Most current fluoroquinolone-resistant E. coli clinical isolates, and the largest share of multidrug-resistant isolates, represent a highly clonal subgroup that likely originated from a single rapidly expanded and disseminated ST131 strain. Focused attention to this strain will be required to control the fluoroquinolone and multidrug-resistant E. coli epidemic.

Objective Crohn’s disease (CD) is a chronic idiopathic inflammatory intestinal disorder associated with fecal dysbiosis. Fecal Microbial Transplant (FMT) is a potential therapeutic option for individuals with CD based on the hypothesis that changing the fecal dysbiosis could promote less intestinal inflammation. Design Nine patients, ages 12–19 years, with mild to moderate symptoms defined by Pediatric Crohn’s disease activity index (PCDAI of 10–29) were enrolled into a prospective open label study of FMT in CD (FDA IND 14942). Patients received FMT by nasogastric tube with follow up evaluations at 2, 6, and 12 weeks. PCDAI, C-reactive protein (CRP), and fecal calprotectin were evaluated at each study visit. Results All reported adverse events (AE) were graded as mild except for one individual who reported moderate abdominal pain after FMT. All AE were self limiting. Metagenomic evaluation of stool microbiome indicated evidence of FMT engraftment in seven out of nine patients. The mean PCDAI score improved with patients having a baseline of 19.7 ± 7.2, with improvement at 2 weeks to 6.4 ± 6.6, and at 6 weeks to 8.6 ± 4.9. Based upon PCDAI, 7/9 patients were in remission at 2 weeks, and 5/9 patients who did not receive additional medical therapy were in remission at week 6 and 12 weeks. No or modest improvement were seen in the patients who did not engraft or whose microbiome was most similar to their donor. Conclusion This is the first study to demonstrate that FMT for CD may be a possible therapeutic option for Crohn’s disease. Further prospective studies are required to fully assess the safety and efficacy of the FMT in patients with Crohn’s disease.

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Nearly one-half of the patients who presented to the emergency department with diarrhea had a definite or plausible pathogen in their stool specimens. We were unable to develop a model that was substantially better than physician judgment in identifying patients for whom bacterial culture would yield positive results. The unexpectedly high rate of C. difficile toxin warrants further examination.

Multilocus sequence typing (MLST) is usually based on the sequencing of 5 to 8 housekeeping loci in the bacterial chromosome and has provided detailed descriptions of the population structure of bacterial species important to human health. However, even strains with identical MLST profiles (known as sequence types or STs) may possess distinct genotypes, which enable different eco-or pathotypic lifestyles. Here we describe a two-locus, sequence-based typing scheme for Escherichia coli that utilizes a 489-nucleotide (nt) internal fragment of fimH (encoding the type 1 fimbrial adhesin) and the 469-nt internal fumC fragment used in standard MLST. Based on sequence typing of 191 model commensal and pathogenic isolates plus 853 freshly isolated clinical E. coli strains, this 2-locus approach-which we call CH (fumC/fimH) typing-consistently yielded more haplotypes than standard 7-locus MLST, splitting large STs into multiple clonal subgroups and often distinguishing different within-ST ecoand pathotypes. Furthermore, specific CH profiles corresponded to specific STs, or ST complexes, with 95% accuracy, allowing excellent prediction of MLST-based profiles. Thus, 2-locus CH typing provides a genotyping tool for molecular epidemiology analysis that is more economical than standard 7-locus MLST but has superior clonal discrimination power and, at the same time, corresponds closely to MLST-based clonal groupings. E scherichia coli infections, which encompass both intestinal syndromes (e.g., diarrhea, dysentery) and extraintestinal syndromes (e.g., urinary tract infection [UTI], septicemia, newborn meningitis), represent a significant public health burden worldwide (17). Most extraintestinal E. coli infections are caused by strains from phylogenetic groups B2 and D, within which are concentrated the horizontally mobile genetic determinants associated with extraintestinal virulence, such as toxins, adhesins, protectins, and iron-scavenging systems (17).Multilocus sequence typing (MLST) is currently the preferred method for characterizing the relatedness of strains within bacterial species (19). Standardized MLST schemes have been established for numerous human pathogens, including E. coli (38). Certain E. coli sequence types (STs, in which MLST profiles are identical) are epidemiologically associated with specific extraintestinal syndromes, e.g., ST127 and ST73 with pyelonephritis (15, 16), while others have been associated with important emerging antimicrobial resistance properties, e.g., ST69 with trimethoprimsulfamethoxazole resistance (20) and ST131 with fluoroquinolone resistance and extended-spectrum beta-lactamase production (22).However, STs are not uniform with regard to genetic properties or ecotypic/pathotypic behaviors. Within ST95, for example, strains from the North American OMP6 clade of serotype O18: K1:H7 encode P fimbriae and hemolysin and are strongly associated with both newborn meningitis and UTI (14), while strains from the European OMP9 clade of O18:K1:H7 encode neither element and are associated only w...

The presence of a copathogen and host factors, including an immunocompromised state, were associated with increased risk for severe LRTD. Recognizing risk factors for severe respiratory illness might assist in risk stratification.

Emerging antibiotic resistance threatens human health. Gut microbes are an epidemiologically important reservoir of resistance genes (resistome), yet prior studies indicate that the true diversity of gut-associated resistomes has been underestimated. To deeply characterize the pediatric gut-associated resistome, we created metagenomic recombinant libraries in an Escherichia coli host using fecal DNA from 22 healthy infants and children (most without recent antibiotic exposure), and performed functional selections for resistance to 18 antibiotics from eight drug classes. Resistance-conferring DNA fragments were sequenced (Illumina HiSeq 2000), and reads assembled and annotated with the PARFuMS computational pipeline. Resistance to 14 of the 18 antibiotics was found in stools of infants and children. Recovered genes included chloramphenicol acetyltransferases, drug-resistant dihydrofolate reductases, rRNA methyltransferases, transcriptional regulators, multidrug efflux pumps, and every major class of beta-lactamase, aminoglycoside-modifying enzyme, and tetracycline resistance protein. Many resistance-conferring sequences were mobilizable; some had low identity to any known organism, emphasizing cryptic organisms as potentially important resistance reservoirs. We functionally confirmed three novel resistance genes, including a 16S rRNA methylase conferring aminoglycoside resistance, and two tetracycline-resistance proteins nearly identical to a bifidobacterial MFS transporter (B. longum s. longum JDM301). We provide the first report to our knowledge of resistance to folate-synthesis inhibitors conferred by a predicted Nudix hydrolase (part of the folate synthesis pathway). This functional metagenomic survey of gut-associated resistomes, the largest of its kind to date, demonstrates that fecal resistomes of healthy children are far more diverse than previously suspected, that clinically relevant resistance genes are present even without recent selective antibiotic pressure in the human host, and that cryptic gut microbes are an important resistance reservoir. The observed transferability of gut-associated resistance genes to a gram-negative (E. coli) host also suggests that the potential for gut-associated resistomes to threaten human health by mediating antibiotic resistance in pathogens warrants further investigation.

The significant association between vaccination and isolate pertactin production suggests that the likelihood of having reported disease caused by PRN(-) compared with PRN(+) strains is greater in vaccinated persons. Additional studies are needed to assess whether vaccine effectiveness is diminished against PRN(-) strains.