Tracing carriage, acquisition, and transmission of ESBL-producing Escherichia coli over two years in a tertiary care hospital.

Background: The impact of community carriage on the influx of extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) into hospitals remains understudied. In this prospective 2-year single-centre study, we investigate the community ESBL-E influx and trace the colonisation, nosocomial acquisition, transmission, and infection dynamics of ESBL-producing Escherichia coli (ESBL-Ec) in non-ICU wards at a tertiary care hospital.

Methods: This study reports primary and post hoc outcomes of the clinical trial NCT01208519 in which hospitalised patients were screened for rectal carriage of ESBL-E.

A microbiological and genomic perspective of globally collected Escherichia coli from adults hospitalized with invasive E. coli disease.

Objectives: Escherichia coli can cause infections in the urinary tract and in normally sterile body sites leading to invasive E. coli disease (IED), including bacteraemia and sepsis, with older populations at increased risk. We aimed to estimate the theoretical coverage rate by the ExPEC4V and 9V vaccine candidates.

Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries.

Gram-negative bacteria (GNB) are a major cause of neonatal sepsis in low- and middle-income countries (LMICs). Although the World Health Organization (WHO) reports that over 80% of these sepsis deaths could be prevented through improved treatment, the efficacy of the currently recommended first- and second-line treatment regimens for this condition is increasingly affected by high rates of drug resistance. Here we assess three well known antibiotics, fosfomycin, flomoxef and amikacin, in combination as potential antibiotic treatment regimens by investigating the drug resistance and genetic profiles of commonly isolated GNB causing neonatal sepsis in LMICs.

Assessment of Colistin Heteroresistance among Multidrug-Resistant Isolated from Intensive Care Patients in Europe.

Heteroresistance (HR) to colistin is especially concerning in settings where multi-drug-resistant (MDR) are prevalent and empiric use of colistin might lead to treatment failures. This study aimed to assess the frequency of occurrence of colistin HR (CHR) among (MDR) ( = 676) isolated from patients hospitalized in 13 intensive care units (ICUs) in six European countries in a clinical trial assessing the impact of decolonization strategies. All isolates were whole-genome-sequenced and studied for in vitro colistin susceptibility.

One Health surveillance of colistin-resistant Enterobacterales in Belgium and the Netherlands between 2017 and 2019.

Background: Colistin serves as the last line of defense against multidrug resistant Gram-negative bacterial infections in both human and veterinary medicine. This study aimed to investigate the occurrence and spread of colistin-resistant Enterobacterales (ColR-E) using a One Health approach in Belgium and in the Netherlands.

Methods: In a transnational research project, a total of 998 hospitalized patients, 1430 long-term care facility (LTCF) residents, 947 children attending day care centres, 1597 pigs and 1691 broilers were sampled for the presence of ColR-E in 2017 and 2018, followed by a second round twelve months later for hospitalized patients and animals.

Insight into Antibiotic Synergy Combinations for Eliminating Colistin Heteroresistant .

Colistin heteroresistance has been identified in several bacterial species, including and , and may underlie antibiotic therapy failures since it most often goes undetected by conventional antimicrobial susceptibility tests. This study utilizes population analysis profiling (PAP) and time-kill assay for the detection of heteroresistance in and for evaluating the association between in vitro regrowth and heteroresistance. The mechanisms of colistin resistance and the ability of combination therapies to suppress resistance selection were also analysed.

Patterns of antibiotic use, pathogens, and prediction of mortality in hospitalized neonates and young infants with sepsis: A global neonatal sepsis observational cohort study (NeoOBS).

Background: There is limited data on antibiotic treatment in hospitalized neonates in low- and middle-income countries (LMICs). We aimed to describe patterns of antibiotic use, pathogens, and clinical outcomes, and to develop a severity score predicting mortality in neonatal sepsis to inform future clinical trial design.

Methods And Findings: Hospitalized infants <60 days with clinical sepsis were enrolled during 2018 to 2020 by 19 sites in 11 countries (mainly Asia and Africa).

Structural and Biochemical Features of OXA-517: a Carbapenem and Expanded-Spectrum Cephalosporin Hydrolyzing OXA-48 Variant.

