Thierry Naas

• Hôpital Bicêtre (Hôpitaux Universitaires Paris-Sud)

Background Escherichia coli is the primary aetiological agent of urinary tract infections (UTIs), a frequent cause of antibiotic prescription. Over the years, E. coli has become increasingly resistant towards several antimicrobial drugs used to treat UTIs. Objectives To compare the population structures and antimicrobial resistance profiles by mol...

Pseudomonas aeruginosa is a problematic pathogen with complex antibiotic resistance patterns. In clinical practice, minimum inhibitory concentration (MIC) tests typically focus on a limited subset of antibiotics, hindering a comprehensive assessment of a strain's resistance profile. Here, we introduce MICFiller, a Denoising AutoEncoder (DAE) model...

Proteus mirabilis (P. mirabilis) is an opportunistic pathogen involved in urinary tract infections as well as various nosocomial infections. Emerging resistances to beta-lactams in this species complicates potential treatment since it is intrinsically resistant to colistin. Eleven isolates of carbapenem-non-susceptible P. mirabilis were identified...

Background Antimicrobial resistance (AMR) is a global threat. Monitoring using an integrated One Health approach is essential to detect changes in AMR occurrence. Aim We aimed to detect AMR genes in pathogenic and commensal Escherichia coli collected 2013–2020 within monitoring programmes and research from food animals, food (fresh retail raw meat...

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 blaOXA-484 genes were carried mostly on an IncX3-type plasmid associated with genetic elements includi...

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. Disc diffusion and broth mi...

Background A drastic increase in carbapenem resistance among Klebsiella pneumoniae isolates occurred during the period 2019–22. Three epidemiological changes could be evidenced: (i) NDM became the predominant carbapenemase; (ii) NDM-5 replaced NDM-1; and (iii) the emergence of NDM-producing K. pneumoniae ST258 (NDM-KpST258). Materials and methods...

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 carbapen...

OXA-244, an R214G variant of OXA-48, is silently spreading worldwide likely because of difficulties in detection using classical screening media. Here, we characterized two clinical isolates of Escherichia coli and Citrobacter youngae that displayed reduced susceptibility to carbapenems but were lacking significant carbapenemase activity as reveale...

Carbapenem-resistant Enterobacterales represent a major health threat and have few approved therapeutic options. Enterobacterales isolates were collected from hospitalized inpatients from 49 sites in six European countries (1 January–31 December 2020) and underwent susceptibility testing to cefiderocol and β-lactam/β-lactamase inhibitor combination...

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. cloacae subspecies cloacae that was involved in an outbreak. Clinicians should be aware of potential antimicrobial resistance among these bacteria.

Background Carbapenem-resistant Pseudomonas aeruginosa are being increasingly described worldwide. Here, we investigated the molecular mechanisms underlying carbapenem resistance in an extremely drug-resistant P. aeruginosa isolate from a neonatal intensive care unit in Morocco. Materials and methods P. aeruginosa strain O82J1 was identified using...

Plasmids carrying antibiotic resistance genes (ARG) are the main mechanism of resistance dissemination in Enterobacterales. However, the fitness-resistance trade-off may result in their elimination. Chromosomal integration of ARGs preserves resistance advantage while relieving the selective pressure for keeping costly plasmids. In some bacterial li...

OXA-48 has rapidly disseminated worldwide and become one of the most common carbapenemases in many countries with more than 45 variants reported with, in some cases, significant differences in their hydrolysis profiles. The R214 residue, located in the ß5-ß6 loop, is crucial for the carbapenemase activity, as it stabilizes carbapenems in the active...

Background VRE are increasingly described worldwide. Screening of hospitalized patients at risk for VRE carriage is mandatory to control their dissemination. Here, we have developed the Bfast [VRE Panel] PCR kit, a rapid and reliable quantitative PCR assay for detection of vanA, vanB, vanD and vanM genes, from solid and liquid cultures adaptable to...

Objectives A multicentre study evaluating NG-Test DetecTool OXA-23 for the detection of OXA-23 carbapenemase directly from positive blood cultures (PBCs). Methods The NG-Test DetecTool OXA-23 is an immunoassay that integrates a sample preparation device. We evaluated NG-Test DetecTool OXA-23 on 189 spiked and 126 clinical PBCs. The clinical sample...

Abscesses represent the most prominent emerging problem in the red meat industry, leading to great economic constraints and public health hazards. Data on etiological agents present in these purulent lesions in Algeria are very scarce. The aim of this study was to identify the bacteria responsible for these abscesses and to determine their antibiot...

