The antibiotic knowledge, attitudes and behaviours of patients purchasing antibiotics with prescription in Russia: a qualitative, comparative analysis.

Objectives: The study aimed to investigate behaviour, knowledge and practices towards antibiotic (AB) use among patients who purchased ABs with a prescription across Russia. Methods: Semi-structured interviews conducted in all eight Federal Districts, Moscow and Saint Petersburg in 2022 by 21 researchers trained specifically for this study. Data were analysed using a directed content analysis approach. Results: In total, 151 respondents were interviewed. Respiratory symptoms were the most common reason for AB prescription. The majority of patients discussed their complaints with family members or friends before consulting the physician and occasionally looked for information on antimicrobial treatment on the internet. The decision to use an AB was usually made by the physician, although patients often anticipated its prescription. Respondents typically chose to go to the nearest drug store to pick up the medicines, not seeking any recommendation from the local pharmacists. The level of knowledge about the effects of ABs was generally low. In most cases, patients were not aware of antimicrobial resistance and rarely recalled any information campaigns targeting prudent AB use. Respondents admitted COVID-19 had an impact on their behaviour: they have become more caring towards their health, but less likely to seek medical care because of the risk of infection. Conclusions: Our findings, in particular low awareness of the population about the effects of ABs and antimicrobial resistance, peculiarities of attitudes and behaviour (significant influence of the environment, tendency to self-diagnose, fairly high level of trust in doctors etc.) can be useful for the development of effective initiatives aiming for prudent AB use.

Antimicrobial Dispensing Practice in Community Pharmacies in Russia during the COVID-19 Pandemic.

COVID-19 has had a significant impact on health care systems, including drug use. The present study aimed to evaluate the patterns of community supply of antimicrobials from community pharmacies during the COVID-19 pandemic in five cities of Russia. In a cross-sectional study, a random sample of pharmacies reported all episodes of antimicrobials supply during a one-week period. Patterns of supply (age and gender of customer, drug name and formulation, prescription availability, indication, etc.) were analyzed. Altogether, 71 pharmacies took part in the study and 5270 encounters were recorded. In total, 4.2% of visits resulted in supply of more than one antimicrobial agent and 5.2% were for parenteral formulations. The rate of prescription-based purchase in participated cities varied from 40.5 to 99.1%. Systemic antibiotics and antivirals accounted for the majority of supplies (60.5 and 26.3%, respectively). Upper respiratory tract infections were reported as the indication for antimicrobials usage in 36.9% of cases, followed by skin and soft tissue infections (12.1%) and urinary tract infections (8.7%); COVID-19 accounted for 8.4% of all supplies. Amoxicillin with clavulanic acid, azithromycin and amoxicillin were indicated as the top three antimicrobials purchased for upper respiratory tract infections, and azithromycin, umifenovir and levofloxacin were the top three for COVID-19. In general, a high rate of drugs dispensing without prescription was revealed. Antibiotics for systemic use remained the most common antimicrobials, whereas presumably viral upper respiratory tract infections were the main reason for their purchase. COVID-19 infection itself was responsible for a small proportion of the supply of antimicrobial agents, but systemic antibiotics accounted for more than a half of supplies.

A Clinical Case of Nosocomial Pneumonia as a Complication of COVID-19: How to Balance Benefits and Risks of Immunosuppressive Therapy?

We report a Russian case of a 61-year-old male patient with confirmed COVID-19 infection who developed nosocomial pneumonia complicated by lung abscess associated with multi-drug-resistant isolates of Klebsiella pneumoniae and Acinetobacter baumannii, which could have been provoked due to the immunosuppressive therapy. We discuss the existing literature highlighting the issue of the prudent balance between benefits and risks when prescribing immunomodulators to hospitalized patients with COVID-19 due to the risk of difficult-to-treat nosocomial infections caused by MDR Gram-negative bacterial pathogens. Currently, there is evidence of a substantial positive effect of dexamethasone on the course of COVID-19 in patients requiring supplemental oxygen or anti-interleukin-6 drugs in individuals with prominent systemic inflammation. However, it seems that in real clinical practice, the proposed criteria for initiating treatment with immunomodulators are interpreted arbitrarily, and the doses of dexamethasone can significantly exceed those recommended.

Current Antimicrobial Stewardship Practice and Education in Russian Hospitals: Results of a Multicenter Survey.

