Emergence of New Non–Clonal Group 258 High-Risk Clones among Klebsiella pneumoniae Carbapenemase–Producing K. pneumoniae Isolates, France

International audienceThe worldwide spread of Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) isolates was reported to be caused by dissemination of 1 clonal complex (i.e., clonal group [CG] 258, which includes sequence types [STs] 258 and 512). We conducted whole-genome sequencing and epidemiologic analysis of all KPC-Kp isolates in France in 2018 and found that new successful high-risk clones of ST147, ST307, ST231, and ST383 are now the main drivers of blaKPC genes. The blaKPC genes were mostly carried by Tn4401a and Tn4401d structures and a new non-Tn4401 element. Our epidemiologic investigations showed that the emergence of these non-CG258 KPC-Kp isolates in France was linked to dissemination of these clones from Portugal. Thus, KPC-Kp epidemiology has changed in Europe, at least in several non-KPC-endemic countries of western Europe, such as France and Portugal, where CG258 is not the most prevalent clone

KPC-39-mediated resistance to Ceftazidime-Avibactam in a Klebsiella pneumoniae ST307 clinical isolate

International audienceResistance 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 revealed a loss of carbapenemase activity and an increased affinity for ceftazidime. KPC-39 was identified in a patient without prior exposure to CAZ-AVI, suggesting silent dissemination in European healthcare settings

Evaluation of the Immunochromatographic NG-Test Carba 5 for Rapid Identification of Carbapenemase in Nonfermenters

International audienceThe immunochromatographic assay NG-Test Carba 5 (NG-Biotech) was evaluated with a collection of 107 carbapenemase-producing nonfermenters (CP-NF) (55 Pseudomonas spp., 51 Acinetobacter spp., and 1 Achromobacter xylosoxidans isolate) and 61 carbapenemase-negative isolates. All KPC, VIM, and NDM carbapenemase producers tested were accurately detected. Of the 16 IMP variants tested, 6 (37.5%) variants were not detected

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. Methods: MICs to ceftazidime/avibactam, imipenem/relebactam, meropenem/vaborbactam, but also temocillin, ceftolozane/tazobactam, ertapenem, colistin, eravacycline and tigecycline were determined by broth microdilution (ThermoFisher) on a collection of 284 CR non-CPE (inhibition zone diameter < 22 mm to meropenem). Whole genome sequencing was performed on 90 isolates to assess the genetic diversity as well as resistome. Results: According to EUCAST breakpoints, susceptibility rates of ceftazidime, imipenem, meropenem and ertapenem used at standard dose were 0.7%, 45.1%, 14.8% and 2.5%, respectively. Increased exposure of ceftazidime, imipenem and meropenem led to reach 3.5%, 68.3% and 67.7% susceptibility, respectively. Using the EUCAST clinical breakpoints, susceptibility rates of ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam were 88.4%, 81.0% and 80.6%, respectively. Susceptibility rates of temocillin, ceftolozane/tazobactam, tigecycline, eravacycline, and colistin were 0%, 4.6%, 27.8%, 54.9% and 90.1%. MICs distributions with and without the presence of the inhibitor demonstrated a better ability of avibactam and relebactam compared to vaborbactam to restore susceptibility to the associated β-lactam. Conclusions: This study demonstrated the in vitro efficacy of ceftazidime/avibactam, imipenem/relebactam and to a lesser extent meropenem/vaborbactam against CR non-CPE. Moreover, to test all β-lactams/β-lactamases inhibitors combinations without a priori for CRE, non-CPE is crucial since resistance to one of the β-lactam/β-lactamase inhibitor combinations does not predict resistance to another molecule, depending on the resistance mechanisms involved

Première apparition de la carbapénémase OXA-198 chez les entérobactéries

A carbapenem-resistant Citrobacter sp. was recovered from routine screening of multidrug-resistant bacteria. This isolate coproduced OXA-48 and OXA-198. OXA-48 was carried by the prototypical IncL plasmid, whereas OXA-198 was carried by a peculiar IncHI-type plasmid. This carbapenemase gene was inserted within a class 1 integron located on a conjugative plasmid. This report describes the first occurrence of OXA-198 in Enterobacterales

Population Analysis of Escherichia coli Sequence Type 361 and Reduced Cefiderocol Susceptibility, France

