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Patrice Nordmann

Publications and source records attributed to Patrice Nordmann.

At least 19 recordsLinked to original sources
PubMed2026

Mechanisms of cefiderocol resistance in carbapenem-resistant Acinetobacter baumannii: a Swiss 2023-2025 collection.

OBJECTIVES: The numbers of infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) are increasing globally and present a significant burden on healthcare systems. This study describes the CRAB isolates received at the Swiss National Reference Centre for Emerging Antibiotic Resistance (NARA) over a 3-year period, from January 2022 to December 2025, and aimed to characterize the prevalence and mechanisms of FDC resistance. METHODS: Two-hundred and thirty-four non-duplicate CRAB isolates were submitted to NARA over the study period from hospitals and laboratories across Switzerland. Susceptibility testing was performed by disk diffusion and broth microdilution, according to EUCAST methodology. Whole-genome sequencing was performed on 11 isolates. ADC alleles were cloned into vector pVRL1 and transformed into Escherichia coli Top10. RESULTS: All isolates exhibited resistance to the carbapenems, and most were resistant to cephalosporins. Most isolates harboured an acquired class D carbapenemase, most frequently OXA-23 (181/234; 77.4%). One quarter of isolates were resistant to cefiderocol (FDC), exhibiting MICs ranging from 4->32 mg/L. Whole genome sequencing analyses, performed on 11 FDC-resistant isolates, identified that FDC resistance was due a combination of mechanisms including NDM and PER-production, mutations within the iron transporters, piuA and pirA, and the overexpression of ADC variants. CONCLUSIONS: This study showed that OXA-23 was the dominant mechanism of carbapenem-resistance in CRAB in Switzerland. Almost one quarter of CRAB isolates were resistant to "last resort" antimicrobial, FDC. The mechanisms of FDC resistance identified in this study emphasise that resistance to this antimicrobial is often complex and multifactorial, requiring high-resolution methods, including WGS, to identify.

Acinetobacter baumannii↗
PubMed2007

Metallo-beta-lactamases as emerging resistance determinants in Gram-negative pathogens: open issues.

The rapid spread of acquired metallo-beta-lactamases (MBLs) among major Gram-negative pathogens is a matter of particular concern worldwide and primarily in Europe, one of first continents where the emergence of acquired MBLs has been reported and possibly the geographical area where the increasing diversity of these enzymes and the number of bacterial species affected are most impressive. This spread has not been paralleled by accuracy/standardisation of detection methods, completeness of epidemiological knowledge or a clear understanding of what MBL production entails in terms of clinical impact, hospital infection control and antimicrobial chemotherapy. A number of European experts in the field met to review the current knowledge on this phenomenon, to point out open issues and to reinforce and relate to one another the existing activities set forth by research institutes, scientific societies and European Union-driven networks.

Anti-Bacterial Agents↗
PubMed2007

Genetics and expression of the carbapenem-hydrolyzing oxacillinase gene blaOXA-23 in Acinetobacter baumannii.

The genetic structures surrounding the plasmid-carried blaOXA-23 oxacillinase gene, encoding resistance to carbapenems, were studied in Acinetobacter baumannii. ISAba1 and the novel element ISAba4 were detected upstream of the blaOXA-23 gene, providing promoter sequences for its expression. These insertion elements were likely involved in transposition processes at the origin of acquisition of this beta-lactamase gene.

Acinetobacter baumannii↗
PubMed2006

CTX-M: changing the face of ESBLs in Europe.

Since around 2000 - earlier in Poland and Spain and later in France and the UK - dramatic shifts have occurred in the prevalence and types of extended-spectrum beta-lactamases (ESBLs) in Europe. Before this watershed, most producers were nosocomial isolates, often Klebsiella spp. or Enterobacter spp. from specialist care units, and had mutant TEM or SHV ESBLs. Subsequently, CTX-M ESBLs have become dominant, with much greater penetration into Escherichia coli, and with many infections in 'complicated community' patients, usually with underlying disease, recent antibiotic usage, or healthcare contact. The degree of clonality among producers varies with the country, as does the enzyme type produced, with group 9 (CTX-M-9 and -14) enzymes dominant in Spain and group 1 enzymes (particularly CTX-M-3 and -15) dominant elsewhere. Irrespective of the particular enzyme, most producers are multiresistant. These changing patterns present major therapeutic and infection control challenges, with the public health intervention points unclear.

