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AIM: To study the clinical manifestations of cryptococcosis, its diagnostic features, and treatment results in patients with hemoblastoses/MATERIAL AND METHODS: The study included adult patients with cryptococcosis treated at the Hematology Research Center (HRC) in 2005 to 2011. The diagnosis of cryptococcosis was established on the basis of isolation of Cryptococcus neoformans from a blood culture or determination of positive cryptococcal antigen in the cerebrospinal fluid (CSF) of patients with infection symptoms/RESULTS: During 7 years, 19 patients aged 19 to 68 years (median 47 years) were diagnosed as having cryptococcosis. In the pattern of cryptococcosis, there was a preponderance of patients with lymphoma (31%) and those with acute lymphoblastic leukemia (26%) at the stages of hemoblastosis remission induction (32%) and consolidation (26%). The diagnosis was made in 9 (47%) patients at the Intensive Care Department, HRC. The major risk factors of cryptococcosis were previous cytostatic drug exposure (68%), use of immunosuppressive and glucocorticoid drugs (63%), and granulocytopenia (42%). Seventeen (78%) patients were diagnosed with cryptococcal meningitis or meningoencephalitis; 1 patient had cryptococcal sepsis and 1 patient had possible cryptococcal pneumonia. All the patients were given antifungal agents. Amphotericin B, fluconazole, and a combination of antimycotics were used as first-line drugs in 16 (84%), 1 (5.5%), and 2 (10.5%), respectively. When their health became better, the patients were treated with voriconazole or fluconazole. Within 30 days after the diagnosis of cryptococcosis, 5 (26%) patients died; of them 2 had tumor progression concurrent with infection/CONCLUSION: In cryptococcosis, the central nervous system is predominantly involved in the infectious process. The determination of cryptococcal antigen in CSF is a necessary diagnostic component in meningitis and meningoencephalitis in patients with blood system tumors, lymphatic ones in particular. When cryptococcosis is timely diagnosed and treated, its mortality, when the tumor is controlled, is lower than that in other invasive mycoses.

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.

Objective: to determine antimicrobial resistance of Enterococcus faecium and Enterococcus faecalis isolated from blood culture of hematological patients during different study periods.Materials and methods. Antimicrobial susceptibility of Enterococcus spp., collected as part of the multicenter study was tested by the broth microdilution method (USA Clinical and Laboratory Standards Institute (CLSI), 2018), to daptomycin by Etest (bioMeriéux, France). High-level gentamicin resistance (HLGR) and high-level streptomycin resistance (HLSR) was performed by the agar dilution method (CLSI (Oxoid, UK), 2018).Results. The susceptibility of 366 E. faecium (157 in 2002-2009 and 209 in 2010-2017) and 86 E. faecalis (44 in 20022009 and 42 in 2010-2017) was studied. In the second study period (2010-2017) the rise of vancomycin-resistant E. faecium (VREF) increased from 8.3 % to 23.4 % (p = 0.0001), and two linezolid-resistant (LREF) were identified. All VREF and LREF remained susceptible to daptomycin and tigecycline. The rate of susceptible to tetracycline E. faecium remained the same (73.9 and 74.6 %), and an increase in susceptibility to chloramphenicol (74.5 and 82.3 %) was observed. Susceptibility of E. faecium to tetracycline was detected with almost the same rate and in a part of isolates, the increase of susceptibility to chloramphenicol was registered during the analyzed periods. The rise of E. faecium susceptible to HLGR and HLSR has increased significantly in 2010-2017 compared to 2002-2009. Erythromycin, levofloxacin, ampicillin and penicillin had the least activity against E. faecium (less than 5 %).All E. faecalis were susceptible to tigecycline, linezolid, and teicoplanin. Only one of E. faecalis had intermediate resistance to vancomycin. High susceptibility to ampicillin in E. faecalis remained unchanged (97.7 and 97.6 %, respectively). In the second period of the study the rise of susceptible E. faecalis decreased significantly to penicillin (from 97.7 % to 76.2 %), to levofloxacin (from 59.1 % to 31 %), to HLSR (from 52.3 % до 31 %), and to HLGR (from 47.7 % to 26.2 %), remained unchanged to chloramphenicol (52.3 % and 50 %) and was minimal to erythromycin and tetracycline.Conclusion. The study demonstrated higher rates of antibiotic resistance among E. faecium, which consisted of an increase in VREF and the appearance of linezolid-resistant strains. High susceptibility to ampicillin remained in E. faecalis, but there was an increase in resistance to penicillin and aminoglycosides.

Relevance. Acinetobacter baumannii is a significant nosocomial pathogen that can cause severe infections, especially in immunocompromised patients. Aims. This study aimed to investigate clonal diversity of A. baumannii isolated from blood culture in hematological patients by random amplified polymorphic DNA assay (RAPD). Materials & Methods. Genotyping of A.baumannii isolated from blood culture in hematological patients in 7 Russian hospitals (2003–2017) was assessed by RAPD-PCR with primer OPA-2 (5’-TGCCGAGCTG-3’). The computer-assisted analysis was performed by using GelJ software by UPGMA method and Dice similarity coefficient for banding patterns comparison. Using a similarity coefficient (SC) of ≥ 65%, the strains were grouped. Based on the similarity coefficient, the strains were determined as genetically related (≥ 80%). Strains had identical RAPD-patterns if the similarity coefficient was 100%. Results. A total of 96 A. baumannii strains were examined, of those 77 (80.2%) were nonsusceptible to carbapenems. Acquired OXA-carbapenemase genes were detected among 79.2% carbapenem non-susceptible strains. RAPD-PCR genotyping revealed 84 RAPD patterns. The four groups (A-D) including 98% strains were defined by similarity coefficient ≥65%. The predominant group A included 58 (60.4%) strains, the C and B groups – had 15 strains (15.6%) each, and the group D – 6 strains (6.3%). A total of 82 (85.4%) genetically related A. baumannii with a similarity coefficient ≥ of 80% were allocated into 20 clusters. Identical RAPD-patterns were defined for 22 strains that belonged to 6 clusters within the group A and 1 cluster within the group B. Strains with identical RAPD-patterns were detected in a single hospital as well as in several hospitals located in different cities. Conclusions. The current study has demonstrated genetic diversity and clonal dissemination of A. baumannii in hematological departments.

The aim of this study was to evaluate incidence and type of infections in patients with acute lymphoblastic leukemia (ALL) treated with ALL-2009 protocol during different chemotherapy cycles.Materials and methods. Prospective study (2013–2015) included patients with de novo ALL, receiving chemotherapy with ALL-2009 protocol. Patients were followed for 6 month. Total of 44 patients with ALL aged 17–61 years (median age 26 years) were enrolled in the study. These patients received 272 chemotherapy cycles (51 – induction, 221 – consolidation). On admission to National Research Center for Hematology hyperleukocytosis was in 25 % of patients, ECOG score ≥ 3 – in 61 %, severe infections – in 22 %, hospitalization to intensive care unit (ICU) – in 9 %.Results. Neutropenia was in 91 (38 %) of 272 chemotherapy cycles, predominantly in induction (71 %) compared to consolidation (25 %), odds ratio (OR) 7.2; p

The article comprises research of the act in the Russian State during period from 11-th to the beginning of 20-th centuries, from the Russian Truth up to the Criminal Code of 1903. The basic aspect of research is availability in the legislation of norms on defamation and structures adjacent, objective and subjective signs of defamation structure, their rise and development.