The contributions of multidrug resistant clones to the success of pandemic extra-intestinal Pathogenic Escherichia coli.

INTRODUCTION: High-risk multidrug (MDR) clones have played essential roles in the global emergence and spread of antimicrobial resistance (AMR), especially among Extra-intestinal Escherichia coli (ExPEC). AREAS COVERED: Successful global ExPEC MDR clones are linked with the acquisition of fluoroquinolone resistance, CTX-M enzymes, and with carbapenemases. This article described the underlying mechanisms of fluoroquinolone resistance, the acquisition of CTX-M and carbapenemase genes among three global ExPEC high-risk MDR clones, namely i) ST1193 as being an example of a fluoroquinolone resistant clone. ii) ST131 as an example of a fluoroquinolone resistant and CTX-M clone. iii) ST410 as an example of a fluoroquinolone resistant, CTX-M and carbapenemase clone. This article also highlighted the contributions of these MDR determinants in the evolution of these high-risk MDR clones. EXPERT OPINION: There is an enormous public health burden due to E. coli MDR high-risk clones such as ST1193, ST131 and ST410. These clones have played pivotal roles in the global spread of AMR. Sparse information is available on which specific features of these high-risk MDR clones have enabled them to become such successful global pathogens in relative short time periods.

Molecular epidemiology of extended-spectrum beta-lactamase-producing extra-intestinal pathogenic Escherichia coli strains over a 2-year period (2017-2019) from Zimbabwe.

This study was designed to characterize extended-spectrum beta-lactamase (ESBL)-producing extra-intestinal pathogenic Escherichia coli (E.coli) (ExPEC) associated with urinary tract infections in nine different geographic regions of Zimbabwe over a 2-year period (2017-2019). A total of 48 ESBL-positive isolates from urine specimen were selected for whole-genome sequencing from 1246 Escherichia coli isolates biobanked at the National Microbiology Reference laboratory using phenotypic susceptibility testing results from the National Escherichia coli Surveillance Programme to provide representation of different geographical regions and year of isolation. The majority of ESBL E. coli isolates produced cefotaximase-Munich (CTX-M)-15, CTX-M-27, and CTX-M-14. In this study, sequence types (ST) 131 and ST410 were the most predominant antimicrobial-resistant clones and responsible for the increase in ESBL-producing E. coli strains since 2017. Novel ST131 complex strains were recorded during the period 2017 to 2018, thus showing the establishment and evolution of this antimicrobial-resistant ESBL clone in Zimbabwe posing an important public health threat. Incompatibility group F plasmids were predominant among ST131 and ST410 isolates with the following replicons recorded most frequently: F1:A2:B20 (9/19, 47%), F2:A1: B (5/19, 26%), and F1:A1:B49 (8/13, 62%). The results indicate the need for continuous tracking of different ESBL ExPEC clones on a global scale, while targeting specific STs (e.g. ST131 and ST410) through control programs will substantially decrease the spread of ESBLs among ExPEC.

Rapid detection of Enterobacterales that produce carbapenemases.

PURPOSE: The rapid detection of carbapenemases among Enterobacterales in clinical laboratories is critical for management of patients, and infection prevention and control efforts. METHODS: A study was designed to evaluate the performances of the RAPIDEC CARBA NP®, ß-CARBA®, NG-Test CARBA 5®, modified carbapenem-inactivation method, and EDTA version (eCIM) assays against a global collection of Enterobacterales (n = 216) with diverse carbapenemases. RESULTS: The RAPIDEC CARBA NP® assay had a sensitivity of 98.6% and specificity of 19.6% and ß-CARBA® a sensitivity of 94% and specificity of 97.8%, but showed low sensitivity with Klebsiella Pneumoniae Carbapenemase (KPC)-containing isolates. The NG-Test CARBA 5® had an overall sensitivity of 96.3% and specificity of 100% and failed to detect isolates with blaIMP-13, blaIMP-14. The eCIM gave false- positive results with Oxacillinase (OXA)-48-like enzymes. CONCLUSION: The NG-Test CARBA 5® assay was technically simple and provided rapid accurate results on the types of carbapenemases. Such information has potential treatment benefits for patients.

Differences in risk-factor profiles between patients with ESBL-producing Escherichia coli and Klebsiella pneumoniae: a multicentre case-case comparison study.

BACKGROUND: Generic epidemiological differences between extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (ESBL-EC) and Klebsiella pneumoniae (ESBL-KP), are poorly defined. Nonetheless, defining such differences and understanding their basis could have strategic implications for infection control policy and practice. METHODS: Between 2009 and 2011 patients with bacteraemia due to ESBL-EC or ESBL-KP across all three acute hospitals in the city of Auckland, New Zealand, were eligible for inclusion. Recognised risk factors for ESBL bacteraemia were compared between species in a retrospective case-case study design using multivariate logistic regression. Representative isolates underwent ESBL gene characterisation and molecular typing. RESULTS: 170 patients and 176 isolates were included in the study (92 patients with ESBL-EC, 78 with ESBL-KP). 92.6% had CTX-Ms. 39% of EC were ST131 while 51% of KP belonged to 3 different STs (i.e. ST20, ST48 & ST1087). Specific sequence types were associated with specific hospitals for ESBL-KP but not ESBL-EC. Variables positively associated with ESBL-EC on multivariate analysis were: community acquired infection (odds ratio [OR] 7.9; 95% CI: 2.6-23.9); chronic pulmonary disease (OR 5.5; 95% CI: 1.5-20.1); and high prevalence country of origin (OR 4.3; 95% CI: 1.6-11.6). Variables negatively associated with ESBL-EC were previous transplant (OR 0.06; 95% CI: 0.007-0.6); Hospital 2 (OR 0.3; 95% CI: 0.1-0.7) and recent ICU admission (OR 0.3; 95% CI: 0.07-0.9). CONCLUSIONS: Differences in risk profiles between patients with ESBL-EC and ESBL-KP suggest fundamental differences in transmission dynamics. Understanding the biological basis for these differences could have implications for infection control practice. Tailoring of infection control measures according to ESBL species may be indicated in some instances.

