Genetic diversity, biochemical properties, epidemiology, and detection methods of IMP- and VIM-type carbapenemases.

SUMMARYMetallo-beta-lactamases are an ever-growing problem. Since the discovery of the beta-lactamase of in the late 1960s, many class B beta-lactamases have been reported, with three main families being NDM-, IMP-, and VIM-like. IMP- and VIM-like carbapenemases have been identified in a wide variety of Gram-negative bacteria.

A novel multilocus sequence typing scheme for Morganella spp.: population structure and introduction of quantitative metric for standardization of MLST scheme.

Objectives: Morganella are opportunistic pathogens increasingly reported in clinical settings. While their phylogeny has been recently updated, no multilocus sequence typing (MLST) scheme is currently available. Developing a MLST scheme can be challenging due to the absence of a strict definition for housekeeping gene selection.

Characterization of Carbapenemase-producing Enterobacterales isolated from patients returning from Sub-Saharan Africa, France, 2015-2022.

Objectives: The rise of carbapenemase-producing Enterobacterales (CPE) represents a major public health threat, as highlighted in numerous reports from international health organizations. However, a significant data gap remains for certain regions, particularly Sub-Saharan Africa (SSA). The aim of this study is to characterize CPE isolates from patients returning from SSA at both phenotypic and genomic levels.

Inoculum effect of cefiderocol against NDM-1 producing Escherichia coli in vitro and in a murine model of peritonitis.

Introduction: Cefiderocol is a siderophore cephalosporin active in vitro against carbapenemase-producing Enterobacterales, including New Delhi metallo-β-lactamases (NDM-1). A significant impact of the size of bacterial inoculum on its efficacy has been described in vitro, the clinical impact of which is unclear. Here, we analyse the inoculum effect of cefiderocol against E.

Evaluation of the Reveal AST (SPECIFIC) for Antimicrobial Susceptibility Testing from Positive Blood Culture Spiked with Carbapenem-Resistant Isolates.

As bloodstream infections and associated septic shock are common causes of mortality in hospitals, rapid antibiotic susceptibility testing (AST) performed directly on positive blood cultures is needed to implement an efficient therapy in clinical settings. We evaluated the Reveal rapid AST system on a collection of 197 fully characterized carbapenem-resistant Enterobacterales, including 177 carbapenemase producers (CPE) spiked in blood culture bottles. The clinical categorization based on the Minimal Inhibitory Concentration (MIC) determination of eighteen antimicrobial molecules was compared to the clinical categorization based on the disk diffusion assay as a reference.

Oxacillinase-484-Producing Enterobacterales, France, 2018-2023.

We examined the emergence and characteristics of oxacillinase-484-producing Enterobacterales in France during 2012-2023. Genomic analysis identified 2 predominant sequence types in Escherichia coli: ST410 and ST1722. Plasmid analysis revealed that bla genes were carried mostly on an IncX3-type plasmid associated with genetic elements including insertion sequences IS3000 and ISKpn19.

Genetic and biochemical characterization of OXA-1186, a novel OXA-198-type carbapenemase hydrolysing cephalosporins in Citrobacter freundii.

Objectives: This study described OXA-1186, a novel carbapenemase related to OXA-198 carbapenemase and produced by a clinical isolate of Citrobacter freundii.

Methods: WGS was used to characterize the resistome, virulome and plasmid types of the C. freundii 315C8 isolate and to reconstruct the blaOXA-1186-carrying plasmid.

IMI-Type Carbapenemase-Producing Enterobacter cloacae Complex, France and Overseas Regions, 2012-2022.

We characterized a collection of IMI-like-producing Enterobacter spp. isolates (n = 112) in France. The main clone corresponded to IMI-1-producing sequence type 820 E.

enteritis associated with bacteremia, spondylodiscitis, and late CIED-related endocarditis, a case report.

Campylobacter sp. is widely considered a leading causative agent of bacterial food-borne gastrointestinal illness. Discitis and endocarditis caused by spp.

Nationwide molecular epidemiology of carbapenemase-producing spp. in France in 2019 and 2020.

The emergence of carbapenemase producers in Enterobacterales mostly involves , , and complex species. However, in France, we observed the emergence and the rapid dissemination of carbapenemase in spp. In this study, we demonstrated that a wide variety of carbapenemases is produced by many different species of spp.

Multidrug-resistant Enterobacterales responsible for septicaemia in a neonatal intensive care unit in Morocco.

Objectives: Neonatal sepsis caused by multidrug-resistant (MDR) bacteria has a high morbidity and mortality, especially in low- and middle-income countries. Here, the molecular mechanisms of multidrug resistance in bacteria responsible for neonatal sepsis were determined.

Methods: From July to December 2019, documented bacteraemia from 524 neonates hospitalised in a neonatal intensive care unit in Morocco were collected.

Evaluation of ceftolozane-tazobactam susceptibility on a French nationwide collection of Enterobacterales.

Objectives: Ceftolozane-tazobactam (C/T) proved its efficacy for the treatment of infections caused by non-carbapenemase producing Pseudomonas aeruginosa and Enterobacterales. Here, we aimed to provide susceptibility data on a large series of Enterobacterales since the revision of EUCAST categorization breakpoints in 2020.

