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.

Acinetobacter Non-baumannii Species: Occurrence in Infections in Hospitalized Patients, Identification, and Antibiotic Resistance.

BACKGROUND: Acinetobacter species other than A. baumannii are becoming increasingly more important as opportunistic pathogens for humans. The primary aim of this study was to assess the prevalence, species distribution, antimicrobial resistance patterns, and carbapenemase gene content of clinical Acinetobacter non-baumannii (Anb) isolates that were collected as part of a sentinel surveillance program of bacterial infections in hospitalized patients. The secondary aim was to evaluate the performance of MALDI-TOF MS systems for the species-level identification of Anb isolates. METHODS: Clinical bacterial isolates were collected from multiple sites across Russia and Kazakhstan in 2016-2022. Species identification was performed by means of MALDI-TOF MS, with the Autobio and Bruker systems used in parallel. The PCR detection of the species-specific blaOXA-51-like gene was used as a means of differentiating A. baumannii from Anb species, and the partial sequencing of the rpoB gene was used as a reference method for Anb species identification. The susceptibility of isolates to antibiotics (amikacin, cefepime, ciprofloxacin, colistin, gentamicin, imipenem, meropenem, sulbactam, tigecycline, tobramycin, and trimethoprim-sulfamethoxazole) was determined using the broth microdilution method. The presence of the most common in Acinetobacter-acquired carbapenemase genes (blaOXA-23-like, blaOXA-24/40-like, blaOXA-58-like, blaNDM, blaIMP, and blaVIM) was assessed using real-time PCR. RESULTS: In total, 234 isolates were identified as belonging to 14 Anb species. These comprised 6.2% of Acinetobacter spp. and 0.7% of all bacterial isolates from the observations. Among the Anb species, the most abundant were A. pittii (42.7%), A. nosocomialis (13.7%), the A. calcoaceticus/oleivorans group (9.0%), A. bereziniae (7.7%), and A. geminorum (6.0%). Notably, two environmental species, A. oleivorans and A. courvalinii, were found for the first time in the clinical samples of patients with urinary tract infections. The prevalence of resistance to different antibiotics in Anb species varied from <4% (meropenem and colistin) to 11.2% (gentamicin). Most isolates were susceptible to all antibiotics; however, sporadic isolates of A. bereziniae, A. johnsonii, A. nosocomialis, A. oleivorans, A. pittii, and A. ursingii were resistant to carbapenems. A. bereziniae was more frequently resistant to sulbactam, aminoglycosides, trimethoprim-sulfamethoxazole, and tigecycline than the other species. Four (1.7%) isolates of A. bereziniae, A. johnsonii, A. pittii were found to carry carbapenemase genes (blaOXA-58-like and blaNDM, either alone or in combination). The overall accuracy rates of the species-level identification of Anb isolates with the Autobio and Bruker systems were 80.8% and 88.5%, with misidentifications occurring in 5 and 3 species, respectively. CONCLUSIONS: This study provides important new insights into the methods of identification, occurrence, species distribution, and antibiotic resistance traits of clinical Anb isolates.

Impact of Molnupiravir Treatment on Patient-Reported COVID-19 Symptoms in the Phase 3 MOVe-OUT Trial: A Randomized, Placebo-Controlled Trial.

BACKGROUND: Molnupiravir is an orally administered antiviral authorized for COVID-19 treatment in adults at high risk of progression to severe disease. Here, we report secondary and post hoc analyses of participants' self-reported symptoms in the MOVe-OUT trial, which evaluated molnupiravir initiated within 5 days of symptom onset in nonhospitalized, unvaccinated adults with mild-to-moderate, laboratory-confirmed COVID-19. METHODS: Eligible participants completed a 15-item symptom diary daily from day 1 (randomization) through day 29, rating symptom severity as "none," "mild," "moderate," or "severe"; loss of smell and loss of taste were rated as "yes" or "no." Time to sustained symptom resolution/improvement was defined as the number of days from randomization to the first of 3 consecutive days of reduced severity, without subsequent relapse. Time to symptom progression was defined as the number of days from randomization to the first of 2 consecutive days of worsening severity. The Kaplan-Meier method was used to estimate event rates at various time points. The Cox proportional hazards model was used to estimate the hazard ratio between molnupiravir and placebo. RESULTS: For most targeted COVID-19 symptoms, sustained resolution/improvement was more likely, and progression was less likely, in the molnupiravir versus placebo group through day 29. When evaluating 5 distinctive symptoms of COVID-19, molnupiravir participants had a shorter median time to first resolution (18 vs 20 d) and first alleviation (13 vs 15 d) of symptoms compared with placebo. CONCLUSIONS: Molnupiravir treatment in at-risk, unvaccinated patients resulted in improved clinical outcomes for most participant-reported COVID-19 symptoms compared with placebo. Clinical Trials Registration. ClinicalTrials.gov: NCT04575597.