Antimicrobial resistance (AMR) is one of the major public health problems worldwide. Multiple strategies have been put in place to address this problem. One of them is the rapid detection of the mechanisms of resistance, such as extended-spectrum beta-lactamases (ESBLs) and/or carbapenemases. We conducted a multicenter study that included nine Euro...

The Enterobacter cloacae complex (ECC) is highly adapted to the hospital environment and is frequently responsible for hospital-acquired infections. ECC can acquire plasmid-borne genes that encode resistance to extended-spectrum cephalosporins and carbapenems, which complicates treatment regimens. Enterobacter xiangfangensis has been described as a...

The emergence of carbapenem resistance, mostly through the dissemination of carbapenemase-producing Enterobacterales (CPE), became a serious public health problem. In Enterobacterales, MBLs (Ambler class B carbapenemases) are mainly represented by VIM and NDM enzymes. MBLs hydrolyse all β-lactams except aztreonam and remain resistant to the recentl...

Background Carbapenem- and extended-spectrum cephalosporin-resistant Enterobacterales (CR-E and ESCR-E, respectively) are increasingly isolated worldwide. Information about these bacteria is sporadic in Lebanon and generally relies on conventional diagnostic methods, which is detrimental for a country that is struggling with an unprecedented econom...

Antimicrobial resistance disproportionately affects displaced and vulnerable populations. Here, we performed an in-depth investigation of blaNDM-5-harbouring Escherichia coli ST617 isolated from disenfranchised Lebanese patients, Syrian refugees, and livestock and the environment of refugee camps. We highlight the need for proactive One Health stra...

Background Since 2021, an emergence of New Delhi metallo-β-lactamase (NDM)-14-producing Klebsiella pneumoniae has been identified in France. This variant with increased carbapenemase activity was not previously detected in Enterobacterales. Aim We investigated the rapid dissemination of NDM-14 producers among patients in hospitals in France. Meth...

Carbapenemase-producing Enterobacterales have emerged in the last decades as one of the main threats in modern medicine. Enterobacter is a genus increasingly recognized as a key player in carbapenemase diffusion besides Escherichia coli and Klebsiella pneumoniae , but information regarding Citrobacter spp. remained scarce. A collection of 803 isola...

Introduction: Metallo-β-lactamases (MBLs) are enzymes produced by bacteria that confer resistance to most β-lactam antibiotics, including carbapenems, which have the broadest spectrum of activity. This resistance mechanism poses a significant threat to public health as it drastically reduces treatment options for severe bacterial infections. Devel...

Cefiderocol resistance is increasingly reported in New Delhi metallo-β-lactamase-producing Enterobacterales. Genomic and phenotypic analysis of Escherichia coli sequence type 361, a primary clone causing carbapenemase spread in France, revealed mutations leading to cefiderocol resistance. Continued genomic surveillance of carbapenem-resistant Enter...

Here, we characterized the first French NDM-9-producing Acinetobacter baumannii isolate. A. baumannii 13A297, which belonged to the STPas25 (international clone IC7), was highly resistant to β-lactams including cefiderocol (MIC >32 mg/L). Whole genome sequencing (WGS) using both Illumina and Oxford Nanopore technologies revealed a 166-kb non-conjug...

The development of novel antibiotics is mandatory to curb the growing antibiotic resistance problem resulting in difficult-to-treat bacterial infections. Here, we have determined the spectrum of activity of cystobactamids and chelocardins, two novel and promising classes of molecules with different modes of action. A panel of 297 clinically relevan...

Objectives: We isolated a highly colistin-resistant Escherichia coli, strain 58, from fresh chicken wings in Lebanon. Here, we performed in-depth phenotypic and genomic analyses to identify the resistome of the isolate, focusing on the determinants that encoded colistin resistance. Methods: The minimum inhibitory concentration (MIC) of colistin...

Piperacillin-tazobactam resistance (P/T-R) is increasingly reported among Escherichia coli isolates. Although in vitro experiments have suggested that blaTEM gene plays a key role in the P/T-R acquisition, no clinical in vivo study has yet confirmed the role of blaTEM or other genes. Therefore, we aimed to identify the mechanisms underlying P/T-R b...

Background: Cefiderocol is a catechol-substituted cephalosporin with potent in vitro activity against carbapenem-resistant (CR) Gram-negative bacteria (GNB). Cefiderocol susceptibility testing is complex because iron concentrations need to be taken into consideration. Here, we assessed the clinical performance of Bruker's UMIC® Cefiderocol and cor...

