Objective: to evaluate and compare the qualitative and quantitative composition of the intestinal microbiota in patients with malignant neoplasms of various localizations. Material and Methods. The study included patients who received different types of treatment in N.N. Blokhin Oncology Research Center, Moscow, Russia in 2023 for gastric cancer, including cardioesophageal adenocarcinoma (group 1), esophageal squamous cell carcinoma (group 2) and metastatic or locally advanced melanoma of the skin (group 3). All patients had to have morphologic verification of the diagnosis at the time of inclusion, be over 18 years old, have an ECOG performance status of ≤1, and have no evidence of intestinal infection, as well as not take antibiotics within 28 days prior to entry into the study. Stool samples were collected during patients’ hospitalization. The quantitative and qualitative composition of microorganisms of 17 taxonomic groups was evaluated. Microorganisms were cultured according to standard microbiological methods, taking into account the growth conditions of a particular group of microorganisms. Species identification of microbial isolates was obtained by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF) and MALDI Biotyper v.3.0 software (Bruker daltonics, Germany). Descriptive statistics methods from the SPSS Statistics, v.27 software package were used. To quantitatively describe the species diversity of the gut microbiota, calculations were performed using the Margalef species richness index (d) and Shannon’s (H) diversity index. The criterion of uniformity of microbial species distribution according to their abundance in the population community was evaluated using the Pielow index (E). The Hutcheson’s T-criterion was used to test the significance of differences between sample sets of Shannon index values and to obtain statistically correct estimates of differences (p≤0.05). Results. A total of 63 samples of biological material (feces) were investigated. A change in the quantitative composition of intestinal microbiota in all study groups was found, which may have a negative impact on the general condition of the patient and the effectiveness of antitumor treatment. The increase in the proportion of Proteobacteria (Enterobacterales) can be considered as a risk factor for the development of infectious complications caused by Gram-negative microorganisms. The analysis of factors influencing the taxonomic diversity of intestinal microbiota revealed no significant differences in the composition of intestinal microbiota between the groups of patients with malignant tumors of different nosological forms (p>0.05).

Aim. To present data on the structure of bacterial pathogens causing infectionsin cancer patients atthe N.N. Blokhin National Research Center of Oncology and analyze them in comparison with data of domestic and foreign literary sources. Materials and methods. The data of 11,853 microorganisms isolated from patients hospitalized in the N.N. Blokhin National Research Center of Oncology in 2023 were analyzed. Results . Bacteria accounted for 90.0 % of all isolated microorganisms and only 10.0 % were fungal pathogens. Despite the fact that gram-negative pathogens have given way to gram-positive pathogens in absolute numbers, gram-negative microorganisms (60.7 %) still prevail in “clinically significant” biomaterials (blood, spinal fluid, urine, wound discharge, BAL, etc.), primarily Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii and others. With the exception of Escherichia coli, a high percentage of carbapenem-resistant strains is noted for other pathogens: Klebsiella pneumoniae – 34 %, Pseudomonas aeruginosa – 50 %, Acinetobacter baumannii – 69 %. Real-time polymerase chain reaction revealed the leading carbapenemases: in Klebsiella pneumoniae strains – KPC or OXA-48 carbapenemases were detected in 55 % of cases, and NDM metallo-β-lactamasesin 45 %; in Pseudomonas aeruginosa strains – VIM metalloβ-lactamases were registered in 29 % of cases. Among gram-positive microorganisms, the most problematic is vancomycinresistant Enterococcus faecium. It accounts for 45 % of all E. faecium strains. Conclusion. Along with modern diagnostics and infection control measures, knowledge of the leading microbiota in a particular clinic will prevent the spread of infection and provide timely medical care to patients.

