Fluoroquinolones have been studied for more than half a century. Since the 1960s, four generations of these synthetic antibiotics have been created and successfully introduced into clinical practice. However, they are still of interest for medicinal chemistry due to the wide possibilities for chemical modification, with subsequent useful changes in the pharmacokinetics and pharmacodynamics of the initial molecules. This review summarizes the chemical and pharmacological results of fluoroquinolones hybridization by introducing different heterocyclic moieties into position 3 of the core system. It analyses the synthetic procedures and approaches to the formation of heterocycles from the fluoroquinolone carboxyl group and reveals the most convenient ways for such procedures. Further, the results of biological activity investigations for the obtained hybrid pharmacophore systems are presented. The latter revealed numerous promising molecules that can be further studied to overcome the problem of resistance to antibiotics, to find novel anticancer agents and more.

The aim. Determine hemodynamic status and its impact on oxygen transport, frequency of adverse events and outcomes in patients with severe SARS-CoV-2 associated with acute respiratory distress syndrome (ARDS). Materials and methods. A single-center prospective comparative study was conducted with 29 patients enrolled over the period of July—October 2020 who suffered a severe course of coronavirus disease and bilateral pneumonia associated with ARDS. Based on the estimated cardiac index (CI), patients were allocated to two groups: Group 1 included 14 patients with severe ARDS and CI 1.9 [1.5–2.5] L/min/m2, whereas Group 2 included 15 patients with CI 4.2 [3.2–8.1] L/min/m2 (p=0.001). Patient`s intensive care was regulated by the relevant orders of the Ministry of Health of Ukraine. Statistical analysis of the results was carried out using Statistica 10 software. Statistical significance of parameters was assessed using the non-parametric Wilcoxon criterion. Results were considered significant at p values <0.05. Data are presented as M [25–75]. Relative risk (RR) and odds ratio (OR) of adverse events were calculated. Results. The severe course of coronavirus disease is associated with significant oxygen transport disorders that increase with hypovolemia. Despite the increase in oxygen delivery in the group with normal CI its high tissue extraction remained, which may be a sign of development mitochondrial distress. Conclusions. Patients admitted to the ICU with severe COVID-19 may be in a state of hypovolemia and require individual assessment of hemodynamic status and the appointment of infusion therapy. Increased oxygen delivery in patients with normal cardiac index was associated with decreased adverse events rate and statistically significant decrease of mortality rate

The aim of the research. The aim of this work was to summarize the scientific literature data on the pathogenesis and intensive care of the severe course of coronavirus infection. Materials and methods. Databases such as PubMed, Google Scholar, Scopus and Web Of Science 2020-2021 were used for literary searches. Results. An intense inflammatory response against the SARS-CoV-2 virus in COVID-19 patients causes a cytokine storm and hypercoagulability with the development of acute respiratory distress syndrome (ARDS) and multiple organ failure. Approximately 17 % to 35 % of hospitalized patients with COVID-19 are treated in the intensive care unit, most often due to hypoxemic respiratory failure and the development of ARDS, and between 29 % and 91 % of patients in intensive care units require invasive ventilation. In addition to acute respiratory failure, hospitalized patients may have acute renal failure (9 %), liver dysfunction (19 %), coagulation disorders (10 %–25 %), and septic shock (6 %). More than 75 % of hospitalized patients require additional oxygen therapy. Respiratory support could vary from the need for oxygen supplementation through a nasal catheter to invasive ventilation or extracorporeal membrane oxygenation in patients with the most severe ARDS. The uncontrolled inflammation and coagulation seen in COVID-19 patients is similar to multifactorial ARDS, where a plethora of evidence has demonstrated the ability of long-term corticosteroid therapy (CST) to reduce inflammation-coagulation-fibroproliferation and accelerate recovery. With regard to the assessment of the benefits of therapeutic anticoagulation in patients with elevated D-dimer, the question has not yet been finally resolved, and research devoted to this is still ongoing. Conclusions. The approaches to respiratory, anticoagulant, anti-inflammatory therapy in critically ill patients with COVID-19 require further research to determine the optimal treatment tactics

Monoclonal antibodies (mAbs) are an important medical innovation in modern medicine. They are an effective therapy for several subtypes of leukaemia but may have undesirable effects, which may be minimised through the provision of interdisciplinary care including a pharmacist. The goals of this narrative review were twofold: first, to summarise the literature on the side effects of mAbs and the challenges of their preparation, and to provide recommendations for the safe preparation of mAb drug formulations for clinicians. Second, to suggest clinical roles for pharmacists to improve patient safety and clinical outcomes for leukaemia patients receiving mAb therapy. The review covers data from 178 scientific and official sources of information on the types of targeted immunobiological drugs for the treatment of various types of leukaemia. The results are a detailed description of the possible side effects from mAb therapy and a list of suggested actions that can be taken to prevent them. Pharmaceutical aspects of the use of mAbs, such as pharmacoeconomics, compounding and stability, are also discussed. The discussion is organised according to the current classification of leukaemia. The drugs considered include blinatumomab, inotuzumab ozogamicin, gemtuzumab ozogamicin, rituximab, ofatumumab, obinutuzumab, and alemtuzumab. The review offers a comprehensive resource to equip pharmacists and other clinicians to optimise mAb therapy and promote the safe use of these novel therapies.

