Background: Currently, there is a trend towards an increasing proportion of Gram-negative microorganisms, including Enterobacterias. Escherichia coli and Klebsiella pneumoniae constitute the major part in the structure of bloodstream pathogens. One important mechanism of Enterobacterias’ resistance is the production of extended-spectrum beta-lactamases (ESBL), AmpC β-lactamases and carbapenemases. Aims: Determination of the antibiotic resistance profile of bloodstream pathogens in patients with acute leukaemia and evaluation of the efficacy of starting antibiotic therapy regimens. Methods: The study included 69 cases of bloodstream infections, confirmed by bacteriological blood testing in patients with acute leukaemia between January 2020 and January 2022, 46.4% of which were male and 53.6% were female, with a median age of 44 years. All patients had myelotoxic agranulocytosis at the time of infectious complications. Results: During the study period and according to the bacteriological examination of blood, 58 strains of E. coli and Kl. pneumoniae were detected. The antibiotic sensitivity pattern is shown in the figure. Bloodstream infection caused by E. coli was detected in 23 cases (32.8%), herewith ESBL production was detected in 47.8% of E. coli strains. In the scope of the empirical antibiotic therapy, the 4th generation cephalosporin (cefepime) was used in 39.1% of cases or carbapenem (meropenem) in 60.9% of cases in combination with the 3rd generation aminoglycoside (amikacin). Herewith the empirical antibiotic therapy was considered as rational in 78.3% of cases, whereas in the remaining cases escalation was essential. The use of the 4th generation cephalosporin (cefepime) in the scope of the empirical therapy was ineffective in 55.6% of cases. Due to the therapy in 95.7% of cases the patient’s condition was stable, and in 4.3% of cases led to a fatal outcome. Bloodstream infection caused by Kl. pneumoniae was detected in 35 cases (50%), and resistance to carbapenems was reported in 68.6% of strains of the Kl. pneumoniae. The share of ESBL-producing Kl. pneumonias trains was 40%, while the proportion of Enterobacteriaceae strains, susceptible to extended-spectrum cephalosporins and carbapenems, reached only 8.8%. During the therapy in 72.4% of cases the patient’s condition stabilised, and in 27.6% of cases a fatal outcome was recorded. In all cases of fatality сarbapenem-resistant strains, including panresistant strains (5.9%) acted as a causative agent. Summary/Conclusion: The most frequent causative agents of bloodstream infections in acute leukaemia patients during myelotoxic agranulocytosis are the Gram-negative bacteria E. coli and Kl. pneumoniae. The empirical antibiotic therapy regimens including 3rd generation cephalosporins (cefepime) was ineffective in 55.6% of cases, as 47.8% of isolated E. coli strains were generating ESBL. This increases the relevance of using carbapenems. Resistance to carbapenems was reported in 68.6% of strains of Kl. pneumoniae. This indicates a high prevalence of carbapenem-resistant strains in the haematological hospital, as well as the low efficacy of empirical antibiotic therapy, including both cephalosporins and carbapenems.