Работа посвящена редко встречающимся бактериальным и грибковым возбудителям инфекций. Эти микроорганизмы создают трудности в диагностике и лечении в связи с возможными ошибками идентификации возбудителя, природной или приобретенной лекарственной резистентностью.Возбудители редких инфекций могут колонизировать больных, образовывать биопленки, персистировать в окружающей среде, передаваться от больного к больному и приводить к развитию вспышек инфекции. Они нередко ухудшают прогноз лечения онкологического больного и приводят к летальному исходу.Информация об особенностях редко встречающихся микроорганизмов и возможных подходах к их лечению позволит врачам-онкологам оказывать своевременную квалифицированную помощь подобным пациентам.

Recent development of molecular and genetic technologies has demonstrated at the molecular level the co-evolutionary principles of interaction between microbiota, virome and the host organism, as well as the role of microorganisms and viruses both in maintaining physiological homeostasis and in the development of various diseases, including malignant neoplasms. The presented review is devoted to the analysis and generalization of modern data on microorganisms and viruses inhabiting the human body, their role in the processes of initiation, promotion and progression of carcinogenesis. The review provides information on known oncogenic viruses and microorganisms according to the modern classification of carcinogenic agents of the International Agency for Research on Cancer. Mechanistic data on the procarcinogenic effect of microbiota and virome are considered in accordance with the modern concept of key characteristics of a carcinogenic agent. Particular attention is paid to the analysis of data on the influence of microbiota and virome on the immunity of the host organism, including both the first results of immunotherapy with Coley toxin of soft tissue sarcomas and osteosarcomas, and data on the influence of individual types of microorganisms on the formation of the immunocompetent cell profile of the host organism. In addition, the influence of intratumor and intracellular microbiota, respectively, on the microenvironment of tumor cells and cellular signaling, including in solid tumors that have no contact with the external environment are also discussed. The data presented are important in terms of the holobiota concept, showing the interdependent existence of the human body, microorganisms and viruses, to improve the prevention and therapy of malignant neoplasms.

Aim . To investigate the species composition and frequency of opportunistic pathogens in cancer patients diagnosed with non-small cell lung cancer (NSCLC) receiving chemotherapeutic treatment at the Federal State Budgetary Institution National Medical Research Center of Oncology named after N. N. Blokhin of the Russian Ministry of Health. Materials and methods . A prospective open single-center study included a cohort of patients with locally advanced or metastatic NSCLC receiving drug antitumor therapy, aged 18 years and older. The study was observational in nature. The endpoint of this phase of the study was to determine the relative number of NSCLC patients with chronic infection (pneumocystis, herpes simplex virus (HSV) 1, HSV-2, cytomegalovirus (CMV), Epstein–Barr virus (EBV), human herpes virus type 6 (HHV-6) and their combinations). Results. Antibodies to herpes viruses and/or pneumocystis were detected in patients (n = 18) diagnosed with NSCLC in 100 % of cases. Antibody titers corresponding to active infection were more characteristic for EBV and CMV, with CMV infection markers more often registered in titers corresponding to the acute stage of the disease, and EBV – in the reactivation stage without obvious clinical manifestations. In most cases, mixed infection with different pathogens was determined: combination of HSV-1 + EBV + CMV was found in 55.5 % (n = 10) of NSCLC patients; HSV-1 + EBV + CMV + HHV-6 – in 33.3 % (n = 6) of cases, HSV-1 + HSV-2 + EBV + CMV – in 5.5 % (n = 1), HSV-1 + HSV-2 + EBV + CMV + HHV-6 also in 5.5 % (n = 1) of patients. During bronchoalveolar lavage examination, pneumocystis were detected in 3 (42.8 %) out of 7 examined patients. Conclusion . Based on the results of studies of a relatively small cohort of patients in the absence of clinical symptoms of infection in NSCLC patients, a high percentage of IgM and IgG antibodies, which are markers of opportunistic infections and their combinations, were detected. Pneumocystis was isolated from bronchoalveolar lavage in 42.8 % of cases. It is necessary to evaluate the results obtained in a larger number of patients to determine approaches to the prevention and treatment of opportunistic infections.

