Extraintestinal Pathogenic Escherichia coli: A Combination of Virulence with Antibiotic Resistance

Escherichia coli represents an incredible versatile and diverse enterobacterial species and can be subdivided into the following; (i) intestinal non-pathogenic, commensal isolates. (ii) Intestinal pathogenic isolates and (iii) extraintestinal pathogenic E. coli or ExPEC isolates. The presence to several putative virulence genes has been positively linked with the pathogenicity of ExPEC. E. coli remains one of the most frequent causes of nosocomial and community-acquired bacterial infections including urinary tract infections, enteric infections, and systemic infections in humans. ExPEC has emerged in 2000s as an important player in the resistance to antibiotics including the cephalosporins and fluoroquinolones. Most importantly among ExPEC is the increasing recognition of isolates producing “newer β-lactamases” that consists of plasmid-mediated AmpC β-lactamases (e.g., CMY), extended-spectrum β-lactamases (e.g., CTX-M), and carbapenemases (e.g., NDM). This review will highlight aspects of virulence associated with ExPEC, provide a brief overview of plasmid-mediated resistance to β-lactams including the characteristics of the successful international sequence types such as ST38, ST131, ST405, and ST648 among ExPEC

Clinical and microbiological characteristics of bloodstream infections due to AmpC β-lactamase producing Enterobacteriaceae: an active surveillance cohort in a large centralized Canadian region

Background: The objective of this study was to describe the clinical and microbiological characteristics of bloodstream infections (BSIs) due to AmpC producing Enterobacteriaceae (AE) in a large centralized Canadian region over a 9-year period. Methods: An active surveillance cohort design in Calgary, Canada. Results: A cohort of 458 episodes of BSIs caused by AE was assembled for analysis. The majority of infections were of nosocomial origin with unknown sources. Enterobacter spp. was the most common species while BSIs due to Serratia spp. had a significant higher mortality when compared to other AE. Delays in empiric or definitive antibiotic therapy were not associated with a difference in outcome. However, patients that did not receive any empiric antimicrobial therapy had increased mortality (3/5; 60% vs. 57/453; 13%; p = 0.018) as did those that did not receive definitive therapy (6/17; 35% vs. 54/441; 12%; p = 0.015). Conclusions: Delays in therapy were not associated with adverse outcomes although lack of active therapy was associated with increased mortality. A strategy for BSIs due to AE where β-lactam antibiotics (including oxyiminocephalosporins) are used initially followed by a switch to non-β-lactam antibiotics once susceptibility results are available is effective.</p

New Delhi Metallo-β-Lactamase from Traveler Returning to Canada1

An Escherichia coli isolate with New Delhi metallo-β-lactamase was isolated from a patient with pyelonephritis and prostatitis who returned to Canada after recent hospitalization in India. The patient was successfully treated with ertapenem and fosfomycin. This patient highlights the role of international travel in the spread of antimicrobial drug resistance and blaNDM-1

Characteristics of Escherichia coli sequence type 131 isolates that produce extended-spectrum β-lactamases: global distribution of the H30-Rx sublineage

We designed a study to describe the characteristics of sequence type 131 (ST131) lineages, including the H30-Rx sublineage, among a global collection of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli isolates from 9 countries collected from 2000 to 2011. A total of 240 nonrepeat isolates from Canada, the United States, Brazil, the Netherlands, France, the United Arab Emirates (UAE), India, South Africa, and New Zealand were included. Established PCR, sequencing, and typing methods were used to define ST131 lineages, H30 and H30-Rx phylogenetic groups, gyrA and parC mutations, virotypes, and plasmid-mediated quinolone resistance determinants. The majority of the isolates produced CTX-M-15 with aac(6′)-lb-cr, belonged to phylogenetic group B2, and were positive for the H30 lineage with the gyrA1AB and parC1aAB mutations. ST131 showed 15 distinct pulsotypes; 43% of the isolates belonged to four pulsotypes, with a global distribution. Seventy-five percent of the ST131 isolates belonged to H30-Rx; this sublineage was present in all the countries and was associated with multidrug resistance, blaCTX-M-15, aac(6′)-lb-cr, and virotypes A and C. The H41 lineage was negative for the ST131 pabB allele-specific PCR. The multidrug-resistant H30-Rx sublineage poses an important public health threat due to its global distribution, association with virotype C, and high prevalence among ST131 isolates that produce CTX-M-15

