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BACKGROUND The medical establishment continues to be complicit in the degradation of native peoples of the United States through the use of the racist phrase “red man syndrome” (RMS) to describe the histamine-release syndrome that accompanies vancomycin infusion. METHODS Five months after the transition from 1 electronic health record to another at our freestanding children’s hospital, our antimicrobial stewardship team reviewed all active allergy records to identify and then replace use of RMS terminology with preferred alternative “vancomycin flushing syndrome.” In partnership with institutional stakeholders, we also launched an educational campaign and instituted in the electronic health record an autocorrect functionality to prevent new RMS entries. RESULTS We identified allergy records for 21 034 individual patients. Vancomycin was an allergen for 445 (2.1%) patients, and RMS-related terminology appeared in 274 (61.6%) of these records; we replaced all RMS instances with the vancomycin flushing syndrome term. During the 3-month period after the intervention, we identified allergy records for 8648 additional patients, with vancomycin as allergen in 65 (0.7%) and with RMS terminology identified and replaced in 29 (44.6%). In addition to the lower rate of RMS among allergy records after the intervention, we detected 3 instances of alternative terminology use. CONCLUSIONS Implementing an institutional-level change in terminology, even for racist language, requires education, reinforcement, and continued surveillance. To effectively replace this term, we need the support of national stakeholders to remove this language from our medical education systems, our textbooks, and our clinical lexicon.

BackgroundFluoroquinolone use for urinary tract infections has been steadily declining. Gut microbiota is the main reservoir for uropathogenicEscherichia colibut whether the carriage of fluoroquinolone-resistantE. colihas been changing is unknown.MethodsWe determined the frequency of isolation and other characteristics ofE. colinonsuceptible to fluoroquinolones (at ≥0.5 mg/L of ciprofloxacin) in 515 and 1605E. coli-positive fecal samples collected in 2015 and 2021, respectively, from non-antibiotic-taking women of age 50+ receiving care in the Seattle area Kaiser Permanente Washington healthcare system.ResultsBetween 2015 and 2021 the prescription of fluoroquinolones dropped nearly three-fold in the study population. During the same period, the rates of gut carriage of fluoroquinolone-resistantE. coliincreased from 14.4 % to 19.9% (P=.005), driven by a significant increase of isolates from the recently emerged, pandemic multi-drug resistant clonal group ST1193 (1.7% to 4.3%; P=.007) and those with an incomplete set of or no fluoroquinolone-resistance determining mutations (2.3% to 7.5%; PConclusionDespite reduction in fluoroquinolone prescriptions, gut carriage of fluoroquinolone-resistant uropathogenicE. coliincreased with a rise of previously sporadic lineages and co-resistance to third generation cephalosporins. Thus, to reduce the rates of antibiotic resistant urinary tract infections, greater focus should be on controlling the gut carriage of resistant bacteria.Short summaryWhile prescription of fluoroquinolones dropped between 2015 and 2021, there was an increase in gut carriage of fluoroquinolone-resistantEscherichia coliamong women of age 50+. Also, a rise of new resistant lineages and co-resistance to 3rdgeneration cephalosporins occurred.

The Practice Guidelines Committee of the American Society of Transplantation and Cellular Therapy partnered with its Transplant Infectious Disease Special Interest Group to update its 2009 compendium-style infectious diseases guidelines for hematopoietic cell transplantation (HCT). A completely fresh approach was taken, with the goal of better serving clinical providers by publishing each stand-alone topic in the infectious diseases series in a concise format of frequently asked questions (FAQs), tables, and figures [1]. Adult and pediatric infectious diseases and HCT content experts developed and then answered FAQs, and then finalized topics with harmonized recommendations that were made by assigning a strength of recommendation ranging from A to E paired with a level of supporting evidence graded I to III. The first topic in the series focuses on potentially life-threatening infections in HCT caused by Enterobacterales, relevant infection risk factors, and practical considerations regarding prevention and treatment of these infections in the setting of emerging multidrug resistance.

Background:Carbapenem-resistant Enterobacterales (CRE) are common causes of healthcare-associated infections and are often multidrug resistant with limited therapeutic options. Additionally, CRE can spread within and between healthcare facilities, amplifying potential harms.Objective:To better understand the burden, risk factors, and source of acquisition of carbapenemase genes in clinical Escherichia coli and Klebsiella spp isolates from patients in Washington to guide prevention efforts.Design:Multicenter prospective surveillance study.Methods:Escherichia coli and Klebsiella spp isolates meeting the Washington state CRE surveillance case definition were solicited from clinical laboratories and tested at Washington Public Health Laboratories using polymerase chain reaction (PCR) for the 5 most common carbapenemase genes: blaKPC, blaNDM, blaIMP, blaVIM, and blaOXA-48. Case patients positive by PCR were investigated by the public health department.Results:From October 2012 through December 2017, 363 carbapenem-resistant E. coli and Klebsiella spp isolates were tested. Overall, 45 of 115 carbapenem-resistant K. pneumoniae (39%), 1 of 8 K. oxytoca (12.5%), and 28 of 239 carbapenem-resistant E. coli (11.7%) were carbapenemase positive. Of 74 carbapenemase-positive isolates, blaKPC was most common (47%), followed by blaNDM (30%), blaOXA-48 (22%), and blaIMP (1%). Although all cases had healthcare exposure, blaKPC acquisition was associated with US health care, whereas non-blaKPC acquisition was associated with international health care or travel.Conclusions:We report that blaKPC, the most prevalent carbapenemase in the United States, accounts for nearly half of carbapenemase cases in Washington state and that most KPC-cases are likely acquired through in-state health care.

