higher with Klebsiella pneumoniae carbapenemase (KPC), lower with metallo-ß-lactamases], global region [highest for Latin America (94%), lowest for Asia-West Pacific (69%)], and US region (80%, South, versus 96%-100%, others). Although reduced susceptibility to comparators often predicted reduced susceptibility to plazomicin, even among comparator-intermediate or -resistant isolates the plazomicin-susceptible fraction was ≥77%, except for amikacin (53%). CONCLUSIONS: The likely utility of plazomicin against CIR E. coli is high overall, but varies with region and multiple bacterial characteristics.

Comparative activity of plazomicin against extended-spectrum cephalosporin-resistant Escherichia coli clinical isolates (2012-2017) in relation to phylogenetic background, sequence type 131 subclones, blaCTX-M genotype, and resistance to comparator agents.

Extended-spectrum cephalosporin-resistant Escherichia coli (ESCREC) are a growing threat. Leading ESCREC lineages include sequence type ST131, especially its (blaCTX-M-15-associated) H30Rx subclone and (blaCTX-M-27-associated) C1-M27 subset within the H30R1 subclone. The comparative activity against such strains of alternative antimicrobial agents, including the recently developed aminoglycoside plazomicin, is undefined, so was investigated here. We assessed plazomicin and 11 comparators for activity against 216 well-characterized ESCREC isolates (Minnesota, 2012-2017) and then compared broth microdilution MICs with phylogenetic and clonal background, beta-lactamase genotype (blaCTX-M; group 1 and 9 variants), and co-resistance. Percent susceptible was > 99% for plazomicin, meropenem, imipenem, and tigecycline; 96-98% for amikacin and ertapenem; and ≤ 75% for the remaining comparators. For most comparators, MICs varied significantly in relation to multiple bacterial characteristics, in agent-specific patterns. By contrast, for plazomicin, the only bacterial characteristic significantly associated with MICs was ST131 subclone: plazomicin MICs were lowest among O16 ST131 isolates and highest among ST131-H30R1 C1-M27 subclone isolates. Additionally, plazomicin MICs varied significantly in relation to resistance vs. susceptibility to comparator agents only for amikacin and levofloxacin. For most study agents, antimicrobial activity against ESCREC varied extensively in relation to multiple bacterial characteristics, including clonal background, whereas for plazomicin, it varied only by ST131 subclone (C1-M27 isolates least susceptible, O16 isolates most susceptible). These findings support plazomicin as a reliable alternative for treating ESCREC infections and urge continued attention to the C1-M27 ST131 subclone.

Complete Genome Sequence of Escherichia coli Strain FEX669, a ColV Plasmid-Containing Isolate from Retail Chicken Meat.

Escherichia coli strain FEX669 was isolated from retail ground chicken and shown to contain the extraintestinal pathogenic E. coli (ExPEC) virulence genes sfaD, focC, and iutA Because this presumptive ExPEC strain was isolated from a retail food item and it was a weak biofilm former, it was characterized using whole-genome sequencing using the PacBio RS II platform. Genomic analysis showed that the FEX669 chromosome is 4,973,943 bp long, with a GC content of 50.47%, and is accompanied by a ColV plasmid that is 237,102 bp long, with a GC content of 50.49%.

Activity of cefiderocol, ceftazidime-avibactam, and eravacycline against extended-spectrum cephalosporin-resistant Escherichia coli clinical isolates (2012-20017) in relation to phylogenetic background, sequence type 131 subclones, blaCTX-M genotype, and coresistance.

Extended-spectrum cephalosporin-resistant Escherichia coli (ESCREC) are a growing threat. Leading ESCREC lineages include sequence type ST131, especially its (blaCTX-M-15-associated) H30Rx subclone and (blaCTX-M-27-associated) C1-M27 subset within the H30R1 subclone. We assessed cefiderocol, ceftazidime-avibactam, eravacycline, and 11 comparators for activity against 216 well-characterized ESCREC isolates (Minnesota, 2012-2017), then compared broth microdilution MICs with phylogenetic and clonal background, beta-lactamase genotype (blaCTX-M; group 1 and 9 variants), and coresistance. Percent susceptible was >95% (cefiderocol, ceftazidime-avibactam, eravacycline, carbapenems, amikacin, piperacillin-tazobactam, tigecycline), 64% to 75% (gentamicin, minocycline), or <40% (ceftazidime, levofloxacin, colistin). MICs varied significantly by multiple bacterial characteristics, in agent-specific patterns. The least-susceptible ST131 subset was the non-C1-M27 fraction within H30R1. Cefiderocol, ceftazidime-avibactam, and eravacycline MICs tended to be higher among isolates resistant (vs. susceptible) to diverse comparators. Thus, cefiderocol, ceftazidime-avibactam, and eravacycline are promising carbapenem-sparing alternatives for treating ESCREC infections, and their strength of activity varies in relation to diverse bacterial characteristics.