Community-Acquired Infections↗
PubMed2006

Novel Ambler class A beta-lactamase LAP-1 and its association with the plasmid-mediated quinolone resistance determinant QnrS1.

The plasmid-mediated quinolone resistance determinant QnrS1 was identified in non-clonally related Enterobacter cloacae isolates in association with a transferable narrow-spectrum beta-lactam resistance marker. Cloning experiments allowed the identification of a novel Ambler class A beta-lactamase, named LAP-1. It shares 62 and 61% amino acid identity with the most closely related beta-lactamases, TEM-1 and SHV-1, respectively. It has a narrow-spectrum hydrolysis of beta-lactams and is strongly inhibited by clavulanic acid and sulbactam and, to a lesser extent, by tazobactam. Association of the blaLAP-1 gene with the qnrS1 gene was identified in E. cloacae isolates from France and Vietnam. These genes were plasmid located and associated with similar insertion sequences but were not associated with sul1-type class 1 integrons, as opposed to the qnrA genes.

Amino Acid Sequence↗
PubMed2006

Identification of CTX-M-type extended-spectrum-beta-lactamase genes using real-time PCR and pyrosequencing.

CTX-M extended-spectrum beta-lactamases (ESBLs) are increasingly prevalent worldwide among Escherichia coli bacteria, mostly in community-acquired urinary tract infections. Finding a fast and reliable technique for identification of CTX-M enzymes is becoming a challenge for the microbiology laboratory. A fast real-time PCR amplification technique, using degenerated primers specific for all the bla(CTX-M) alleles, coupled to real-time pyrosequencing was developed. The five CTX-M groups were unambiguously identified by pyrosequencing a 13-bp DNA region. Further sequencing of an additional 16-bp region allowed further division into subgroups. Phylogenetic trees constructed with the entire bla(CTX-M) genes and with both pyrosequenced regions (29 bp) gave similar results, suggesting that this technique, termed the real-time detection and sequencing method, has a powerful discriminatory ability. This high-throughput technique has been evaluated by screening 48 ESBL-producing E. coli isolates recovered from the Bicêtre hospital (France) in 2004. Forty-four of these strains were CTX-M positive by real-time PCR detection and direct pyrosequencing of the PCR products, which identified CTX-M-15 as the main CTX-M-type beta-lactamase. Pulsed-field gel electrophoresis analysis of these strains revealed that several clones, of which one CTX-M-15-positive clone was predominant (60%), were identified both in nosocomial and in community-acquired isolates. The combination of real-time PCR with pyrosequencing represents a powerful tool for epidemiological studies of CTX-M producers. This assay has the potential to be used in a diagnostic laboratory since up to 96 bacterial isolates may be screened in less than 3 h.

Base Sequence↗
PubMed2006

Prevalence and genetic analysis of plasmid-mediated quinolone resistance determinants QnrA and QnrS in Enterobacteriaceae isolates from a French university hospital.

The spread of plasmid-mediated quinolone resistance determinants QnrA and QnrS was evaluated in a collection of 186 extended-spectrum beta-lactamase (ESBL)-positive enterobacterial isolates from 2002 to 2005 and 185 nalidixic acid-resistant strains isolated during the first 6 months of 2005 at the Bicêtre hospital, France. Out of these 186 ESBL-positive isolates, 2.2 and 1.6% carried a QnrA1 and a QnrS1 determinant, respectively. The ESBLs associated with QnrA1 were VEB-1, SHV-12, and CTX-M-1, whereas those associated with QnrS1 were TEM-52, SHV-12, and CTX-M-1. Among the 185 nalidixic acid-resistant strains isolated in 2005, 0.5 and 2.7% had a QnrA1 determinant and a QnrS1 determinant, respectively. The genetic environments of the qnrA1 gene differed but were always associated with sul1 type integrons. In contrast, qnrS1 genes were not embedded in class 1 integrons but located often (but not systematically) downstream of the insertion sequence ISEcl2 on plasmids that often carried a novel beta-lactamase gene, bla(LAP-1). This is the first study identifying the QnrS resistance determinant in Europe and indicating that this determinant might also be widespread.