Methods: First, C/T susceptibility was determined on characterized Enterobacterales resistant to third generation cephalosporins (3GCs) (extended spectrum β-lactamase [ESBL] production or different levels of AmpC overexpression) (n = 213) and carbapenem-resistant Enterobacterales (CRE) (n = 259), including 170 carbapenemase producers (CPE).

In Vitro Activity of Imipenem-Relebactam, Meropenem-Vaborbactam, Ceftazidime-Avibactam and Comparators on Carbapenem-Resistant Non-Carbapenemase-Producing Enterobacterales.

Background: Avibactam, relebactam and vaborbactam are β-lactamase inhibitors that proved their efficiency against KPC-producing Enterobacterales. Regarding their inhibitor activity towards Ambler’s class A extended spectrum β-lactamases (ESBL) and Ambler’s class C cephalosporinase (AmpC), they should be active on most of the carbapenem-resistant non-carbapenemase-producing Enterobacterales (CR non-CPE). Objectives: Determine the in vitro activity of ceftazidime-avibactam, imipenem-relebactam and meropenem-vaborbactam and comparators against CR non-CPE.

Polyclonal Dissemination of OXA-232 Carbapenemase-Producing Klebsiella pneumoniae, France, 2013-2021.

During 2013-2021, increased prevalence of oxacillinase 232-producing Enterobacterales was observed in France, mostly driven by its emergence in Klebsiella pneumoniae. Whole-genome sequencing identified that oxacillinase 232-producing K. pneumoniae belonged to 14 sequence types (STs), among which 2 polyclonal high-risk clones, ST-231 and ST-2096, were overrepresented.

Susceptibility of OXA-48-producing Enterobacterales to imipenem/relebactam, meropenem/vaborbactam and ceftazidime/avibactam.

Relebactam and vaborbactam are among the newest β-lactamase inhibitors marketed. They were originally designed to inhibit the Ambler class A carbapenemase KPC. In this study, susceptibility to imipenem/relebactam and meropenem/vaborbactam was determined against a collection of OXA-48-like-producing Enterobacterales (n = 407).

Activity of mecillinam against carbapenem-resistant Enterobacterales.

Background: Despite the fact that carbapenem-resistant Enterobacterales (CRE) mostly cause urinary tract infections (UTIs), only few studies have focused on the efficacity of mecillinam against these CRE.

Objectives: To evaluate the mecillinam susceptibility of a huge collection of CRE, including carbapenemase-producing Enterobacterales (CPE) and non-CPE (ESBL and AmpC producers with decreased permeability of the outer membrane).

Methods: A total of 8310 non-duplicate clinical CRE, including 4042 OXA-48-like producers, 1094 NDM producers, 411 VIM producers, 174 KPC producers, 42 IMI producers, 153 multiple-carbapenemase producers and 45 isolates producing other types of carbapenemases (such as IMP-like enzymes or GES-5), were included in the study.

Comparison of disk diffusion, MIC test strip and broth microdilution methods for cefiderocol susceptibility testing on carbapenem-resistant enterobacterales.

Objectives: Cefiderocol is a catechol-substituted cephalosporin dedicated to the treatment of infections caused by multidrug resistant gram-negative rods. Cefiderocol susceptibility testing might be complex. We compared cefiderocol susceptibility testing methods on a relevant collection of carbapenem-resistant Enterobacterales.

Outbreak of CTX-M-15 Extended-Spectrum β-Lactamase-Producing ST394 in a French Intensive Care Unit Dedicated to COVID-19.

Infections caused by extended-spectrum β-lactamase-producing (ESBL-KP) are constantly rising worldwide and are often reported as causative agent of outbreaks in intensive care units (ICUs). During the first wave of the COVID-19 pandemic, bacterial cross-transmission was thought unlikely to occur due to the reinforcement of hygiene measures and prevention control. However, we report here an ESBL-producing (ST394) isolate responsible for a nosocomial outbreak in an ICU dedicated to COVID-19 patients.

KPC-39-Mediated Resistance to Ceftazidime-Avibactam in a Klebsiella pneumoniae ST307 Clinical Isolate.

Resistance to the ceftazidime (CAZ)-avibactam (AVI) combination is increasingly being reported. Here, we report a CAZ-AVI-resistant Klebsiella pneumoniae strain belonging to the high-risk sequence type 307 (ST307) clone and producing Klebsiella pneumoniae carbapenemase 39 (KPC-39), a single-amino-acid variant of KPC-3 (A172T). Cloning experiments, steady-state kinetic parameters, and molecular dynamics simulations revealed a loss of carbapenemase activity and increased affinity for CAZ.

Emergence and Polyclonal Dissemination of OXA-244-Producing Escherichia coli, France.

Since 2016, OXA-244-producing Escherichia coli has been increasingly isolated in France. We sequenced 97 OXA-244-producing E. coli isolates and found a wide diversity of sequence types and a high prevalence of sequence type 38.

Genetic Diversity, Biochemical Properties, and Detection Methods of Minor Carbapenemases in Enterobacterales.

Gram-negative bacteria, especially Enterobacterales, have emerged as major players in antimicrobial resistance worldwide. Resistance may affect all major classes of anti-gram-negative agents, becoming multidrug resistant or even pan-drug resistant. Currently, β-lactamase-mediated resistance does not spare even the most powerful β-lactams (carbapenems), whose activity is challenged by carbapenemases.