E. coli was isolated from the Salish Sea (Puget Sound) ecosystem, including samples of marine and fresh water, and wildlife dependent on this environment. E. coli isolates were assessed for phenotypic and genotypic resistance to antibiotics. A total of 305 E. coli isolates was characterized from samples collected from: marine water obtained in four quadrants of the Salish Sea, select locations near beaches, fresh water from streams near marine beaches, and fecal samples from harbor porpoises (Phocoena phocoena), harbor seals (Phoca vitulina), river otters (Lontra canadensis), and English sole (Parophrys vetulus). Isolates were evaluated using antimicrobial susceptibility typing, whole-genome sequencing, fumC, and multilocus sequence typing. Resistance and virulence genes were identified from sequence data. Of the 305 isolates from Salish Sea samples, 20 (6.6%) of the E. coli were intermediate, and 31 (10.2%) were resistant to ≥1 class of antibiotics, with 26.9% of nonsusceptible (resistant and intermediate resistant) E. coli isolates from marine mammals and 70% from river otters. The proportion of nonsusceptible isolates from animals was significantly higher than samples taken from marine water (p &lt, 0.0001). A total of 196 unique STs was identified including 37 extraintestinal pathogenic E. coli (ExPEC)-associated STs [ST10, ST38, ST58, ST69, ST73, ST117, ST131, and ST405]. The study suggests that animals may be potential sentinels for antibiotic-resistant and ExPEC E. coli in the Salish Sea ecosystem.

The significance of pneumatosis intestinalis (PI) in pediatric patients following hematopoietic stem cell transplantation (HSCT) is poorly understood. A knowledge gap remains with respect to the etiology, risk factors, and evidence-based treatment of these patients. As a result, management is frequently based on each center's clinical practice, without standardization across treatment centers. In this single-center trial, we aimed to validate both previously proposed and additional risk factors for the development of PI and to examine our management and outcomes for these patients. We performed a retrospective case-control study examining risk factors for the development of PI in pediatric HSCT patients at a single tertiary referral children's hospital. We used univariate and multivariable conditional logistic regression analysis to explore differences in pharmacologic and other transplantation-specific risk factors. Between 2012 and 2019, PI was diagnosed in 212 patients at our pediatric hospital, of whom 42 were HSCT recipients. The majority of patients (88%; n = 37 of 42) with PI were diagnosed by X-ray. Eighteen patients (43%) were asymptomatic and diagnosed incidentally after imaging was obtained for standard post-transplantation surveillance or other nonrelated indications. All patients with PI were hospitalized and placed on strict bowel rest while receiving parenteral nutrition and antibiotics. Recurrence of PI occurred in 4 patients (10%) following their initial diagnosis. Increased doses of steroid exposure within 30 days of PI diagnosis (odds ratio [OR], 5.7; 95% confidence interval [CI], 2.1 to 15.3; P = .0006), presence of grade II-IV gastrointestinal acute graft-versus-host disease (GVHD) (OR, 5.3; 95% CI, 1.0 to 28.1; P = .05), and receipt of50% of total daily nutrition by nasogastric (NG) tube feeds (OR, 22.0; 95% CI, 1.3 to 370.2; P = .03) were identified as independent risk factors for the development of PI. Intensity of the conditioning regimen, exposure to total body irradiation, stem cell source, donor type, HLA matching, use of mycophenolate mofetil, and presence of bacterial or viral infection at the time of PI diagnosis were not demonstrably associated with the development of PI in our study. We conclude that development of asymptomatic PI is a benign condition following HSCT, and that the risk for PI is increased in patients with gastrointestinal GVHD, patients receiving steroid therapy, and patients relying on supplemental NG tube feeds for at least one-half of their total daily nutrition.

Background Management of acute, uncomplicated cystitis in outpatients benefits from knowledge of drug resistance patterns in the population. However, antibiograms are often not available for the outpatient setting, and the role of host factors such as sex and age in assessing the likelihood of resistance are not well understood. We investigated whether antibiotic resistance patterns of outpatient urinary Escherichia coli isolates vary by age group and sex in a large database of antibiotic susceptibility test (AST) results from Washington State. Methods We retrospectively analyzed AST data for outpatient urinary E. coli isolates in Washington State tested at a clinical reference laboratory from 2013 to 2017. In logistic regression models stratified by sex, we tested the associations of antibiotic resistance with patient age. Results We found females >50 years had greater odds than females younger than 19 for resistance to amoxicillin-clavulanate (odds ratio [OR], 1.43; 95% confidence interval [CI], 1.22–1.69), ciprofloxacin (OR, 3.04; 95% CI, 2.48–3.74), ceftriaxone (OR, 2.58; 95% CI, 1.77–3.92), and gentamicin (OR, 1.62; 95% CI, 1.27–2.08) (all P < .001). Compared to males younger than 19, males >50 years had greater odds of resistance to ciprofloxacin (OR, 2.59; 95% CI, 1.18–5.69) and lower odds of resistance to amoxicillin-clavulanate (OR, 0.56; 95% CI, .34–.96) (all P < .05). Conclusions These findings demonstrate that age and sex are associated with variability in antibiotic resistance patterns in the outpatient setting. Availability of outpatient antibiotic resistance data based on sex and age may be useful to inform empiric prescribing for outpatient UTIs and to support antibiotic stewardship efforts.

Carbapenem-resistant Enterobacterales (CRE) are common causes of healthcare-associated infections and are often multidrug resistant with limited therapeutic options. Additionally, CRE can spread within and between healthcare facilities, amplifying potential harms.To better understand the burden, risk factors, and source of acquisition of carbapenemase genes in clinical Escherichia coli and Klebsiella spp isolates from patients in Washington to guide prevention efforts.Multicenter prospective surveillance study.Escherichia coli and Klebsiella spp isolates meeting the Washington state CRE surveillance case definition were solicited from clinical laboratories and tested at Washington Public Health Laboratories using polymerase chain reaction (PCR) for the 5 most common carbapenemase genes: blaKPC, blaNDM, blaIMP, blaVIM, and blaOXA-48. Case patients positive by PCR were investigated by the public health department.From October 2012 through December 2017, 363 carbapenem-resistant E. coli and Klebsiella spp isolates were tested. Overall, 45 of 115 carbapenem-resistant K. pneumoniae (39%), 1 of 8 K. oxytoca (12.5%), and 28 of 239 carbapenem-resistant E. coli (11.7%) were carbapenemase positive. Of 74 carbapenemase-positive isolates, blaKPC was most common (47%), followed by blaNDM (30%), blaOXA-48 (22%), and blaIMP (1%). Although all cases had healthcare exposure, blaKPC acquisition was associated with US health care, whereas non-blaKPC acquisition was associated with international health care or travel.We report that blaKPC, the most prevalent carbapenemase in the United States, accounts for nearly half of carbapenemase cases in Washington state and that most KPC-cases are likely acquired through in-state health care.