Assessment of Antimicrobial Consumption in Multi-Field Hospitals with Pediatric Inpatients: Conventional vs. Novel Pediatric-Adjusted Methodologies.

BACKGROUND: the objective of this study was to propose a methodology for the assessment of antimicrobial consumption (AMC) in pediatric inpatients and to estimate variances in consumption levels in multi-field hospitals with pediatric inpatients, calculated by means of the pediatric-adjusted methodology vs. the conventional methodology. METHODS: the pediatric-adjusted methodology based on the conventional ATC/DDD method and children's DDDs (cDDD) for antimicrobials were proposed and validated in a series of probabilistic sensitivity analyses of real clinical data extracted from the receipt notes of three multi-field hospitals. Differences in AMC in multi-field hospitals with pediatric inpatients, calculated by means of the proposed methodology vs. the conventional methodology, were assessed for a virtual cohort of inpatients, with the pediatric share increasing by 1%. RESULTS: in children ≤12 years old, assessment by the standard methodology resulted in a 59% underestimation of AMC from the levels based on prescribed doses, vs. a 25% underestimation for the proposed methodology. In a mixed-age virtual population of inpatients, the underestimation of consumption levels rose to 321% for the ATC/DDD methodology compared to the proposed one. CONCLUSIONS: the proposed methodology demonstrated a higher accuracy of AMC estimates compared to the conventional one and can be considered for the quantification of antimicrobial utilization in pediatric institutions and multi-field hospitals with a substantial share of pediatric inpatients.

Development of a Real-Time PCR Assay for Detection of Macrolide Resistance Mutations in Mycoplasma genitalium and Its Application for Epidemiological Surveillance in Russia.

A real-time PCR assay based on probe fluorescence quenching by a primer was developed and validated for detection of macrolide resistance (MR)-associated mutations in the 23S rRNA gene of Mycoplasma genitalium. The assay involves identification of any nucleotide substitutions at positions 2058, 2059, and 2611 of 23S rRNA (Escherichia coli numbering) by the probe-based melting curve analysis immediately after amplification and was capable of detecting target mutations in clinical specimens and spiked samples with 92% sensitivity and 100% specificity. We applied this new assay to assess the prevalence of MR-associated mutations in 949 nonduplicate urogenital samples positive for M. genitalium by routine diagnostic PCR, which were collected from symptomatic patients in five cities in the European part of Russia during the period 2009-2019. Forty-three (4.92%) samples revealed the presence of MR mutations, and no trend toward an increase in resistance prevalence was observed over the 10-year period of the study. The most commonly detected mutations were A2058G (26/43; 60.47%) and A2059G (13/43; 30.23%), while other mutations were rare: A2058T (3/43; 6.98%) and C2611T (1/43; 2.33%). The data obtained underline the need for regular epidemiological monitoring to ensure effective patient management, rational use of antibiotics, and prevention of further spread of resistance.

Genetic Determinants of Macrolide and Fluoroquinolone Resistance in Mycoplasma genitalium and Their Prevalence in Moscow, Russia.

Macrolide (MLR) and fluoroquinolone (FQR) resistance in Mycoplasma genitalium (MG) has recently become a major problem worldwide. The available data on the prevalence of MLR and FQR in MG in Russia are limited. In this study, we aimed to evaluate the prevalence and pattern of mutations in 213 MG-positive urogenital swabs from patients in Moscow between March 2021 and March 2022. MLR- and FQR-associated mutations were searched in 23S rRNA as well as in the parC and gyrA genes using Sanger sequencing. The prevalence of MLR was 55/213 (26%), with A2059G and A2058G substitutions being the two most common variants (36/55, 65%, and 19/55, 35%, respectively). FQR detection showed 17% (37/213); two major variants were D84N (20/37, 54%) and S80I (12/37, 32.4%) and three minor variants were S80N (3/37, 8.1%), D84G (1/37, 2.7%), and D84Y (1/37, 2.7%). Fifteen of the fifty-five MLR cases (27%) simultaneously harbored FQR. This study revealed the high frequency of MLR and FQR. We conclude that the improvement of patient examination algorithms and therapeutic approaches should be combined with the routine monitoring of antibiotic resistance based on the sensitivity profiles presented. Such a complex approach will be essential for restraining the development of treatment resistance in MG.

