Objective. To study in vitro activity of antimicrobials against clinical isolates obtained from patients with community-acquired urinary tract infections (UTIs) in various regions of Russia in 2023. Materials and Methods. The study included 1098 isolates obtained from the urine of children and adults of both sexes of all age groups with acute and exacerbation of recurrent community-acquired UTIs, including pregnant women with asymptomatic bacteriuria. Isolates were collected in 29 centers in 21 cities of Russia in 2023 as part of a multicenter prospective epidemiological study of the dynamics of antibiotic resistance of pathogens causing community-acquired UTIs in different subsets of patients ("DARMIS-2023"). The categories of susceptibility of isolates to antimicrobial drugs were based on the breakpoint values of minimum inhibitory concentrations (MIC) in accordance with the Russian recommendations "Determination of susceptibility of microorganisms to antimicrobial drugs" (Version 2024-02) and the updated EUCAST criteria (v. 14.0, 2024). Results. Enterobacterales accounted for a total of 88.1% of all isolated bacterial pathogens (89.6% in the adult subpopulation; 82.8% in the pregnant subpopulation and 89.6% in the subpopulation of children and adolescents under 18 years of age). The most prevalent species were Escherichia coli (72.2% in the adult subpopulation; 72.8% in the pregnant women subpopulation and 68.9% in the children and adolescents under 18 years of age subpopulation) and Klebsiella pneumoniae (10.8% in the adult subpopulation; 4.8% in the pregnant women subpopulation and 9.8% in the children and adolescents under 18 years of age subpopulation). Of the oral drugs, the minimal resistance in E. coli was demonstrated for nitrofurantoin (0.4% of isolates in the adult subpopulation; 0.0% in the pregnant women subpopulation and 1.6% in the children and adolescents under 18 years of age subpopulation) and fosfomycin (9.6% of isolates in the adult subpopulation; 4.4% in the pregnant women subpopulation and 1.6% in the children and adolescents under 18 years of age subpopulation). Of the parenteral agents, meropenem and amikacin had the highest activity: 0.8% and 1.0% resistant E. coli in the adult subpopulation; no resistant E. coli in the pregnant subpopulation; 0.0% and 0.8% in the children and adolescents under 18 years of age subpopulation, respectively. For each patient subpopulation, antimicrobial resistance of E. coli to ampicillin, amoxicillin/clavulanic acid, cefotaxime, cefixime, and trimethoprim-sulfamethoxazole was more than 20%. Rates of E. coli resistance to ciprofloxacin were 36.7% in the adult subpopulation; 22.1% in the pregnant subpopulation; and 22.2% in the children and adolescents under 18 years of age subpopulation. The rate of extended-spectrum beta-lactamase production based on phenotypic test results was 29.6% in the adult subpopulation; 23.6% in the pregnant subpopulation and 33.3% in the children and adolescents under 18 years of age subpopulation. Conclusions. In community-acquired UTIs the main clinical problem is the persistent high rate of E. coli resistance to cephalosporins, fluoroquinolones, aminopenicillins/beta-lactamase inhibitors, as well as the increase of the extended-spectrum beta-lactamases production. Remaining high in vitro activity of fosfomycin and nitrofurans allows to consider them as drugs of choice in uncomplicated lower urinary tract infections.

Objective. To study the antimicrobial susceptibility profile of Moraxella catarrhalis isolates from different regions of Russia in 2010–2021. Materials and Methods. The study included 352 isolates of M. catarrhalis isolated in 11 cities of Russia (Volgograd, Irkutsk, Kazan, Kirov, Moscow, Murmansk, Perm, Seversk, Togliatti, Tomsk, and Ulan-Ude) in 2010–2021. Identification was done by MALDI-TOF mass spectrometry. Antimicrobial susceptibility testing was determined by broth microdilution method in accordance with the ISO 20776-1:2020. Interpretation of results was done in accordance with EUCAST guidelines (v.14.0). Results. Most of the isolates were isolated from respiratory specimens: 225 (63.9%) from sputum, 49 (13.9%) from nasal swabs, 41 (11.6%) from sinus aspirates, 17 (4.8%) from bronchoalveolar lavage, 8 (2.3%) from middle ear fluid, 6 (1.7%) from pharyngeal swabs, and 5 (1.4%) from conjunctival secretions. All tested isolates were susceptible to beta-lactams for which interpretive criteria have been established (amoxicillin-clavulanate, cefixime, ceftriaxone, cefuroxime). The susceptibility to clarithromycin and azithromycin was 99.7% and 100%, respectively. Ciprofloxacin, levofloxacin and moxifloxacin were active against 98.9%, 99.2% and 99.7% of isolates tested, respectively. Susceptibility to tetracycline was 99.7% and to trimethoprim-sulfamethoxazole was 99.4% (92% of isolates susceptible, 7.4% – susceptible at increased exposure). Conclusions. In the Russian Federation there is a favorable situation regarding the susceptibility of M. catarrhalis to antimicrobials. Amoxicillin-clavulanic acid, cefixime, ceftriaxone, azithromycin, clarithromycin, ciprofloxacin, levofloxacin, moxifloxacin and tetracycline retain high in vitro activity