OXA-48-producing Enterobacterales have now widely disseminated throughout the world. Several variants have now been reported, differing by just a few amino-acid substitutions or deletions, mostly in the region of the loop β5-β6. As OXA-48 hydrolyzes carbapenems but lacks significant expanded-spectrum cephalosporin (ESC) hydrolytic activity, ESCs were suggested as a therapeutic option.

Screening of global microbiomes implies ecological boundaries impacting the distribution and dissemination of clinically relevant antimicrobial resistance genes.

Understanding the myriad pathways by which antimicrobial-resistance genes (ARGs) spread across biomes is necessary to counteract the global menace of antimicrobial resistance. We screened 17939 assembled metagenomic samples covering 21 biomes, differing in sequencing quality and depth, unevenly across 46 countries, 6 continents, and 14 years (2005-2019) for clinically crucial ARGs, mobile colistin resistance (mcr), carbapenem resistance (CR), and (extended-spectrum) beta-lactamase (ESBL and BL) genes. These ARGs were most frequent in human gut, oral and skin biomes, followed by anthropogenic (wastewater, bioreactor, compost, food), and natural biomes (freshwater, marine, sediment).

In vitro Activity of Cefiderocol and Comparators against Carbapenem-Resistant Gram-Negative Pathogens from France and Belgium.

Infections with carbapenem-resistant (CR) Gram-negative (GN) pathogens have increased in many countries worldwide, leaving only few therapeutic options. Cefiderocol (CFDC) is approved in Europe for the treatment of aerobic GN infections in adults with limited treatment options. This study evaluated the in vitro activity of cefiderocol and comparators against multidrug-resistant (MDR) bacteria including meropenem-resistant (MR) or pandrug-resistant (PR) GN clinical isolates from France and Belgium.

Characterization of hypervirulent Klebsiella pneumoniae isolates in Belgium.

Hypervirulent Klebsiella pneumoniae (hvKp) raised concern worldwide. We studied 22 hvKp clinical invasive isolates referred to the Belgian national reference laboratory between 2014 and 2020. Sixty-four percent of the isolates expressed K2 capsular serotype and belonged to 7 different MLST lineages, while 32% expressed K1 (all belonging to ST23) and were associated with liver abscesses.

Diversity in the Characteristics of ST101 of Human, Environmental, and Animal Origin.

Background: ST101 is an emerging high-risk clone which exhibits extensive drug resistance. Bacterial strains residing in multiple hosts show unique signatures related to host adaptation. In this study, we assess the genetic relationship of ST101 isolated from hospital samples, the environment, community, and livestock using whole genome sequencing (WGS).

Novel vancomycin resistance gene cluster in ST1486, Belgium, June 2021.

We identified a novel gene cluster in a clinical isolate with vancomycin minimum inhibitory concentration (MIC) of 4 µg/mL. The ligase gene, , was part of a operon cluster of 4,589 bp on a putative novel integrative conjugative element located in a ca 98 kb genomic region presumed to be acquired by horizontal gene transfer from and sp. 499.

COMBACTE LAB-Net: building a European laboratory network for clinical trials on anti-infectives.

LAB-Net, the laboratory network of COMBACTE, has established itself as an indispensable network for clinical trials in infectious diseases that plays a crucial part across 30 clinical studies not only within, but also outside the COMBACTE consortium. Since its official launch in January 2013, LAB-Net has expanded more than threefold and in Q4 2020 it encompasses 841 labs across 41 countries in Europe. In addition, LAB-Net has crossed the European borders and collaborates with more than 300 laboratories spread across the globe.

Phenotypic and molecular characterizations of carbapenem-resistant Acinetobacter baumannii isolates collected within the EURECA study.

Multi-drug-resistant Acinetobacter baumannii isolates are key pathogens that contribute to the global burden of antimicrobial resistance. This study aimed to investigate the phenotypic and molecular characteristics of carbapenem-resistant A. baumannii (CRAB) isolates from the EURECA clinical trial.

resistance to antibiotics in Europe in 2018 and its relationship to antibiotic consumption in the community.

Objective: Our aim was to prospectively assess the antibiotic resistance rates in strains in Europe in 2018 and to study the link between antibiotic consumption in the community and resistance levels in the different countries.

Design: The proportion of primary antibiotic resistance cases of and their corresponding risk factors were investigated in 24 centres from 18 European countries according to a standardised protocol. Data on antibiotic consumption in the community were collected for the period 2008-2017.