Global molecular epidemiology of IMP-producing Enterobacteriaceae

International data on the molecular epidemiology of Enterobacteriaceae with IMP carbapenemases are lacking. We performed short read (Illumina) whole genomic sequencing on a global collection of 38 IMP-producing clinical Enterobacteriaceae (2008-14). IMP-producing Enterobacteriaceae (7 varieties within 11 class 1 integrons) were mainly present in South Pacific and Asia. Specific blaIMP containing integrons (In809 with blaIMP-4, In722 with blaIMP-6, In687 with blaIMP-14) were circulating among different bacteria in countries such as Australia, Japan and Thailand. In1312 with blaIMP-1 was present in K. pneumoniae from Japan and C. freundii from Brazil. Klebsiella pneumoniae (n=22) was the most common species; clonal complex (CC) 14 from the Philippines and Japan was the most common clone and contained In1310 with blaIMP-26 and In1321 with blaIMP-6. Enterobacter cloacae complex (n=9) consisted of E. hormaechei and E. cloacae cluster III. CC78 (from Taiwan) containing In73 with blaIMP-8, was the most common clone among E. cloacae complex. This study highlights the importance of surveillance programs using the latest molecular techniques in providing insight into the characteristics and global distribution of Enterobacteriaceae with blaIMPs.This work was supported by the John Mung Program from Kyoto University, Japan (Y.M.), a research grant from the Calgary Laboratory Services (#10015169; J.D.D.P) and federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services under Award Number U19AI110819 (MDA).http://aac.asm.org2017-10-30hb2017Medical Microbiolog

Faecal carriage of ESBL producing and colistin resistant Escherichia coli in avian species over a 2-year period (2017-2019) in Zimbabwe

DATA AVAILABILITY STATEMENT : The data presented in this study are deposited in the NCBI BioProject Number PRJNA 799483 with accession numbers listed in the Supplementary Datasheet 1.INTRODUCTION : Extended spectrum beta-lactamase (ESBL) producing Escherichia coli have become widespread among food producing animals. These strains serve as a reservoir of antibiotic resistance genes (ARGs) and act as a possible source of infection to humans as transmission can occur by direct or indirect contact. METHODS : This study investigated the faecal carriage of ESBL producing and colistin resistant E. coli in poultry over a 2-year period (2017-2019) from Zimbabwe. A total of 21 ESBL positive isolates from poultry cloacal specimens were selected for whole genome sequencing from animal E. coli isolates biobanked at the National Microbiology Reference laboratory using phenotypic susceptibility testing results from the National Escherichia coli Surveillance Program to provide representation of different geographical regions and year of isolation. Cloacal swabs were collected from 3000 broiler live birds from farm 1 and fromfarm2, 40 backyard chickens and 10 duckswere sampled. Antimicrobial susceptibility and ESBL testing were performed as per Clinical Laboratory Standards Institute guidelines. Whole genome sequencing of ESBL producing isolates was used to determine sequence types (STs), ARGs, and phylogroups. RESULTS : Twenty-one of the included E. coli isolates were confirmed as ESBL producers. Three defined sequence type clonal complexes (CCs) were identified (ST10CC, ST155CC and ST23CC), with ST10CC associated with the most antibiotic resistant profile. The ESBL phenotype was linked to the presence of either cefotaximase-Munich-14 (CTX-M-14) or CTX-M-79. Plasmid mediated quinolone resistant determinants identified were qnrB19 and qnrS1 and one ST10CC isolate from farm 1 broiler chickens harbored a mobile colistin resistance gene (mcr-1). Phylogenetic groups most identified were B1, A and unknown. DISCUSSIONS : The avian ESBL producing E. coli belonged to a diverse group of strains. The detection of several ARGs highlights the importance of implementing enhanced control measures to limit the spread in animals, environment, and humans. This is the first report of mcr-1 in Zimbabwe, which further underscores the importance of the One Health approach to control the spread and development of AMR.The National Health Laboratory Service (NHLS) and the University of Pretoria, South Africa, a strategic partnership between National Microbiology Reference Laboratory and Quadram BioSciences Institute.https://www.frontiersin.org/journals/cellular-and-infection-microbiologyam2023Medical Microbiolog

