The novel coronavirus infection (COVID-19) is characterized by damage, along with the lungs, to many other vital organs and systems. The prevalence and severity of the resulting lesions are determined by the ability of the SARS-CoV-2 virus to cause excessive activation of the immune response, accompanied by changes in both cellular and humoral components. Among humoral disorders, the most significant is the hypersecretion of cytokines, including interleukins (IL), in particular IL-6 and IL1β. Elevated levels of IL-6 are one of the main predictors of severe COVID-19 and death. So, blocking the effects of this cytokine is of fundamental importance for improving the clinical outcomes of patients. Monoclonal antibodies against human interleukin-6 receptor or against IL-6 have been widely studied in patients with extremely severe COVID-19, and to a lesser extent in mild and moderate severity. Regardless of the severity, maximum effectiveness is achieved when these drugs are administered as early as possible, which made it possible to create such a tool as preventive anti-inflammatory therapy. Preventive prescription of IL-6 inhibitors may be useful not only for hospitalized inpatients, but also for outpatients. This review is aimed to assess the effectiveness of early use of IL-6 inhibitors both in hospitalized and ambulatory patients with varying degrees of severity of COVID-19.

The aim of the study was to analyze the literature sources for pharmacodynamic and pharmacokinetic features of gabapentin, providing its use in patients with neuropathic pain, as well as a comparative evaluation of its efficacy and safety when used in different doses.Materials and methods. PubMed, Google Scholar, EMBASE, ResearchGate scientific information network and elibrary.ru databases were used as search resources. The keywords used for the search were “gabapentin”, “mechanism of action”, “gabapentin targets”, “gabapentin pharmacodynamics”, “pharmacokinetics”, “pharmacokinetic parameters”, “neuropathic pain”, and “randomized clinical trials”. The depth of the search was 26 years (from 1998 to 2024). This review resulted in 87 literature sources.Results. Neuropathic pain (NeP) is one of the most common types of chronic pain, characterized by a high prevalence among people of the working age. Effective pharmacotherapy aimed at eliminating the pain syndrome is a key tool for improving the quality of life and preserving the work capacity of patients. Heterogeneity of etiologic factors involved in the genesis of NeP indicates the need to use drugs the analgesic effect of which is based on weakening the transmission of pain impulses in the CNS. In clinical trials, gabapentin has demonstrated efficacy in reducing the severity of pain in patients with postherpetic NeP, painful diabetic neuropathy and many other conditions accompanied by NeP. The dose of gabapentin 300 mg/day is the initial dose in the therapy of NeP and requires a further slow titration depending on the patient’s response to therapy and tolerability of the drug, especially in elderly and senile patients, as well as in patients with an impaired renal function. According to the published data, the most pronounced analgesic effect is achieved in the patients against the background of the gabapentin administration at a dose of 3600 mg/day.Conclusion. Gabapentin is the drug of choice in the management of patients with NeP of different etiology and intensity. A satisfactory safety profile and pharmacodynamic effects make gabapentin possible, despite the long history of its use, to remain a relevant drug used by a wide range of physicians, specialties, for pharmacotherapy of NeP patients.

The aim of the work was to search and analyze works on pharmacokinetic (PK) and pharmacodynamic (PD) parameters of spiramycin, allowing to evaluate the potential of this macrolide in the therapy of community-acquired infections.Materials and мethods. The abstract databases of PubMed, Google Scholar, EMBASE, the ResearchGate scientific information network and elibrary.ru were used to search for the materials. The following key queries were used in the work: “pharmacokinetics of spiramycin”, “pharmacokinetic parameters of spiramycin”, “pharmacodynamics of spiramycin”, “mechanism of action of spiramycin”, “targets for spiramycin”, “pharmacodynamic effects of spiramycin”. The search depth – 69 years (1955–2024), the total number of publications included in the literature review in the areas of “pharmacokinetics” and “pharmacodynamics” was 72. The total number of the sources used in the article amounted is 152.Results. With the spread of the antibiotic resistance (AR) among the pathogens of both nosocomial and community-acquired infections, it is important for physician to search for strategies to preserve the possibility of using first-line antibacterial drugs (ABDs) in patients with infectious diseases. Spiramycin has been characterized by a minimal consumption by the population in the last decades, thus, it has a potential for the therapy of infectious diseases. The analysis of the PK spiramycin parameters indicates the ability to form effective concentrations in various tissues and organs, as well as a minimal risk of drug interactions that can alter the therapeutic response. The evaluation of its antibacterial activity in vitro and in vivo yields different results, indicating the ability of the drug to exhibit significantly greater efficacy in vivo. This paradox may be based on pleiotropic effects of spiramycin involving both host cells (immunomodulatory and anti-inflammatory effects, the ability to favorably affect the tissue regeneration, the antitumor activity, the inhibition of adipogenesis) and pathogen targets (the ability to reduce the virulence of P. aerugenosa, the antiviral effect, the reduction of the adhesion ability of cocci).Conclusion. The PK and PD parameters and the properties of spiramycin along with the results of the published clinical studies evaluating its efficacy indicate that, despite its lower in vitro activity, the presence of additional pleiotropic effects may be the key to its superiority over the traditional macrolides in in vivo methods.

