Vancomycin and daptomycin are first-line drugs for the treatment of complicated methicillin-resistant Staphylococcus aureus (MRSA) infections, including bacteremia. However, their effectiveness is limited not only by their resistance to each antibiotic but also by their associated resistance to both drugs. It is unknown whether novel lipoglycopeptides can overcome this associated resistance. Resistant derivatives from five S. aureus strains were obtained during adaptive laboratory evolution with vancomycin and daptomycin. Both parental and derivative strains were subjected to susceptibility testing, population analysis profiles, measurements of growth rate and autolytic activity, and whole-genome sequencing. Regardless of whether vancomycin or daptomycin was selected, most of the derivatives were characterized by a reduced susceptibility to daptomycin, vancomycin, telavancin, dalbavancin, and oritavancin. Resistance to induced autolysis was observed in all derivatives. Daptomycin resistance was associated with a significant reduction in growth rate. Resistance to vancomycin was mainly associated with mutations in the genes responsible for cell wall biosynthesis, and resistance to daptomycin was associated with mutations in the genes responsible for phospholipid biosynthesis and glycerol metabolism. However, mutations in walK and mprF were detected in derivatives selected for both antibiotics.

During a prospective multicenter non-interventional observational study, a comparative assessment was made of the serotype structure of pneumococci circulating among healthy children under the age of 5 years and children of the same age group with signs of respiratory infections in the periods 2016-2018 and 2020-2022. Data on the serotype structure of pneumococci in the period from 2016-2018 were obtained from our previous works. In 2020-2022 the study included 2066 healthy children and 603 children with respiratory infections. Streptococcus pneumoniae and their DNA were detected in nasopharyngeal swabs by classical culture and molecular methods. Typing was carried out by molecular methods. On the territory of the Russian Federation, pneumococci belonging to the serotypes included in the 13-valent vaccine are being forced out of circulation and replaced by non-vaccine serotypes. Before the introduction of mass antipneumococcal vaccination (until 2015), the 13-valent conjugate vaccine covered from 66.2% to 92% of pneumococci, after the start of mass anti-pneumococcal vaccination in the period 2016-2018, coverage decreased to 57.3%. Between 2020 and 2022, coverage was less than 40%. The main “non-vaccine” serotypes/serogroups circulating in the Russian Federation are 15AF, 11AD, 23A, 9LN and 16F.

The paper presents optimized methods for PCR and sequence typing of Streptococcus pneumoniae. The serotype composition of pneumococci isolated from children under 5 years of age with infections of the upper respiratory tract was analyzed using optimized methods. Between 2016 and 2021, there was a decrease in the frequency of serotypes included in the pneumococcal 13-valent conjugate vaccine (PCV13) from 94.1 to 25.8%, mainly due to the 6ABCD serogroup and the 19F serotype. The coverage of serotypes circulating in children with PCV15 and PCV20 vaccines was 28.1% and 41.6% in 2021, respectively. During the study period, the number of non-vaccine serogroups 11AD and 15AF, as well as serotypes that are not detected under this capsular PCR typing protocol, increased most significantly.

Objective: to investigate the regional peculiarities of Streptococcus pneumoniae carriage in the pediatric population and characterize the dominant serotypes of the pathogen. Materials and methods. The clinical study group consisted of 509 healthy children attending preschool institutions. Examination of nasopharyngeal samples for the detection of S. pneumonae was carried out by classical bacteriological and molecular biological methods. The serotype was determined by real-time PCR. Genome-wide sequencing of the serogroups 15 and 11 isolates and bioinformatic analysis were performed. Results. The S. pneumoniae bacterial carriers in the group of healthy children was detected in 207 children (40.7%), while the frequency of detection of S. pneumoniae in urban children living in Kazan was significantly higher than in children living in rural area and amounted to 53.4 and 31.1%, respectively (p 0.05). Among children vaccinated with the 13-valent pneumococcal conjugate vaccine (PCV-13), S. pneumoniae carriers were not detected in 57.5% of cases. There were no significant differences in the degree of nasopharyngeal contamination depending on the vaccination status. Analysis of the serotype composition indicates the predominance of vaccine serotypes (57.7%), while the share of serotypes included in the PСV-13 vaccine accounts for only 24.7%, the share of non-vaccine serotypes was 32.1%, untyped — 10.2%. In unvaccinated children, vaccine serotypes that are part of the PCV-13 and 23-valent polysaccharide pneumococcal vaccine prevailed (PPSV-23): 6ABCD (21%), 11 AD (15%), 14 (13%). In vaccinated children, serotypes not included in the active vaccines dominated: 15AF (17.4%), 23A (19.2%), as well as 11AD (19.6%) (11А is included in PPSV-23). The 27 Kz isolate (serotype 15C) belonged to one of the most common sequence types ST1025. The 105_Kz isolate (serotype 11D) belonged to another common sequence type ST 62. Conclusion. In order to improve epidemiological surveillance of pneumococcal infection, it is necessary to introduce the monitoring of circulating clonal complexes of dominant S. pneumoniae serogroups and analyze the genetic determinants of antibiotic resistance and virulence depending on the sequence type.

COVID-19 is caused by an airborne virus, SARS-CoV-2. The upper respiratory tract (URT) is, therefore, the first system to endure the attack. Inhabited by an assemblage of microbial communities, a healthy URT wards off the invasion. However, once invaded, it becomes destabilised, which could be crucial to the establishment and progression of the infection. We examined 696 URT samples collected from 285 COVID-19 patients at three time-points throughout their hospital stay and 100 URT samples from 100 healthy controls. We used 16S ribosomal RNA sequencing to evaluate the abundance of various bacterial taxa, α-diversity, and β-diversity of the URT microbiome. Ordinary least squares regression was used to establish associations between the variables, with age, sex, and antibiotics as covariates. The URT microbiome in the COVID-19 patients was distinctively different from that of healthy controls. In COVID-19 patients, the abundance of 16 genera was significantly reduced. A total of 47 genera were specific to patients, whereas only 2 were unique to controls. The URT samples collected at admission differed more from the control than from the samples collected at later stages of treatment. The following four genera originally depleted in the patients grew significantly by the end of treatment: Fusobacterium, Haemophilus, Neisseria, and Stenotrophomonas. Our findings strongly suggest that SARS-CoV-2 caused significant changes in the URT microbiome, including the emergence of numerous atypical taxa. These findings may indicate increased instability of the URT microbiome in COVID-19 patients. In the course of the treatment, the microbial composition of the URT of COVID-19 patients tended toward that of controls. These microbial changes may be interpreted as markers of recovery.