Genomic analysis of the international high-risk clonal lineage Klebsiella pneumoniae sequence type 395.

BACKGROUND: Klebsiella pneumoniae, which is frequently associated with hospital- and community-acquired infections, contains multidrug-resistant (MDR), hypervirulent (hv), non-MDR/non-hv as well as convergent representatives. It is known that mostly international high-risk clonal lineages including sequence types (ST) 11, 147, 258, and 307 drive their global spread. ST395, which was first reported in the context of a carbapenemase-associated outbreak in France in 2010, is a less well-characterized, yet emerging clonal lineage. METHODS: We computationally analyzed a large collection of K. pneumoniae ST395 genomes (n = 297) both sequenced in this study and reported previously. By applying multiple bioinformatics tools, we investigated the core-genome phylogeny and evolution of ST395 as well as distribution of accessory genome elements associated with antibiotic resistance and virulence features. RESULTS: Clustering of the core-SNP alignment revealed four major clades with eight smaller subclades. The subclades likely evolved through large chromosomal recombination, which involved different K. pneumoniae donors and affected, inter alia, capsule and lipopolysaccharide antigen biosynthesis regions. Most genomes contained acquired resistance genes to extended-spectrum cephalosporins, carbapenems, and other antibiotic classes carried by multiple plasmid types, and many were positive for hypervirulence markers, including the siderophore aerobactin. The detection of "hybrid" resistance and virulence plasmids suggests the occurrence of the convergent ST395 pathotype. CONCLUSIONS: To the best of our knowledge, this is the first study that investigated a large international collection of K. pneumoniae ST395 genomes and elucidated phylogenetics and detailed genomic characteristics of this emerging high-risk clonal lineage.

Course of Lower Respiratory Tract Infection in Young People Treated at the Military Hospital of Smolensk Garrison with Detected Mycoplasma pneumoniae Carrying a Macrolide-Resistant Mutation in 23S rRNA Gene.

We evaluated the effect of macrolide-resistant mutations in the Mycoplasma pneumoniae 23S rRNA gene on the severity of lower respiratory tract infections in immunocompetent young adults treated at the Smolensk Military Hospital between 25 October 2017, and 17 November 2021. All analyzed cases represented a non-severe infection of the lower respiratory tract: 44 case histories with community-acquired pneumonia and 20 cases with acute bronchitis. The presence of mutations in the gene 23S rRNA of M. pneumoniae was determined with standard Sanger sequencing. The macrolide-resistant genotype was found in 4/44 (9.1%) of the samples of the patients with pneumonia and in 3/20 (15%) of the samples of the patients with acute bronchitis. The analyzed cases with identified M. pneumoniae carrying a mutation in the 23S rRNA gene did not show any differences in the clinical presentation in terms of disease severity caused by M. pneumoniae with the wild-type (WT) phenotype.

Detection of carbapenemase-producing Enterobacterales by means of matrix-assisted laser desorption ionization time-of-flight mass spectrometry with ertapenem susceptibility-testing disks as source of carbapenem substrate.

