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.

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.

Infections caused by extended-spectrum β-lactamase-producing Klebsiella pneumoniae (ESBL-KP) are constantly rising worldwide and are often reported as causative agent of outbreaks in intensive care units (ICUs). During the first wave of the COVID-19 pandemic, bacterial cross-transmission was thought unlikely to occur due to the reinforcement of hygiene measures and prevention control. However, we report here an ESBL-producing K. pneumoniae (ST394) isolate responsible for a nosocomial outbreak in an ICU dedicated to COVID-19 patients.

SUMMARY: Metallo-beta-lactamases are an ever-growing problem. Since the discovery of the beta-lactamase of Bacillus cereus in the late 1960s, many class B beta-lactamases have been reported, with three main families being NDM-, IMP-, and VIM-like. IMP- and VIM-like carbapenemases have been identified in a wide variety of Gram-negative bacteria. VIM-type carbapenemases are widely distributed, primarily represented by two main clusters, VIM-1 and VIM-2, and have been found in both Enterobacterales and non-fermenters. IMP-type carbapenemases are characterized by a significant genetic diversity and low identity between subgroups. This carbapenemase is more prevalent in Asia but has been identified globally, in both Enterobacterales and non-fermenters, as observed for VIM-type carbapenemases. The genetic diversity of IMP- and some VIM-type carbapenemases limits their detection. This review aims to discuss the genetic diversity, epidemiology, and biochemical characteristics of VIM- and IMP-type carbapenemases. It also evaluates the efficacy of commercially available detection tests and the in vitro activity of recently developed inhibitors.

We evaluated the in vitro activity of aztreonam-avibactam and other agents against 593 metallo-β-lactamase (MBL)-producing Enterobacterales collected in France in 2024. Aztreonam-avibactam showed the highest activity (98% susceptible), with resistance mainly observed in NDM-5-producing Escherichia coli belonging to ST167, ST405, and ST361. Cefepime-zidebactam also exhibited strong activity (96.6% of susceptibility). Cefepime-taniborbactam and cefiderocol showed reduced overall activity (76.4% and 74.9% susceptibility, respectively), with reduced efficacy mainly observed among NDM-producing isolates. Comparison with 1,465 isolates from 2023 showed no increase in aztreonam-avibactam resistance.

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 carbapenem-resistant Enterobacterales, including 177 carbapenemase producers (CPE) spiked in blood culture bottles. The clinical categorization based on the Minimal Inhibitory Concentration (MIC) determination of eighteen antimicrobial molecules was compared to the clinical categorization based on the disk diffusion assay as a reference. The Reveal AST system provided results within a mean time to result of 5 h. Overall, the categorical agreement (CA) between the two techniques was 94.1%. The rates of very major errors (VMEs), major errors (MEs) and minor errors (mEs) were 3.8%, 3.7% and 5.6%, respectively. Imipenem was the antimicrobial with the lowest CA rate (78.7%), with rates of 15% VMEs and 10.7% MEs, but the performances were better when considering only the non-CPE category (CA of 89%). On this resistant collection of Enterobacterales with numerous acquired β-lactamases, the Specific Reveal assay proved to be useful for a rapid determination of AST compatible with a quick adaptation of the patient’s antimicrobial treatment.