Objective In this report, we aim to describe the epidemiology of extended-spectrum cephalosporin-resistant (ESC-R) and carbapenem-resistant (CR) Enterobacteriaceae infections in children. Methods ESC-R and CR Enterobacteriaceae isolates from normally sterile sites of patients aged

Background Limited studies have investigated the microbial diversity of wild marine mammals. Objectives This study characterized Escherichia coli isolates collected from fresh faecal samples of endangered southern resident killer whales (Orcinus orca) located by detection dogs. Methods WGS of each strain was done to determine ST (using MLST), clonotype (C:H), antimicrobial resistance and virulence profile. Conjugation experiments were done to determine the mobility of the tet(B) tetracycline resistance gene. Results All isolates belonged to extraintestinal pathogenic E. coli (ExPEC) clonal lineages ST73 (8/9) and ST127 (1/9), often associated with human community-acquired urinary tract disease. Clonotyping using fumC and fimH alleles showed divergence in clonal lineages, with ST73 isolates belonging to the C24:H10 clade and the ST127 isolate belonging to C14:H2. The eight ST73 isolates carried multiple acquired antibiotic resistance genes, including aadA1, sul1 and tet(B), encoding aminoglycoside, sulphonamide and tetracycline resistance, respectively. Conjugative transfer of the resistance gene tet(B) was observed for three of the eight isolates. ST127 did not carry any of these acquired resistance genes. Virulence-associated genes identified included those encoding adhesins (iha, papC, sfaS), toxins (sat, vat, pic, hlyA, cnf1), siderophores (iutA, fyuA, iroN, ireA), serum survival/protectins (iss, ompT), capsule (kpsM) and pathogenicity island marker (malX). Conclusions Orca whales can carry antibiotic-resistant potentially pathogenic strains of E. coli. Possible sources include contamination of the whale’s environment and/or food. It is unknown whether these isolates cause disease in southern resident killer whales, which could contribute to the ongoing decline of this critically endangered population.

Although carbapenem-resistant Enterobacteriaceae (CRE) have been recognised worldwide, there are important gaps in regional prevalence data. This study sought to determine the occurrence and type of CRE in the Cincinnati tri-state region. Clinical microbiology laboratories in the region screened patient stool and rectal swab samples using chromogenic screening agar. Isolates of Enterobacteriaceae resistant to carbapenems were characterised using molecular methods. Area institutions screened 1939 patient samples. Of 18 Enterobacteriaceae that grew on the screening agar, 8 isolates were resistant to one or all carbapenems and 6 isolates (all Klebsiella spp.) tested positive for a blaKPC gene. This study provides guidance on the prevalence of KPC and the genetic characteristics of carbapenem-resistant Klebsiella pneumoniae isolates in the Cincinnati tri-state area. Additional similar local epidemiology studies are warranted to provide an understanding and control of the spread of CRE.

We used the Pediatric Health Information System database to assess the use of antibiotics reserved for the treatment of resistant Gram-negative infections in children from 2004 to 2014. Overall, use of these agents increased in children from 2004 to 2007 and subsequently decreased.Infect Control Hosp Epidemiol 2016:37:967–970

Multi-locus sequence typing (MLST) is a useful system for phylogenetic and epidemiological studies of multidrug-resistant Escherichiacoli. Most studies utilize a seven-locus MLST, but an alternate two-locus typing method (fumC and fimH; CH typing) has been proposed that may offer a similar degree of discrimination at lower cost. Herein, we compare CH typing to the standard seven-locus method for typing commensal E. coli isolates from dairy cattle. In addition, we evaluated alternative combinations of eight loci to identify combinations that maximize discrimination and congruence with standard seven-locus MLST among commensal E. coli while minimizing the cost. We also compared both methods when used for typing uropathogenic E. coli (UPEC). CH typing was less discriminatory for commensal E. coli than the standard seven-locus method (Simpson's Index of Diversity=0.933 [0.902-0.964] and 0.97 [0.96-0.979], respectively). Combining fimH with housekeeping gene loci improved discriminatory power for commensal E. coli from cattle but resulted in poor congruence with MLST. We found that a four-locus typing method including the housekeeping genes adk, purA, gyrB and recA could be used to minimize cost without sacrificing discriminatory power or congruence with Achtman seven-locus MLST when typing commensal E. coli.

Background The H30 subclone within Escherichia coli sequence type 131 (ST131-H30) has emerged rapidly to become the leading antibiotic-resistant E. coli strain. Hypervirulence, multidrug resistance, and opportunism have been proposed as explanations for its epidemic success. Methods We assessed 1133 consecutive unique E. coli clinical isolates from 5 medical centers (2010-2011) for H30 genotype, which we compared with epidemiological and clinical data extracted from medical records by blinded reviewers. Using univariable and multivariable logistic regression analysis, we explored associations of H30 with underlying host characteristics, clinical presentations, management, and outcomes, adjusting for host characteristics. Results The H30 (n = 107) isolates were associated with hosts who were older, male, locally and systemically compromised, and healthcare and antibiotic exposed. With multivariable adjustment for host factors, H30 lost its numerous significant univariable associations with initial clinical presentation, but remained strongly associated with clinical persistence (odds ratio [OR], 3.47; 95% confidence interval [CI], 1.89-6.37), microbiological persistence (OR, 4.46; 95% CI, 2.38-8.38), subsequent hospital admission (OR, 2.68; 95% CI, 1.35-5.33), and subsequent new infection (OR, 1.73; 95% CI, 1.01-3.00). These host-adjusted associations remained strong even with added adjustment for resistance to the initially prescribed antibiotics, and the adverse outcome associations (subsequent hospital admission, new infection) were independent of clinical and microbiological persistence. Conclusions In addition to targeting compromised hosts and resisting multiple antibiotics, H30 isolates may have an intrinsic ability to cause highly persistent infections and later adverse outcomes. The basis for these host- and resistance-independent associations is unclear, but they should be considered when managing patients with H30 infections.