MALDI-TOF mass spectrometry has become widely used in clinical microbiology and has proved highly accurate for detection of carbapenemases in Gram-negative bacteria. However, the use of carbapenem-hydrolysis assays in routine diagnostics is hampered by the need for antibiotic substances and for making their fresh solutions each time an assay is conducted. Here, we evaluated the use of commercial antibiotic susceptibility-testing disks as source of ertapenem substrate in MALDI-TOF MS-based assay for detection of carbapenemase-producing Enterobacterales (CPE). The assay was validated on 48 CPE isolates of 8 different species expressing NDM-, VIM-, KPC- and OXA-48-type carbapenemases and exhibiting various levels of resistance to carbapenems (MIC range: 0.25- > 32 mg/l), as well as on 48 carbapenemase-non-producing isolates. The assay conditions were optimized as follows: 10-µl loopful of bacterial colonies was suspended in 150 µl 0.01 M Na-PBS buffer, pH 7.4, a 10 µg ertapenem susceptibility-testing disk was immersed in the suspension and incubated 3 h at 35°C, after which supernatant was obtained by centrifugation and applied on a target plate with alpha-cyano-4-hydroxycinnamic acid matrix. Mass spectra were analyzed between 440 and 560 m/z. Carbapenemase activity was detected in all tested CPE isolates by the appearance of m/z peaks corresponding to ertapenem hydrolysis products: [Mh + H]+:494.2, [Mh + Na]+:516.2, [Mh + 2Na]+:538.2, [Mh/d + H]+:450.2, [Mh/d + Na]+:472.2, and simultaneous decrease or loss of peaks of intact antibiotic: [M + H]+:476.2, [M + Na]+:498.1, [M + 2Na]+:520.1. No hydrolysis peaks or loss of intact ertapenem peaks were observed for carbapenemase-negative strains. We therefore report the development of a sensitive, specific and cost-effective MALDI-TOF MS-based assay for detection of CPE, which makes use of antibiotic disks readily available in most laboratories.

Molecular Epidemiology of mcr-1-Positive Escherichia coli and Klebsiella pneumoniae Isolates: Results from Russian Sentinel Surveillance (2013-2018).

BACKGROUND: The dissemination of mobile colistin resistance (mcr) genes is a serious healthcare threat because polymyxins represent "last-line" therapeutics for multi-drug-resistant Gram-negative pathogens. This study aimed to assess the prevalence of colistin resistance and mcr genes and characteristics of clinical Escherichia coli (Eco) and Klebsiella pneumoniae (Kpn) isolates and plasmids carrying these genes in Russia. METHODS: A total of 4324 Eco and 4530 Kpn collected in the frame of sentinel surveillance in 2013-2018 were tested for susceptibility to colistin and other antibiotics using the broth microdilution method. mcr genes were screened by real-time PCR. Phylogeny, genomic features and plasmids of mcr-positive isolates were assessed using whole-genome sequencing and subsequent bioinformatic analysis. RESULTS: Colistin resistance was detected in 2.24% Eco and 9.3% Kpn. Twenty-two (0.51%) Eco and two (0.04%) Kpn from distant sites carried mcr-1.1. Most mcr-positive isolates co-harbored ESBLs and other resistance determinants to various antibiotic classes. The mcr-positive Eco belonged to 16 MLST types, with ST359 being most common; Kpn belonged to ST307 and ST23. mcr-1.1 was carried mainly in IncI2 (n = 18) and IncX4 (n = 5) plasmids highly similar to those identified previously in human, animal and environmental isolates. CONCLUSION: This study demonstrated a dissemination of "typical" mcr-bearing plasmids among diverse Eco and Kpn genotypes and across a wide geographic area in Russia. Given the frequent association of mcr with other resistance determinants and potential clinical impact, the continual surveillance of this threat is warranted.

Country data on AMR in Russia in the context of community-acquired respiratory tract infections: links between antibiotic susceptibility, local and international antibiotic prescribing guidelines, access to medicine and clinical outcome.

BACKGROUND: Antimicrobial reistance (AMR) is one of the biggest threats to global public health. Selection of resistant bacteria is driven by inappropriate use of antibiotics, amongst other factors. COVID-19 may have exacerbated AMR due to unnecessary antibiotic prescribing. Country-level knowledge is needed to understand options for action. OBJECTIVES: To review AMR in Russia and any initiatives addressing it. Identifying any areas where more information is required will provide a call to action to minimize any further rise in AMR within Russia and to improve patient outcomes. METHODS: National AMR initiatives, antibiotic use and prescribing, and availability of susceptibility data, in particular for the key community-acquired respiratory tract infection (CA-RTI) pathogens Streptococcus pneumoniae and Haemophilus influenzae, were identified. National and international antibiotic prescribing guidelines commonly used locally for specific CA-RTIs (community-acquired pneumonia, acute otitis media and acute bacterial rhinosinusitis) were also reviewed, plus local antibiotic availability. Insights from both a local clinician and a local clinical microbiologist were sought to contextualize this information. CONCLUSIONS: Russia launched a national strategy in 2017 to prevent the spread of AMR and the WHO reports that as of 2020-21, it is being implemented and actively monitored. Reports suggest outpatient antibiotic use of antibiotics is high and that non-prescription access and self-medication are very common. Antibiotic susceptibility studies in Russia include PeHASus, a multicentre epidemiological study focusing on susceptibilities of community-acquired respiratory pathogens and international studies such as Survey of Antibiotic Resistance (SOAR), Antimicrobial Testing Leadership and Surveillance (ATLAS) and SENTRY Antimicrobial Surveillance Program. International guidelines are used to support the development of local guidelines in Russia, and for the common CA-RTIs Russian clinicians use of several country-specific local antibiotic prescribing guidelines. A standardized inclusive approach in developing local guidelines, using up-to-date surveillance data of isolates from community-acquired infections in Russia, could make guideline use more locally relevant for clinicians. This would pave the way for a higher level of appropriate antibiotic prescribing and improved adherence. This would, in turn, potentially limit AMR development and improve patient outcomes.