Objective. To study the prevalence and mechanisms of antibiotic resistance, including carbapenemase production, in clinical isolates of Klebsiella pneumoniae and Escherichia coli isolated in different regions of Russia as part of the sentinel multicenter surveillance study in 2020–2021, and to explore the population structure of K. pneumoniae and the impact of “high-risk clones” on antibiotic resistance. Materials and Methods. Consecutive, non-duplicate isolates of K. pneumoniae (n = 2503) and E. coli (n = 2055) isolated from various specimens (blood, cerebrospinal fluid, respiratory samples, urine, wound secretions, etc.) of hospitalized patients with clinical signs of infection in 55 hospitals of 29 cities of Russia were studied. Species identification of isolates was performed by matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry (MALDI-TOF MS). Antibiotic susceptibilities were determined by serial broth microdilution or, in the case of fosfomycin, by agar dilution method, and results were interpreted according to EUCAST v13 MIC breakpoints. Carbapenemase production was determined phenotypically by carbapenem inactivation method (CIM), the presence of genes of the most common serine carbapenemases (KPC, OXA-48) and metallo-β-lactamases (VIM, IMP, NDM) was determined by real-time PCR. K. pneumoniae clinical isolates were genotyped and assigned to the known clonal complexes (CC) and sequence types (ST) using SNP typing and multilocus sequencing typing (MLST) methods. K- and O-serotypes, acquired resistance and virulence genes, and plasmids carrying these genes were characterized using whole-genome sequencing of selected isolates (n = 215). Results. The resistance rates of nosocomial/community-acquired isolates of K. pneumoniae were as follows: amoxicillin-clavulanate – 88.63⁄57.99%, piperacillin-tazobactam – 82.92⁄45.49%, cefotaxime – 87.74⁄56.97%, ceftazidime – 84.76⁄53.07%, cefepime – 81.43⁄49.18%, aztreonam – 1.63⁄53.28%, ceftazidime-avibactam – 30, 88⁄9.22%, ceftolozan-tazobactam – 70.06/31.35%, ertapenem – 72.10⁄28.69%, meropenem – 49.60⁄15.16%, imipenem – 44.54⁄13.73%, gentamicin – 60.82⁄30.33%, amikacin – 42.06/17.21%, ciprofloxacin – 85.10⁄49.39%; trimethoprimsulfamethoxazole – 74.38⁄48.16%, colistin – 5.96⁄2.25%. The resistance of nosocomial/outpatient isolates of E. coli were: ampicillin – 84.93⁄67.67%, amoxicillin-clavulanate – 57.37⁄39.73%, piperacillin-tazobactam – 19.48⁄8.70%, cefotaxime – 63.83⁄34.19%, ceftazidime – 45.32⁄20.34%, cefepime – 35.95⁄16.61%, aztreonam – 51.78⁄26.11%, ceftazidime-avibactam – 5.71⁄0.80%, ceftolozane-tazobactam – 11, 95⁄2.22%, ertapenem – 8.18⁄1.42%, meropenem – 5.17⁄0.53%, imipenem – 4.95⁄0.36%, gentamicin – 24.54⁄13.68%, amikacin – 5.49⁄1.42%, ciprofloxacin – 54, 14⁄32.50%, trimethoprim-sulfamethoxazole – 52.21⁄38.54%, fosfomycin – 2.48⁄1.43%, colistin – 1.60⁄1.07%, tigecycline – 6.35⁄3.11%. The frequency of carbapenemase production among K. pneumoniae nosocomial isolates was 65.32% (OXA-48 – 40.75%, NDM – 30.28%, KPC – 8.74%, OXA-48 + NDM – 10.62%, OXA-48 + KPC – 2.98%, NDM + KPC – 0.45%, OXA-48 + NDM + KPC – 0.20%). More than 70% of nosocomial isolates of K. pneumoniae belonged to only 7 major genetic lineages known as “high-risk international clones”: CC395 – 37.40%, CC23 – 9.59%, CC307 – 8.64%, CC147 – 7.61%, CC15 – 2.95%, CC258 – 2.92%, and CC11 – 2.41%. The population of community-acquired K. pneumoniae was characterized by significantly greater genetic diversity (Simpson diversity index: D = 0.919; 95% CI: 0.904 to 0.933) compared with the population of nosocomial strains (Simpson diversity index: D = 0.815; 95% CI: 0.802 to 0.827). Strains of the “hypervirulent” genetic lineage of K. pneumoniae CC23 were more common in community-acquired infections. Conclusions. The extremely high frequency of resistance to cephalosporins in K. pneumoniae (> 80%) and E. coli (> 60%), as well as the high frequency of combined resistance to aminoglycosides and fluoroquinolones precludes their empirical use for the treatment of serious nosocomial infections caused by these pathogens. K. pneumoniae shows a rapid increase in resistance to carbapenems, mainly due to the spread of carbapenemases of three major groups: OXA-48, NDM and KPC. The overall increase in the frequency of carbapenemase production is accompanied by the growing diversity of carbapenemases, the increasing prevalence of strains producing NDM and KPC enzymes and those co-producing multiple carbapenemases simultaneously. In community-acquired infections, the high prevalence of resistance to cephalosporins in E. coli (> 30%) and K. pneumoniae (> 50%) remains the most important problem.