Anti-Bacterial Agents↗
PubMed2006

Outbreak of infection by carbapenem-resistant Acinetobacter baumannii producing the carbapenemase OXA-58 in Belgium.

Carbapenem-resistant Acinetobacter baumannii isolates were obtained from 17 patients between September 2004 and August 2005 at the Academisch Ziekenhuis Vrije Universiteit Brussel, Brussels, Belgium. These multidrug-resistant isolates, which belonged to a single clone, remained susceptible to colistin and tigecycline only and produced the carbapenem-hydrolyzing oxacillinase OXA-58. This study highlights the importance of the intercountry spread of this beta-lactamase-mediated resistance mechanism and its epidemic evolution.

Acinetobacter Infections↗
PubMed2006

Emergence of PER and VEB extended-spectrum beta-lactamases in Acinetobacter baumannii in Belgium.

OBJECTIVES: Strains of Acinetobacter baumannii producing the extended-spectrum beta-lactamase (ESBL) PER-1 are widespread in Turkey and have also been reported from Korea and France. In contrast, A. baumannii producing the ESBL VEB-1 have only been reported from France, where one strain was responsible for a nationwide outbreak in 2003-2004. Here we describe the emergence of strains of A. baumannii producing VEB-1 and PER- 1 in Belgium. METHODS: Belgian hospitals were alerted in December 2003 to the emergence in France of VEB-1-producing A. baumannii susceptible only to meropenem and colistin. Isolates with a compatible susceptibility profile were sent to a single central laboratory for VEB-1 confirmation, molecular characterization and typing. RESULTS: From December 2003 to March 2005, three hospitals located close to the French border and one in the Brussels area reported isolation of eight A. baumannii isolates compatible with the French epidemic clone. Using PCR, six were identified as VEB-1-positive and two as PER-1-positive. All the VEB-1-positive isolates were clonally related by PFGE and by integron analysis to the French epidemic strain. The PER-1-positive strains were indistinguishable by PFGE but not related to the known French isolate or to several Turkish isolates. Both genes were chromosomally encoded. CONCLUSIONS: This work illustrates the inter-country spread of VEB-1-producing A. baumannii isolates as well as the emergence of PER-1-producing A. baumannii strains in Belgium.

Acinetobacter Infections↗
PubMed2006

Comparative genomics of multidrug resistance in Acinetobacter baumannii.

Acinetobacter baumannii is a species of nonfermentative gram-negative bacteria commonly found in water and soil. This organism was susceptible to most antibiotics in the 1970s. It has now become a major cause of hospital-acquired infections worldwide due to its remarkable propensity to rapidly acquire resistance determinants to a wide range of antibacterial agents. Here we use a comparative genomic approach to identify the complete repertoire of resistance genes exhibited by the multidrug-resistant A. baumannii strain AYE, which is epidemic in France, as well as to investigate the mechanisms of their acquisition by comparison with the fully susceptible A. baumannii strain SDF, which is associated with human body lice. The assembly of the whole shotgun genome sequences of the strains AYE and SDF gave an estimated size of 3.9 and 3.2 Mb, respectively. A. baumannii strain AYE exhibits an 86-kb genomic region termed a resistance island--the largest identified to date--in which 45 resistance genes are clustered. At the homologous location, the SDF strain exhibits a 20 kb-genomic island flanked by transposases but devoid of resistance markers. Such a switching genomic structure might be a hotspot that could explain the rapid acquisition of resistance markers under antimicrobial pressure. Sequence similarity and phylogenetic analyses confirm that most of the resistance genes found in the A. baumannii strain AYE have been recently acquired from bacteria of the genera Pseudomonas, Salmonella, or Escherichia. This study also resulted in the discovery of 19 new putative resistance genes. Whole-genome sequencing appears to be a fast and efficient approach to the exhaustive identification of resistance genes in epidemic infectious agents of clinical significance.

Acinetobacter Infections↗
PubMed2006

Plasmid-mediated quinolone resistance in Australia.

