Introduction.Strains of microorganisms resistant to antimicrobial agents are commonly found in medical units throughout most regions of the world, including Russia. This leads to lower antimicrobial therapy efficacy when treating nosocomial infections. In this regard, the timely implementation of adequate antibiotic therapy is of great importance.The objective of the guidelines:To provide summarized information on contemporary approaches to microbiological diagnostics and the assessment of results, as well as the principles of rational use of antimicrobial and antifungal agents, including treatment of infections caused by multiple drug-resistant strains of microorganisms.Subjects and methods.These guidelines are based on published data obtained in the course of randomized trials, as well as information presented in the provisions of international guidelines supported by high-level evidence. The guidelines were prepared by a working group of Russian experts with extensive experience in research and practical work in this area. On October 11, 2019, the final version of the guidelines was reviewed and approved at a joint meeting of the working group and representatives of the public organizations which initiated the development of these guidelines (Association of Anesthesiologists-Intensivists, the Interregional Non-Governmental Organization Alliance of Clinical Chemotherapists and Microbiologists, the Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy (IACMAC), NGO Russian Sepsis Forum).Conclusion.The guidelines reflect an interdisciplinary consensus of approaches to the diagnostics and antibiotic therapy of infections caused by multiresistant microorganisms. The provisions set forth should be used to decide on the strategy of empirical and etiotropic therapy of the most severe infections.

Infections are important factors contributing to the morbidity and mortality among elderly patients. High rates of consumption of antimicrobial agents by the elderly may result in increased risk of toxic reactions, deteriorating functions of various organs and systems and leading to the prolongation of hospital stay, admission to the intensive care unit, disability, and lethal outcome. Both safety and efficacy of antibiotics are determined by the values of their plasma concentrations, widely affected by physiologic and pathologic age-related changes specific for the elderly population. Drug absorption, distribution, metabolism, and excretion are altered in different extents depending on functional and morphological changes in the cardiovascular system, gastrointestinal tract, liver, and kidneys. Water and fat content, skeletal muscle mass, nutritional status, use of concomitant drugs are other determinants of pharmacokinetics changes observed in the elderly. The choice of a proper dosing regimen is essential to provide effective and safe antibiotic therapy in terms of attainment of certain pharmacodynamic targets. The objective of this review is to perform a structure of evidence on the age-related changes contributing to the alteration of pharmacokinetic parameters in the elderly.

Neonatal Infections are among the most common reasons for admission to the intensive care unit. Neonatal sepsis (NS) significantly contributes to mortality rates. Empiric antibiotic therapy of NS recommended by current international guidelines includes benzylpenicillin, ampicillin/amoxicillin, and aminoglycosides (gentamicin). The rise of antibacterial resistance precipitates the growth of the use of antibiotics of the Watch (second, third, and fourth generations of cephalosporines, carbapenems, macrolides, glycopeptides, rifamycins, fluoroquinolones) and Reserve groups (fifth generation of cephalosporines, oxazolidinones, lipoglycopeptides, fosfomycin), which are associated with a less clinical experience and higher risks of toxic reactions. A proper dosing regimen is essential for effective and safe antibiotic therapy, but its choice in neonates is complicated with high variability in the maturation of organ systems affecting drug absorption, distribution, metabolism, and excretion. Changes in antibiotic pharmacokinetic parameters result in altered efficacy and safety. Population pharmacokinetics can help to prognosis outcomes of antibiotic therapy, but it should be considered that the neonatal population is heterogeneous, and this heterogeneity is mainly determined by gestational and postnatal age. Preterm neonates are common in clinical practice, and due to the different physiology compared to the full terms, constitute a specific neonatal subpopulation. The objective of this review is to summarize the evidence about the developmental changes (specific for preterm and full-term infants, separately) of pharmacokinetic parameters of antibiotics used in neonatal intensive care units.