The Dynamics of Antimicrobial Resistance among Enterobacteriaceae Isolates in Russia: Results of the 2012-2018 INFORM and ATLAS International Program Studies.

Background: The increasing prevalence of multidrug-resistant Enterobacteriaceae limits the range of active antimicrobial agents, thus worsening clinical outcomes. The objective of this study was to identify the trends in antimicrobial resistance for Enterobacteriaceae in Russia using the databases for the International Network for Optimal Resistance Monitoring (INFORM) and Antimicrobial Testing Leadership and Surveillance (ATLAS) studies between 2012 and 2018. Methods: This subanalysis was performed for 3811 non-duplicate clinical isolates of Enterobacteriaceae to evaluate the in vitro activity of the main classes of antibiotics against relevant clinical isolates from hospitalized patients with complicated infections of different anatomical locations. Results: The lowest susceptibility was observed for colistin (0%), ampicillin (16.4%), and ampicillin/sulbactam (31.1%), whereas the best susceptibility was observed for all combinations containing avibactam (>96%). Among individual antimicrobials, doripenem (3.2%), tigecycline (1.6%), and meropenem (5.9%) exhibited the lowest resistance. Important trends included the decreasing resistance of Enterobacteriaceae to glycylcyclines and the increasing resistance to aminoglycosides and carbapenems. K. pneumoniae strains were most aggressive in terms of the percentage of strains having multidrug resistance (8.3−18.3%, depending on location) and the percentage of ESBL-positive strains (44.8−86.8%). Conclusions: The current patterns and trends of antimicrobial resistance in different bacterial species should be taken into consideration for timely updating of clinical guidelines and local treatment protocols to ensure effective antimicrobial therapy.

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.

Antimicrobial Prescribing Patterns in Patients with COVID-19 in Russian Multi-Field Hospitals in 2021: Results of the Global-PPS Project.

The COVID-19 pandemic is a global public health challenge with understudied effects on antimicrobial usage. We aimed to analyze antimicrobial prescribing patterns in COVID-19 patients in Russian multi-field hospitals by means of the Global-PPS Project developed by the University of Antwerp. Out of 999 patients in COVID-19 wards in six hospitals surveyed in 2021, 51.3% received antimicrobials (79% in intensive care, 47.5% in medical wards). Systemic antivirals and antibiotics were prescribed to 31% and 35.1% of patients, respectively, and a combination of both to 14.1% of patients. The top antivirals administered were favipiravir (65%), remdesivir (19.2%), and umifenovir (15.8%); the top antibiotics were ceftriaxone (29.7%), levofloxacin (18%), and cefoperazone/sulbactam (10.4%). The vast majority of antibiotics was prescribed for treatment of pneumonia or COVID-19 infection (59.3% and 25.1%, respectively). Treatment was based on biomarker data in 42.7% of patients but was targeted only in 29.6% (6.7% for antibiotics). The rate of non-compliance with guidelines reached 16.6%. Antimicrobial prescribing patterns varied considerably in COVID-19 wards in Russian hospitals with groundlessly high rates of systemic antibiotics. Antimicrobial usage surveillance and stewardship should be applied to inpatient care during the COVID-19 pandemic.

Analysis of the Clinical Pipeline of Treatments for Drug-Resistant Bacterial Infections: Despite Progress, More Action Is Needed.