Objective. To evaluate in vitro activity of various macrolide antibiotics against a current collection of clinical isolates of Streptococcus pneumoniae and Streptococcus pyogenes isolated from patients with community-acquired infections in different regions of the Russian Federation. Materials and Methods. A total of 350 clinical isolates from patients with community-acquired infections, including 200 S. pneumoniae and 150 S. pyogenes, were included in the study. To further evaluate the in vitro activity of 16-member macrolides against erythromycin-resistant isolates (MIC ≥ 0.5 mg/L), a retrospective collection of 253 erythromycin-resistant S. pneumoniae and 112 S. pyogenes isolates was tested. Susceptibility to antimicrobials was determined by broth microdilution method in accordance with the recommendations of the European Committee on Antimicrobial Susceptibility Testing (EUCAST, v.14.0). Results. Resistant to 14- and 15-member macrolides erythromycin, clarithromycin, and azithromycin were 41.5%, 42% and 40.5% of S. pneumoniae isolates (MIC50/MIC90 values were 0.06/128, 0.03/128, and 0.125/128 mg/L, respectively). MIC50/MIC90 values for spiramycin and josamycin were 0.06/128 mg/L and 25/32 mg/L, respectively. When the previously used 1996 French Society for Microbiology (SFM) criteria (Ch, ≤ 1 mg/L; P, > 4 mg/L) were applied, 70.5% of S. pneumoniae isolates could be considered as susceptible to spiramycin. MIC value ≥0.5 mg/L accounted for 31.5% of isolates for spiramycin and 48% for josamycin. Among the retrospective collection of erythromycin-resistant S. pneumoniae isolates, 64.0% of isolates could be considered as resistant to spiramycin using the old SFM interpretative criteria; 74.9% of isolates had spiramycin MIC ≥ 0.5 mg/L. Among the S. pyogenes isolates, 19.3%, 22%, and 26.7% were resistant to the 14- and 15-member macrolides erythromycin, clarithromycin, and azithromycin (MIC50/MIC90 0.03/1, 0.03/2, and 0.06/8 mg/L, respectively). MIC50/MIC90 values for the 16-member macrolides spiramycin and josamycin were 0.25/0.5 mg/L and 0.125/0.5 mg/L, respectively. When the 1996 SFM criteria (S – ≤ 1 mg/L; R – > 4 mg/L) were applied, 94.7% of S. pyogenes isolates could be considered as susceptible to spiramycin; MIC values ≥ 0.5 mg/L had 15.3% of isolates for spiramycin and 16.5% for josamycin. Conclusions. The 16-member macrolide spiramycin can retain in vitro activity against a significant proportion of S. pneumoniae and S. pyogenes isolates resistant to 14- and 15-member macrolides, which should be taken into account when choosing therapy for infections caused by these microorganisms.

