Background: Antimicrobial resistance is a serious public health problem. Fecal carriage of drug-resistant bacteria has been suggested as an important source of antimicrobial resistant genes (ARGs). We aimed to identify risk factors associated with fecal carriage of drug-resistant commensal Escherichia coli among healthy adult population. Methods: We conducted a systematic review and meta-analysis following the PRISMA guideline. We identified observational studies published from 2014 to 2019 through PubMed, Embase, and Web of Science. Studies were eligible if they investigated and reported risk factors and accompanying measure of associations for fecal carriage of drug-resistant E. coli for healthy population aged 18-65. Data on risk factors assessed in three or more studies were extracted. Results: Fifteen of 395 studies involving 11480 healthy individuals were included. The pooled prevalence of drug-resistant Enterobacteriaceae was 14% (95% confidence interval [CI] 8-23%). Antimicrobial use within the 12 months prior to stool culture (odds ratio [OR] 1.84 [95%CI 1.35-2.51]), diarrhea symptoms (OR 1.56 [95%CI 1.09-2.25]), travel to India (OR 4.15 [95%CI 2.54-6.78]), and vegetarian diet (OR 1.60 [95%CI 1.00(1.0043)-2.56(2.5587)]) were associated with increased risk of fecal carriage of drug-resistant E. coli. Among travellers, antimicrobial use (OR 2.81 [95%CI 1.47-5.36]), diarrhea symptoms (OR 1.65 [95%CI 1.02-2.68]), travel to India (OR 3.80 [95%CI 2.23-6.47]), and vegetarian diet (OR 1.92 [95%CI 1.13-3.26]) were associated with increased risk. Among general adult population, antimicrobial use (OR 1.51 [95%CI 1.17-1.94]), diarrhea symptoms (OR 1.53 [95%CI 1.27-1.84]), and travel to Southeast Asia (OR 1.67 [95%CI 1.02-2.73]) were associated with the increased risk of drug-resistant E. coli carriage. Conclusions:The findings indicate that dietary habit as well as past antimicrobial use and travel to high-risk country are associated with the risk of fecal carriage of drug-resistant commensal E. coli.
Community‐acquired urinary tract infections (UTIs) are one of the most common bacterial infections worldwide. Escherichia coli is the most common cause of community‐acquired UTI. In general, UTI results from E. coli in the intestine that enters the bladder via the urethra. However, whether these E. coli strains that cause UTI represent members of the intestinal commensal E. coli or a distinct subgroup of pathogenic E. coli remains unestablished. Here, we analyzed E. coli isolates from fecal samples of healthy volunteers and urine samples of UTI patients obtained from a university‐affiliated health center. The E. coli isolates were genotyped by multilocus sequence typing (MLST). From May to October 2018, we analyzed 89 E. coli isolates from 76 (75%) rectal swabs from 113 unique healthy volunteers. We also analyzed 106 (27%) E. coli isolates from 398 unique urine samples collected between August and October 2018. Fecal and urine E. coli isolates each contained 31 distinct sequence types (STs). Nine STs were shared by fecal and urine E. coli isolates, which accounted for approximately 50% of urine isolates typed by MLST. Among the shared genotypes, ST10 and ST131 were significantly more frequently found in fecal samples, whereas ST95 and ST127 were significantly more frequently recovered from UTI samples. ST73 was found only among urine samples. These E. coli genotypes clustered and fluctuated over time. These observations suggest that E. coli genotypes found to cause UTI transiently colonize the intestine and that their primary reservoir may reside outside of the human intestine.
The rising incidence of resistance to expanded-spectrum cephalosporins among Escherichia coli strains, the most common cause of UTIs, is threatening our ability to successfully empirically treat these infections. ESCR E. coli strains are often MDR; therefore, UTI caused by these organisms often leads to treatment failure, increased length of hospital stay, and severe complications (D. G. Mark, Y.-Y. Hung, Z. Salim, N. J. Tarlton, et al., Ann Emerg Med 78:357–369, 2021, https://doi.org/10.1016/j.annemergmed.2021.01.003 ).
Mechanisms underlying the acute respiratory distress syndrome (ARDS)-like clinical manifestations leading to deaths in patients who develop COVID-19 remain uncharacterized. While multiple factors could influence these clinical outcomes, we explored if differences in transmissibility and pathogenicity of SARS-CoV2 variants could contribute to these terminal clinical consequences of COVID-19. We analyzed 34,412 SARS-CoV2 sequences deposited in the Global Initiative for Sharing All Influenza Data (GISAID) SARS-CoV2 sequence database to determine if regional differences in circulating strain variants correlated with increased mortality in Europe, the United States, and California. We found two subclades descending from the Wuhan HU-1 strain that rapidly became dominant in Western Europe and the United States. These variants contained nonsynonymous nucleotide mutations in the Orf1ab segment encoding RNA-dependent RNA polymerase (C14408T), the spike protein gene (A23403G), and Orf1a (G25563T), which resulted in non-conservative amino acid substitutions P323L, D614G, and Q57H, respectively. In Western Europe, the A23403G-C14408T subclade dominated, while in the US, the A23403G-C14408T-G25563T mutant became the dominant strain in New York and parts of California. The high cumulative frequencies of both subclades showed inconsistent but significant association with high cumulative CFRs in some of the regions. When the frequencies of the subclades were analyzed by their 7-day moving averages across each epidemic, we found co-circulation of both subclades to temporally correlate with peak mortality periods. We postulate that in areas with high numbers of these co-circulating subclades, a person may get serially infected. The second infection may trigger a hyperinflammatory response similar to the antibody-dependent enhancement (ADE) response, which could explain the ARDS-like manifestations observed in people with co-morbidity, who may not mount sufficient levels of neutralizing antibodies against the first infection. Further studies are necessary but the implication of such a mechanism will need to be considered for all current COVID-19 vaccine designs.