β-Lactams are among the most prescribed antibiotics worldwide, mainly due to their weak toxicity and good efficacy [...]

The production of PER-like extended-spectrum β-lactamases has recently been associated with reduced susceptibility to the last resort drugs aztreonam/avibactam and cefiderocol. PER-2 have been mainly confined to Argentina and neighboring countries. Until now, only three plasmids harboring blaPER-2 genes have been characterized but very little is kn...

Background Morganella are opportunistic pathogens involved in various infections. In Morganella, intrinsic resistance to multiple antibiotics including colistin combined with the emergence of carbapenemase-producers (CP) strongly limits the antimicrobial armamentarium. Methods From 2013 to 2021, 172 highly drug-resistant (XDR) Morganella isolates f...

Piperacillin-tazobactam resistance (P/T-R) is increasingly reported among Escherichia coli isolates. Although in vitro experiments have suggested that blaTEM gene plays a key role in the P/T-R acquisition, no clinical in vivo study has yet confirmed the role of blaTEM or other genes. Therefore, we aimed to identify the mechanisms underlying P/T-R b...

Background: As carbapenemase-producing Enterobacterales are increasingly reported worldwide, their rapid detection is crucial to reduce their spread and prevent infections and outbreaks. Lateral flow immunoassays (LFIAs) have become major tools for the detection of carbapenemases. However, as for most commercially available assays, only the five m...

Cefiderocol is a novel siderophore-conjugated cephalosporin that is very promising for the treatment of infections caused by MDR bacteria. Its main advantages reside in its stability against MBLs for which no other commercially β-lactam can be used to date, and its uptake using the bacterial iron transport system in addition of porins.¹ However, it...

Background: Neonatal sepsis with multidrug resistant (MDR) bacteria is an important cause of morbidity and mortality, especially in low- and middle-income countries. Here, the molecular mechanisms of MDR in bacteria responsible of sepsis in neonates was determined. Methods: From July to December 2019, documented bacteraemia from 524 neonates hos...

Objectives: Apramycin is an aminoglycoside (AG) with a unique structure that is little affected by plasmid-mediated mechanisms of AG resistance, including most AG-modifying enzymes and 16S rRNA methyltransferases (16S-RMTases). We evaluate the activity of apramycin against a collection of 16S-RMTase-producing isolates, including Enterobacterales,...

Culture media is fundamental in clinical bacteriology for the detection and isolation of bacterial pathogens. However, in-house media preparation could be challenging in low-resource settings. InTray® cassettes (Biomed Diagnostics) could be a valid alternative as they are compact, ready-to-use media preparations. In this study, we evaluate the use...

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 we...

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 n...

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, we...

This study evaluated the performances of immunoassays (LFIA and ELISA) designed for SARS-CoV-2 Antigen (Ag)-detection in nasopharyngeal (NP) and serum samples in comparison to RT-PCR. NP samples from patients with respiratory symptoms (183 RT-PCR-positive and 74 RT-PCR-negative samples) were collected from March to April and November to December 20...

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 comparato...

Carbapenem resistance (CR) is an emerging health issue. Epidemiological surveys on carbapenem-resistant Gram-negative bacilli (CR-GNB) in Lebanon remain scarce. In this study, we determined the prevalence of CR-GNB isolated between 2015 to 2019 in three hospitals in northern Lebanon: 311 CR-Enterobacterales (out of 11210; 2.8%), 155 CR-Pseudomonas...

Early detection of multidrug resistant bacteria is of paramount importance for implementing appropriate infection control strategies and proper antibacterial therapies. We have evaluated a novel real-time PCR assay using fluorescent probes and 3base® technology, the EasyScreenTM ESBL/CPO Detection Kit (Genetic Signatures, Newtown, Australia), for t...

Carbapenem resistant Acinetobacter baumannii are spreading worldwide and represent a major health threat for immunocompromised patients. In this study, we describe for the first time NDM-producing A. baumannii and Acinetobacter nosocomialis isolates from Côte d’Ivoire, Africa. Four carbapenem-resistant Acinetobacter spp. isolates were isolated from...

Carbapenem resistant Acinetobacter baumannii are spreading worldwide and represent a major health threat for immunocompromised patients. In this study, we describe for the first time NDM-producing A. baumannii and Acinetobacter nosocomialis isolates from Côte d'Ivoire, Africa. Four carbapenem-resistant Acinetobacter spp. isolates were isolated from...