Administrative data are often used as a proxy for medication-administration record (MAR) data. Multicenter MAR data were compared retrospectively with administrative data from January 2010 through June 2013 from the Pediatric Health Information Systems database. We found that administrative data were more concordant with bill-upon-administration than bill-upon-dispense data.

The first Oregon case of New Delhi metallo-β-lactamase-1 (NDM-1)-producing Escherichia coli was reported during November 2013. Epidemiologic investigation revealed only local outpatient medical care and no travel outside Oregon for both the patient and his household contact. Environmental sampling discovered a matching isolate from the patient’s household vacuum cleaner, suggesting environmental persistence.

Background Annual cumulative antibiograms are routinely used by clinicians to guide selection of empirical antibiotic therapies. CLSI guidelines recommend that these antibiograms to analyze data yearly, include only final, verified results, include bacterial species with > 30 isolates and to include only the first isolate for each species/patient instance per analysis period. Handling multiple isolates from individual patients in cumulative antibiograms is a controversial topic within the antimicrobial stewardship community. Current practice favors removing subsequent isolates, thereby discarding data reflecting impact of selective antibiotic pressure on resistance patterns in recurring urinary tract infection (UTI). In this study we analyzed a five-year data set of deidentified outpatient antibiotic results from a commercial laboratory to determine whether there were significant differences in resistance patterns between first and subsequent isolates from the same patient. Methods The 5-year antibiotic susceptibility data was restricted to urinary Escherichia coli (EC) isolates. Patient occurrence(s) of urinary EC were categorized by frequency: 1st occurrence, 2nd occurrence, 3rd occurrence, and 4th or greater occurrence. A logistic regression analysis using a binary outcome for resistance and independent variable of patient isolate occurrence was run for amoxicillin-clavulanate, ampicillin, ceftriaxone, ciprofloxacin, gentamicin, levofloxacin, nitrofurantoin, and trimethoprim-sulfa. Results From a logistic regression analysis, we estimate that for each occurrence in the data, an isolate’s odds of resistance were higher for every increase in a patient’s number of occurrences in the data for all antibiotics reported with p values < 0.0001. Table 1: Odds ratios (OR) of resistance for each subsequent urinary EC isolate occurrence over 5 years Conclusion Our findings suggest that individuals with higher numbers of urinary EC occurrences have more resistant EC than the first EC occurrence, with effects that vary by antibiotic class. Although traditional antibiograms include only the first occurrence of urinary EC from a single patient, this approach may underestimate levels of reservoir resistance in a community. Such an underestimation likely impacts efficacy of empiric therapeutic choice, healthcare outcomes, and cost. Disclosures All Authors: No reported disclosures

We describe the rapid and ongoing emergence across multiple US cities of a new multidrug-resistant Escherichia coli clone-sequence type (ST) 1193-resistant to fluoroquinolones (100%), trimethoprim-sulfamethoxazole (55%), and tetracycline (53%). ST1193 is associated with younger adults (age

Objectives Children with urinary tract infection (UTI) are often diagnosed in emergency and urgent care settings and increasingly are unnecessarily treated with broad-spectrum antibiotics. This study evaluated the effect of a quality improvement intervention on empiric antibiotic prescribing for the treatment of uncomplicated UTI in children. Methods A local clinical pathway for uncomplicated UTI, introduced in June 2010, recommended empiric treatment with cephalexin, a narrow-spectrum (first-generation) cephalosporin antibiotic. A retrospective quasi-experimental study of pediatric patients older than 1 month presenting to emergency and urgent care settings from January 1, 2009, to December 31, 2014, with uncomplicated UTI was conducted. Hospitalized patients and those with chronic conditions or urogenital abnormalities were excluded. Control charts and interrupted time-series analysis were used to analyze the primary outcome of narrow-spectrum antibiotic prescribing rates and the balancing measures of 72-hour revisits, resistant bacterial isolates, and subsequent inpatient admissions for UTI. Results A total of 2134 patients were included. There was an immediate and sustained significant increase in cephalexin prescribing before (19.2%) versus after (79.6%) pathway implementation and a concurrent significant decline in oral third-generation cephalosporin (cefixime) prescribing from 50.3% to 4.0%. There was no significant increase in 72-hour revisits, resistant bacterial isolates, or inpatient admissions for UTI. Conclusions A clinical pathway produced a significant and sustained increase in narrow-spectrum empiric antibiotic prescribing for pediatric UTI. Increased empiric cephalexin prescribing did not result in increased treatment failures or adverse patient outcomes. Future studies on implementing clinical pathways for children outside a pediatric hospital network are needed.

Laboratory interpretation of susceptibility data concerning the AmpC-producing Enterobacteriaceae is confusing to clinicians. Typical organisms included in this category are Enterobacter cloacae, Enterobacter aerogenes, Citrobacter freundii, Morganella morganii, and Serratia marcescens. These organisms frequently appear susceptible to extended spectrum cephalosporins by standard in vitro testing, although this is highly contested by treatment failures in cases of invasive infections. The mechanisms of resistance were postulated to be ampC induction or de-repression during therapy. As an alternative to carbapenems, piperacillin-tazobactam has been commonly used for its apparent activities against AmpC producers. In this laboratory study, when cefoxitin was used as an ampC-inducing agent in vitro, piperacillin-tazobactam showed activity in only a limited number of AmpC producers. Most notably, a temporal disc co-diffusion method detected inducible piperacillin- tazobactam resistance in all 20 strains of S. marcescens tested. With more standardized measurement, this method improves our previous Kirby-Bauer disc approximation method for the detection of ampC-mediated inducible resistance.