Activity of meropenem/vaborbactam against international carbapenem-resistant Escherichia coli isolates in relation to clonal background, resistance genes, resistance to comparators and region.

OBJECTIVES: Carbapenem resistance has emerged inEscherichia coli, including sequence type 131 (ST131) and its fluoroquinolone-resistant H30R subclone, the leading cause of extraintestinal E. coli infections globally. Meropenem/vaborbactam (MVB) is a recently approved carbapenem/ß-lactamase inhibitor combination with broad-spectrum inhibition of ß-lactamases, including serine carbapenemases. The activity of MVB against carbapenem-resistant (CR) E. coli infections in relation to phylogenetic background, resistance genotype and geographical region is unknown. METHODS: We characterised 140 contemporary CR clinicalE. coli isolates from 17 non-US countries (2003-2017) for phylogroup, clonal group (including ST131, H30R and the CTX-M-15-associated H30Rx subset), relevant ß-lactamase genes, and broth microdilution MICs for MVB and 11 comparators. RESULTS: Overall, MVB was moderately active (66% susceptible), more so than all comparators except tigecycline and amikacin (100% and 74% susceptible, respectively). Most MVB-non-susceptible isolates carried metallo-ß-lactamase or OXA-48 resistance genes. MVB's activity varied significantly in relation to phylogroup, clonal background, resistance genotype and global region: it was greatest among phylogroup F, ST131-H30R, H30Rx, Klebsiella pneumoniae carbapenemase (KPC)-positive and Latin American isolates, and lowest among phylogroup B1, metallo-ß-lactamase gene-containing and Asia-West Pacific region isolates. Enhancement of meropenem's activity by vaborbactam was most evident for isolates from phylogroups B2, C and D, and those containing KPC. MVB retained appreciable (albeit somewhat reduced) activity against isolates resistant to comparator agents. CONCLUSION: MVB should be useful for treating international CRE. coli infections, largely independent of other resistance phenotypes, although this likely will vary with the local prevalence of specific E. coli lineages and carbapenem resistance mechanisms.

Draft genome sequences of concurrent Escherichia coli blood and fecal isolates from a patient with bacteremia and diarrhea belie BioFire-based detection of fecal enteropathogenic E. coli.

The BioFire FilmArray® Gastrointestinal panel is a multiplex PCR assay widely used to determine the etiology of infectious gastroenteritis directly from stool specimens. Recently a positive BioFire result for fecal enteropathogenic Escherichia coli (EPEC) was reported by a clinical microbiology laboratory for an adult patient with diarrhea and bacteremia. Since EPEC infrequently infects adults and rarely causes bacteremia, we isolated fecal E. coli and characterized the patient's blood and fecal E. coli isolates. Draft genome sequencing using a combination of methods indicated that the blood and fecal strains are virtually identical, are from sequence type 963 (phylogroup D) and exhibit neither the virulence genes characteristic of EPEC and extraintestinal pathogenic E. coli (ExPEC) nor classic EPEC-associated phenotypes. These findings support a gut source for the patient's bacteremia but exclude EPEC as the causative organism, and suggest that results of multiplex PCR assays from complex samples can be misleading, and should be interpreted with caution when they are discordant with clinical information. BioProject accession numbers for strains MVAST5574 and MVAST5635 genomes are PRJNA611789 and PRJNA611804, respectively.

In Silico Genotyping of Escherichia coli Isolates for Extraintestinal Virulence Genes by Use of Whole-Genome Sequencing Data.

Extraintestinal pathogenic Escherichia coli (ExPEC) is the leading cause in humans of urinary tract infection and bacteremia. The previously published web tool VirulenceFinder (http://cge.cbs.dtu.dk/services/VirulenceFinder/) uses whole-genome sequencing (WGS) data for in silico characterization of E. coli isolates and enables researchers and clinical health personnel to quickly extract and interpret virulence-relevant information from WGS data. In this study, 38 ExPEC-associated virulence genes were added to the existing E. coli VirulenceFinder database. In total, 14,441 alleles were downloaded. A total of 1,890 distinct alleles were added to the database after removal of redundant sequences and analysis of the remaining alleles for open reading frames (ORFs). The database now contains 139 genes-of which 44 are related to ExPEC-and 2,826 corresponding alleles. Construction of the database included validation against 27 primer pairs from previous studies, a search for serotype-specific P fimbriae papA alleles, and a BLASTn confirmation of seven genes (etsC, iucC, kpsE, neuC, sitA, tcpC, and terC) not covered by the primers. The augmented database was evaluated using (i) a panel of nine control strains and (ii) 288 human-source E. coli strains classified by PCR as ExPEC and non-ExPEC. We observed very high concordance (average, 93.4%) between PCR and WGS findings, but WGS identified more alleles. In conclusion, the addition of 38 ExPEC-associated genes and the associated alleles to the E. coli VirulenceFinder database allows for a more complete characterization of E. coli isolates based on WGS data, which has become increasingly important considering the plasticity of the E. coli genome.

