Banerjee, Ritu

ABSTRACT 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 .

Abstract Background. Emerging data implicate long-term care facilities (LTCFs) as reservoirs of fluoroquinolone-resistant (FQ-R) Escherichia coli of sequence type 131 (ST131). We screened for ST131 among LTCF residents, characterized isolates molecularly, and identified risk factors for colonization. Methods. We conducted a cross-sectional study using a single perianal swab or stool sample per resident in 2 LTCFs in Olmsted County, Minnesota, from April to July 2013. Confirmed FQ-R E. coli isolates underwent polymerase chain reaction-based phylotyping, detection of ST131 and its H30 and H30-Rx subclones, extended virulence genotyping, and pulsed-field gel electrophoresis (PFGE) analysis. Epidemiological data were collected from medical records. Results. Of 133 fecal samples, 33 (25%) yielded FQ-R E. coli, 32 (97%) of which were ST131. The overall proportion with ST131 intestinal colonization was 32 of 133 (24%), which differed by facility: 17 of 41 (42%) in facility 1 vs 15 of 92 (16%) in facility 2 (P = .002). All ST131 isolates represented the H30 subclone, with virulence gene and PFGE profiles resembling those of previously described ST131 clinical isolates. By PFGE, certain isolates clustered both within and across LTCFs. Multivariable predictors of ST131 colonization included inability to sign consent (odds ratio [OR], 4.16 [P = .005]), decubitus ulcer (OR, 4.87 [ P = .04]), and fecal incontinence (OR, 2.59 [P = .06]). Conclusions. Approximately one fourth of LTCF residents carried FQ-R ST131 E. coli resembling ST131 clinical isolates. Pulsed-field gel electrophoresis suggested intra- and interfacility transmission. The identified risk factors suggest that LTCF residents who require increased nursing care are at greatest risk for ST131 colonization, possibly due to healthcare-associated transmission.

ABSTRACT Escherichia coli sequence type 131 (ST131) is an extensively antimicrobial-resistant E. coli clonal group that has spread explosively throughout the world. Recent molecular epidemiologic and whole-genome phylogenetic studies have elucidated the fine clonal structure of ST131, which comprises multiple ST131 subclones with distinctive resistance profiles, including the (nested) H30, H30-R, and H30-Rx subclones. The most prevalent ST131 subclone, H30, arose from a single common fluoroquinolone (FQ)-susceptible ancestor containing allele 30 of fimH (type 1 fimbrial adhesin gene). An early H30 subclone member acquired FQ resistance and launched the rapid expansion of the resulting FQ-resistant subclone, H30-R. Subsequently, a member of H30-R acquired the CTX-M-15 extended-spectrum beta-lactamase and launched the rapid expansion of the CTX-M-15-containing subclone within H30-R, H30-Rx. Clonal expansion clearly is now the dominant mechanism for the rising prevalence of both FQ resistance and CTX-M-15 production in ST131 and in E. coli generally. Reasons for the successful dissemination and expansion of the key ST131 subclones remain undefined but may include increased transmissibility, greater ability to colonize and/or persist in the intestine or urinary tract, enhanced virulence, and more-extensive antimicrobial resistance compared to other E. coli . Here we discuss the epidemiology and molecular phylogeny of ST131 and its key subclones, possible mechanisms for their ecological success, implications of their widespread dissemination, and future research needs.

ABSTRACT We assessed Escherichia coli ST131 and its H30 and H30-Rx subclones for virulence genes, antimicrobial resistance, and extended-spectrum beta-lactamase (ESBL) type. Although both subclones were associated with ESBL production, H30-Rx isolates had higher resistance scores and were associated specifically with CTX-M-15. Three virulence genes ( iha , sat , and iutA ) were more prevalent among H30 than non-H30 ST131 isolates. Thus, the H30 and H30-Rx subclones are more antimicrobial resistant and have virulence profiles that are distinct from those of non-H30 ST131 isolates.

ABSTRACT The clonal distribution of Escherichia coli across an unselected population in the current era of widespread antimicrobial resistance is incompletely defined. In this study, we used a newly described clonal typing strategy based on sequencing of fum C and fim H (i.e., CH typing) to infer multilocus sequence types (STs) for 299 consecutive, nonduplicate extraintestinal E. coli isolates from all cultures submitted to Olmsted County, MN, laboratories in February and March 2011 and then compared STs with epidemiological data. Forty-seven different STs were identified, most commonly ST131 (27%), ST95 (11%), ST73 (8%), ST127 (6%), and ST69 (5%). Isolates from these five STs comprised two-thirds of health care-associated (HA) isolates but only half of community-associated (CA) isolates. ST131 was represented overwhelmingly (88%) by a single recently expanded H30 subclone, which was the most extensively antimicrobial-resistant subclone overall and was especially predominant in HA infections and among adults >50 years old. In contrast, among patients 11 to 50 years old, ST69, -95, and -73 were more common. Because of the preponderance of the H30 subclone of ST131, ST diversity was lower among HA than CA isolates, and among antimicrobial-resistant than antimicrobial-susceptible isolates, which otherwise had similar ST distributions. In conclusion, in this U.S. Midwest region, the distribution and diversity of STs among extraintestinal E. coli clinical isolates vary by patient age, type of infection, and resistance phenotype. ST131 predominates among young children and the elderly, HA infections, and antimicrobial-resistant isolates, whereas other well-known pathogenic lineages are more common among adolescents and young adults, CA infections, and antimicrobial-susceptible isolates.

BackgroundVancomycin treatment failure has been associated with low serum vancomycin trough concentrations, prompting recommendations to increase the daily doses in adults and children. Despite more aggressive vancomycin dosing, there continues to be significant variability in vancomycin trough concentrations in pediatric patients.MethodsTo determine if vancomycin trough concentrations in pediatric patients differ by age and weight, we reviewed records of hospitalized patients who received vancomycin between 2008 and 2012. Patients were divided into groups that received vancomycin 40 mg/kg/day (2008–2009) or 60 mg/kg/day (2010–2012). Vancomycin trough concentrations were compared between groups and within the 60 mg/kg/day group, stratified by patient age and weight.ResultsAfter increasing the vancomycin dose from 40 to 60 mg/kg/day, initial trough concentrations increased significantly in patients younger than 2 and greater than 6 years of age, but not in patients between the ages of 2 and 5 years. In the 60 mg/kg/day group, only 16.7% of patients between 2 and 5 years of age had initial trough concentrations in the therapeutic range (10–20 μg/ml). Initial trough concentrations were therapeutic in a greater proportion of patients ages 6–12 years (38.7%) and 13–18 years (63.0%). Patients between the ages of 13 and 18 had the highest proportion of supratherapeutic initial vancomycin trough concentrations (14.8%). Patients weighing over 50 kg had significantly higher trough concentrations than patients 50 kg or less (17.1 μg/ml vs 9.3 μg/ml, p<0.001).ConclusionAlthough increasing the vancomycin dose from 40 to 60 mg/kg/day led to a significant increase in vancomycin trough concentrations, a large proportion of patients receiving 60 mg/kg/day of vancomycin had trough concentrations outside of the therapeutic range. Specifically, patients younger than 6 years tended to have low trough concentrations, whereas adolescents and children over 50 kg were more likely to have elevated trough concentrations. Vancomycin dosing strategies in pediatric patients should consider age and weight as well as renal function and indication.

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.