Multicenter study of automated systems for colistin susceptibility testing.

Purpose: Broth microdilution (BMD) stays as the reference testing method for determination of antimicrobial susceptibility testing (AST) to colistin and is considered essential for patient management and for monitoring of colistin resistance. This multicenter study aimed to evaluate the performance of automated systems for colistin AST among Enterobacterales as an alternative for BMD since the majority of laboratories use automated systems as first-line method.

Methods: Twenty colistin resistant (COL-R) including 10 MCR producers and 10 colistin-susceptible (COL-S) Enterobacterales isolates were blindly tested for colistin susceptibility with the routine automated AST systems used by 8 laboratories (3 with BD Phoenix, 3 with Vitek2 and 2 with MicroScan).

A single Proteus mirabilis lineage from human and animal sources: a hidden reservoir of OXA-23 or OXA-58 carbapenemases in Enterobacterales.

In Enterobacterales, the most common carbapenemases are Ambler's class A (KPC-like), class B (NDM-, VIM- or IMP-like) or class D (OXA-48-like) enzymes. This study describes the characterization of twenty-four OXA-23 or OXA-58 producing-Proteus mirabilis isolates recovered from human and veterinary samples from France and Belgium. Twenty-two P.

Evaluation of the Novodiag CarbaR+, a Novel Integrated Sample to Result Platform for the Multiplex Qualitative Detection of Carbapenem and Colistin Resistance Markers.

This study evaluated the performance of the Novodiag CarbaR+ an automated qualitative nucleic acid-based diagnostic assay detecting the , , , , , , , , and IS1 associated carbapenemase genes and colistin resistance gene from clinical isolates or directly from rectal swabs. CarbaR+ was evaluated on 201 clinical isolates and on 100 rectal swabs (80 selected swabs from patients that were evaluated by culture method and/or Xpert Carba-R assay and 20 spiked samples). PCR-sequencing on colonies was considered as the gold standard.

Optimization of the MALDIxin test for the rapid identification of colistin resistance in Klebsiella pneumoniae using MALDI-TOF MS.

Background: With the dissemination of carbapenemase producers, a revival of colistin was observed for the treatment of infections caused by MDR Gram-negatives. Unfortunately, the increasing usage of colistin led to the emergence of resistance. In Klebsiella pneumoniae, colistin resistance arises through addition of 4-amino-l-arabinose (l-Ara4N) or phosphoethanolamine (pEtN) to the native lipid A.

A recurrent and transesophageal echocardiography-associated outbreak of extended-spectrum β-lactamase-producing complex in cardiac surgery patients.

Background: We report a recurrent outbreak of postoperative infections with extended-spectrum β-lactamase (ESBL)-producing complex in cardiac surgery patients, describe the outbreak investigation and highlight the infection control measures.

Methods: Cases were defined as cardiac surgery patients in Ghent University Hospital who were not known preoperatively to carry ESBL-producing complex and who postoperatively had a positive culture for this multiresistant organism between May 2017 and January 2018. An epidemiological investigation, including a case-control study, and environmental investigation were conducted to identify the source of the outbreak.

Prevalence of multidrug-resistant organisms in nursing homes in Belgium in 2015.

Objectives: Following two studies conducted in 2005 and 2011, a third prevalence survey of multidrug-resistant microorganisms (MDRO) was organised in Belgian nursing homes (NHs) using a similar methodology. The aim was to measure the prevalence of carriage of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), extended-spectrum β-lactamase producing Enterobacteriaceae (ESBLE) and carbapenemase-producing Enterobacteriaceae (CPE) in NH residents. Risk factors for MDRO carriage were also explored.

Evaluation of the RESIST-4 K-SeT assay, a multiplex immunochromatographic assay for the rapid detection of OXA-48-like, KPC, VIM and NDM carbapenemases.

Objectives: Accurate and fast identification of carbapenemase producers is essential for optimal patient management. Here, a new lateral flow immunochromatographic RESIST-4 K-SeT assay was assessed for the detection of carbapenemases in Enterobacteriaceae and non-fermenters.

Methods: The RESIST-4 K-SeT assay targets OXA-48-like, KPC, VIM and NDM, but not IMP carbapenemases.