Objective . To conduct a systematic analysis of data on the results of studies published in scientific journals on the pro-carcinogenic and anticarcinogenic role of microbiota, as well as on the therapeutic potential of microorganisms in oncogenesis. Material and Methods . The articles were searched using the Web of Science, Scopus, PubMed, Medline, and eLIBRARY databases. More than 150 sources dedicated to the study of the carcinogenic function of the microbiota and the possible influence of its species and quantitative composition on the efficacy and toxicity of antitumor therapy were found. Data from 71 articles were included in the review. Results . The relationship between the gut microbiota and cancer is multifactorial and bilateral: pro-carcinogenic on the one hand and anti-carcinogenic on the other hand. Microorganisms can induce tumor growth and cancer development through DNA damage and induction of mutagenesis, trigger oncogenic signals, disruption of barrier function, as well as immune response system disruption. Depletion of microbiota, the development of dysbiosis and induction of chronic inflammatory state are negative factors in the development of cancer. The anticancer effect of microorganisms is presumably based on the production of tumor-suppressive metabolites that function through multiple immune reactions. Maintenance of barrier function, competitive exclusion of pathogenic bacteria, and direct action on immune cells to prevent inflammation are also important protective factors. The presence of intratumor microorganisms in various tumors has been noted. Changes in species and quantitative composition of cancer patients’ microbiota are influenced by diet, taking antibacterial drugs, chemo-, immuno- and radiation therapy. In turn, the microbiota can affect the ongoing treatment. Numerous studies on the influence of the gut microbiota on the efficacy of immunotherapy, particularly in disseminated melanoma, have been conducted. It has been suggested that primary resistance to immunotherapy may be related to the abnormal composition of the gut microbiota. The level of gut microfora composition diversity and the number of Faecalibacterium or Bacteroidales in the fecal microbiota have been suggested to be the predictor of response to anti-PD-1 therapy. To change the composition and activity of the gut microbiota, several therapeutic methods, such as the administration of prebiotics, probiotics, synbiotics, postbiotics, fecal microbiota transplantation, as well as the change in the microbiota composition through a specific diet, are available.

Цель: представить литературные и собственные данные по распространенности карбапенемаз у микроорганизмов, вызывающих тяжелые инфекции у онкологических больных и дать сведения о предпочтительном лечении при выделении основных карбапенем-резистентных грамотрицательных возбудителей ( Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae ). Методы исследования: обзор литературы за последние 10 лет, включая международные рекомендации по лечению мультирезистентных инфекций (2021–2022 гг.). Также представлены собственные данные по частоте выделения карбапенемаз в биоматериалах от больных с нозокомиальными инфекциями, находившимися в НМИЦ онкологии им. Н. Н. Блохина, в 2021–2022 гг. Результаты: представлены обобщенные данные, касающиеся возможностей комбинированной терапии нозокомиальных инфекций, вызванных трудно поддающимися лечению возбудителями (карбапенемазопродуцирующими грамотрицательными микроорганизмами), дан подробный разбор механизмов резистентности, обусловленных бета-лактамазами (карбапенемазами). Заключение: При наличии тяжелых инфекций, сепсиса / септического шока универсальных схем антибиотикотерапии не существует. Необходимо знание особенностей лечения в зависимости от молекулярно-генетических характеристик возбудителей инфекции.

The objective of the study was to analyze the taxonomic structure of urinary infection pathogens and determine the susceptibility of ESKAPE group microorganisms (Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterococcus spp.) isolated from cancer patients with nosocomial infections in 2018—2020 to antimicrobials.Materials and methods. 413 (71.9 %) strains of ESKAPE group bacteria from 228 patients were studied. Microorganisms were identified and antibiotic resistance was determined using Vitek-2 System (France) and MicroScan WalkAway (Germany / USA) analyzers.Results and conclusion. All gram-positive microorganisms were highly sensitive to vancomycin and teicoplanin, linezolid, tigecycline, and daptomycin, which can be used in the treatment if clinical indications are seen. Among gram-negative bacteria, the percentage of ESBL producers was 60—70 %, the percentage of carbapenem-resistant bacteria was minimalfor E. coli, rnmpared to the rest - 40—50 %, demonstrating the need to limit the use of carbapenems in the clinic.