Objective. To determine in vitro activity of thiamphenicol and other clinically available antimicrobials against clinical isolates of Haemophilus influenzae, Streptococcus pneumoniae and Streptococcus pyogenes. Materials and Methods. We included in the study 875 clinical isolates from 20 Russian cities during 2018–2019. Among tested strains, 126 were H. influenzae, 389 – S. pneumoniae, 360 – S. pyogenes. Antimicrobial susceptibility testing was performed using broth microdilution method according to ISO 20776-1:2006. AST results were interpreted according to EUCAST v.11.0 clinical breakpoints. Results. The minimum inhibitory concentrations (MICs) of thiamphenicol did not exceed 2 mg/L for 94.4% of H. influenzae strains (MIC50 and MIC90 were 0.5 and 1 mg/L, respectively). Thiamphenicol was active against 76.9% of ampicillin-resistant H. influenzae strains (MIC of thiamphenicol < 2 mg/L). The MIC of thiamphenicol was in the range of 0.06–2 mg/L for 96.7% of S. pneumoniae strains (MIC50 and MIC90 were 0.5 and 2 mg/L, respectively). The MIC of thiamphenicol for 90.6% of S. pneumoniae strains with reduced susceptibility to penicillin (MIC of penicillin > 0.06 mg/L) did not exceed 2 mg/L. A total of 88.1% of S. pneumoniae strains resistant to erythromycin were highly susceptible to thiamphenicol (MIC < 2 mg/L). The MIC of thiamphenicol did not exceed 8 mg/L for 96.1% of S. pyogenes strains (MIC50 and MIC90 were 2 and 4 mg/L, respectively). Conclusions. Thiamphenicol was characterized by relatively high in vitro activity, comparable to that of chloramphenicol, against tested strains of H. influenzae, S. pneumoniae and S. pyogenes, including S. pneumoniae isolates with reduced susceptibility to penicillin.

Pneumococcal conjugate vaccines contain a limited number of serotype-specific antigens of S. pneumoniae. It is important for vaccination programmes effectiveness assessment to control a variety of circulating S. pneumoniae serotypes. This review provides an analysis of pneumococcal serotyping approaches and further ways of improving pneumococcal serotype detection within the microbiological surveillance. Serological methods and multiplex PCR can identify a limited number of pneumococcal serotypes only. Whole-genome sequencing-based approaches can predict almost all serotypes and sequence types as well as detect antimicrobial resistance and virulence genes.

The objective of this study was to characterize and compare antigenic and genetic characteristics of Streptococcus pneumoniae strains isolated from patients with invasive and non-invasive pneumococcal infections (PIs) by using the data of high-throughput sequencing.Materials and methods. A total of 158 S. pneumoniae strains were studied. All of them were isolated during different stages of the PEHASus multicenter study performed in 2015-2020. The data analysis was based on the information about whole-genome sequences of 46 strains isolated during the above study. Real-time PCR methods and high-throughput sequencing (the Illumina platform) were used for identification of serotypes. The SeroBA, PneumoCaT software and PubMLST.org website resources were used in the data processing.Results and discussion. The serotypes of all the studied strains were identified. A number of discrepancies among serotypes in serogroup 6 and one discordant result were revealed by the analysis of whole-genome sequences using 2 programs. The PCR methods were effectively used to characterize serotypes in 87% and 69% of the pathogens of invasive and non-invasive PIs, respectively. The serotypes contained in PCV13 accounted for 59% and 37%, while PPV23 serotypes accounted for 78% and 53% of the strains isolated from patients with invasive and non-invasive PIs, respectively. The data analysis was unable to identify either the dominant sequence type (a total of 81 sequence types have been identified) or clonal complexes, except for serotype 3 strains, thus demonstrating consistency with the data from previous studies suggesting the absence of a well-represented clonal structure of S. pneumoniae associated with pneumococcal meningitis in Russia.Conclusion. The obtained data made it possible to identify the distribution of the circulating serotypes and genetic characteristics of the strains isolated from PI patients, thus being instrumental for assessment of the effectiveness of the existing polyvalent vaccines and providing information for improvement of the PCR-based methods of serotyping.