Improvement of the clinical outcomes of newborns with hospital-acquired infections requires microbiological monitoring to ensure timely initiation of appropriate empirical therapy. In our study we investigated the patterns of pathogens responsible for hospital-acquired infections in neonatal intensive care units and assessed the levels of antibiotic resistance among these pathogens. The study included 4,891 samples from newborns. Gram — positive microflora was found in 55.9% of the samples and gram-negative — in 44.1%. The antibiotic resistance profile revealed high resistance to penicillin-based antibiotics among staphylococci. Gram-negative microorganisms remained sensitive to most antibacterial drugs.

Relevance. Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are cutaneous hypersensitivity reactions that can be induced by drugs and are particularly severe in children.Objective. To study the structure of antibacterial drugs (ABs) involved in the development of SJS and TEN in pediatric populations.Methods. Retrospective pharmacoepidemiologic study of spontaneous reports (SRs) entered into the Russian National Pharmacovigilance database during the period 01.04.2019 – 31.12.2023.Results. The majority of suspected drugs were β-lactams (76.0%), with penicillin accounting for 47.4% and cephalosporins — for 52.6%. Amphenicols (12.0%), macrolides (8.0%), and fluoroquinolones (4.0%) were less frequently reported.Conclusion. The most common group of ABs that induce SJS and TEN in children is the group of β-lactam antibiotics.

Chronic musculoskeletal pain (CMSP) is one of the most common pathological conditions that limits patients' physical activity and reduces their quality of life. The analgesic and anti-inflammatory effects of non-steroidal anti-inflammatory drugs (NSAIDs) make them the basis of pharmacotherapy for patients with chronic conditions affecting various parts of the musculoskeletal system. The main target of NSAIDs, cyclooxygenase (COX), exists in the form of two main isoforms, COX-1 and COX-2, the inhibition of each of which leads to a cascade of reactions at the cellular and tissue level that can cause both targeted pharmacological effects and side effects. The diversity of the chemical structures of NSAIDs leads to differences in their pharmacodynamic and pharmacokinetic parameters and correspondingly to differences in their efficacy and safety profile. Selective COX-2 inhibitors, coxibs, have shown an increased risk of cardiovascular side effects, which has led to significant restrictions on their use. Cardiotoxicity is not as pronounced with the non-selective COX inhibitors, but the range of their side effects is extremely wide. These side effects are dose-dependent and are characteristic, first of all, of systemic NSAIDs.The combination of systemic and topical NSAIDs makes it possible to reduce the dose of the former and improve the safety profile of anti-inflammatory therapy. Among the non-selective COX inhibitors with a satisfactory safety profile and high anti-inflammatory activity, the group of oxicams and especially tenoxicam should be emphasised, which are characterised by a maximum duration of action, which is an advantage in the treatment of patients with CMSP. This review addresses the issues of rational selection of NSAIDs based on comparative data on pharmacodynamics, pharmacokinetics and clinical trial results.

Introduction. Nosocomial infections are a common complication in patients treated in the intensive care unit (ICU). Microorganisms with multidrug resistance are one of the significant risk factors for death in this category of patients. Aim. To study structure of infectious agents in ICU patients and parameters of their antibiotic resistance. Materials and methods. Retrospective pharmacoepidemiological study of medical records of adult patients with infections diagnosed in ICU who were treated in City Clinical Hospital No. 24 of the Department of Health (Moscow, Russian Federation) in the period 08/20/2022 — 07/31/2023 (n=199). The analysis (gender, age of patients, localization of the infectious process, data on the structure of pathogens and sensitivity to antibacterial drugs) included records with data on bacterial culture ( n=141). Results. In the structure of pathogens detected in ICU patients, gram-negative microflora predominated (54 %). Among the pathogens with a clinically significant growth, leaders were K. pneumoniae (22 %), Candida spp. (20 %) and Staphylococcus spp. (19 %). K. pneumoniae was characterized by resistance to beta-lactams, aminoglycosides, and levofloxacin, the highest susceptibility was reported to colistin, 88.9 %. Candida spp. was overwhelmingly susceptible to all drugs used. Among Staphylococ caceae, S. aureus was the most common (70 % resistance to ampicillin and cefoxitin). Conclusion. In the structure of infectious agents detected in ICU patients, a predominance of ESKAPE pathogens (the most prognostically important microorganisms: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.) was observed, including K. pneumoniae, S. aureus, A. baumannii, P. aeruginosa. For all these microorganisms, except for Staphylococcaceae, a high level of antibiotic resistance was demonstrated.