BACKGROUND AND OBJECTIVE: Single-center evaluations of pediatric antimicrobial stewardship programs (ASPs) suggest that ASPs are effective in reducing and improving antibiotic prescribing, but studies are limited. Our objective was to compare antibiotic prescribing rates in a group of pediatric hospitals with formalized ASPs (ASP+) to a group of concurrent control hospitals without formalized stewardship programs (ASP−). METHODS: We evaluated the impact of ASPs on antibiotic prescribing over time measured by days of therapy/1000 patient-days in a group of 31 freestanding children’s hospitals (9 ASP+, 22 ASP−). We compared differences in average antibiotic use for all ASP+ and ASP− hospitals from 2004 to 2012 before and after release of 2007 Infectious Diseases Society of America guidelines for developing ASPs. Antibiotic use was compared for both all antibacterials and for a select subset (vancomycin, carbapenems, linezolid). For each ASP+ hospital, we determined differences in the average monthly changes in antibiotic use before and after the program was started by using interrupted time series via dynamic regression. RESULTS: In aggregate, as compared with those years preceding the guidelines, there was a larger decline in average antibiotic use in ASP+ hospitals than in ASP− hospitals from 2007 to 2012, the years after the release of Infectious Diseases Society of America guidelines (11% vs 8%, P = .04). When examined individually, relative to preimplementation trends, 8 of 9 ASP+ hospitals revealed declines in antibiotic use, with an average monthly decline in days of therapy/1000 patient-days of 5.7%. For the select subset of antibiotics, the average monthly decline was 8.2%. CONCLUSIONS: Formalized ASPs in children’s hospitals are effective in reducing antibiotic prescribing.

Objectives In vitro trends of cefazolin and ceftriaxone susceptibilities from pediatric clinical isolates of methicillin-susceptible Staphylococcus aureus (MSSA) between 2011 and 2016 were analyzed for surveillance. Methods Our laboratory continues to use agar disk diffusion for staphylococcal susceptibilities applying Clinical Laboratory Standard Institute’s 2012 breakpoints. Results A total of 3992 MSSA clinical isolates in the last 6 years were analyzed for their in vitro cefazolin and ceftriaxone susceptibilities. While all MSSA isolates exhibited cefazolin susceptibilities within the “susceptible” zone range, there have been a proportion of isolates with ceftriaxone susceptibilities falling in “intermediate” zones, ranging from 2.6% in 2011 to 8.3% in 2016. Conclusions Cefazolin continues to be the recommended agent for MSSA treatment at our institution, reflected by the finding that only 2% (6/321) of patients who received ceftriaxone as definitive therapy for MSSA bacteremia during the study period. We have confirmed the cefoxitin-predicted MSSA susceptibility to cefazolin, but have found concerning drifts in ceftriaxone susceptibilities by continued in vitro monitoring over the last 6 years. Electronic supplementary material The online version of this article (10.1186/s12941-018-0257-x) contains supplementary material, which is available to authorized users.

Background Escherichia coli sequence type (ST) 131-H30 is a globally important pathogen implicated in rising rates of multidrug resistance among E. coli causing extraintestinal infections. Previous studies have focused on adults, leaving the epidemiology of H30 among children undefined. Methods We used clinical data and isolates from a case-control study of extended-spectrum cephalosporin-resistant E. coli conducted at 4 US children's hospitals to estimate the burden and identify host correlates of infection with H30. H30 isolates were identified using 2-locus genotyping; host correlates were examined using log-binomial regression models stratified by extended-spectrum cephalosporin resistance status. Results A total of 339 extended-spectrum cephalosporin-resistant and 1008 extended-spectrum cephalosporin-susceptible E. coli isolates were available for analyses. The estimated period prevalence of H30 was 5.3% among all extraintestinal E. coli isolates (95% confidence interval [CI], 4.6%-7.1%); H30 made up 43.3% (81/187) of extended-spectrum β-lactamase (ESBL)-producing isolates in this study. Host correlates of infection with H30 differed by extended-spectrum cephalosporin resistance status: Among resistant isolates, age ≤5 years was positively associated with H30 infection (relative risk [RR], 1.83 [95% CI, 1.19-2.83]); among susceptible isolates, age ≤5 years was negatively associated with H30 (RR, 0.48 [95% CI, .27-.87]), while presence of an underlying medical condition was positively associated (RR, 4.49 [95% CI, 2.43-8.31]). Conclusions ST131-H30 is less common among extraintestinal E. coli collected from children compared to reported estimates among adults, possibly reflecting infrequent fluoroquinolone use in pediatrics; however, it is similarly dominant among ESBL-producing isolates. The H30 subclone appears to disproportionately affect young children relative to other extended-spectrum cephalosporin-resistant E. coli.

BackgroundE. coli ST131-H30 is a globally important pathogen implicated in rising rates of multidrug resistance among E. coli causing extraintestinal infections. Previous studies have focused on adults, leaving the epidemiology of H30 among children undefined.MethodsWe used clinical data and isolates from a case-control study of extended-spectrum cephalosporin-resistant E. coli conducted at four US children’s hospitals to estimate the burden and identify host correlates of infection with H30. H30 isolates were identified using two-locus genotyping; host correlates were examined using log-binomial regression models stratified by extended-spectrum cephalosporin resistance status.ResultsA total of 339 extended-spectrum cephalosporin-resistant and 1008 extended-spectrum cephalosporin-susceptible E. coli isolates were available for analyses. The estimated period prevalence of H30 was 5.3% among all extraintestinal E. coli isolates (95% confidence interval [CI] 4.6%-7.1%); H30 made up 43.3% (81/187) of ESBL-producing isolates in this study. Host correlates of infection with H30 differed by extended-spectrum cephalosporin resistance status: among resistant isolates, age ≤5 years was positively associated with H30 infection (relative risk [RR] 1.83, 95% CI 1.19-2.83); among susceptible isolates, age ≤5 years was negatively associated with H30 (RR 0.48, 95% CI 0.27-0.87), while presence of an underlying medical condition was positively associated (RR 4.49, 95% CI 2.43-8.31).ConclusionsST131-H30 is less common among extraintestinal E. coli collected from children compared to reported estimates among adults, possibly reflecting infrequent fluoroquinolone use in pediatrics; however, it is similarly dominant among ESBL-producing isolates. The H30 subclone appears to disproportionately affect young children relative to other extendedspectrum cephalosporin-resistant E. coli.SummaryST131-H30 was responsible for 5.3% of all extraintestinal E. coli infections and 43.3% of ESBL-producing extraintestinal E. coli infections among US children. The clinical and demographic correlates of infection with ST131-H30 differed between extended-spectrum cephalosporin-resistant and -sensitive isolates.

