In Vitro Activity of Ceftazidime-Avibactam against Gram—Negative Bacteria Recovered from Blood and Fecal Samples of Patients after Hematopoietic Stem-Cell Transplantation ^†

Patients receiving hematopoietic stem-cell transplantation (HSCT) are prone to develop invasive infections due to disease and transplantation-related immunosuppression. The main causative agents often originate from the digestive tract and are multidrug-resistant. Our aim was to investigate the in vitro activity of ceftazidime-avibactam (CZA) against extended spectrum beta-lactamase (ESBL)-producing and carbapenem-resistant (CR) Gram-negative bacteria recovered from blood and fecal samples of patients following HSCT, hospitalized in University Hospital “Saint Marina”—Varna, during 2019–2021.

A total of 48 isolates (E. coli, n = 20; Enterobacter cloacae, n = 9; Klebsiella pneumoniae, n = 6; Serratia marcescens, n = 1; Acinetobacter baumannii, n = 2; Pseudomonas putida, n = 4; Pseudomonas aeruginosa, n = 4; Pseudomonas mendocina, n = 1; Pseudomonas composti, n = 1) were studied. MALDI Biotyper Sirius (Bruker, Bremen, Germany) and the automated Phoenix system (BD, Franklin Lakes, NJ, USA) were used for species identification and susceptibility testing. Twenty-four isolates, included in this study, were resistant to third- and fourth-generation cephalosporins and, therefore, were identified as ESBL producers (E. coli, n = 12; E. cloacae, n = 7; K. pneumoniae, n = 4; S. marcescens, n = 1). A multiplex polymerase chain reaction was used for gene detection, associated with carbapenem resistance. In the studied group, eleven isolates (23%) were CR (E. cloacae, n = 1; Pseudomonas spp., n = 8; A. baumannii, n = 2). All 24 ESBL-producing isolates were CZA-susceptible. In the group of CR isolates, only 1 P. aeruginosa was susceptible to CZA, while 10 CR isolates were resistant. Genes associated with class B and class D carbapenemases were detected by PCR (bla_VIM and bla_OXA-like).

In conclusion, in our study, all ESBL producers were susceptible to CZA, while 91% of the CR isolates (all class B and class D carbapenemase producers) were resistant. CZA is a drug combination that is highly active against ESBL producers, but its spectrum of activity is limited against carbapenemase producers. Therefore, other novel antimicrobial agents are urgently needed.