Dosage forms for topical ocular administration are the basis of patient management in ophthalmology. The eye is a structure evolutionarily protected from the effects of xenobiotics by a number of physiological and anatomical barriers. The development of dosage forms, the targeted delivery into the eye structures is carried out due to the inclusion of special excipients, is aimed at improving the efficiency of managing patients with eye diseases. The action mechanisms of the most common groups of excipients used in ophthalmology underlie their effectiveness and safety, as well as create a basis for the various dosage forms development. Cellulose derivatives, due to their physicochemical and pharmacological characteristics, are one of the preferred groups for the development of topical dosage forms used in ophthalmology. Hypromellose (hydroxypropyl methylcellulose) is one of the most studied cellulose derivatives, which is characterized by a wide range of indications for both the active substance (artificial tear component) and the excipient. The favorable pharmacological properties of hypromellose (the ability to provide long-term exposure to effective concentrations of drugs used topically in ophthalmology, the ability to increase the degree of hydration of the cornea) contribute to the active study of this substance to assess the possibilities of its use in the development of new dosage forms (nanoparticles), as well as expanding the existing list of indications. This review is devoted to the analysis of clinical and experimental studies of the efficacy and safety of hypromellose.

Pregnant women are a very special category of patients. The risk-benefit ratio of using various drugs in this case presents a significant medical, social and ethical problem. The increase in the age of onset of the first pregnancy is associated with the increasing prevalence of chronic pathology. Obesity, cardiovascular diseases, diabetes mellitus, hypo- or hyperfunction of the thyroid gland, as well as many other conditions contribute to the active use of drugs of various pharmacological groups throughout the entire period of pregnancy, including early periods. The current practice of pharmacotherapy in pregnant women is based mainly on the use of drugs with an uncertain teratogenic risk. Not including pregnant women in clinical trials is an ethical issue as significant as their potential inclusion. Previously, for a long time, vulnerable categories included generally all women of reproductive age, whose inclusion in clinical trials became possible only in the mid-1990s. Pregnant women were considered vulnerable until 2019. The orphan status of pregnant women in terms of inclusion in clinical trials limits their right to receive highly effective and safe medical care, which makes it relevant to review the existing ethical principles in relation to this category of patients and a to perform a detailed analysis of existing barriers for certain types of drug trials.

Objective. To analyze the characteristics of patients with severe COVID-19 and lethal outcome. Materials and Methods. This retrospective pharmacoepidemiological study (March – April 2021) enrolled 172 patients with confirmed COVID-19 and death in the intensive care unit of City Clinical Hospital No. 24. Results. The mean age was 74.4 ± 7.4 years, patients over 65 years old – 81% (n = 139), over 75 years old – 44% (n = 75). Males – 66% (n = 113). All patients had a secondary bacterial infection. The predominant COVID-19 complications were respiratory failure (100%), pulmonary edema (96%), multiorgan failure (96%), and acute respiratory distress syndrome (92.4%). All patients had concomitant diseases (cardiovascular – 94.2%, gastrointestinal tract – 81.2%, endocrine – 72.0%). The mean Charlson Comorbidity Index was 7.4 points. The mean length of hospital stay was 12.4 ± 11.0 days (range: 1–36 days), the maximum number of deaths was observed on the 9th day. Analysis of laboratory parameters revealed a significant increase in ferritin, lactate dehydrogenase, and C-reactive protein levels, WBC, absolute lymphocyte count, as well as a decrease in RBC and platelet count at the last measurement before death. All patients received antibiotic therapy (carbapenems – 24%, fluoroquinolones and cephalosporins – 20% each). Antiviral therapy was performed in 62% (n = 106), predominantly with favipiravir (88%). Conclusions. The population of patients with fatal outcome due to COVID-19 was characterized by older age, high Charlson comorbidity index, predominance of cardiovascular, GI tract and endocrine diseases, and high levels of laboratory acute-phase inflammation markers.