The objective of this study was to assess the association between previous antibiotic use, particularly long-term prophylaxis, and the occurrence of subsequent resistant infections in children with index infections due to extended-spectrum-cephalosporin-resistant Enterobacteriaceae . We also investigated the concordance of the index and subsequent isolates. Extended-spectrum-cephalosporin-resistant Escherichia coli and Klebsiella spp. isolated from normally sterile sites of patients aged fumC-fimH ( E. coli ) or tonB ( Klebsiella pneumoniae ) type were identical to those of the index isolate. In total, 323 patients had 396 resistant isolates; 45 (14%) patients had ≥1 subsequent resistant infection, totaling 73 subsequent resistant isolates. The median time between the index and first subsequent infections was 123 (interquartile range, 43 to 225) days. In multivariable Cox proportional hazards analyses, patients were 2.07 times as likely to have a subsequent resistant infection (95% confidence interval, 1.11 to 3.87) if they received prophylaxis in the 30 days prior to the index infection. In 26 (58%) patients, all subsequent isolates were concordant with their index isolate, and 7 (16%) additional patients had at least 1 concordant subsequent isolate. In 12 of 17 (71%) patients with E. coli sequence type 131 (ST131)-associated type 40-30, all subsequent isolates were concordant. Subsequent extended-spectrum-cephalosporin-resistant infections are relatively frequent and are most commonly due to bacterial strains concordant with the index isolate. Further study is needed to assess the role prophylaxis plays in these resistant infections.

The objective of this study is to describe the epidemiology of intestinal carriage with extended-spectrum-cephalosporin-resistant Enterobacteriaceae in children with index infections with these organisms. Patients with resistant Escherichia coli or Klebsiella bacteria isolated from the urine or a normally sterile site between January 2006 and December 2010 were included in this study. Available infection and stool isolates underwent phenotypic and molecular characterization. Clinical data relevant to the infections were collected and analyzed. Overall, 105 patients were identified with 106 extended-spectrum-cephalosporin-resistant E. coli ( n = 92) or Klebsiella ( n = 14) strains isolated from urine or a sterile site. Among the 27 patients who also had stool screening for resistant Enterobacteriaceae , 17 (63%) had intestinal carriage lasting a median of 199 days (range, 62 to 1,576). There were no significant differences in demographic, clinical, and microbiological variables between those with and those without intestinal carriage. Eighteen (17%) patients had 37 subsequent resistant Enterobacteriaceae infections identified: 31 urine and 6 blood. In a multivariable analysis, antibiotic intake in the 91 days prior to subsequent urine culture was significantly associated with subsequent urinary tract infection with a resistant organism (hazard ratio, 14.3; 95% confidence interval [CI], 1.6 to 130.6). Intestinal carriage and reinfection were most commonly due to bacterial strains of the same sequence type and with the same resistance determinants as the index extended-spectrum-cephalosporin-resistant Enterobacteriaceae , but carriage and reinfection with different resistant Enterobacteriaceae strains also occurred.

BACKGROUND: Empirical combination antibiotic regimens consisting of a β-lactam and an aminoglycoside are frequently employed in the pediatric population. Data to demonstrate the comparative benefit of empirical β-lactam combination therapy relative to monotherapy for culture-proven Gram-negative bacteremia are lacking in the pediatric population. METHODS: We conducted a retrospective cohort study of children treated for Gram-negative bacteremia at The Johns Hopkins Hospital from 2004 through 2012. We compared the estimated odds of 10-day mortality and the relative duration of bacteremia for children receiving empirical combination therapy versus empirical monotherapy using 1:1 nearest-neighbor propensity-score matching without replacement, before performing regression analysis. RESULTS: We identified 226 matched pairs of patients well balanced on baseline covariates. Ten-day mortality was similar between the groups (odds ratio, 0.84; 95% confidence interval [CI], 0.28 to 1.71). Use of empirical combination therapy was not associated with a decrease in the duration of bacteremia (−0.51 days; 95% CI, −2.22 to 1.48 days). There was no survival benefit when evaluating 10-day mortality for the severely ill (pediatric risk of mortality III score ≥15) or profoundly neutropenic patients (absolute neutrophil count ≤100 cells/mL) receiving combination therapy. However, a survival benefit was observed when empirical combination therapy was prescribed for children growing multidrug-resistant Gram-negative organisms from the bloodstream (odds ratio, 0.70; 95% CI, 0.51 to 0.84). CONCLUSIONS: Although there appears to be no advantage to the routine addition of an aminoglycoside to a β-lactam as empirical therapy for children who have Gram-negative bacteremia, children who have risk factors for MDRGN organisms appear to benefit from this practice.