Objective. To evaluate in vitro activity of biapenem and other clinically available carbapenems against Russian clinical isolates of Enterobacterales, Pseudomonas aeruginosa и Acinetobacter spp., including isolates with acquired fermentative mechanisms of resistance to β-lactams. Materials and Methods. A total of 3139 Enterobacterales isolates, 793 P. aeruginosa isolates and 634 Acinetobacter spp. isolates from hospitalized patients in 63 hospitals from 35 Russian cities were included in the study during 2018-2019. Minimal inhibitory concentrations (MIC) for biapenem and other antimicrobials were determined in accordance with ISO 20776-1:2006. Carbapenemases genes were detected by commercially available real-time PCR kits AmpliSens® MDR KPC/OXA-48-FL and AmpliSens® MDR MBL-FL (Central Research Institute of Epidemiology, Russia). Data analysis and reporting was performed using AMRcloud online platform (www.amrcloud.net). Results. For all tested Escherichia coli isolates MIC50/90 were 0.06/0.125 mg/l for biapenem, 0.125⁄0.25 mg/l for imipenem, and 0.06/0.06 mg/l for meropenem. When MIC50/90 for ertapenem (0.015/0.125 mg/l for all isolates tested) were comparable to those of biapenem, a greater number of nosocomial E. coli isolates had MIC >4 mg/l for ertapenem (3.6%) than for biapenem (2.6%). MIC50/90 of Klebsiella pneumoniae for biapenem were 0.5⁄16 mg/l, for both imipenem and meropenem – 0.5⁄32 mg/l, for ertapenem – 2⁄32 mg/l. Resistance to oxyimino-β-lactams had no significant influence on activity of biapenem against Enterobacterales isolates. For 321 carbapenemase-producing K. pneumoniae isolates (ОХА-48 – 63.9%, NDM – 27.7%) biapenem has shown no advantages over imipenem and meropenem. МПК50/90 for nosocomial and community-acquired P. aeruginosa isolates were 8⁄64 mg/l and 0,5⁄16 mg/l for biapenem, 8⁄128 mg/l and 1⁄16 mg/l – for imipenem, 16⁄64 mg/l and 0,5⁄32 mg/l – for meropenem. All carbapenems, including biapenem, had very low in vitro activity against carbapenemaseproducing P. aeruginosa isolates. МПК50/90 of Acinetobacter spp. were 64⁄128 mg/l for biapenem, 64⁄128 mg/l – for imipenem, and 128⁄128 mg/l – for meropenem. Conclusions. According to the MIC distributions and MICs50/90 values independently of the presence of fermentative mechanisms of resistance to β-lactams, in vitro activity of biapenem against Russian clinical isolates of Enterobacterales, P. aeruginosa and Acinetobacter spp. was comparable to those of imipenem and meropenem.

Objective. To assess the in vitro activity of ceftazidime-avibactam against clinical Enterobacterales and Pseudomonas aeruginosa isolates in various regions of Russia based on results of local susceptibility testing by disk diffusion method. Materials and Methods. Overall, 160 laboratories located in 61 Russian cities participated in this surveillance during 2018-2020. All consecutive clinical isolates of Enterobacterales and Pseudomonas aeruginosa in each participating laboratory were included in the study. Ceftazidime-avibactam susceptibility testing was done by disc-diffusion method in accordance with current EUCAST recommendations. Susceptibility data for carbapenems and III-IV generation cephalosporins, as well as results of carbapenemases detection, were also reported, if available. All the data were recorded in electronic case report form developed on the OpenClinica online platform (www.openclinica.com). Data analysis and reporting were done using AMRcloud online platform (https://amrcloud.net/). Results. In total, we received information on antimicrobial susceptibility of 22,121 isolates, including 17,456 (78.9%) Enterobacterales and 4,665 (21.1%) P. aeruginosa. Less than 9% of Enterobacterales isolates were resistant to ceftazidime-avibactam. At the same time rates of resistance to ceftazidime, cefotaxime, cefepime, ertapenem, imipenem, and meropenem were 54.1%, 58.9%, 59.4%, 41.4%, 23.9%, and 21.3%. Among Enterobacterales the highest level of resistance to ceftazidime-avibactam was detected in K. pneumoniae (16.5%), lowest – in E. coli (2.1%). Some increase of resistance to ceftazidimeavibactam was noted during the study – from 7.8% in 2018-2019 to 9.6% in 2020 (p = 0.0001). Rate of resistance to ceftazidime-avibactam in P. aeruginosa was 33.1%. At the same time rates of resistance to ceftazidime, cefepime, imipenem, and meropenem were 51.1%, 54.5%, 50%, and 47.3%. During the study there was statistically significant decrease in resistance to ceftazidime-avibactam in P. aeruginosa (p = 0.0001). Resistance rates for all beta-lactams for both Enterobacterales and P. aeruginosa were higher in nosocomial isolates than in community-acquired isolates. Conclusions. Ceftazidime-avibactam demonstrated significantly higher in vitro activity against Enterobacterales and P. aeruginosa Russian clinical isolates comparing with commonly used carbapenems and extended spectrum cephalosporins. Access for all study data available at the AMRcloud online platform (https://amrcloud.net/ru/project/cazavi-1-2/).