Proper antibiotic usage education and training of medical students and healthcare professionals is the cornerstone to implement antimicrobial stewardship (AMS) programs worldwide. We conducted this voluntary and anonymous survey on current and preferred educational provision of AMS in Russia. Among 1358 polled respondents from six participating Centers located in geographically remote Federal Districts of Russia, the majority were nurses (52.8%) and doctors (42.0%). Results of the survey demonstrated better coverage of education in AMS on an undergraduate level (57.1%). More than half of respondents in total (52.4%) stated they had not received any postgraduate training. Those 38.4% respondents who received postgraduate teaching in AMS stated that it had been provided substantially by an employing hospital (28.4%) or by a medical university/college (22.3%). According to the conducted survey, the methods of education in AMS in Russian Federation mainly include traditional face-to-face lectures, presentations and provision with clinical guidelines, recommendations and printed materials. The involvement of e-learning and web-based online approaches was lacking. The survey allowed us the identify the key problems associated with training of healthcare workers in this field, in particular the varying availability of under- and postgraduate education in different parts of Russia.

Office-based approach to urinary tract infections in 50 000 patients: results from the REWIND study.

OBJECTIVES: The REWIND study sought to describe the real-world clinical and prescribing practices for the management of urinary tract infection (UTI) in Italy, Belgium, Russia and Brazil in order to compare current practices with international, European and national guidelines. METHODS: An integrated mixed-methods approach was adopted that used information from primary care electronic medical records in longitudinal patient databases available in Italy and Belgium, and surveys of physicians in Russia (general practitioners) and Brazil (gynaecologists). RESULTS: In total, 49 548 female patients were included in the study. Antibiotics were the most common management option for UTI in Italy (71.1%, n=27 600), Belgium (92.4%, n=7703), Russia (81.9%, n=1231) and Brazil (82.4%, n=740). Fosfomycin trometamol was the first-choice antibiotic for the treatment of UTI in all countries. Ciprofloxacin was also commonly prescribed in Italy (24.6%, n=6796), Belgium (17.8%, n=1373), Russia (14.9%, n=184) and Brazil (9.6%, n=71), while prescription of nitrofurantoin was common in Belgium (24.5%, n=1890) alone. CONCLUSIONS: Despite differences in study designs and data sources, fosfomycin trometamol was found to be the most commonly prescribed treatment for UTI in all participating countries. In Belgium, real-world prescribing practices for UTI adhered more closely to European guidelines than national guidelines. Although not recommended in international and European guidelines for lower UTI management, the use of fluoroquinolones was still widespread.

Antimicrobial resistance of Escherichia coli isolates from outpatient urinary tract infections in women in six European countries including Russia.

OBJECTIVES: In the Northern Dimension Antibiotic Resistance Study (NoDARS), Finland, Germany, Latvia, Poland, Russia and Sweden collected urine samples from outpatient women (aged 18-65years) with symptoms of uncomplicated urinary tract infection (UTI) to investigate the levels of antimicrobial resistance (AMR) among Escherichia coli isolates. METHODS: A total of 775 E. coli isolates from 1280 clinical urine samples were collected from October 2015 to January 2017. Antimicrobial susceptibility testing was performed and the results were interpreted according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. RESULTS: Overall AMR rates to the commonly used antibiotics nitrofurantoin, fosfomycin and mecillinam (except for Germany that was missing a result for mecillinam) were 1.2%, 1.3% and 4.1%, respectively. The highest overall resistance rates were determined for ampicillin (39.6%), trimethoprim (23.8%), trimethoprim/sulfamethoxazole (22.4%), amoxicillin/clavulanic acid (16.7%) and ciprofloxacin (15.1%), varying significantly between countries. The rate of extended-spectrum ß-lactamase (ESBL) production was 8.7%. None of the isolates showed resistance to meropenem. CONCLUSIONS: In most cases, low AMR rates were detected against the first-line antibiotics recommended in national UTI treatment guidelines, giving support to their future use. These results also support the European Association of Urology guidelines stating that nitrofurantoin, fosfomycin and mecillinam are viable treatment options for uncomplicated UTI.

Large variation in ESBL-producing Escherichia coli carriers in six European countries including Russia.