Klebsiella pneumoniae causes a range of clinical disease in paediatric patients and is of increasing concern due to growing antibiotic resistance, yet little is known about the relative distribution of commensal and pathogens throughout the population structure of K. pneumoniae. We conducted a prospective, observational study of 92 isolates from Seattle Children’s Hospital, including 49 disease isolates from blood and urine (13 and 36 isolates, respectively) and 43 colonization isolates from stool. Susceptibility to 20 antimicrobials was evaluated using disc diffusion, VITEK 2 and Etest. Strain relatedness was investigated using multilocus sequence typing (MLST). Demographic and clinical characteristics were largely similar between disease and colonization cohorts, with 85.7 and 74.4 % of disease and colonization cohort patients, respectively, having an underlying medical condition; the sole exception was a relative abundance of patients with urologic or renal abnormalities in the disease cohort, consistent with the predominance of urine specimens among the disease isolates. With regard to antibiotic susceptibility properties, no significant differences were noted between the disease and colonization cohorts. Using molecular analysis, 71 unique sequence types (STs) were distinguished, with novel MLST findings evident in both cohorts; 43 (46.7 %) isolates represented novel STs, including 22 with a novel allele sequence. Thirteen STs contained multiple isolates and all seven isolates with resistance to three or more antibiotic classes were within one of four multirepresentative STs. This study demonstrates that nearly half of paediatric Klebsiella isolates represent novel STs, with clustering of multidrug resistance within specific STs. These findings expand our understanding of the intersection of bacterial population structure, human colonization ecology and multidrug resistance in K. pneumoniae.

Background Antibiotic-resistant E. coli (EC) infections represent a major cause of morbidity and mortality, and pose a challenge to antibiotic stewardship. At present, clinicians in outpatient facilities may not have access to local antibiogram data to guide stewardship. Additionally, antibiotic resistance may vary between types of outpatient practices. Methods Using the database of a major clinical reference lab, this study analyzed several years of antibiotic susceptibility results for outpatient urinary EC isolates from Washington State. We compared rates of resistance to antibiotics between different types of outpatient practices, categorized using a modification of published ambulatory practice categories. Logistic regression was used to examine the association of outpatient practice type with antibiotic resistance, controlling year, sex, and age. Results After adjusting for year, sex, and age, logistic regression found significantly higher odds of resistance in urology compared with the reference groups of general family practice for ampicillin (OR 1.35), ciprofloxacin (OR 2.27), trimethoprim-sulfa (OR 1.51) and gentamicin (OR 1.73). We also saw increased odds of resistance to ciprofloxacin in patients from an oncology clinic (OR 1.56) as well as patients from “All other specialties” (OR 1.37). A lower odds of resistance was found in OBGYN clinics for ampicillin (OR 0.86), trimethoprim-sulfa (0.81) while a greater odds or resistance in OBGYN clinics was found for nitrofurantoin (OR 1.36). Conclusion Antibiotic resistance in EC urinary isolates can vary across types of outpatient practices according to clinical practice type. This may reflect differences in patient morbidity and/or differences in antibiotic stewardship practices and deserves further investigation. Patients with recurrent cases of resistant UTIs are generally referred to a urologist, and this was reflected in our data as there a higher odds of resistance was found in urology clinics. Similarly, we found higher odds of resistance into nitrofurantoin, a commonly prescribed antibiotic for UTIs in pregnant women, in OBGYN clinics that may reflect prescribing practices. Use of clinical data to create facility and specialty-specific antibiograms in outpatient settings may enable improved and “precise” antibiotic stewardship. Disclosures All authors: No reported disclosures.

The ability to identify bacterial pathogens at the subspecies level in clinical diagnostics is currently limited. We investigated whether splitting Escherichia coli species into clonal groups (clonotypes) predicts antimicrobial susceptibility or clinical outcome. A total of 1,679 extraintestinal E. coli isolates (collected from 2010 to 2012) were collected from one German and 5 U.S. clinical microbiology laboratories. Clonotype identity was determined by fumC and fimH (CH) sequencing. The associations of clonotype with antimicrobial susceptibility and clinical variables were evaluated. CH typing divided the isolates into >200 CH clonotypes, with 93% of the isolates belonging to clonotypes with ≥2 isolates. Antimicrobial susceptibility varied substantially among clonotypes but was consistent across different locations. Clonotype-guided antimicrobial selection significantly reduced “drug-bug” mismatch compared to that which occurs with the use of conventional empirical therapy. With trimethoprim-sulfamethoxazole and fluoroquinolones, the drug-bug mismatch was predicted to decrease 62% and 78%, respectively. Recurrent or persistent urinary tract infection and clinical sepsis were significantly correlated with specific clonotypes, especially with CH40-30 (also known as H30), a recently described clonotype within sequence type 131 (ST131). We were able to clonotype directly from patient urine samples within 1 to 3 h of obtaining the specimen. In E. coli , subspecies-level identification by clonotyping can be used to significantly improve empirical predictions of antimicrobial susceptibility and clinical outcomes in a timely manner.

BACKGROUND AND OBJECTIVES:Appendicitis guidelines recommend either narrower- or extended-spectrum antibiotics for treatment of complicated appendicitis. The goal of this study was to compare the effectiveness of extended-spectrum versus narrower-spectrum antibiotics for children with appendicitis.METHODS:We performed a retrospective cohort study of children aged 3 to 18 years discharged between 2011 and 2013 from 23 freestanding children’s hospitals with an appendicitis diagnosis and appendectomy performed. Subjects were classified as having complicated appendicitis if they had a postoperative length of stay ≥3 days, a central venous catheter placed, major or severe illness classification, or ICU admission. The exposure of interest was receipt of systemic extended-spectrum antibiotics (piperacillin ± tazobactam, ticarcillin ± clavulanate, ceftazidime, cefepime, or a carbapenem) on the day of appendectomy or the day after. The primary outcome was 30-day readmission for wound infection or repeat abdominal surgery. Multivariable logistic regression, propensity score weighting, and subgroup analyses were used to control for confounding by indication.RESULTS:Of 24 984 patients, 17 654 (70.7%) had uncomplicated appendicitis and 7330 (29.3%) had complicated appendicitis. Overall, 664 (2.7%) patients experienced the primary outcome, 1.1% among uncomplicated cases and 6.4% among complicated cases (P < .001). Extended-spectrum antibiotic exposure was significantly associated with the primary outcome in complicated (adjusted odds ratio, 1.43 [95% confidence interval, 1.06 to 1.93]), but not uncomplicated, (adjusted odds ratio, 1.32 [95% confidence interval, 0.88 to 1.98]) appendicitis. These odds ratios remained consistent across additional analyses.CONCLUSIONS:Extended-spectrum antibiotics seem to offer no advantage over narrower-spectrum agents for children with surgically managed acute uncomplicated or complicated appendicitis.

