A high level of resistance to carbapenems in Acinetobacter baumannii strains severely limits therapeutic possibilities. Colistin is the last resort drug against such strains, although the cases of resistance to this drug have become more frequent. This article presents the epidemiological features and genetic diversity of colistin nonsusceptible A. baumannii strains collected as part of a national multicenter epidemiological study of the antibiotic resistance of pathogens of nosocomial infections (MARATHON), which was conducted in 2013-2014 in Russia. A total of 527 A. baumannii isolates were collected, 10 (1.9%) of which were nonsusceptible to colistin. The majority of nonsusceptible A. baumannii isolates to colistin showed resistance to carbapenems and had the genes of the acquired OXA-40-like carbapenemases (n=6). In one case, a combination of OXA-23-like + OXA-40-like (n=1) genes was identified. One strain had the multidrug-resistant (MDR) phenotype, 6 isolates had extensively drug-resistant (XDR) phenotype, and 3 isolates had pandrug-resistant (PDR) phenotype. Among the colistin nonsusceptible A. baumannii isolates, 6 individual genotypes were identified, most of which belonged to successful international clones (CC92OXF/CC2PAS, n=4; CC944OXF/ST78PAS, n=4; CC109OXF/CC1PAS, n=1).

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 antimicrobial resistance patterns of clinical Haemophilus influenzae isolates from different regions of Russia during 2014–2017. Materials and Methods. We included in the study 185 clinical H. influenzae isolates from 13 Russian cities. Susceptibility testing was performed by reference broth microdilution method (ISO 207761:2006). Susceptibility testing results were interpreted using EUCAST v. 10.0 breakpoints. Results. H. influenzae isolates were highly susceptible to all (96.8%-100%) β-lactams tested (amoxicillin/ clavulanate, cefixime, ceftaroline, ceftibuten, cefditoren, ertapenem) with the exception of ampicillin (15.1% isolates were resistant). Fluoroquinolones, – ciprofloxacin, levofloxacin, moxifloxacin were active against 95.7%, 94.6% and 97.9% of isolates, respectively. Chloramphenicol was active against 97.9% of isolates, tetracycline – against 98.4% of isolates. Activity of trimethoprim/sulfamethoxazole was low (69.2% of susceptible isolates). Conclusions. In general, we can state the favorable situation with the susceptibility of H. influenzae to antimicrobials in Russia. However, the increasing of resistance to aminopenicillins and emerging of quinolone-resistant strains could become a problem in the future. Study Results are deposited at on-line resource AMRmap (http://AMRmap.ru).

Objective. To evaluate antimicrobial resistance patterns of clinical Streptococcus pneumoniae isolates from different regions of Russia during 2014–2017. Materials and Methods. We included in the study 519 clinical S. pneumoniae isolates from 18 Russian cities. Susceptibility testing was performed by reference broth microdilution method (ISO 20776-1:2006). Susceptibility testing results were interpreted according to EUCAST v.9.0 breakpoints. Results. Using EUCAST non-meningeal interpretation criteria, 65.1% of isolates tested were susceptible (S) to penicillin; in addition 28.

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.

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/).