The aim of this study was to search for plasmid-encoded quinolone resistance determinants QnrA and QnrS in fluoroquinolone-resistant and extended-spectrum beta-lactamase (ESBL)-producing enterobacterial isolates recovered in Sydney, Australia, in 2002. Twenty-three fluoroquinolone-resistant, of which 16 were also ESBL-positive, enterobacterial and nonrelated isolates were studied. PCR with primers specific for qnrA and qnrS genes and primers specific for a series of ESBL genes were used. A qnrA gene was identified in two ESBL-positive isolates, whereas no qnrS-positive strain was found. The QnrA1 determinant was identified in an Enterobacter cloacae isolate and in a carbapenem-resistant Klebsiella pneumoniae isolate, both of which expressed the same ESBL SHV- 12. Whereas no plasmid was identified in the E. cloacae isolate, K. pneumoniae K149 possessed two conjugative plasmids, one that harbored the qnrA and bla (SHV)-12 genes whereas the other expressed the carbapenemase gene bla (IMP-4). The qnrA gene, was located in both cases downstream of the orf513 recombinase gene and upstream of the qnrA1 gene, a structure identical to that found in sul1-type integron In36 and qnrA-positive strains from Shanghai, China. However, the gene cassettes of the sul1-type integrons were different. This study identified the first plasmid-mediated quinolone resistance determinant in Enterobacteriaceae in Australia.

Anti-Bacterial Agents↗
PubMed2006

Regulation of class D beta-lactamase gene expression in Ralstonia pickettii.

Ralstonia pickettii, an environmental bacterium that may also be responsible for human infections, produces two unrelated, inducible and chromosomally encoded oxacillinases, OXA-22 and OXA-60. In order to study the molecular basis of the induction process of these oxacillinase genes, the induction kinetics, the promoter/operator regions necessary for expression and induction, and the role of several ORFs located upstream and downstream of the bla(OXA) genes were investigated. The beta-lactamase production reached a maximal level after 1 h induction, returned to its basal level within the following 3 h and was then again inducible. Using 5'RACE experiments, the promoter sequences of both oxacillinases were determined. These sequences showed weak promoter activities, which could, however, be increased approximately 200-fold by mutating the -35 promoter sequence. Deletion of the sequences located upstream of the promoter regions did not modify the basal beta-lactamase expression in R. pickettii, but resulted in the lack of induction. A minimum of 240 and 270 bp upstream of the transcription initiation sites was required for inducible expression of the bla(OXA-22) and bla(OXA-60) genes, respectively. Analysis of the genetic environment of both bla(OXA) genes revealed several ORFs that were inactivated by homologous recombination. Disruption of ORF-RP3, located 190 bp upstream of bla(OXA-60) and divergently transcribed, abolished induction of both beta-lactamases. ORF-RP3, which encoded a polypeptide of 532 aa with an estimated molecular mass of 58.7 kDa, displayed no obvious sequence homology with known regulatory proteins. Trans-complementation of ORF-RP3 restored the basal and inducible expression of both oxacillinase genes, indicating that the induction of both enzymes was related to the presence of ORF-RP3. In addition to the loss of induction, inactivation of the ORF-RP3 in R. pickettii resulted in a complex pleiotropic phenotype, with increased lag phase and reduced survival after heat exposure, suggesting that ORF-RP3 might be a global regulator involved in unrelated regulatory pathways.

Amino Acid Sequence↗
PubMed2006

Cloning and functional characterization of the ambler class C beta-lactamase of Yersinia ruckeri.

Yersinia ruckeri is a gram-negative pathogen causing enteric redmouth disease in salmonids. Previous studies have reported that Y. ruckeri harbors an ampC gene that is expressed at low level. In this present work, the entire ampC gene of Y. ruckeri was cloned and expressed in Escherichia coli. The AmpC enzyme confers resistance to aminopenicillins and narrow-spectrum cephalosporins, which fit well with the kinetic properties of the purified enzyme. Phylogenetic analysis showed that YRC-1 did not share significant sequence identity with known plasmid-mediated or chromosomal AmpC enzymes. This work provides further evidence that fish-pathogenic gram-negative rod species may constitute a reservoir of antibiotic resistance genes.

Animals↗
PubMed2006

Common region CR1 for expression of antibiotic resistance genes.

The CR1 element defined by an orf513 gene encoding a putative recombinase and a recombination crossover site has been identified upstream of several antibiotic resistance genes in Enterobacteriaceae. This CR1 element was shown to bring promoter sequences that play a role in the expression of unrelated antibiotic resistance genes.

Anti-Bacterial Agents↗