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 ß-lactams/ß-lactamase inhibitors (ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-relebactam, and meropenem-vaborbactam) at usual and high inocula (105 and 107 CFU/mL, respectively). RESULTS: At usual inoculum, 15% were resistant to cefiderocol (n = 6), 30% to meropenem-vaborbactam (n = 12), 42.5% to ceftazidime-avibactam (n = 17), 55% to imipenem-relebactam (n = 22), and 90% to ceftolozane-tazobactam (n = 36). At higher inoculum, a switch from susceptible to resistant category was observed for 88% (n = 30/34; CI, 71.6-96.2), 75% (n = 3/4; CI, 21.9-98.7), 72% (n = 13/18; CI, 46.4-89.3), 50% (n = 14/28; CI, 31.1-68.9), and 8.7% (n = 2/23; CI, 1.5-29.5) isolates regarding cefiderocol, ceftolozane-tazobactam, imipenem-relebactam, meropenem-vaborbactam, and ceftazidime-avibactam, respectively. DISCUSSION: Cefiderocol and meropenem-vaborbactam were the most efficient against carbapenemase-producing Enterobacterales at usual inoculum. When increasing inoculum to 107 CFU/mL, all of the molecules were impacted, particularly cefiderocol and imipenem-relebactam, while others, such as ceftazidime-avibactam, remain mildly affected. Our in vitro results deserved to be confirmed in vivo.

Detection of Carbapenemase-Producing Enterobacteriaceae in Positive Blood Culture Using an Immunochromatographic RESIST-4 O.K.N.V. Assay.

We evaluated the performance of the RESIST-4 O.K.N.V. assay (Coris) with 98 isolates to detect OXA-48-like and KPC-, NDM-, and VIM-type carbapenemases directly on positive human blood cultures. OXA-48-like and KPC-type isolates were correctly detected, but the detection of NDM- and VIM-type carbapenemases was weak and variable. We show that repeating the test on a 4-h subculture improves the detection of NDM- and VIM-type carbapenemases to 100%.

Within-a-Day Detection and Rapid Characterization of Carbapenemase by Use of a New Carbapenem Inactivation Method-Based Test, CIMplus.

The dissemination of carbapenemase-producing Enterobacteriaceae (CPE) is a major threat to public health. Rapid and accurate detection of CPE is essential for initiating appropriate antimicrobial treatment and establishing infection control measures. The carbapenem inactivation method (CIM), which has good sensitivity and specificity but a detection time of 20 h, was recently described. In this study, we evaluated the performances of a new version, the CIMplus test, which allows detection of carbapenemases in 8 h and characterization of carbapenemase classes, according to the Ambler classification, in 20 h. A panel of 110 carbapenem-resistant Enterobacteriaceae strains, including 92 CPE strains (with NDM, VIM, IMP, KPC, GES, OXA-48, and OXA-48-like enzymes), was used to evaluate test performance. Carbapenemase activity was detected at 8 h and 20 h. Characterization of carbapenemase classes, using specific inhibitors, was possible in 20 h. The CIMplus test had sensitivities of 95.7% and 97.8% at 8 h and 20 h, respectively, and a specificity of 94.4%, independent of the culture duration. Using a decision algorithm, this test was successful in identifying the carbapenemase class for 98.9% of tested CPE isolates (87/88 isolates). In total, the characterization was correct for 100%, 96.9%, and 100% of Ambler class A, B, and D isolates, respectively. Therefore, this test allows detection of carbapenemase activity in 8 h and characterization of carbapenemase classes, according to the Ambler classification, in 20 h. The CIMplus test represents a simple, affordable, easy-to-read, and accurate tool that can be used without any specific equipment.