There is an urgent global need for new strategies and drugs to control and treat multidrug-resistant bacterial infections. In 2017, the World Health Organization (WHO) released a list of 12 antibiotic-resistant priority pathogens and began to critically analyze the antibacterial clinical pipeline. This review analyzes "traditional" and "nontraditional" antibacterial agents and modulators in clinical development current on 30 June 2021 with activity against the WHO priority pathogens mycobacteria and Clostridioides difficile. Since 2017, 12 new antibacterial drugs have been approved globally, but only vaborbactam belongs to a new antibacterial class. Also innovative is the cephalosporin derivative cefiderocol, which incorporates an iron-chelating siderophore that facilitates Gram-negative bacteria cell entry. Overall, there were 76 antibacterial agents in clinical development (45 traditional and 31 nontraditional), with 28 in phase 1, 32 in phase 2, 12 in phase 3, and 4 under regulatory evaluation. Forty-one out of 76 (54%) targeted WHO priority pathogens, 16 (21%) were against mycobacteria, 15 (20%) were against C. difficile, and 4 (5%) were nontraditional agents with broad-spectrum effects. Nineteen of the 76 antibacterial agents have new pharmacophores, and 4 of these have new modes of actions not previously exploited by marketed antibacterial drugs. Despite there being 76 antibacterial clinical candidates, this analysis indicated that there were still relatively few clinically differentiated antibacterial agents in late-stage clinical development, especially against critical-priority pathogens. We believe that future antibacterial research and development (R&D) should focus on the development of innovative and clinically differentiated candidates that have clear and feasible progression pathways to the market.

Biomarker Value in the Diagnosis of Community-Acquired Pneumonia with Concomitant Chronic Heart Failure.

The diagnosis of community-acquired pneumonia (CAP) with chronic heart failure (CHF) is associated with objective difficulties. Our case-control study aims to establish whether established serum inflammatory biomarkers are relevant to the diagnosis of CAP in patients with CHF. Seventy inpatients with previously diagnosed CHF and suspected non-severe CAP were recruited and then stratified into two subgroups with confirmed and rejected diagnosis of CAP. C-reactive protein (CRP), procalcitonin (PCT), tumor necrosis factor α (TNFα), interleukin-6 (IL-6) and brain natriuretic peptide (BNP) were measured. The value of biomarkers was determined using logistic regression, and their discriminatory efficacy was assessed by analyzing receiver operating characteristic (ROC) curves. Significantly higher levels of CRP 50.0 (35.5-98.5) mg/L, PCT 0.10 (0.05-0.54) ng/mL and IL-6 46.1(21.4-150.3) pg/mL in cases were identified as compared to the control group-15.0 (9.5-25.0) mg/L, 0.05 (0.05-0.05) ng/mL and 13.6 (9.5; 25.0) pg/mL, respectively. The Area Under the ROC Curve (95% CI) was the highest for CRP-0.91 (0.83-0.98), followed by PCT-0.81 (0.72-0.90) and IL-6-0.81 (0.71-0.91). A CRP value of >28.5 mg/L had an optimal sensitivity and specificity ratio (85.7/91.4%). In conclusion, the measurement of serum CRP, PCT and IL-6 levels can be useful for the diagnosis of CAP in patients with CHF. CRP showed optimal diagnostic utility in this population.

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.

AMRmap: An Interactive Web Platform for Analysis of Antimicrobial Resistance Surveillance Data in Russia.

Surveillance of antimicrobial resistance (AMR) is crucial for identifying trends in resistance and developing strategies for prevention and treatment of infections. Globally, AMR surveillance systems differ in terms of organizational principles, comprehensiveness, accessibility, and usability of data presentation. Until recently, the data on AMR in Russia were scarcely available, especially to international community, despite the fact that the large prospective multicenter surveillance in Russia was conducted and data were accumulated for over 20 years. We describe the source of data, structure, and functionality of a new-generation web platform, called AMRmap (https://amrmap.net/), for analysis of AMR surveillance data in Russia. The developed platform currently comprises susceptibility data of >40,000 clinical isolates, and the data on abundance of key resistance determinants, including acquired carbapenemases in gram-negatives, are updated annually with information on >5,000 new isolates. The AMRmap allows smart data filtration by multiple parameters and provides interactive data analysis and visualization tools: MIC and S/I/R distribution plots, time-trends and regression plots, associated resistance plots, prevalence maps, statistical significance graphs, and tables.