Recent changes in the epidemiology and management of extended-spectrum β-lactamase-producing Enterobacteriaceae

Since 2000, Escherichia coli producing CTX-M enzymes (especially CTX-M-15) have emerged worldwide as important causes of community-onset urinary tract and blood stream infections due to extended-spectrum β-lactamase (ESBL) producing bacteria. Studies suggest that the sudden worldwide increase of CTX-M-15-producing E. coli is mostly due to a single clone named ST131 and that foreign travel to high-risk areas, such as the Indian subcontinent, play in part a role in the spread of this clone across different continents. Empiric antibiotic coverage for these resistant organisms should be considered in community patients presenting with sepsis involving the urinary tract, especially if a patient recently traveled to a high-risk area. If this emerging public health threat is ignored, it is possible that the medical community may be forced in the near future to use carbapenems as the first choice for the empirical treatment of serious infections associated with urinary tract infections originating in the community

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

Population dynamics of Escherichia coli causing bloodstream infections over extended time periods

Escherichia coli is a leading cause of community-acquired and health careassociated bloodstream infections (BSIs) worldwide. Limited information is available regarding the changes in population dynamics of human E. coli over extended time periods, especially among nonbiased E. coli isolates in large well-defined geographical regions. Coque and colleagues (I. Rodríguez, A. S. Figueiredo, M. Sousa, S. Aracil-Gisbert, et al., mSphere 6: e00868-21, 2021, https://doi.org/10.1128/msphere.00868-21) conducted a longitudinal study of E. coli BSIs in a Madrid hospital over a 21-year period (1996 to 2016). Certain E. coli B2 phylogroups (i.e., ST131 and ST73) dominated the community E. coli population in Madrid. These community clones were often introduced into the hospital setting. This study and other longitudinal surveys from England and Canada showed that ST131 subclades C1 and C2 were mainly responsible for the increase in fluoroquinolone and cephalosporin resistance among E. coli during the mid- to late 2000s.https://msphere.asm.orgam2022Medical Microbiolog

The significance of epidemic plasmids in the success of multidrug-resistant drug pandemic extraintestinal pathogenic Escherichia coli

DATA AVAILABILITY : Data sharing is not applicable to this article as no data sets were generated or analyzed during the current study.Epidemic IncF plasmids have been pivotal in the selective advantage of multidrug-resistant (MDR) extraintestinal pathogenic Escherichia coli (ExPEC). These plasmids have offered several advantages to their hosts that allowed them to coevolve with the bacterial host genomes and played an integral role in the success of ExPEC. IncF plasmids are large, mosaic, and often contain various types of antimicrobial resistance (AMR) and virulence associated factor (VAF) genes. The presence of AMR, VAF genes, several addition/restriction systems combined with truncated transfer regions, led to the fixation of IncF plasmids in certain ExPEC MDR clones, such as ST131 and ST410. IncF plasmids entered the ST131 ancestral lineage in the mid 1900s and different ST131 clade/CTX-M plasmid combinations coevolved over time. The IncF_CTX-M-15/ST131-C2 subclade combination emerged during the early 2000s, spread rapidly across the globe, and is one of the greatest clone/plasmid successes of the millennium. The ST410-B3 subclade containing blaCTX-M-15 incorporated the NDM-5 carbapenemase gene into existing IncF platforms, providing an additional positive selective advantage that included the carbapenems. A ‘‘plasmid-replacement’’ clade scenario occurred in the histories of ST131 and ST410 as different subclades gained different AMR genes on different IncF platforms. The use of antimicrobial agents will generate selection pressures that enhance the risks for the continuous emergence of MDR ExPEC clone/IncF plasmid combinations. The reasons for clade/IncF replacements and associations between certain clades and specific IncF plasmid types are unknown. Such information will aid in designing management and prevention strategies to combat AMR.Research grants from the JPIAMR/Canadian Institute Health Research program and National Institute of Health. The study is in part supported by NIAID grant R01AI090155.https://www.springer.com/journal/40121am2024Medical MicrobiologySDG-03:Good heatlh and well-bein

The ins and outs of susceptibility testing for new b-lactam/b-lactamase inhibitor combinations for gram-negative organisms

Ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam are among the newest b-lactam/b-lactamase inhibitors (BL/BLIs) introduced to the North American antibiotic market. All have broad Gram-negative activity, including against certain carbapenemases. Despite this, susceptibility testing is warranted due to variable activity against certain b-lactamases (e.g., oxacillinases) and the presence of acquired resistance mechanisms in some isolates. Here, we discuss what we know about these new antimicrobial agents and how to navigate implementation of susceptibility testing and reporting of these agents in clinical laboratories.https://journals.asm.org/journal/jcmMedical Microbiolog

Recent advances in the laboratory detection of carbapenemase-producing Enterobacteriaceae

Carbapenemase-producing Enterobacteriaceae (CPE), mainly Klebsiella pneumoniae and Escherichia coli, have been increasing rapidly on a global scale and are considered to be significant health threats. The most common carbapenemases are KPCs, NDMs, OXA-48-like, IMPs and VIMs but their distribution and prevalence differs between countries. The accurate, simple, cost effective and rapid detection of carbapenemases in clinical laboratories is an important initial step to control the spread of CPE within institutions. The diversity of carbapenemases in general, has challenged a simple approach for the detection of most types of CPE. This article summarizes the current and describes newer techniques available for the detection of carbapenemases among Enterobacteriaceae. The authors also provide a simplified approach for the accurate and rapid detection of CPEs that can easily be implemented in a clinical diagnostic laboratoryCalgary Laboratory Services (#10009392) and Kyoto University Graduate School of Medicine (#10012050).http://www.tandfonline.com/loi/ierz202017-07-31hb2016Medical Microbiolog

Population-based laboratory surveillance of Hafnia alvei isolates in a large Canadian health region

BACKGROUND: Hospital-based series have characterized Hafnia alvei primarily as an infrequent agent of polymicrobial nosocomial infections in males with underlying illness. METHODS: We conducted population-based laboratory surveillance in the Calgary Health Region during 2000–2005 to define the incidence, demographic risk factors for acquisition, and anti-microbial susceptibilities of Hafnia alvei isolates. RESULTS: A total of 138 patients with Hafnia alvei isolates were identified (2.1/100,000/year) and two-thirds were of community onset. Older age and female gender were important risk factors for acquisition. The most common focus of isolation was urine in 112 (81%), followed by lower respiratory tract in 10 (7%), and soft tissue in 5 (4%), and the majority (94; 68%) were mono-microbial. Most isolates were resistant to ampicillin (111;80%), cephalothin (106; 77%), amoxicillin/clavulanate (98; 71%), and cefazolin (95; 69%) but none to imipenem or ciprofloxacin. CONCLUSION: Hafnia alvei was most commonly isolated as a mono-microbial etiology from the urinary tract in women from the community. This study highlights the importance of population-based studies in accurately defining the epidemiology of an infectious disease

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

Population-based Laboratory Surveillance for AmpC β-Lactamase–producing Escherichia coli, Calgary

AmpC β-lactamase–producing E. coli are commonly isolated from the urinary tract of older women

Carbapenemase-producing Klebsiella pneumoniae : a key pathogen set for global nosocomial dominance

The management of infections due to Klebsiella pneumoniae has been complicated by the emergence of antimicrobial resistance, especially to the carbapenems. Resistance to the carbapenems in K. pneumoniae involves multiple mechanisms, including the production of carbapenemases (e.g. KPC, NDM, VIM, OXA-48-like), as well as alterations in outer membrane permeability mediated by the loss of porins, and the up regulation of efflux systems. The latter two mechanisms are often combined with high levels of other types of β-lactamases (e.g.AmpC). K. pneumonaie ST258 emerged during the early to mid-2000s as important human pathogens and has spread extensively throughout the world. ST258 comprises of 2 distinct lineages namely clade I and clade II and it seems that ST258 is a hybrid clone that was created by a large recombination event between ST11 and ST442. Incompatiblity group F plasmids with blaKPC have contributed significantly to the success of ST258. The optimal treatment of infections due to carbapenemase-producing K. pneumoniae remains unknown. Some newer agents show promise for treating infections due to KPC-producers, however effective options for the treatment of NDM-producers remain elusive.This work was supported in part by a research grant from the Calgary Laboratory Services (#10009392).http://aac.asm.org2016-10-13hb201