Objective. To estimate prevalence and antimicrobial susceptibility of circulated S. pneumoniae serotypes in adult population in different regions of the Russian Federation. Materials and Methods. A total of 500 isolates of S. pneumoniae obtained from patients with invasive pneumococcal disease (IPD), community-acquired pneumonia (CAP), sinusitis/acute otitis media (AOM) and healthy carriers from 29 centers were included in the study from 01 June 2019 to 15 January 2020. Re-identification, typing using real-time PCR with 27 primer pairs and antimicrobial susceptibility testing were performed in the central laboratory by standardized methods. Results. Among 50 isolates from patients with IPD, the following serotypes were detected: 3 (20.0%), 23F (10.0%), 6ABCD (8.0%), 19F (6.0%), 12ABF, 4, 7AF, 8, 9NL, 9VA, 15B (4.0% each), 1, 10A, 11AD, 14, 15AF, 18ABCF, 22AF, 33F/33A/37 (2.0% each). PCV-13 and PPV-23 covered 62.0% and 86.0% of those serotypes, respectively. Among 357 isolates from patients with CAP, the following serotypes were detected: 19F (12.3%), 6ABCD (11.5%), 3 (10.1%), 23F (5.9%), 14 (5.3%), 22AF (5.0%), 11AD (4.8%), 9NL (3.4%), 15AF (2.8%), 9VA (2.2%), 18ABCF (2.0%), 19A (1.7%), 12ABF (1.4%), 17F (0.8%), 16, 33F/33A/37, 7AF and 8 (0.6% each), 10A and 4 (0,3% each); serotypes were not specified due to the PCR typing protocol limitations for 106 (29.8%) isolates. PCV-13 and PPV-23 covered 51.9% and 68.7% of those serotypes, respectively. In patients with sinusitis/AOM (n = 48), serotypes were: 19F (18.8%), 6ABCD (16.7%), 23F (12.5%), 3 (12.5%), 18ABCF (6.3%), 11AD (4.2%), 14 (4.2%), 22AF (4.2%), 15AF, 4, 9VA (2.1% each). PCV-13 and PPV-23 covered 75.0% and 83.3% of those serotypes, respectively. In healthy nasopharyngeal carriers (n = 45), the following serotypes were detected: 19F (24.4%), 3 (17.8%), 6ABCD (17.8%), 11AD (13.3%), 23F (8.9%), 22AF (6.7%), 14 and 15AF (2.2% each). PCV-13 and PPV-23 covered 71.1% and 91.1% of those serotypes, respectively. Serotypes 14, 19F, and 19A were frequently resistant to three antibiotics – penicillin, erythromycin, and tetracycline. Resistance to respiratory quinolones was very low (0.7%) and detected among serotypes 14 and 9NL only. The majority of non-vaccine serotypes did not have substantial antimicrobial resistance problems. Conclusions. Despite the relatively low number of isolates in all but CAP group and limitations of PCR typing protocol, results of our study support the use of pneumococcal vaccines (PPV-23 and PCV-13) in Russian adult population, with some advantages of PPV-23 over PCV-13.

Currently, there is a steady growth antimicrobial resistance (AMP) worldwide. This is especially true now when antibiotic use has become uncontrolled due to its use in COVID-19 treatment regimens. Antibiotics do not have antiviral effect, their appointment is justified only with complicated forms of COVID-19. Moreover, such a massive use antibiotics creates the prerequisites for the formation antibiotic resistance, including among the causative agents of community-acquired infections. Due to the relentless the growth of antibiotic resistance of community-acquired pathogens of respiratory diseases, it becomes necessary to revise approaches to antibacterial therapy (ABT) and assessing the potential use of thiamphenicol for the treatment of community-acquired infections caused by respiratory pathogens.

Objective. To determine antigenic and genetic characteristics of Neisseria meningitidis isolated from the patients with invasive meningococcal infections in Smolensk region in comparison with those circulating in other regions. Materials and Methods. A total of 14 cerebrospinal fluid samples obtained in 2016–2019 and containing N. meningitidis DNA were tested using AmpliSens® Nm-ABCW kit, multilocus sequence typing and antigenic finetyping of outer membrane proteins. The results were analyzed by the BURST algorithm and other functionalities available at PubMLST.org (Jolley K. et al. 2018). Results. The variable region alleles, sequence types and clonal complexes were determined for the tested isolates. The genotyping results were published in the PubMLST database (https://pubmlst.org/neisseria/). Most of N. meningitidis serogroup B isolates (n = 6) belonged to sequence types which have not been described previously: ST-14705, ST-14710, ST-14711, ST-14713 and ST-14717. Sequence types of serogroup C isolates (n = 7) were usual for strains circulating in other Russian regions (4 of 7 belonged to ST-8416). The only serogroup Y isolate belonged to ST-11585. Conclusions. Most studied N. meningitidis sequence types belonged to clonal complexes designated in PubMLST database and groups of isolates, determined by the BURST algorithm, which were usual for Russian regions. The antigenic and genetic characteristics suggest no circulation of epidemiologically significant N. meningitidis strains or hypervirulent strains on the observed territory.