The association of tuberculosis and type 2 diabetes mellitus has been a recognized re-emerging challenge in management of the convergence of the two epidemics. Though much of the literature has studied this association, there is less knowledge in the field of genetic diversities that might occur in strains infecting tuberculosis patients with and without diabetes. Our study focused on determining the extent of diversity of genotypes of Mycobacterium tuberculosis in both these categories of patients. We subjected 55 M. tuberculosis isolates from patients diagnosed with pulmonary TB with and without type 2 diabetes mellitus to whole-genome sequencing on Illumina Hi Seq platform. The most common lineage identified was lineage 1, the Indo-Oceanic lineage (n = 22%), followed by lineage 4, the Euro-American lineage (n = 18, 33%); lineage 3, the East-African Indian lineage (n = 13, 24%); and lineage 2, the East-Asian lineage (n = 1, 2%). There were no significant differences in the distribution of lineages in both diabetics and non-diabetics in the South Indian population, and further studies involving computational analysis and comparative transcriptomics are needed to provide deeper insights.
The genome sequence of a uropathogenic Escherichia coli sequence type 420 strain isolated from a patient with urinary tract infection in northern California is described here. The draft genome sequence includes a 4.8-Mb chromosome, accompanied by a 114-kb plasmid containing IncFIB/IncFII/Col156 and a 35-kb plasmid containing IncN3.
BackgroundBacterial antimicrobial resistance is a serious global public health threat. Intestinal commensal drug-resistant bacteria have been suggested as an important reservoir of antimicrobial resistant genes (ARGs), which may be acquired via food. We aimed to identify risk factors associated with fecal carriage of drug-resistant commensal Escherichia coli (E. coli) among healthy adults focused on their dietary habit.MethodsWe conducted a cross-sectional study targeting healthy adult volunteers in a college community. Fecal samples and questionnaires were obtained from 113 volunteers. We conducted backward elimination logistic regression and least absolute shrinkage and selection (LASSO) methods to identify risk factors.ResultsWe analyzed responses from 81 of 113 volunteers who completed the questionnaire. The logistic regression and LASSO methods identified red meat consumption to be associated with increased risk (OR = 6.13 [1.83-24.2] and 1.82, respectively) and fish consumption with reduced risk (OR = 0.27 [0.08-0.85] and 0.82) for the carriage of multidrug-resistant E. coli, adjusted for gender, employment status, frequently-used supermarket, and previous travel.ConclusionsDietary habits are associated with the risk of fecal carriage of multidrug-resistant E. coli. This study supports the growing evidence that food may be an important source of ARGs present in human commensal E. coli.
Extraintestinal pathogenic Escherichia coli (ExPEC) belonging to multilocus sequence type 95 (ST95) is one of the most widespread ExPEC lineages associated with bloodstream infections (BSI) and urinary tract infections (UTI). In contrast to other widespread ExPEC sequence types, a large proportion ST95 strains remains susceptible to all antimicrobial agents used to treat BSI or UTI. We aimed to identify genomic features of ST95 associated with persistent drug susceptibility. We conducted a genome-wide association study of 80 ExPEC ST95 isolates from patients with BSI or UTI in Northern California, and 1669 ST95 isolates deposited in the Enterobase database. Of the total of 1749 ST95 isolates, we compared whole-genome sequences of 887 drug-susceptible strains and 862 strains resistant to one or more drugs (defined genotypically as strains harboring drug-resistance genes annotated in the ResFinder database) to identify genetic features associated with strains devoid of drug-resistance genes. By a genome-wide association study of 553 UTI and BSI ST95 isolates, we found 44 accessory genes significantly associated with drug susceptibility, six of which encoded hypothetical proteins. Fifteen of these were not found in any of the WGSs of ST131 ExPEC strains, which are frequently multidrug-resistant, and eight of these genes were annotated to encode transporter or transfer systems. These findings highlight the potential mechanisms by which ST95 strains may resist the acquisition of mobile DNA elements carrying drug-resistance genes.ImportanceDespite the increasing prevalence of antibiotic resistance in Escherichia coli strains that cause common infections such as urinary tract and bloodstream infections, a major pandemic lineage of extraintestinal pathogenic E. coli ST95 has remained susceptible to most drugs used to treat these infections. We compared genomes of 1749 ST95 isolates to identify genetic features that may explain why most strains of ST95 resist becoming drug-resistant. Identification of such genomic features could contribute to the development of novel strategies to prevent the spread of antibiotic-resistant genes and devise new measures to control antibiotic-resistant infections.
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