Background. The situation regarding the prevalence of resistant pathogens, types of β-lactamase products, and, accordingly, the justification of rational approaches to antibacterial therapy in Ukraine remains insufficiently studied. Objective: based on the determination of the etiological structure of the causative agents of hospital infections in the Kharkiv region and the state of their resistance due to the production of β-lactamases, to propose rational approaches to antibacterial therapy and assess the feasibility of using aztreonam as a potentially effective mean of treating infections caused by resistant bacteria. Materials and methods. In 251 patients, samples of biomaterials were tested by the polymerase chain reaction for the presence of the following gram-negative pathogens: P.aeruginosa, Enterobacter, E.coli, K.pneumoniae, Proteus spp. and A.baumanii. A molecular genetic study was also conducted to identify certain types of β-lactamases. Results. In the structure of hospital pathogens, the absolute majority of gram-negative bacteria belong to the enterobacteria family. When determining the profile of β-lactamases, we found that in 59.38 % of cases, E.coli was able to produce metallo-β-lactamases, which makes the therapy with carbapenems or ceftazidime-avibactam impossible. An alternative in such cases is a combination of aztreonam and ceftazidime-avibactam. When the causative agent K.pneumoniae is detected, in some cases there may also be a need for combined therapy with the use of aztreonam. It was found that Enterobacter spp. in most cases is sensitive to carbapenems. A.baumanii is completely insensitive to carbapenems and requires alternative approaches to antibacterial therapy, including aztreonam, ceftazidime-avibactam, and polymyxins. P.aeruginosa was found only as part of polymicrobial associations, so it was impossible to analyze its β-lactamase production profile. Conclusions. The results of the conducted study demonstrate an extremely high detection of gram-negative antibiotic-resistant pathogens in patients of the intensive care units in the Kharkiv region. Microorganisms such as E.coli and A.baumanii have the most unfavorable profile of antibiotic resistance, which is due to the high frequency of production of serine carbapenemases and metallo-β-lactamases, whose presence makes the effective use of carbapenems impossible.

Background. Despite the official statement by the World Health Organization regarding the end of coronavirus disease (COVID-19) pandemic, the risk of an epidemic rise in morbidity remains due to the active circulation of the pathogen and its mutation. Social, natural, environmental, and other factors can contribute to the spread of COVID-19. Air pollutants are extremely dangerous for humans, and a mixture of aerosols and dust particles in the air can serve as factors for the severe acute respiratory syndrome coronavirus 2 transmission. So, the purpose of the study was to reveal the impact of air pollutants on COVID-19 severity in Kharkiv. Materials and methods. The influence of environmental factors on the manifestations of COVID-19 epidemic was assessed for 425 days. 16,723 cases of hospitalizations, 1,883 deaths, and 15,146 confirmed cases of COVID-19 in various age groups were studied. There were on average 4,663 active cases every day. Statistical analysis on assessing the impact of environmental factors on COVID-19 morbidity with different degrees of severity was performed using the non-parametric Kruskal-Wallis test in the IBM SPSS Statistics software package, and the normality of the distribution was checked using the Kolmogorov-Smirnov test. Microsoft Office Excel 2016 spreadsheet tools were used for some auxiliary calculations and graphing. Results. The influence of sulfur dioxide, nitrogen dioxide, nitrous oxide, hydrogen sulfide, phenol, soot, and formaldehyde on COVID-19 morbidity in different severity of infection course with incubation periods of 3–4, 6–7, and 10–14 days was revealed. The effect of high concentrations of nitrogen dioxide, nitrogen oxide, and formaldehyde was most significant on active, confirmed, hospitalized, and fatal cases of COVID-19. At the same time, a rise in active cases of COVID-19 was observed with increasing concentrations of sulfur dioxide and hydrogen sulfide, and high concentrations of phenol and soot had an impact on severe forms. Conclusions. Air pollution can contribute to the spread of COVID-19 and lead to its severe forms, which should be considered when predicting morbidity at different levels (national, regional, local) of epidemiological surveillance. Further research is needed to reveal causal relationships between the incidence of COVID-19 and air pollutants, considering the influence of social and natural factors.