Biological therapy of bronchial asthma (BA) is a modern method of treating severe forms of the disease, that are uncontrolled by traditional pharmacotherapeutic approaches. Currently, 5 monoclonal antibody (AT) preparations are registered in the world for the treatment of severe bronchial asthma (SBA) of the T2 endotype (T2-SBA) – antibodies, binding to immunoglobulin (Ig) E (anti-IgE – omalizumab), interleukin antagonists (IL)-5 (anti-IL-5 – mepolizumab, resizumab) and its receptor (anti-IL-5Rα – benralizumab), as well as antibodies, that selectively bind to the IL-4 and -13 receptor (anti-IL-4 /13Rα – dupilumab). The article presents data on the effectiveness of these drugs in relation to the key characteristics of SBA, formulates clinical and laboratory criteria, the study of which in real practice can potentially predict the likelihood of a clinical response to a particular type of biological therapy. An algorithm is proposed for choosing a targeted therapy strategy for patients with SBA, clinically associated with allergies, for patients with severe non-allergic eosinophilic BA and for patients with eosinophilic BA of a combined phenotype.

(1) Background: National health system databases represent an important source of information about the epidemiology of adverse drug reactions including drug-induced allergy and anaphylaxis. Analysis of such databases may enhance the knowledge of healthcare professionals regarding the problem of drug-induced anaphylaxis. (2) Methods: A retrospective descriptive analysis was carried out of spontaneous reports (SRs) with data on drug-induced anaphylaxis (SRsAs) extracted from the Russian National Pharmacovigilance database (analyzed period 2 April 2019–21 June 2023). The percentage of SRsAs among SRs of drug-induced allergy (SRsDIAs) was calculated, as well as of pediatric, elderly, and fatal SrsAs. Drugs involved in anaphylaxis were assessed among total SRsAs, pediatric, and elderly SRsAs, and among fatal SRsAs. Demographic parameters of patients were assessed. (3) Results: SRsAs were reported in 8.3% of SRsDIAs (2304/27,727), the mean age of patients was 48.2 ± 15.8 years, and females accounted for 53.2% of cases. The main causative groups of drugs were antibacterials (ABs) for systemic use (44.6%), local anesthetics (20.0%), and cyclooxygenase (COX) inhibitors (10.1%). Fatal SRsAs were reported in 9.5% (218/2304) of cases, the mean age of patients was 48.0 ± 16.7 years, and females accounted for 56.4% of cases. Pediatric SRsAs accounted for 3.9% of pediatric SRsDIAs and 5.8% of all SRsAs, with a mean age of 11.8 ± 4.5 years, and females acccounted for 51.9% of cases. Elderly SRsAs accounted for 2% of elderly SRsDIAs and 2.8% of all SRsAs, and the mean age was 73.0 ± 5.3 years, and females accounted for 43.5% of cases. ABs caused 40% of SRsAs in the elderly, 42.9% in children, and 50% of fatal SRsAs. (4) Conclusions: Our study revealed a relatively high proportion of anaphylaxis among SRs of drug-induced allergy. ABs were the most prevalent causative agents, especially in fatal SRsAs.

(1) Background: Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are extremely severe cutaneous adverse drug reactions which are relatively rare in routine clinical practice. An analysis of a national pharmacovigilance database may be the most effective method of obtaining information on SJS and TEN. (2) Methods: Design—a retrospective descriptive pharmacoepidemiologic study of spontaneous reports (SRs) with data on SJS and TEN retrieved from the Russian National Pharmacovigilance database for the period from 1 April 2019 to 31 December 2023. Descriptive statistics was used to assess the demographic data of patients and the structure of suspected drugs. (3) Results: A total of 170 SRs on SJS and TEN were identified, of which 32.9% were SJS and 67.1%—TEN. In total, 30% were pediatric SRs, 21.2%—SRs of the elderly. There were 12 lethal cases, and all cases were TEN. The leading culprit drugs were anti-infectives for systemic use and nervous system agents. The top 10 involved drugs are as follows: lamotrigine (23.5%), ibuprofen (12.9%), ceftriaxone (8.8%), amoxicillin and amoxicillin with beta-lactam inhibitors (8.8%), paracetamol (7.6%), carbamazepine (5.9%), azithromycin (4.1%), valproic acid (4.1%), omeprazole (3.5%), and levetiracetam (3.5%). (4) Conclusions: Our study was the first study in Russia aimed at the assessment of the structure of the drugs involved in SJS and TEN on the national level.