AIM:to study the etiology of severe community - acquired pneumonia (SCAP) in adults in Russian Federation. SCAP is distinguished by high mortality and socio - economic burden. Both etiology and antimicrobial resistance are essential for appropriate antibiotic choice.MATERIALS AND METHODS:A prospective cohort study recruited adults with confirmed diagnosis of SCAP admitted to multi - word hospitals of six Russian cities in 2014-2018. Etiology was confirmed by routine culture of blood, respiratory (sputum, endotracheal aspirate or bronchoalveolar lavage) and when appropriate, autopsy samples, urinary antigen tests (L. pneumophila serogroup 1, S. pneumoniae); real - time PCR for identification of "atypical" bacterial pathogens (M. pneumoniae, C. pneumoniae, L. pneumophila) and respiratory viruses (influenza viruses A and B, parainfluenza, human metapneumovirus, etc.) was applied.RESULTS:Altogether 109 patients (60.6% male; mean age 50.8±18.0 years old) with SCAP were enrolled. Etiological agent was identified in 65.1% of patients, S. pneumoniae, rhinovirus, S. aureus and K. pneumoniae were the most commonly isolated pathogens (found in 43.7, 15.5, 14.1 and 11.3% of patients with positive results of microbiological investigations, respectively). Bacteriemia was seen in 14.6% of patients and most commonly associated with S. pneumoniae. Co - infection with 2 or more causative agents was revealed in 36.6% of cases. Combination of bacterial pathogens (mainly S. pneumoniae with S. aureus or/and Enterobacterales) prevailed - 57.7% of cases; associations of bacteria and viruses were identified in 38.5% of patients, different viruses - in one case.CONCLUSION:S. pneumoniae was the most common pathogen in adults with SCAP. A high rate of respiratory viruses (mainly rhinovirus and influenza viruses) identification both as mixt infection with bacteria and mono - infection should be taken into account.

Objective. Objectives. To assess the rates of antibiotic resistance, production of acquired carbapenemases, genotypes and prevalence of «international high-risk clones» among nosocomial strains of Pseudomonas aeruginosa isolated in various regions of Russia within the «MARATHON 2015–2016» study. Materials and Methods. A total of 1006 non-duplicate nosocomial isolates of P. aeruginosa collected in 44 hospitals from 25 cities in Russia in 2015–2016 were studied. Species identification of isolates was performed by means of MALDI-TOF mass-spectrometry. Antimicrobial susceptibility was determined using broth microdilution method according to ISO 20776-1:2006 and interpreted using EUCAST MIC clinical breakpoints v.9.0. The presence of acquired carbapenemase genes of VIM, IMP, NDM, GES-2 and GES-5 groups was determined using real-time PCR. Genotyping of isolates was performed by analysis of selected single nucleotide polymorphisms in 7 chromosomal loci used for multi-locus sequence typing (MLST) of this species. Results. P. aeruginosa comprised of 17.4% of all bacterial pathogens isolated within the «MARATHON 2015–2016» study. The resistance rates to antibiotics were (in decreasing order of in vitro activity): 1.4% to colistin, 41.5% to aztreonam, 41.6% to ceftazidime/avibactam, 47.7% to amikacin, 51.5% to cefepime, 54.2% to tobramycin, 55.5% to meropenem, 56.3% to gentamicin, 56.8% to ceftazidime, 62.0% to piperacillin/tazobactam, 63.3% to ciprofloxacin, 65.2% to piperacillin, 67.5% to imipenem, and 97,6% to ticarcillin/clavulanic acid. Acquired carbapenemase genes were detected in 35% of the isolates including those for metallo-β-lactamases of VIM- (30.5%) and IMP-type (0.3%) and for GES-5-like serine carbapenemases. MBL producers were highly resistant to all antibiotics except for aztreonam (49%) and polymyxins (0%); GES-5-producers were resistant to most antibiotics except for aztreonam (4.8%), ceftazidime/avibactam (11.9%) and polymyxins (0%). The majority of carbapenemase producing strains belonged to the international “high-risk” CC235 (76.3%) and CC654 (21%) clones. All CC235 isolates revealed the presence of specific variant of the gene encoding secreted phospholipase A2, ExoU, which is a major virulence factor of P. aeruginosa. Conclusions. The results of this study indicate an increase in resistance rates to most antibiotics, including carbapenems, and in prevalence of carbapenemase production in nosocomial strains of P. aeruginosa. This can be largely attributed to the expansion of “high-risk” clones.