Population-based surveillance for hypermucoviscosity Klebsiella pneumoniae causing community-acquired bacteremia in Calgary, Alberta.

The characteristics of hypermucoviscosity isolates among Klebsiella pneumoniae causing community-acquired bacteremia were investigated. The hypermucoviscous phenotype was present in 8.2% of K pneumoniae isolates, and was associated with rmpA and the K2 serotype; liver abscesses were the most common clinical presentation. The present analysis represents the first population-based surveillance study of hypermucoviscosity among K pneumoniae causing bacteremia.

Les chercheurs ont examiné les caractéristiques des isolats d'hypermucoviscosité en cas de Klebsiella pneumoniae responsable de bactériémie d'origine non nosocomiale. Ils ont constaté la présence du phénotype hypermucovisqueuxdans 8,2 % des isolats de K pneumoniae, qui s'associait au rmpA et au sérotype K2. Les abcès hépatiques en étaient la présentation clinique la plus courante. La présente analyse est la première étude de surveillance en population de l'hypermucoviscosité en cas de K pneumoniae responsable d'une bactériémie.

Antimicrobial resistance surveillance systems: Are potential biases taken into account?

BACKGROUND: The validity of surveillance systems has rarely been a topic of investigation. OBJECTIVE: To assess potential biases that may influence the validity of contemporary antimicrobial-resistant (AMR) pathogen surveillance systems. METHODS: In 2008, reports of laboratory-based AMR surveillance systems were identified by searching Medline. Surveillance systems were appraised for six different types of bias. Scores were assigned as '2' (good), '1' (fair) and '0' (poor) for each bias. RESULTS: A total of 22 surveillance systems were included. All studies used appropriate denominator data and case definitions (score of 2). Most (n=18) studies adequately protected against case ascertainment bias (score = 2), with three studies and one study scoring 1 and 0, respectively. Only four studies were deemed to be free of significant sampling bias (score = 2), with 17 studies classified as fair, and one as poor. Eight studies had explicitly removed duplicates (score = 2). Seven studies removed duplicates, but lacked adequate definitions (score = 1). Seven studies did not report duplicate removal (score = 0). Eighteen of the studies were considered to have good laboratory methodology, three had some concerns (score = 1), and one was considered to be poor (score = 0). CONCLUSION: Contemporary AMR surveillance systems commonly have methodological limitations with respect to sampling and multiple counting and, to a lesser degree, case ascertainment and laboratory practices. The potential for bias should be considered in the interpretation of surveillance data.

Clinical outcome of empiric antimicrobial therapy of bacteremia due to extended-spectrum beta-lactamase producing Escherichia coli and Klebsiella pneumoniae.

BACKGROUND: Prompt administration of adequate empiric antimicrobial therapy is a major determinant influencing the outcome of serious infections. The objective of this study was to describe empiric antimicrobial therapy employed and assess its effect on the outcome of patients bacteremic with extended-spectrum beta-lactamase (ESBL) producing Escherichia coli and Klebsiella pneumoniae. FINDINGS: A retrospective surveillance study of all patients with bacteremias caused by ESBL-producing E. coli and K. pneumoniae (EK-ESBL) from 2000-2007 in the Calgary Health Region was conducted. Data were available for 79 episodes of bacteremia among 76 patients. Forty-four (56%) were male, the median age was 70.0 yrs [interquartile range (IQR) 60.6-70.1 yrs], and 72 (91%) episodes were E. coli. Seventy-four episodes (94%) were treated with empiric therapy within the first 48 hours. A non-statistically significant increased mortality occurred in those treated empirically with a beta-lactam/beta-lactamase inhibitor combination (6/16; 38% vs. 10/53; 18%; p = 0.063) while empiric carbapenem therapy was associated with lower mortality (0/10 died vs. 16/53 (30%), p = 0.089). Only 42 (53%) episodes received adequate therapy within the first 48 hours. The median time to first adequate antibiotic therapy was 41.0 hours [IQR 5.8-59.5] (n = 75). The case-fatality rate was not different among those that received adequate compared to inadequate therapy by 48 hours as compared to inadequate empiric therapy (9/42; 21% vs. 7/37; 19%; p = 1.0). CONCLUSION: Inadequate empiric therapy is common among patients with EK-ESBL bacteremia in our region but was not associated with adverse mortality outcome.

Recent changes in the epidemiology and management of extended-spectrum ß-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 ß-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.