We describe a 16-year-old neutropenic patient from the Middle East with bloodstream infection caused by two carbapenemase-producing Escherichia coli isolates that we characterized by whole-genome sequencing. While one displayed meropenem resistance and was bla NDM positive, the other demonstrated meropenem susceptibility yet harbored bla OXA181 (which encodes a bla OXA48 -like enzyme). This report highlights the challenge of laboratory detection of bla OXA48 -like enzymes and the clinical implications of genotypic resistance detection in carbapenemase-producing Enterobacteriaceae .

The objective of this study was to determine whether antibiotic exposure is associated with extended-spectrum-beta-lactamase- or AmpC-producing Escherichia coli or Klebsiella pneumoniae infections in children. We collected extended-spectrum-beta-lactamase- or AmpC-producing E. coli or K. pneumoniae isolates and same-species susceptible controls from normally sterile sites of patients aged ≤21 years, along with associated clinical data, at four free-standing pediatric centers. After controlling for potential confounders, the relative risk of having an extended-spectrum-beta-lactamase-producing isolate rather than a susceptible isolate was 2.2 times higher (95% confidence interval [CI], 1.49 to 3.35) among those with antibiotic exposure in the 30 days prior to infection than in those with no antibiotic exposure. The results were similar when analyses were limited to exposure to third-generation cephalosporins, other broad-spectrum beta-lactams, or trimethoprim-sulfamethoxazole. Conversely, the relative risk of having an AmpC-producing versus a susceptible isolate was not significantly elevated with any antibiotic exposure in the 30 days prior to infection (adjusted relative risk ratio, 1.12; 95% CI, 0.65 to 1.91). However, when examining subgroups of antibiotics, the relative risk of having an AmpC-producing isolate was higher for patients with exposure to third-generation cephalosporins (adjusted relative risk ratio, 4.48; 95% CI, 1.75 to 11.43). Dose-response relationships between antibiotic exposure and extended-spectrum-beta-lactamase-producing or AmpC-producing isolates were not demonstrated. These results reinforce the need to study and implement pediatric antimicrobial stewardship strategies, and they indicate that epidemiological studies of third-generation cephalosporin-resistant E. coli and K. pneumoniae isolates should include resistance mechanisms when possible.

Antimicrobial stewardship programs (ASPs) are an effective strategy for improving the quality and safety of antimicrobial prescribing for hospitalized patients. Pediatric ASPs are in their early stages of development, and there are unique issues relevant to children. The imperative to ensure that antimicrobials are prescribed judiciously is highlighted by the ongoing epidemic increase in antimicrobial-resistant infections and the simultaneous decline in the rate of new drug development. In this review we describe the process of ASP development for pediatrics, review existing data regarding the impact of pediatric ASPs, and describe the priorities and challenges for ASP research including study design and appropriate end points.

FimH, the adhesive subunit of type 1 fimbriae expressed by many enterobacteria, mediates mannose-sensitive binding to target host cells. At the same time, fine receptor-structural specificities of FimH from different species can be substantially different, affecting bacterial tissue tropism and, as a result, the role of the particular fimbriae in pathogenesis. In this study, we compared functional properties of the FimH proteins from Escherichia coli and Klebsiella pneumoniae , which are both 279 amino acids in length but differ by some ∼15% of residues. We show that K. pneumoniae FimH is unable to mediate adhesion in a monomannose-specific manner via terminally exposed Manα(1-2) residues in N-linked oligosaccharides, which are the structural basis of the tropism of E. coli FimH for uroepithelial cells. However, K. pneumoniae FimH can bind to the terminally exposed Manα(1-3)Manβ(1-4)GlcNAcβ1 trisaccharide, though only in a shear-dependent manner, wherein the binding is marginal at low shear force but enhanced sevenfold under increased shear. A single mutation in the K. pneumoniae FimH, S62A, converts the mode of binding from shear dependent to shear independent. This mutation has occurred naturally in the course of endemic circulation of a nosocomial uropathogenic clone and is identical to a pathogenicity-adaptive mutation found in highly virulent uropathogenic strains of E. coli , in which it also eliminates the dependence of E. coli binding on shear. The shear-dependent binding properties of the K. pneumoniae and E. coli FimH proteins are mediated via an allosteric catch bond mechanism. Thus, despite differences in FimH structure and fine receptor specificity, the shear-dependent nature of FimH-mediated adhesion is highly conserved between bacterial species, supporting its remarkable physiological significance.

Core genes comprising the ubiquitous backbone of bacterial genomes are not subject to frequent horizontal transfer and generally are not thought to contribute to the adaptive evolution of bacterial pathogens. We determined, however, that at least one-third and possibly more than one-half of the core genes in Escherichia coli genomes are targeted by repeated replacement substitutions in the same amino acid positions—hotspot mutations. Occurrence of hotspot mutations is driven by positive selection, as their rate is significantly higher than expected by random chance alone, and neither intragenic recombination nor increased mutability can explain the observed patterns. Also, commensal E. coli strains have a significantly lower frequency of mutated genes and mutations per genome than pathogenic strains. E. coli strains causing extra-intestinal infections accumulate hotspot mutations at the highest rate, whereas the highest total number of mutated genes has been found among Shigella isolates, suggesting the pathoadaptive nature of such mutations. The vast majority of hotspot mutations are of recent evolutionary origin, implying short-term positive selection, where adaptive mutations emerge repeatedly but are not sustained in natural circulation for long. Such pattern of dynamics is consistent with source-sink model of virulence evolution.