Activity of Cefiderocol, Ceftazidime-Avibactam, and Eravacycline against Carbapenem-Resistant Escherichia coli Isolates from the United States and International Sites in Relation to Clonal Background, Resistance Genes, Coresistance, and Region.

Emerging carbapenem resistance in Escherichia coli, including sequence type 131 (ST131), the leading cause of extraintestinal E. coli infections globally, threatens therapeutic efficacy. Accordingly, we determined broth microdilution MICs for three distinctive newer agents, i.e., cefiderocol (CFDC), ceftazidime-avibactam (CZA), and eravacycline (ERV), plus 11 comparators, against 343 carbapenem-resistant (CR) clinical E. coli isolates, then compared susceptibility results with bacterial characteristics and region. The collection comprised 203 U.S. isolates (2002 to 2017) and 141 isolates from 17 countries in Europe, Latin America, and the Asia-West Pacific region (2003 to 2017). Isolates were characterized for phylogenetic group, resistance-associated sequence types (STs) and subsets thereof, and relevant beta-lactamase-encoding genes. CFDC, CZA, and ERV exhibited the highest percent susceptible (82% to 98%) after tigecycline (TGC) (99%); avibactam improved CZA's activity over that of CAZ (11% susceptible). Percent susceptible varied by phylogroup and ST for CFDC and CZA (greatest in phylogroups B2, D, and F, and in ST131, ST405, and ST648). Susceptibility also varied by resistance genotype, being higher with the Klebsiella pneumoniae carbapenemase (KPC) for CZA, lower with metallo-beta-lactamases for CFDC and CZA, and higher with the beta-lactamase CTX-M for ERV. Percent susceptible also varied by global region for CZA (lower in Asia-Pacific) and by U.S. region for ERV (lower in the South and Southeast). Although resistance to comparators often predicted reduced susceptibility to a primary agent (especially CFDC and CZA), even among comparator-resistant isolates the primary-agent-susceptible fraction usually exceeded 50%. These findings clarify the likely utility of CFDC, CZA, and ERV against CR E. coli in relation to multiple bacterial characteristics and geographical region.

Income-Based Disparities in a Yearly Dental Visit in United States Adults and Children: Trend Analysis 1997 to 2016.

OBJECTIVE: To determine how income-based disparities in a yearly dental visit (the Healthy People 2020 Leading Health Indicator for Oral Health) changed since legislation to expand dental coverage and to compare disparity trends in children and adults. METHODS: We analyzed Medical Expenditure Panel Survey 1997 to 2016 to determine yearly dental visit rates for US children and adults by family income. We determined measures of income disparity, including the Slope Index of Inequality and the Relative Index of Inequality and examined trends in yearly dental visit, Slope Index of Inequality, and Relative Index of Inequality using joinpoint regression. RESULTS: Income-based disparities, absolute and relative, narrowed over time for children. Steady upward trends in yearly dental visit rates were observed for poor and low-income/poor children and no joinpoint was identified that corresponded to legislation expanding dental care coverage for lower income children. Relative income-based disparities in yearly dental visit rates widened for adults over 20 years. After declining for 14 years, yearly dental visit rate increased for poor adults from 2013 to 2016 suggesting a possible positive effect in adult dental care use trends following enactment of the Affordable Care Act. CONCLUSIONS: In 1997, US children and adults had similar levels of income-based disparity in yearly dental visits, but by 2016, they differed markedly. Trends in income-based disparities in yearly dental visit rate narrowed for children but widened for adults. There are lessons from the expansion of dental care coverage for children that could be applied to improve access to dental care for adults.

Activity of ceftazidime-avibactam against Escherichia coli isolates from U.S. veterans (2011) in relation to co-resistance and sequence type 131 (ST131) H30 and H30Rx status.

Escherichia coli ST131, with its multidrug-resistance-associated H30R1 and H30Rx clonal subsets within the H30R subclone, causes most antimicrobial-resistant E. coli infections. The activity of ceftazidime-avibactam (CZA) against ST131 strains is undefined. We determined CZA MICs for 595 E. coli clinical isolates from 24 Veterans Affairs Medical Centers (2010-2011). Resistance status and MICs were compared with study resistance category (fluoroquinolone-susceptible, fluoroquinolone-resistant, and extended-spectrum beta-lactamase (ESBL)-producing); ST131, H30R1, and H30Rx status; blaCTX-M-15-like genotype; and MICs for piperacillin-tazobactam, levofloxacin, gentamicin, ceftazidime, and meropenem. Proportion resistant ranged from zero (CZA, meropenem) to 61% (levofloxacin). MICs generally increased by resistance category (from fluoroquinolone-susceptible through fluoroquinolone-resistant to ESBL), clonal subgroup (from non-ST131-H30 through H30R1 to H30Rx), and blaCTX-M-15-like status. CZA MICs were slightly but significantly greater in association with resistance (or elevated MICs) to each comparator yet remained in the susceptible range. CZA was reliably active and outperformed noncarbapenem comparators, so it should prove useful as a carbapenem-sparing alternative.