Exploring mutational possibilities of KPC variants to reach high level resistance to cefiderocol.

Klebsiella pneumoniae carbapenemase (KPC) is a frequent and widespread carbapenemase, with over 260 variants identified. While KPC often evolves resistance to ceftazidime-avibactam, cefiderocol remains a key treatment option. Some variants, such as KPC-33 (D179Y), reduce cefiderocol susceptibility, but typically with only modest MIC increases.

Prospective and Multicenter Evaluation of Community Fecal Carriage of Carbapenemase-Producing Enterobacterales in French Children (2022-2024).

Community fecal carriage of carbapenemase-producing Enterobacterales in 637 French children (6-24 months) was 0.5%, with no typical risk factors identified (antibiotics, hospitalization, recent travel). Of note, one isolate of Escherichia coli ST38 with blaOXA-244 and blaCTX-M-27 belonging to a clonal group with high diffusion was found, highlighting the need for enhanced surveillance.

Epidemiology of aminoglycosides resistance and phenotypic detection of aac(6')-Ib-cr gene in ESBL-producing Enterobacterales in febrile urinary tract infection in children.

Objectives: ESBL-producing Enterobacterales (ESBL-E) poses a growing challenge in managing febrile urinary tract infections (FUTIs) in children, leaving amikacin as a good probabilistic once-daily and outpatient treatment option. This epidemiological study investigates aminoglycoside resistance patterns among pediatric ESBL-E isolates, with a particular focus on the aac(6')-Ib-cr gene - a common resistance determinant that elevates amikacin MICs and may compromise its efficacy. We also aimed to evaluate a phenotypic method to detect aac(6')-Ib-cr in clinical practice.

Evaluation of phenotypic and genotypic methods for detecting KPC variants.

carbapenemases (KPCs) have spread and diversified extensively. To date, 242 clinical variants have been identified and harbor different hydrolytic capacities, thereby interfering with rapid diagnostic tests. The accurate detection of KPC variants is crucial to guide treatment and control measures in healthcare settings.

Validation of rectal swabbing for total and aerobic gut microbiota study.

Unlabelled: In microbiota research, whole stool sampling is the conventional approach but can be problematic or infeasible for certain patients. This study aims to validate the use of rectal swabbing as an alternative method for microbiota analysis and determine optimal storage conditions suitable for various clinical settings, including intensive care units. We evaluated different sampling techniques and storage temperatures.

TWENTY-THREE PEDIATRIC CASES OF CITROBACTER KOSERI MENINGITIS IN THE LAST 20 YEARS: STILL A DRAMATIC PROGNOSIS.

Among 7578 cases of pediatric bacterial meningitis recorded in France (2001-2021), including 1313 neonatal cases, 23/7578 (0.3%) and 18/1313 (1.4%) were due to Citrobacter koseri.

[Recommendations for clinical practice: Prevention and management of varicella zoster virus (VZV) infection during pregnancy and the perinatal period (extended version)].

The Société de Pathologie Infectieuse de Langue Française released in 2024 a new national recommendation for clinical practice on the prevention and management of varicella zoster virus (VZV) infection during pregnancy and the perinatal period. The previous recommendation was issued in 1998, at a time of anti-VZV immunoglobulins shortage; it has hence become obsolete. This recommendation is a formalized expert consensus focusing on infectious diseases management; it is drawn up by a multidisciplinary working group (infectiologists, obstetricians, pediatricians, microbiologists, midwives, hygienists).

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.

Network of epistatic interactions in an enzyme active site revealed by large-scale deep mutational scanning.

Cooperative interactions between amino acids are critical for protein function. A genetic reflection of cooperativity is epistasis, which is when a change in the amino acid at one position changes the sequence requirements at another position. To assess epistasis within an enzyme active site, we utilized CTX-M β-lactamase as a model system.

The mechanism of ceftazidime and cefiderocol hydrolysis by D179Y variants of KPC carbapenemases is similar and involves the formation of a long-lived covalent intermediate.

carbapenemase (KPC) variants have been described that confer resistance to both ceftazidime-avibactam and cefiderocol. Of these, KPC-33 and KPC-31 are D179Y-containing variants derived from KPC-2 and KPC-3, respectively. To better understand this atypical phenotype, the catalytic mechanism of ceftazidime and cefiderocol hydrolysis by KPC-33 and KPC-31 as well as the ancestral KPC-2 and KPC-3 enzymes was studied.

Early-Onset Infection Caused by Escherichia coli Sequence Type 1193 in Late Preterm and Full-Term Neonates.

Using whole-genome sequencing, we characterized Escherichia coli strains causing early-onset sepsis (EOS) in 32 neonatal cases from a 2019-2021 prospective multicenter study in France and compared them to E. coli strains collected from vaginal swab specimens from women in third-trimester gestation. We observed no major differences in phylogenetic groups or virulence profiles between the 2 collections.