Easy and robust antimicrobial susceptibility testing (AST) methods are essential in clinical bacteriology laboratories (CBL) in low-resource settings (LRS). We evaluated the Beckman Coulter MicroScan lyophilized broth microdilution panel designed to support Médecins Sans Frontières (MSF) CBL activity in difficult settings, in particular with the Mi...

The EPIC consortium brings together experts from a wide range of fields that include clinical, molecular and basic microbiology, infectious diseases, computational biology and chemistry, drug discovery and design, bioinformatics, biochemistry, biophysics, pharmacology, toxicology, veterinary sciences, environmental sciences, and epidemiology. The m...

Background Lateral flow immunoassays (LFIA) have shown their usefulness for detecting CTX-M- and carbapenemase-producing Enterobacterales (CPEs) in bacterial cultures. Here, we have developed and validated the BL-DetecTool to detect CTX-M enzymes and carbapenemases directly from clinical samples. Methods The BL-DetecTool is an LFIA that integrates...

Background Relebactam and vaborbactam are among the last β-lactamase inhibitors marketed. They were originally designed to inhibit the Ambler class A carbapenemase KPC. Material and methods Here, imipenem-relebactam and meropenem-vaborbactam susceptibilities were determined on a collection of 407 OXA-48-like-producing Enterobacterales. The clonali...

The global spread of antimicrobial resistant (AMR) bacteria represents a considerable public health concern, yet their detection and identification of their resistance mechanisms remain challenging. Optimal diagnostic tests should provide rapid results at low cost to enable implementation in any microbiology laboratory. Lateral flow assays (LFA) me...

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 no...

We have read the article published by Mitteregger et al. [...]

Carbapenemase-producing Klebsiella pneumoniae (CPKp) have disseminated globally and represent a major threat in hospitals with few therapeutic options and high mortality rates. Isolates producing the carbapenemase KPC (KPC-Kp) might be classified as susceptible according to clinical breakpoints by antibiotic susceptibility testing (AST), allowing t...

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. Methods CE-IVD broth...

Patients infected with severe acute respiratory syndrome coronavirus 2 might have bacterial and fungal superinfections develop. We describe a clinical case of coronavirus disease with pulmonary aspergillosis associated with Bordetella hinzii pneumonia in an immunocompetent patient in France. B. hinzii infections are rare in humans and develop secon...

MDR Gram-negatives constitute a global public health concern, as they may cause severe, difficult-to-treat and often deadly infections, such as bloodstream infections and pneumonia. Carbapenem-resistant (CR) Acinetobacter spp., Pseudomonas spp. and Enterobacterales are among the most worrisome.¹ Even though these bacteria are increasingly described...

Next Generation Sequencing technologies significantly impact the field of Antimicrobial Resistance (AMR) detection and monitoring, with immediate uses in diagnosis and risk assessment. For this application and in general, considerable challenges remain in demonstrating sufficient trust to act upon the meaningful information produced from raw data,...

We read with great attention the comments made by Nordmann and Poirel.¹ Our work² was meant to challenge the rapid Carbapenem Inactivation Method (rCIM) test with isolates that pose problems for carbapenemase-producing Enterobacterales (CPE) confirmation using many currently available tests, including the Carba NP test, which is considered as the r...

During recent decades, carbapenem resistance in Gram negatives has become a worldwide threat leading to more restricted antimicrobial treatment options.1,2 In Enterobacterales, carbapenem resistance is linked to the emergence and dissemination of carbapenemase producers.1,2 In Enterobacterales, the most prevalent carbapenemases belong to the Ambler...

Since the first description of OXA-48, more than forty variants have been recovered from Enterobacterales isolates. Whereas some OXA-48-related enzymes have been reported as conferring similar resistance patterns, namely, the hydrolysis of carbapenems and penicillins with very weak or almost no activity against expanded-spectrum cephalosporins, som...

Objectives: To genetically characterize VIM-producing Enterobacter cloacae complex (ECC) isolates recovered in France from 2015 to 2018. Methods: WGS, species determination, MLST, clonal relationship and genetic characterization were performed on 149 VIM-producing ECC isolates. Results: Among VIM-producing Enterobacterales, the prevalence of E...