Considering patients of elderly and senile age, pronounced discrimination continues to be observed, expressed in their insufficient inclusion or non-inclusion in randomized clinical trials. As a result, the clinical recommendations based on the results of such studies cannot be fully applicable to this category of patients. The problems of inclusion/non-inclusion of older people in clinical trials are numerous. The reasons for their occurrence and solutions affect, among other things, the ethical sphere. Compliance with basic ethical principles such as respect for persons, beneficence and justice should underlie the decision to include a patient in a study. In general, when evaluating these ethical principles from the point of view of the well-being of the entire population of elderly and senile patients, it is necessary to rethink the principles according to which this category of patients was excluded from clinical trials.

Increased life expectancy along with an increasing share of elderly and senile patients in the structure of the population make the tasks of longer healthy life expectancy pressing. A set of activities aimed at optimization of management of patients within the framework of gerontological practice should include elimination and prevention of diagnostic and therapeutic errors. The basic risk factors of medical errors include high heterogeneity of elderly and senile patients, overburdened healthcare system, polypharmacy, including due to parallel prescription of drugs to the same patient by multiple medical professionals, concomitant diseases, and high comorbidity, measured by the Charlson Comorbidity Index. Mismanagement of elderly patients can result both from underestimated severity of the patient’s conditions, and from hyperdiagnostics. Typical errors of pharmacotherapy include use of potentially inappropriate medications, potential prescribing omissions, simultaneous prescription of drugs with high risk of clinically significant interactions, incorrect selection of dosage without taking into account the renal failure, which is associated with high risk of toxic effects. Affordability of medical aid for an elderly patient is another important social aspect influencing the patient’s quality of life. As far as basic ethical principles of management of elderly and senile patients go, it is necessary to respect independence, well-being and justice for the patients regarding possible obtaining of qualitative medical aid as compared with other age groups.

The symptoms of most pathological conditions in ophthalmology are based on inflammations of varying severity. Valuable tools against inflammation are topical glucocorticoids (tGCs), whose molecules are able to actively overcome biological membranes and ensure a rapid clinical response. The use of tGCs is accompanied by a wide range of effects, including side effects, a rise in intraocular pressure being one of the most significant ones. The review focuses on a comparative analysis of the efficacy and safety of various tGCs, including “soft steroids”. We show the relationship between the structure of the drugs, their pharmacodynamic effects and the possibility of being used in various eye diseases.

Objective. To assess biapenem PK parameters in critically ill adult patients and define the optimal dosing regimens based on TDM data. Materials and Methods. An open, prospective, uncontrolled, single-center study based on City Clinical Hospital No. 24, Moscow (October 2022 – April 2023), included patients over 18 years of age with a diagnosed severe bacterial infection received 600 mg of biapenem as 3-hour intravenous infusion every 12 hours in the intensive care unit. Blood sampling during the TDM included taking blood samples immediately before the next infusion of biapenem to determine the residual concentration (Ctrough) and immediately after the end of the infusion to determine the peak concentration (Cmax). Concentrations were assessed using HPLC-UV method. Results. Total population – 20 patients (75% ≥ 60 years; 65% women). The main indications for biapenem were lower respiratory tract infections (80%) and intra-abdominal infections (35%). Bacterial culture tests revealed growth in 45% (Klebsiella pneumoniae – 87,5%). During the TDM 40 samples were obtained (Cmax from 15 to 42 mg/l (mean – 28.7 mg/l), Ctrough from 0.5 to 15 mg/l (mean – 3.56 mg/l)). The Kel value ranged from 0.09 to 0.48 1/h (mean – 0.29 1/h); Vd – from 7.41 to 42.49 l (mean – 16.33 l); T1/2 – from 1.4 to 7.5 hours (mean 2.94 hours). Probability of target attainment (%fT ≥ MIC) was assessed depending on MIC. For MIC of 2 mg/l, 40%fT ≥ MIC was achieved in 100%, 60%fT ≥ MIC – in 100%; 80%fT ≥ MIC – in 75%. For MIC – 8 mg/l, 40%fT ≥ MIC was achieved in 90%, 60%fT ≥ MIC – in 45%, 80%fT ≥ MIC – in 15%. Conclusions. The dosing regimen 600 mg of biapenem as 3-hour intravenous infusion every 12 hours demonstrated achievement of effective antibiotic concentrations in blood plasma of critically ill patients exceeding the MIC (2 mg/l). To manage patients infected with resistant strains (MIC of 4–16 mg/l) it is necessary to perform additional studies assessing PK parameters of biapenem at higher doses.