В работе обсуждается проблема бактериальных инфекций, вызывающих осложнения у онкологических больных. Продемонстрированы данные, полученные в «НМИЦ онкологии им. Н. Н. Блохина» МЗ РФ о частоте выявления резистентных грамотрицательных и грамположительных бактерий из биоматериалов от больных клиники. Приводятся данные исследований механизмов резистентности, которые проводились на молекулярно-генетическом уровне. Отмечено относительное увеличение доли грамположительных микроорганизмов, в частности, коагулазонегативных стафилококков. Резистентность стафилококков обусловлена наличием генов mecA. В то же время ген резистентности к антибиотикам cfr отсутствует. Однако, выявленная у коагулазонегативных стафилокококков мутация 23SrRNA свидительствует о формировании резистентности. Среди мультирезистентных грамотрицательных микроорганизмов превалируют Klebsiella pneumoniae, Pseudomonas aeruginosa. 88,2 % изолятов клебсиелл имеют гены продукции сериновых карбапенемаз OXA-48. 46,7 % изолятов синегнойных палочек имеют гены продукции металло-беталактамаз VIM. 97,1 % изолятов Acinetobacter baumannii имеют гены продукции серино- вых карбапенемаз OXA-23. В большинстве случаев продукции карбапенемаз сопутствовал механизм нарушения проникновения карбапенемов в микробную клетку. Знание механизмов резистентности основных возбудителей инфекции дает возможность врачу выбирать оптимальные комбинации антибиотиков. Увеличение разнообразия выделяемых от больных бактериальных микроорганизмов косвенно говорит о возможности появления новых резистентных возбудителей, таких как Burkholderia cepacia, Achromobacter xylosoxidans и др. Также возможен рост числа резистентных штаммов среди обычно чувствительных возбудителей — кишечной палочки, энтеробактеров и протеев.

Онкологические больные являются группой риска в отношении возникновения внутри-и внебольничных инфекций вследствие ряда факторов. Автоматизация микробиологической лаборатории позволяет снизить частоту ошибок, связанных с человеческим фактором, ускорить выдачу антибиотикограммы и своевременно начать антибиотикотерапию, что приведет к снижению летальности и повышению качества жизни пациентов.

The purpose of the study was to analyze the prevalence of multidrug-resistant (MDR) pathogens (Escherichia coli and Klebsiella pneumonia) isolated from cancer patients. material and methods. 862 strains of E. coli and 1 461 strains of K. pneumoniae isolated from wound, blood, urine and other pathological materials from cancer patients treated at N.N. Blokhin National Medical Research Center of Oncology (Moscow) between 2014 and 2016 were analyzed. results. Over the last 3 years, there has been a significant increase in the number of E.coli resistant to piperacillin-tazobactam (from 8.1 to 25 %), ceftriaxone (from 15.7 to 100 %), ertapenem (from 8.1 to 97.7 %), and amikacin (c 4.5 to 14.6 %). The number of E. coli producing carbapenemases has increased from 5.8 to 20.8 % (p≤0.0001). Among K. pneumoniae, a significant increase in the number of strains resistant to piperacillin-tazobactam (from 59.7 to 89.7 %), ceftazidime (from 62.8 to 82.8 %), ceftriaxone (from 62.8 to 100 %), cefepime (from 63.1 to 83.8 %), ertapenem (from 62.1 to 100 % ), imipenem (from 30.0 to 81.0 %), and meropenem (from 53.9 to 86.8% ) is observed. conclusion. Evaluation of the frequency of isolation of MDR microorganisms over time is an essential element of epidemiological surveillance and is necessary for the correct treatment of patients with infectious complications.