Rapid detection of expanded-spectrum cephalosporins (ESC) hydrolysing enzymes is crucial to implement infection control measures and antibiotic stewardship. Here, we have evaluated three biochemical ESC hydrolysis assays (ESBL NDP test, β-LACTA™ test, LFIA-CTX assay) and the NG-Test® CTX-M MULTI that detects CTX-M enzymes, on 93 well-characterized...

Background: Early detection of expanded-spectrum cephalosporinase (ESC) hydrolyzing ß-lactamases is essential for antibiotic stewardship. Here we have developed a multiplex lateral flow immunoassay (LFIA) that detects cefotaxime-hydrolyzing activity as well as the most prevalent ESC-hydrolyzing ß-lactamases: the CTX-M-like. Methods: The Rapid LFIA...

Carbapenemase-producing Escherichia coli (CP- Ec ) might be difficult to detect, as MICs can be very low. However, their absolute number and their proportion among carbapenem-resistant Enterobacterales have been increasing, as reported by WHO and national surveillance programs.

Introduction Pathogen-focused, randomized, controlled trials (PF-RCT) are important in the fight against carbapenem-resistant (CR) Gram-negative infections. Some recently approved antibiotics and older generic antibiotics with activity against CR Gram-negative bacteria were investigated in PF-RCTs in a variety of infections. Areas covered We searc...

The differential expression of VIM-1 in Atlantibacter hermannii WEB-2 and Enterobacter hormaechei ssp. hoffmannii WEB-1 clinical isolates from a rectal swab of a hospitalized patient in France was investigated. A. hermannii WEB-2 was resistant to all β-lactams except carbapenems. It produced ESBL SHV-12, but the Carba NP test failed to detect any c...

Resistance to ceftazidime–avibactam (CAZ-AVI) combination is being increasingly reported. Here, we report a CAZ-AVI resistant Klebsiella pneumoniae belonging to the high-risk ST307 clone and producing KPC-39, a single amino-acid variant of KPC-3 (A172T). Cloning experiments, steady state kinetic parameters and molecular dynamics simulations reveale...

Carbapenemase-producing Escherichia coli (CP- Ec ) represent a major public health threat with a risk of dissemination in the community as it has occurred for lineages producing extended spectrum ß-lactamases. To characterize the extend of CP- Ec spread in France, isolates from screening and infection samples received at the French National Referen...

Over the last two decades, antimicrobial resistance has become a global health problem. In Gram-negative bacteria, metallo-β-lactamases (MBLs), which inactivate virtually all β-lactams, increasingly contribute to this phenomenon. The aim of this study is to characterize VIM-52, a His224Arg variant of VIM-1, identified in a Klebsiella pneumoniae cli...

We report evaluation of 30 assays’ (17 rapid tests (RDTs) and 13 automated/manual ELISA/CLIA assay (IAs)) clinical performances with 2594 sera collected from symptomatic patients with positive SARS-CoV-2 rRT-PCR on a respiratory sample, and 1996 pre-epidemic serum samples expected to be negative. Only 4 RDT and 3 IAs fitted both specificity (> 98%)...

Vancomycin-resistant enterococci (VREs) have become one of the most important nosocomial pathogens worldwide, associated with increased treatment costs, prolonged hospital stays and high mortality. Rapid detection is crucial to reduce their spread and prevent infections and outbreaks. The lateral flow immunoassay NG-Test VanB (NG Biotech) was evalu...

Antimicrobial peptides constitute one of the most promising alternatives to antibiotics since they could be used to treat bacterial infections, especially those caused by multidrug-resistant pathogens. Many antimicrobial peptides, with various activity spectra and mechanisms of actions, have been described. This review focuses on their use against...

Early detection of patients colonized with carbapenemase-producing Enterobacterales is crucial to limit their spread. Molecular biology tests are rapid but might miss low-level carriage. At the opposite, culture-based methods using enrichment are cheap and detect low-level carriage but induce delay. Here, we reported two clinical cases where we dem...

Early detection of expanded‐spectrum cephalosporin (ESC) resistance is essential not only for an effective therapy but also for the prompt implementation of infection control measures to prevent dissemination in the hospital. We have developed and validated a lateral flow immunoassay (LFIA), called LFIA‐CTX test, for the detection of ESC (cefotaxim...

[This corrects the article DOI: 10.1093/jacamr/dlab081.].

Background Enterobacter cloacae complex contains nosocomial pathogens responsible for infection outbreaks. Identification at the species level within the E cloacae complex remains difficult. Using whole genome sequencing, our aim was to decipher the transmission routes that led to the death of six of seven neonates who had bacteraemia caused by E c...