Nordmann poirel

OBJECTIVES: To evaluate the occurrence of plasmid-mediated fos genes among fosfomycin-resistant Escherichia coli isolates collected from patients in Lisbon, Portugal, and characterize the fos-positive strains. METHODS: A total of 19,186 E. coli isolates were prospectively collected between April 2022 and January 2023 from inpatients and outpatients at a private laboratory in Lisbon. Fosfomycin resistance was initially assessed by semi-automated systems and further confirmed by the disc diffusion method...

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OBJECTIVES: The treatment options for infections caused by carbapenem-resistant Enterobacterales are scarce and the development of new antibiotics is an urgent necessity. Imipenem/relebactam (IPR) has been recently introduced for treating severe infections related to multidrug-resistant bacteria. However, IPR resistance has already been reported in Enterobacterales, thus its rapid detection may be interesting for clinical decision-making. The aim of the study was to develop a rapid and accurate test, namely the Rapid IPR NP test, for the identification of IPR resistance among multidrug-resistant Enterobacterales...

OBJECTIVES: Resistance genes can be genetically transmitted and exchanged between commensal and pathogenic bacterial species, and in different compartments including the environment, or human and animal guts (One Health concept). The aim of our study was to evaluate whether subdosages of antibiotics administered in veterinary medicine could enhance plasmid transfer and, consequently, resistance gene exchange in gut microbiota. METHODS: Conjugation frequencies were determined with Escherichia coli strains carrying IncL- (blaOXA-48) or IncI1-type (blaCTX-M-1) plasmids subjected to a series of subinhibitory concentrations of antibiotics used in veterinary medicine, namely amoxicillin, ceftiofur, apramycin, neomycin, enrofloxacin, colistin, erythromycin, florfenicol, lincomycin, oxytetracycline, sulfamethazine, tiamulin and the ionophore narasin...

Following the observation of an increased number of isolation of OXA-23- and ArmA-producing Acinetobacter baumannii at the national level, our aim was to evaluate whether some given clone(s) might actually be spreading and/or emerging in Switzerland. To evaluate this possibility, our study investigated and characterized all A. baumannii isolates harboring both the blaOXA-23 and armA genes that had been collected at the Swiss National Reference Center for Emerging Antibiotic Resistance (NARA) from 2020 to 2021...

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Cefiderocol (FDC) is a siderophore cephalosporin with a broad spectrum of activity against many multidrug-resistant Gram-negative bacteria. Acquired resistance to FDC has been already reported among Gram-negative isolates, thus highlighting the need for rapid and accurate identification of such resistant pathogens, in order to control their spread. Therefore, the SuperFDC medium was developed to screen FDC-resistant Enterobacterales , Pseudomonas aeruginosa, and Acinetobacter baumannii. After testing several culture conditions, a selective medium was set up by supplementing an iron-depleted agar medium with 8 μg/mL of FDC and evaluated with a collection of 68 FDC-susceptible and 33 FDC-resistant Gram-negative isolates exhibiting a variety of β-lactam resistance mechanisms...

Acinetobacter baumannii is a Gram-negative bacterium increasingly implicated in hospital-acquired infections and outbreaks. Effective prevention and control of such infections are commonly challenged by the frequent emergence of multidrug-resistant strains. Here we introduce Ab-web (https://www.acinetobacterbaumannii.no), the first online platform for sharing expertise on A. baumannii . Ab-web is a species-centric knowledge hub, initially with 10 articles organized into two main sections, 'Overview' and 'Topics', and three themes, 'epidemiology', 'antibiotic resistance', and 'virulence'...

The impact of broad-spectrum β-lactamases on the susceptibility to novel β-lactamase/β-lactamase inhibitor combinations was evaluated both in Pseudomonas aeruginosa and Escherichia coli using isogenic backgrounds. Cefepime-zidebactam displayed low MICs, mainly due to the significant intrinsic antibacterial activity of zidebactam. Cefepime-taniborbactam showed excellent activity against recombinant E. coli strains, including metallo-β-lactamase producers, whereas aztreonam-avibactam remained the best therapeutic option against class B β-lactamase-producing P...

The in vitro activity of imipenem-relebactam, meropenem-vaborbactam, ceftazidime-avibactam, and cefiderocol was evaluated against both clinical and isogenic enterobacterial isolates producing carbapenemases of the SME, NmcA, FRI, and IMI types. Ceftazidime-avibactam and meropenem-vaborbactam showed the highest activity against all tested isolates; imipenem-relebactam showed only moderate activity. All isolates remained susceptible to cefiderocol. Furthermore, avibactam and vaborbactam have greater inhibitory activity than relebactam against the tested carbapenemases...

BACKGROUND: Aztreonam/avibactam is one of the last therapeutic options for treating infections caused by NDM-like-producing Enterobacterales. However, PBP3-modified and NDM-producing Escherichia coli strains that co-produce CMY-42 have been shown to be resistant to this drug combination. The aim of our study was to assess the in vitro activity of cefepime/taniborbactam and cefepime/zidebactam against such aztreonam/avibactam-resistant E. coli strains. METHODS: MIC values of aztreonam, aztreonam/avibactam, cefepime, cefepime/taniborbactam, cefepime/zidebactam and zidebactam alone were determined for 28 clinical aztreonam/avibactam-resistant E...