Objective. To estimate the prevalence of S. pneumoniae serotypes in adults aged of 18 years and older, including healthy carriers and patients with acute otitis media (AOM), community-acquired pneumonia (CAP) and invasive pneumococcal infection (IPI). Materials and Methods. A total of 230 isolates of S. pneumoniae from 10 centers were included in the study from 01.06.2019 to 01.10.2019. Re-identification and typing using real-time PCR with 22 primer pairs were performed in the central laboratory (Institute of Antimicrobial Chemotherapy, Russia). Results. In healthy nasopharyngeal carriers (n = 31), the following serotypes of S. pneumoniae were detected: 19F (29.0%), 6А/В (22.6%), 3 (16.1%), 11A/D and 23F (9.7% each), 23A (6.4%), 14 and 15A/F (3.2% each); PCV-13 and PPV-23 covered 80.6% and 90.3% of those serotypes, respectively. In patients with AOM (n = 18), serotypes were: 3 (16.7%), 11A/D and 6A/B (11.1%, each), 16, 19А, 19F, 23F, 7A/F (5.55%, each); PCV-13 and PPV-23 covered 50% and 61.1% of those serotypes, respectively. Among 166 isolates from patients with CAP, the following serotypes were detected: 3 (12.0%), 19F and 6A/B (10.2%, each), 14 and 11A/D (5.4% each), 15A/F and 23A (4.8% each), 9N/L (4.2%), 18 and 22A/F (2.4% each), 19A and 23F (1.8% each), 16, 9V/A (1.2% each), 4 and 33A/33F/37 (0.6% each), non-vaccine serotypes (30.3%); PCV-13 and PPV-23 covered 45.6% and 57.0% of those serotypes, respectively. Isolates from patients with IPI (n=15) belonged to the following serotypes: 3 (26.7%), 12F, 23F and 9N/L (13.3% each), serotypes 4 and 15A/F (6.7%), non-vaccine serotype – 1 isolate (6.7%); PCV-13 and PPV-23 covered 46.7% and 73.3% of those serotypes, respectively. Conclusions. The majority of S. pneumoniae serotypes in adult population in Russia are included in PPV-23, but not in PCV-13 (primarily due to serotype 11A/D). There was a high PCV-13 and PPV-23 coverage of serotypes from healthy nasopharyngeal carriers. PPV-23 covered more than 60% of clinical isolates, whereas PCV-13 covered less than 60% (AOM – 50.0%, CAP – 45.6%, IPI – 46.7%), thus indicating a potentially lower efficacy of PCV-13 in adult population.

Objective.To evaluate antimicrobial resistance patterns of clinical Streptococcus pyogenes isolates from different regions of Russia during 2014–2017.Materials and Methods.A total of 792 clinical S. pyogenes isolates from 14 Russian cities were included in the study. Susceptibility testing was performed using reference broth microdilution method (ISO 207761:2006). Susceptibility testing results were interpreted using EUCAST v.10.0 breakpoints.Results.Penicillin G was active against all tested isolates with the MIC50–90 values of 0.016 mg/l and the highest MIC value of 0.25 mg/l. No resistance to linezolid, tedizolid and vancomycin were observed. Respiratory fluoroquinolones, moxifloxacin and levofloxacin, showed a high activity with the only 0.3% and 0.8% of resistant isolates, respectively. Almost all isolates (99.9%) were susceptible to trimethoprim/ sulfamethoxazole. The resistance rates to 14- and 15-membered macrolides varied from 12.1% to 17.2%. The only 2.4% of isolates were resistant to clindamycin. Resistance to chloramphenicol was 6.1%, to tetracycline – 17.2%.Conclusions.The comparison of this study results with the previously published Russian data on antimicrobial resistance of S. pyogenes shows there were no significant changes in the susceptibility of this pathogen over the past two decades, with the exception of macrolides. The growing resistance to 14and 15-membered macrolides raises a question on the further use of this antibiotic class for the empiric treatment of streptococcal infections in Russia.