A Fatal Bacteremia Caused by Hypermucousviscous KPC-2 Producing Extensively Drug-Resistant K64-ST11 Klebsiella pneumoniae in Brazil

We report a fatal bacteremia caused by Klebsiella pneumoniae in a 60–70-year-old patient from Brazil. The genomic analysis of three isolates (from blood culture, nasal and anal swabs) showed that the bacteremia was caused by a KPC-2 producing extensively drug-resistant K64-ST11 hypermucousviscous K. pneumoniae (hmKP) harboring several virulence and antimicrobial resistance genes. Although the isolates did not present virulence markers associated with hypervirulent K. pneumoniae (hvKP), they showed invasion and toxicity to epithelial Hep-2 cells; resistance to cell microbicidal mechanisms; and blood and human serum survival, evidencing their pathogenic potential. This study highlights the risk of infection caused by hmKp strains not characterized as hvKP as well as the clinical implications and difficulty of treatment, especially in elderly or immunocompromised patients

Geographical variation in therapy for bloodstream infections due to multidrug-resistant enterobacteriaceae: a post hoc analysis of the INCREMENT study

We aimed to describe regional differences in therapy for bloodstream infection (BSI) caused by extended-spectrum ?-lactamase-producing Enterobacteriaceae (ESBL-E) or carbapenemase-producing Enterobacteriaceae (CPE). 1,482 patients in 12 countries were included from an observational study of BSI caused by ESBL-E or CPE. Multivariate logistic regression was used to calculate adjusted odds ratios (aORs) for the influence of country of recruitment on empirical use of ?-lactam/?-lactamase inhibitors (BLBLI) or carbapenems, targeted use of BLBLI for ESBL-E and use of targeted combination therapy for CPE. The use of BLBLI for empirical therapy was least likely in sites from Israel (aOR 0.34, 95% CI 0.14-0.81), Greece (aOR 0.49, 95% CI 0.26-0.94) and Canada (aOR 0.31, 95% CI 0.11-0.88) but more likely in Italy (aOR 1.58, 95% CI 1.11-2.2) and Turkey (aOR 2.09, 95% CI 1.14-3.81), compared to Spain as a reference. Empirical carbapenems were more likely to be used in sites from Taiwan (aOR 1.73, 95% CI 1.03-2.92) and USA (aOR 1.89; 95% CI 1.05-3.39), and less likely in Italy (aOR 0.44, 95% CI 0.28-0.69) and Canada (aOR 0.10, 95% CI 0.01-0.74). Targeted BLBLI for ESBL-E was more likely in sites from Italy. Treatment at sites within Israel, Taiwan, Turkey and Brazil was associated with less combination therapy for CPE. Although this study does not provide precise data on the relative prevalence of ESBL-E or CPE, significant variation in therapy exists across countries even after adjustment for patient factors. A better understanding of what influences therapeutic choices for these infections will aid antimicrobial stewardship efforts.PH is supported by an Australian Postgraduate Award from the University of Queensland. The study was funded by the Ministerio de Economía y Competitividad, Instituto de Salud Carlos III - co-financed by European Development Regional Fund "A way to achieve Europe" ERDF, Spanish Network for the Research in Infectious Diseases (REIPI RD12/0015). BGG, JRB, APH and YC also received funds from the COMBACTE-CARE project (grant agreement 115620), Innovative Medicines Initiative (IMI), the European Union's Seventh Framework Programme (FP7/2007-2013) and in-kind contributions from EFPIA companies