We investigated the faecal carriage prevalence of extended-spectrum ß-lactamase production in Escherichia coli (EP-EC) and/or Klebsiella pneumoniae (EP-KP) and risk factors associated with carriage among adult study subjects in Finland, Germany, Latvia, Poland, Russia and Sweden (partner countries). The aim was to get indicative data on the prevalence of ESBL-carriage in specific populations in the region. Faecal samples were collected from four study populations and screened on ChromID-ESBL and ChromID-OXA-48 plates. Positive isolates were further characterised phenotypically. Our results show a large variation in carrier prevalence ranging from 1.6% in Latvia to 23.2% in Russia for EP-EC. For the other partner countries, the prevalence of EP-EC were in increasing numbers, 2.3% for Germany, 4.7% for Finland, 6.6% for Sweden, 8.0% for Poland and 8.1% for all partner countries in total. Carriers of EP-KP were identified only in Finland, Russia and Sweden, and the prevalence was < 2% in each of these countries. No carriers of carbapenemase-producing isolates were identified. This is the first study reporting prevalence of carriers (excluding traveller studies) for Finland, Latvia, Poland and Russia. It contributes with important information regarding the prevalence of EP-EC and EP-KP carriage in regions where studies on carriers are limited.

Identification of cellular proteins that maintain retroviral epigenetic silencing: evidence for an antiviral response.

Integrated retroviral DNA is subject to epigenetic gene silencing, resulting in loss of expression of viral genes as well as reporter or therapeutic genes transduced by retroviral vectors. Possible mediators of such silencing include the histone deacetylase (HDAC) family of cellular proteins. We previously isolated HeLa cell populations that harbored silent avian sarcoma virus-based green fluorescent protein (GFP) vectors that could be reactivated by treatment with HDAC inhibitors. Here, we developed a small interfering RNA (siRNA)-based approach to identify specific host factors that participate in the maintenance of silencing. Knockdown of HDAC1, the transcriptional repressor Daxx (a binding partner of HDAC1), or heterochromatin protein 1 gamma resulted in robust and specific GFP reporter gene reactivation. Analyses of cell clones and diverse GFP vector constructs revealed that the roles of HDAC1 and Daxx in retroviral silencing are largely independent of the integration site or the promoter controlling the silent GFP reporter gene. Previous findings from our laboratory and those of others have suggested that Daxx and HDAC proteins may act broadly as part of an antiviral response to repress viral gene transcription. Expression of presumptive viral "countermeasure" proteins that are known to inhibit Daxx or HDACs (pp71, IE2, and Gam1) resulted in the reactivation of GFP reporter gene expression. This study has identified individual host factors that maintain retroviral silencing and supports the proposal that these factors participate in an antiviral response. Furthermore, our results indicate that siRNAs can be used as specific reagents to interrupt the maintenance of epigenetic silencing.

High-frequency epigenetic repression and silencing of retroviruses can be antagonized by histone deacetylase inhibitors and transcriptional activators, but uniform reactivation in cell clones is restricted by additional mechanisms.

Integrated retroviral DNA is subject to epigenetic gene silencing, but the viral and host cell properties that influence initiation, maintenance, and reactivation are not fully understood. Here we describe rapid and high-frequency epigenetic repression and silencing of integrated avian sarcoma virus (ASV)-based vector DNAs in human HeLa cells. Initial studies utilized a vector carrying the strong human cytomegalovirus (hCMV) immediate-early (IE) promoter to drive expression of a green fluorescent protein (GFP) reporter gene, and cells were sorted into two populations based on GFP expression [GFP(+) and GFP(-)]. Two potent epigenetic effects were observed: (i) a very broad distribution of GFP intensities among cells in the GFP(+) population as well as individual GFP(+) clones and (ii) high-frequency GFP reporter gene silencing in GFP(-) cells. We previously showed that histone deacetylases (HDACs) can associate with ASV DNA soon after infection and may act to repress viral transcription at the level of chromatin. Consistent with this finding, we report here that treatment with the histone deacetylase inhibitor trichostatin A (TSA) induces GFP activation in GFP(-) cells and can also increase GFP expression in GFP(+) cells. In the case of the GFP(-) populations, we found that after removal of TSA, GFP silencing was reestablished in a subset of cells. We used that finding to enrich for stable GFP(-) cell populations in which viral GFP reporter expression could be reactivated by TSA; furthermore, we found that the ability to isolate such populations was independent of the promoter driving the GFP gene. In such enriched cultures, hCMV IE-driven, but not the viral long terminal repeat-driven, silent GFP reporter expression could be reactivated by the transcriptional activator prostratin. Microscopy-based studies using synchronized cells revealed variegated reactivation in cell clones, indicating that secondary epigenetic effects can restrict reactivation from silencing. Furthermore we found that entry into S phase was not required for reactivation. We conclude that HDACs can act rapidly to initiate and maintain promoter-independent retroviral epigenetic repression and silencing but that reactivation can be restricted by additional mechanisms.