The purpose of the study was to analyze infectious complications caused by multi-drug-resistant organisms depending on anticancer therapy.Material and Methods. A total of 229 cancer patients with infectious complications of cancer therapy were included into the study.Results. Lung cancer was the most predominant cancer (26.6 %) followed by gastric cancer (25.3 %) and esophageal cancer (14.4 %). Infectious complications occurring after surgery were observed in 83.4 % of the patients. Infectious complications caused by Acinetobacter baumannii were the most common (40.6 %), followed by Klebsiella pneumoniae (28.5 %), Pseudomonas aeruginosa (19.5 %), Staphylococcus spp. (9.4 %), and Enterococcus spp. (1.8 %).Conclusion. Infectious complications occurred more frequently in postoperative cancer patients (p<0.02), and the ESKAPE group pathogens were the leading cause of these infections.

The purpose of the study was to evaluate the frequency of isolation of multi-resistant Acinetobacter baumannii in cancer patients and identify the mechanisms of resistance to carbapenems.Material and Methods. We analyzed 942 strains of A. baumannii isolated from clinical samples of cancer patients in the period 2014–16. The level of resistance to ampicillin-sulbactam, piperacillin-tazobactam, ceftazidime, cefepime, imipenem, meropenem, ciprofloxacin, amikacin, and to other antibiotics was determined. Carbapenem-resistant (Car-R) strains were examined for the presence of carbapenemases.Results. Between 2014 and 2016, the number of strains resistant to: ampicillin-sulbactam was 95.5–74.6 % (p≤0.0001), piperacillin – tazobactam 64.3–98.1 % (p<0.01), ceftazidime – 66.1–44.3 % (p≤0.0001), cefepime – 94.7–98.3 % (p≤0.01), ciprofloxacin – 95.8–91.8 % (p<0.05), amikacin – 77.7–91.0 % (p≤0.0001). An increase in the number of Car-R strains from 77.2 % in 2014 to 84.1 % in 2015 (p<0.05) and up to 90.0 % in 2016 (p<0.05) was observed. The resistance to imipenem was 100 %. The analysis of 6 strains in relation to acquired carbapenemases revealed the production of serine carbapenemases of the OXA-23 group in 100 % of cases.Conclusion. A. baumannii remains to be highly resistant to almost all classes of antibiotics, and the resistance to carbapenems is caused by the production of carbapenemases OXA-23.

The purpose of the study was to evaluate the frequency of isolation of multi-resistant Pseudomonas aeruginosa and identify the mechanisms of resistance to carbapenems.Material and methods. We analyzed 866 strains of Pseudomonos aeruginosaisolated from clinical samples from cancer patients in the period 2014–2016. the level of resistance to piperacillin/tazobactam, ceftazidime, cefepime, imipenem, meropenem, ciprofloxacin, amikacin in dynamics was determined. carbapenem-resistant (car-R) strains were examined for the presence of enzymes.Results. Between 2014 and 2016, the number of strains resistant to piperacillin/tazobactam was 20.1–12.9 %, to ceftazidime – 33.0–32.9 %, to cefepime – 25.6–32.9 %, ciprofloxacin – 36.8–43.8 %, amikacin – 23.8–24.9 %. No statistically significant differences were found (p>0.05). However, an increase in the number of car-R strains from 31.7 to 43.8 % was observed (p<0.05). of 7 strains of P. aeruginosainvestigated for the presence of acquired carbapenemases, the production of metal-beta-lactamase of group Vimwas detected in 2 strains, and class acarbapenemases of the gEs-5 group in one strain.Conclusion. P. aeruginosaresistance to all antibiotic groups did not exceed 50 % and remained almost unchanged for 3 years, with the exception of the increase in car-R strains. three out of 7 (42.9 %) carbapenem-resistant strains were genetically stable.