Unexpected Increase in Invasive Group A Streptococcal Infections in Children After Respiratory Viruses Outbreak in France: A 15-Year Time-Series Analysis.

In a 15-year pediatric time-series analysis, we showed a rise of invasive Group A streptococcal (iGAS) infections since October 2022, mainly involving pleural empyema, simultaneously to a respiratory virus outbreak. Physicians should be aware of this increased risk of pediatric iGAS infections, especially in settings with intense respiratory viruses' circulation.

Meningitis caused by extended-spectrum β-lactamase-producing in infants in France: a case series.

Objectives: We report the first case series focusing on clinical and biological characteristics of meningitis caused by ESBL-producing in infants.

Methods: Between 2001 and 2020, data on all cases of meningitis were prospectively collected from a network of 259 paediatric wards and 168 microbiology laboratories in France. We analysed the clinical and biological characteristics, short-term complications and long-term sequelae of ESBL-producing meningitis cases in patients <6 months old.

Klebsiella pneumoniae Carbapenemase Variants Resistant to Ceftazidime-Avibactam: an Evolutionary Overview.

First variants of the Klebsiella pneumoniae carbapenemase (KPC), KPC-2 and KPC-3, have encountered a worldwide success, particularly in K. pneumoniae isolates. These beta-lactamases conferred resistance to most beta-lactams including carbapenems but remained susceptible to new beta-lactam/beta-lactamase inhibitors, such as ceftazidime-avibactam.

Case Report: Hyperammonemic Encephalopathy Linked to spp. and/or Systemic Infection in Patients Treated for Leukemia, an Emergency Not to Be Missed.

Background: Hyperammonemic encephalopathy caused by spp. and infection has been reported in immunocompromised patients undergoing lung transplant, but data are scarce in patients with hematological malignancies.

Case Presentation: We describe the cases of 3 female patients aged 11-16 years old, developing initially mild neurologic symptoms, rapidly evolving to coma and associated with very high ammonia levels, while undergoing intensive treatment for acute leukemia (chemotherapy: 2 and hematopoietic stem cell transplant: 1).

Evaluation of the inoculum effect of new antibiotics against carbapenem-resistant enterobacterales.

Objectives: New antibiotics have been developed to treat multidrug-resistant Enterobacterales. We evaluated the impact of the inoculum size on minimal inhibitory concentrations (MICs) of recently commercialized antibiotics.

Methods: We focused on 40 clinical carbapenemase-producing Enterobacterales and evaluated the impact of the inoculum size on the MICs to cefiderocol and to new β-lactams/β-lactamase inhibitors (ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-relebactam, and meropenem-vaborbactam) at usual and high inocula (10 and 10 CFU/mL, respectively).

A Microbiota-Dependent Response to Anticancer Treatment in an Human Microbiota Model: A Pilot Study With Hydroxycarbamide and Daunorubicin.

Background: Anticancer drug efficacy is linked to the gut microbiota's composition, and there is a dire need to better understand these interactions for personalized medicine. microbiota models are promising tools for studies requiring controlled and repeatable conditions. We evaluated the impact of two anticancer drugs on human feces in the MiniBioReactor Array (MBRA) microbiota system.

Local and Global Protein Interactions Contribute to Residue Entrenchment in Beta-Lactamase TEM-1.

Due to their rapid evolution and their impact on healthcare, beta-lactamases, protein degrading beta-lactam antibiotics, are used as generic models of protein evolution. Therefore, we investigated the mutation effects in two distant beta-lactamases, TEM-1 and CTX-M-15. Interestingly, we found a site with a complex pattern of genetic interactions.

Comparative genomic analysis of ESBL-producing from faecal carriage and febrile urinary tract infection in children: a prospective multicentre study.

Background: The reliability of ESBL-producing (ESBL-Ec) faecal carriage monitoring to guide probabilistic treatment of febrile urinary tract infection (FUTI) in children remains unclear.

Objectives: To compare the genomic characteristics of ESBL-Ec isolates from faecal carriage and FUTI to assess their correlation and identify a FUTI-associated virulence profile.

Methods: We conducted a prospective multicentre hospital and ambulatory-based study.

The interplay between anticancer challenges and the microbial communities from the gut.

Cancer being an increasing burden on human health, the use of anticancer drugs has risen over the last decades. The physiological effects of these drugs are not only perceived by the host's cells but also by the microbial cells it harbors as commensals, notably the gut microbiota. Since the early '50 s, the cytotoxicity of anticancer chemotherapy was evaluated on bacteria revealing some antimicrobial activities that result in an established perturbation of the gut microbiota.

Azithromycin Resistance in Shiga Toxin-Producing Escherichia coli in France between 2004 and 2020 and Detection of (C)-(G) Genes.

We described and characterized Shiga-toxin-producing Escherichia coli (STEC) strains with high levels of resistance to azithromycin isolated in France between 2004 and 2020. Nine of 1,715 (0.52%) STEC strains were resistant to azithromycin, with an increase since 2017.