In vitro activity of cefepime / sulbactam and biapenem against Enterobacterales and Pseudomonas aeruginosa isolated from blood culture from patients with hematological diseases: results of a multicenter study

Abstract

Background. Activity against Gram negative bacteria, including Pseudomonas aeruginosa, is required for first line antibiotic therapy in patients with febrile neutropenia.Aim. To study in vitro activity of cefepime / sulbactam and biapenem against Enterobacterales and P. aeruginosa strains in patients with bloodstream infection and hematologic diseases.Materials and methods. Susceptibility of cefepime / sulbactam and biapenem in comparison to anibiotics used for febrile neutropenia was studied among Escherichia coli (n = 100), Klebsiella pneumoniae (n = 100), Enterobacter cloacae complex (n = 30), and P. aeruginosa (n = 70) isolated from blood culture (2017–2021) from patients with hematological diseases and infection in 4 Russian hospitals. Activity was determined by broth microdilution method, interpretation was according to Clinical and Laboratory Standards Institute (CLSI, 2022) and European Committee on Antimicrobial Susceptibility Testing (EUCAST , 2022) criteria, for cefepime / sulbactam we used cefepime criteria. The values of the minimum inhibitory concentration (MIC), MIC50 and MIC90 were studied.Results. MIC90 of cefepime / sulbactam were lower in comparison with piperacillin / tazobactam for E. coli without extended spectrum beta-lactamase (ESBL) production (0.125 μg / mL vs 1 μg / mL), K. pneumoniae without ESBL-production (0.125 μg / mL vs 2 μg / mL), K. pneumoniae with ESBL-production (32 μg / mL vs 128 μg / mL) with comparable frequency of resistant strains. For P. aeruginosa, preference of cefepime / sulbactam over piperacillin / tazobactam were found both by lower MIC90 (8 μg / mL vs 32 μg / mL) and by lower frequency of resistant strains according to EUCAST criteria (4.3 % vs 25.7 %). The MIC90 values of cefepime / sulbactam compared to cefepime and ceftazidime were 4 times lower for K. pneumoniae with ESBL-production and for Enterobacter cloacea complex, 2–4 times lower for P. aeruginosa, 64 times lower for E. coli with ESBL production.Values of biapenem MIC90 for E. coli without and with ESBL-production (0.032 μg / mL) were in intermediate position between meropenem and imipenem; for K. pneumoniae without ESBL-production – identical to imipenem (0.064 μg / mL), for K. pneumoniae with ESBL – minimal (0.064 μg / mL) against imipenem and meropenem; for E. cloacae – comparable to meropenem (0.032 μg / mL). For P. aeruginosa without carbapenemase production, the MIC50 / MIC90 values of biapenem (0.125 / 16 μg / mL) were minimal compared to meropenem (0.25 / 64 μg / mL) and imipenem (0.5 / 64 μg / mL).Conclusion. The favorable in vitro activity of cefepime / sulbactam and biapenem are fully comply with the requirements for febrile neutropenia.