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 Enterobacterales could clarify prevalence of cefiderocol-resistant E. coli in Europe

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

International audienceObjectives: 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 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 3rd generation cephalosporins (3GC) (ESBL production or different levels of AmpC overexpression) (n=213) and carbapenem resistant Enterobacterales (CRE) (n=259) including 170 carbapenemase producers (CPE). Then, 1,632 consecutive clinical Enterobacterales responsible for infection were prospectively collected in 23 French hospitals. C/T susceptibility was determined by Etest® (biomérieux) and broth microdilution (BMD) (Sensititre™, Thermo Scientific) to perform method comparison.Results: Within the collection isolates, 88% of 3GC resistant strains were susceptible to C/T, with important variation depending on the resistance mechanism: 93% vs 13% susceptibility for CTX-M and SHV-ESBL producers, respectively. Only 20% of the CRE were susceptible to C/T. Among CPE, 80 % of OXA-48-like producers were susceptible to C/T, whereas all metallo-β-lactamase producers were resistant. The prospective study revealed that 95.6% of clinical isolates were susceptible to C/T. Method comparison performed on these 1,632 clinical isolates demonstrated 99 % of categorization agreement between MIC to C/T determined by Etest® compared to BMD (reference) and only 74% of essential agreement.Conclusion: Overall, C/T showed good activity against wild-type Enterobacterales, AmpC producers and ESBL-producing E. coli but is less active against ESBL-producing K. pneumoniae and CRE. Etest® led to an underestimation of the MICs in comparison to BMD

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

International audienceObjectives: 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 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 3rd generation cephalosporins (3GC) (ESBL production or different levels of AmpC overexpression) (n=213) and carbapenem resistant Enterobacterales (CRE) (n=259) including 170 carbapenemase producers (CPE). Then, 1,632 consecutive clinical Enterobacterales responsible for infection were prospectively collected in 23 French hospitals. C/T susceptibility was determined by Etest® (biomérieux) and broth microdilution (BMD) (Sensititre™, Thermo Scientific) to perform method comparison.Results: Within the collection isolates, 88% of 3GC resistant strains were susceptible to C/T, with important variation depending on the resistance mechanism: 93% vs 13% susceptibility for CTX-M and SHV-ESBL producers, respectively. Only 20% of the CRE were susceptible to C/T. Among CPE, 80 % of OXA-48-like producers were susceptible to C/T, whereas all metallo-β-lactamase producers were resistant. The prospective study revealed that 95.6% of clinical isolates were susceptible to C/T. Method comparison performed on these 1,632 clinical isolates demonstrated 99 % of categorization agreement between MIC to C/T determined by Etest® compared to BMD (reference) and only 74% of essential agreement.Conclusion: Overall, C/T showed good activity against wild-type Enterobacterales, AmpC producers and ESBL-producing E. coli but is less active against ESBL-producing K. pneumoniae and CRE. Etest® led to an underestimation of the MICs in comparison to BMD

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

International audienceObjectives: 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 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 3rd generation cephalosporins (3GC) (ESBL production or different levels of AmpC overexpression) (n=213) and carbapenem resistant Enterobacterales (CRE) (n=259) including 170 carbapenemase producers (CPE). Then, 1,632 consecutive clinical Enterobacterales responsible for infection were prospectively collected in 23 French hospitals. C/T susceptibility was determined by Etest® (biomérieux) and broth microdilution (BMD) (Sensititre™, Thermo Scientific) to perform method comparison.Results: Within the collection isolates, 88% of 3GC resistant strains were susceptible to C/T, with important variation depending on the resistance mechanism: 93% vs 13% susceptibility for CTX-M and SHV-ESBL producers, respectively. Only 20% of the CRE were susceptible to C/T. Among CPE, 80 % of OXA-48-like producers were susceptible to C/T, whereas all metallo-β-lactamase producers were resistant. The prospective study revealed that 95.6% of clinical isolates were susceptible to C/T. Method comparison performed on these 1,632 clinical isolates demonstrated 99 % of categorization agreement between MIC to C/T determined by Etest® compared to BMD (reference) and only 74% of essential agreement.Conclusion: Overall, C/T showed good activity against wild-type Enterobacterales, AmpC producers and ESBL-producing E. coli but is less active against ESBL-producing K. pneumoniae and CRE. Etest® led to an underestimation of the MICs in comparison to BMD