INTRODUCTION. Newly identified risks associated with the use of fluoroquinolones and the spread of antimicrobial resistance make the identification and analysis of medication errors (MEs) in prescribing fluoroquinolones especially important for providing rational antibiotic therapy. Fluoroquinolones that are most commonly used in real-world clinical settings include levofloxacin.AIM. This study aimed to examine the pattern of MEs associated with fluoroquinolones, exemplified by levofloxacin, through an analysis of spontaneous reports (SRs) submitted to the Russian pharmacovigilance database.MATERIALS AND METHODS. The authors retrospectively analysed the SRs of adverse drug reactions (ADRs) submitted to the Russian pharmacovigilance database between 1 April 2019 and 28 February 2023. According to the selected inclusion criteria, the study focused on the SRs that specified levofloxacin as a suspect medicinal product and described ADRs that took place in the Russian Federation. ME identification used summaries of product characteristics for levofloxacin approved in Russia, official clinical guidelines, and the antimicrobial stewardship guidelines Strategy for the Control of Antimicrobial Therapy (SCAT).RESULTS. The analysis included 950 SRs. MEs were identified in 307 (32.3%) of these SRs, and the total number of MEs was 332. MEs associated with the selection of the medicinal product included prescribing levofloxacin to patients without an indication for antibacterial therapy (38.9%, n=129, with 76.0% of cases being viral infections), incorrect selection of levofloxacin as a first-line antibacterial agent (18.1%, n=60), and irrational and excessive prescribing of levofloxacin in combination with other antibacterial agents (15.4%, n=51). Less frequently identified MEs were related to inappropriate dosing (13.0%, n=43), levofloxacin use in patients with contraindications (8.7%, n=29), and incorrect selection of the route of administration (3.9%, n=13) and the dosage form (2.1%, n=7).CONCLUSIONS. According to the results of this study, the practice of prescribing antibacterial agents for viral infections persists despite strong evidence of ineffectiveness in such cases. Antibacterial agents can be used effectively and safely only if prescribed for approved indications, administered at recommended doses, and delivered via specified routes of administration. The overuse of antibiotics may have negative sequelae not only for the health of an individual patient but for the health of the general population because of the increased risk of antimicrobial resistance. Therefore, there is a need to develop measures to limit the excessive use of antibiotics.

The purpose of the study: to analyze the pharmacotherapy of senile patients in the intensive care unit (ICU).

The spread of cardiovascular diseases has the nature of an epidemic, which is enhanced by lipid profile disorders, manifested by hypercholesterolemia. Numerous conventional pharmacological tools for lowering cholesterol associated with low density lipoproteins do not make it possible to achieve target values in various categories of patients. Inhibition of proprotein convertase subtilisin/ kexin type 9 (PCSK9) is a promising target in the management of patients with atherosclerotic diseases and includes two main tools — monoclonal antibodies (Alirocumab and Evolocumab) and a small interfering RNA drug (Inclisiran). The presented review is devoted to a comparative analysis of the efficacy and safety of drugs from these groups.

Возможным инструментом повышения эффективности и безопасности ведения пациентов пожилого и старческого возраста с хронической болью может являться использование адъювантных анальгетиков, в частности антидепрессантов. Имеющиеся клинические данные указывают на возможность использования антидепрессантов в качестве альтернативы опиоидным анальгетикам и нестероидным противовоспалительным средствам. Обзор посвящен анализу сравнительных характеристик и особенностям назначения трициклических антидепрессантов, селективных ингибиторов обратного захвата серотонина и норадреналина, селективных ингибиторов обратного захвата серотонина в качестве обезболивающих средств пациентам пожилого возраста. Представлены рекомендации по применению антидепрессантов у пожилых пациентов с различными типами боли, направленные на минимизацию возможных нежелательных реакций и повышение качества жизни данной категории больных. A possible tool to improve the efficacy and safety of managing elderly and senile patients with chronic pain may be the use of adjuvant analgesics, in particular, antidepressants. Available clinical data indicate the possibility of using antidepressants as an alternative to opioid analgesics and non-steroidal anti-inflammatory drugs. The review includes the analysis of the comparative characteristics and peculiarities of prescribing tricyclic antidepressants, selective serotonin and norepinephrine reuptake inhibitors, and selective serotonin reuptake inhibitors as painkillers in elderly patients. Recommendations are given on the use of various representatives of the antidepressant group in elderly patients with various types of pain, aimed at minimizing possible adverse drug reactions and improving the quality of life of this category of patients.