Klebsiella oxytoca complex ( Ko C) species may overproduce their chromosomal class A OXY β-lactamases, conferring reduced susceptibility to piperacillin-tazobactam, expanded-spectrum cephalosporins and aztreonam. Moreover, since clavulanate maintains its ability to inhibit these enzymes, the resulting resistance phenotype may falsely resemble the production of acquired extended-spectrum β-lactamases (ESBLs). In this work, a collection of 44 Ko C strains of human and animal origin was characterized with whole-genome sequencing (WGS) and broth microdilution (BMD) susceptibility testing...

Carbapenem-resistant Enterobacterales, including KPC-producing Klebsiella pneumoniae, represent a major threat to public health due to their rapid spread. The beta-lactam/beta-lactamase inhibitor (BL/BLI) combination ceftazidime-avibactam (CAZ-AVI) has recently been introduced and shown to exhibit excellent activity toward multidrug-resistant KPC-producing Enterobacterales strains. However, CAZ-AVI-resistant K. pneumoniae isolates are being increasingly reported, mostly corresponding to producers of KPC variants that confer resistance to CAZ-AVI but at a cost of carbapenem resistance...

Increasing occurrence of multidrug-resistant (MDR) and hypervirulent (hv) Klebsiella pneumoniae (MDR-hvKp) convergent clones is being observed. Those strains have the potential of causing difficult-to-treat infections in healthy adults with an increased capacity for mortality. It is therefore crucial to track their dissemination to prevent their further spread. The aim of our study was to investigate the occurrence of carbapenemase-producing hvKp isolates in Switzerland and to determine their genetic profile...

OBJECTIVES: A novel ß-lactam-β-lactamase inhibitor (BLBI), meropenem (MEM), combined with the boronate-based inhibitor vaborbactam (VAB), has recently been introduced for the treatment of infections caused by Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales. The purpose of this study was to select for MEM-VAB resistance using a collection of eight KPC-producing K. pneumoniae clinical isolates, including three that produce KPC variants conferring ceftazidime-avibactam (CAZ-AVI) resistance, and subsequently decipher the corresponding resistance mechanisms...

A rapid (<3 hours) and reliable multiplex PCR was developed for detecting simultaneously known plasmid-mediated fos genes conferring acquired resistance to fosfomycin. Our technique was tested on a collection of Escherichia coli isolates previously identified as bearing the fosA-, fosC- and fosL-like genes, showing a sensitivity and a specificity of 100%.

We report in vivo development of cefiderocol (FDC) resistance among four sequential Pseudomonas aeruginosa clinical isolates ST244 recovered from a single patient, without exposure to FDC, which raises concern about the effectiveness of this novel drug. The first recovered P. aeruginosa isolate (P-01) was susceptible to FDC (2 μg/mL), albeit this MIC value was higher than that of a wild-type P. aeruginosa (0.12-0.25 μg/ml). The subsequent isolated strains (P-02, P-03, P-04) displayed increasing levels of FDC MICs (8, 16, and 64 μg/ml, respectively)...

An extensively drug-resistant Escherichia coli clinical isolate (N1606) belonging to Sequence Type 361 was recovered from the urine of a patient hospitalized in Switzerland. The strain showed resistance to virtually all β-lactams including the latest generation antibiotics cefiderocol and aztreonam-avibactam. Whole genome sequencing revealed that it possessed two carbapenemase-encoding genes, namely bla NDM-5 and bla KPC-3 , and a series of additional β-lactamase genes, including bla CTX-M-15 and bla SHV-11 encoding extended-spectrum β-lactamases (ESBLs), bla CMY-145 encoding an AmpC-type cephalosporinase, and bla OXA-1 encoding a narrow-spectrum class D ß-lactamase...

OBJECTIVES: To evaluate the in vitro activity of aztreonam in combination with novel β-lactamase inhibitors, namely avibactam, nacubactam, taniborbactam and zidebactam, against MDR MBL-producing Enterobacterales and Pseudomonas aeruginosa clinical isolates. METHODS: MIC values of aztreonam, aztreonam/β-lactam inhibitor but also cefiderocol as comparator were determined for 64 and 39 clinical Enterobacterales or P. aeruginosa isolates, respectively, producing representative MBLs, i...

BACKGROUND: Cefiderocol is among the latest generation of commercialized antibiotics against a large variety of MDR Gram-negative bacteria including carbapenem-resistant Enterobacterales and non-fermenters such as Pseudomonas aeruginosa and Acinetobacter baumannii. Cefiderocol susceptibility testing, a key element for implementing rapidly a cefiderocol-based treatment, might be still challenging. OBJECTIVES: To develop a rapid culture-based test, Rapid Cefiderocol NP test, for the identification of cefiderocol resistance among MDR Enterobacterales...