The purpose of the study was to analyze infectious complications caused by multi-drug-resistant organisms depending on anticancer therapy.Material and Methods. A total of 229 cancer patients with infectious complications of cancer therapy were included into the study.Results. Lung cancer was the most predominant cancer (26.6 %) followed by gastric cancer (25.3 %) and esophageal cancer (14.4 %). Infectious complications occurring after surgery were observed in 83.4 % of the patients. Infectious complications caused by Acinetobacter baumannii were the most common (40.6 %), followed by Klebsiella pneumoniae (28.5 %), Pseudomonas aeruginosa (19.5 %), Staphylococcus spp. (9.4 %), and Enterococcus spp. (1.8 %).Conclusion. Infectious complications occurred more frequently in postoperative cancer patients (p<0.02), and the ESKAPE group pathogens were the leading cause of these infections.

We studied capabilities of the Bruker Microflex MALDI-TOF device for species identification of anaerobic gramnegative cocci isolated from clinical specimens of cancer patients. Seventy clinical isolates of Veillonella spp. and one Acidaminococcus spp were analyzed. All isolates were identified to the species level with a scores greater than 1.9. The most common species were V. parvula (37 strains), followed by V. dispar (16), V. atypical (16) and V. denticariosi (1). Susceptibilities of the isolates were determined by the E-test methodology. All Veillonella isolates were susceptible to imipenem, whereas high resistance rates were observed for penicillin G, amoxicillin/clavulanate and metronidazole. The proportion of resistant isolates of V. parvula, V. dispar and V. atypica to penicillin was 86 %, 85 % and 100 %, respectively. The resistance to amoxicillin/clavulanate was observed in 28.6 % of V. parvula isolates, 23.1 % of V. dispar isolates and in 6.7 % of V. atypica isolates. Resistance to metronidazole (MIC ≥ 8 µg/ml) of V. parvula, V. dispar and V. atypica was 88.6 %, 53.8 % and 40 %, respectively.

Nosocomial infections caused by gram-positive organisms, including Staphylococcus aureus and enterococci (Enterococcus faecium and Enterococcus faecalis) are steadily increasing in almost all clinics around the world. Cancer patients have a higher risk of hospital-acquired infections than non-cancer patients. Cancer patients are immunosuppressed due to increased use of broad-spectrum antibiotics and chemotherapy drugs, radiation therapy, surgery and use of steroids. This paper presents an analysis of resistance of gram-positive bacterial pathogens to antimicrobial agents to determine treatment strategy for cancer patients.

Introduction. Urinary tract infections are among the most frequently seen bacterial infections. Worldwide, about 150 million people are diagnosed with urinary tract infections each year, costing the global economy in excess of 3.5 billion US dollars. Urinary tract infections occur more frequently and exhibit more severe symptoms in cancer patients than in patients with other diseases. Material and methods. The paper analyzes the etiology of urinary tract infections in cancer patients during their stay in the hospital. Results. The presented data concern antibiotic-resistant ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). Comparative data on the sensitivity to different antibiotics were shown. Recommendations for treatment aimed at reducing the selective pressure of certain groups of antibiotics, in particular carbapenems, were given.

В эпоху применения различных металлических и других устройств с лечебной целью отмечается появление инфекций, связанных с установкой и длительным нахождением этих устройств (англ. – device) в организме человека. Помимо широкораспространенных катетер-ассоциированных инфекций (КАИ) кровотока и КАИ мочевых путей, а также инфекционных эндокардитов, связанных с протезированием клапанов, все большее значение приобретают перипротезные инфекции (в ортопедии, онкоортопедии), инфекции, связанные с установкой сеток (в хирургии), стентов (в сосудистой хирургии и др.), водителей ритма (в кардиохирургии) и др. В основе подобных инфекций лежит формирование биопленок, которые затрудняют микробиологическую диагностику инфекции и ее лечение в связи с антибиотикорезистентностью микроорганизмов в биопленке. Подробно представлены данные по инфекциям в ложе эндопротеза, их этиологии, подходам к диагностике и лечению.