EXPERIMENTAL STUDIES
Three unified procedures have been developed. The possibility of quantitative determination using the methods of kinetiс spectrophotometry, voltammetry, and redox titration of ampicillin (Amp) as a pure substance and in a drug using potassium hydrogen peroxomonosulfate (KHSO5) as an analytical reagent has been shown.
The possibility of antibacterial activity assay using an acoustic non-contact biological sensor based on two piezoelectric
plates separated by an air gap was demonstrated on the example of amoxicillin and Escherichia coli for the first time. An acoustic wave with transverse horizontal polarization is excited in the bottom plate of the sensor. The upper plate serves as the bottom of the container with the studied cell suspension. It was shown that the addition of an antibiotic to the cell suspension leads to a change in the parameters of the sensor. The effect of amoxicillin on microbial cells was monitored by laser microscopy and standard microbiological culture. The possibility of express analysis of the drug’s antibacterial activity using a biological sensor based on the use of a slit acoustic wave is shown.
GUIDELINES FOR PRACTITIONERS
Relevance. Pentanedioic acid imidazolyl ethanamide (PAIE) has been used clinically as an antiviral agent for a long time, however, there is no information in the available literature concerning the dependence of PAIE pharmacokinetics on isoenzymes polymorphism of the cytochrome P450 system (CYP), as well as on the variability of pharmacokinetic parameters in humans. The aim of the study is to determine the main pharmacokinetic parameters of PAIE in healthy volunteers and to assess the contribution of polymorphism of CYP P450 isoenzymes to the variability of pharmacokinetic parameters.
Material and methods. The study included 12 healthy volunteers (5 men and 7 women) of the Caucasian race, who took In[1]gavirin® at a dose of 180 mg (2 capsules of 90 mg) on an empty stomach during two dosing periods, separated by a 7-day washout period. Determination of PAIE concentration in blood plasma and urine samples was carried out by high-performance liquid chromatography–mass spectrometry. Polymorphism of CYP genes was analyzed using the polymerase chain re[1]action method in order to analyze the pharmacogenetic features of PAIE metabolism in volunteers during the study.
Results. After oral administration, PAIE quickly reached the systemic circulation: the maximum concentration of 578.88±145.21 ng/ml was observed after about 2 hours. Pharmacokinetic parameters of PAIE did not show high intraindividual variability and did not depend on polymorphism of isoenzymes CYP1A1, CYP2C9, and CYP2D6. Within 48 hours after the administration of the studied drug, about half of the taken dose of PAIE was excreted in the urine unchanged, which indicates a significant contribution of the kidneys to the elimination of PAIE. The only adverse event registered in 1 volunteer was a clinically insignificant decrease in the level of leukocytes, which did not require medical intervention and was resolved without consequences.
Conclusion. PAIE is characterized by predictable pharmacokinetics, low intraindividual variability of pharmacokinetic parameters, and a favorable safety profile.
Relevance. In the context of the ongoing pandemic of coronavirus infection, the course of viral pneumonia is often complicated by the addition of bacterial microflora due to a decrease in the body's immune status. The causative agents of such a co-infection can exhibit multiple drug resistance, which significantly reduces the effectiveness of etiotropic therapy. In this regard, it seems expedient to provide microbiological support to patients in order to select the most optimal treatment regimens.
Aim. To study the composition of bacterial pathogens’ species, that cause community-acquired pneumonia (CAP) in corona-positive (COVID-19+) and corona-negative (COVID-19–) patients and to determine the spectrum of their sensitivity/resistance to antibacterial drugs.
Material and methods. The species composition of microorganisms in sputum samples from 723 patients with CAP, who were admitted from the healthcare facility in Rostov-on-Don in August and December 2020 were studied. The isolated cultures were identified using bacteriological and mass spectrometric methods. The sensitivity of bacteria to antibiotics was determined by the disk diffusion method.
Results. It was shown that in August pneumococci and staphylococci prevailed in the spectrum of CAP pathogens, while in December the percentage of excretions of Acinetobacter spp. and S. haemolyticus increased. Various types of p. Candida yeast were found with a high degree of isolation, COVID-19 + patients showed a tendency towards greater contamination (I104 mcl/ml). Some pathogens (A.baumannii, S.haemolyticus, P.aeruginosa, S.maltophilia) are characterized by polydrug resistance, and some strains of these species are pan-resistant to all groups of antibiotics.
Conclusion. The data obtained demonstrate that severe forms of community-acquired pneumonia can be caused by viral-bacterial and viral-bacterial-yeast combinations of pathogens, including bacteria with a narrow spectrum of sensitivity to antibacterial drugs.
Aim. Evaluation of the efficacy, safety, and tolerability of Riamilovir (trade name «Triazavirin®») in patients with mild COVID-19.
Materials and methods. The randomized open-label study included 120 patients with clinical and epidemiological manifestations of coronavirus infection and its laboratory (PCR) confirmation.
Results. The efficacy, safety, as well as good tolerability of Riamilovir in the treatment of new coronavirus infection (COVID-19) have been established.
Conclusion. The results of the study on the efficacy, safety, and tolerability of Riamilovir allow us to recommend it as a means of etiotropic therapy of the new coronavirus infection (COVID-19).
In the study of 125 patients after radical surgery for non-small cell lung cancer (NSCLC), distinctive clinicopathological parameters of this disease were found. Thus, the majority of patients with NSCLC were smokers (73%), men had significantly higher rate of the disease than women (80% vs 20%). Patients of different sex varied by the tumor histological type: squamous cell carcinoma was characteristic of male patients (70%), while adenocarcinoma predominated in women (80%). Authors conclude that the described incidence patterns and the association of NSCLC with significant clinical features are comparable with the literature data, which indicates the absence of significant changes over the past 8 years. Survival rates of the patients after radical surgery for NSCLC also coincided with results of the previous studies. Overall survival rate varied by the stage of the disease, smoking status, and the tumor histological type: patients with earlier stage at diagnosis, never-smokers and patients with adenocarcinoma rather than squamous cell carcinoma were associated with a more favorable prognosis. The heterogeneity of the patients who survived 5 years after surgical treatment was shown: the group included patients not only with stage I of the disease, but also with more advanced II and even III stages of the disease. Finally, the absence of gender differences in the overall survival of the patients with NSCLC was demonstrated; this fact differs from the literature data on the better survival of female patients compared to men. The authors suggest that the result may indicate the emergence of factors in the Russian population that improve the course of disease in men or adversely affect the disease in women.
The effects of baricitinib, a selective reversible inhibitor of Janus kinase 1 and 2, in the treatment of COVID-19 are associated with different aspects of pathogenesis — inhibition of viral endocytosis, reduction of excessive inflammatory response, and mitigation of vascular and pulmonary damage, which is a strong rationale for using baricitinib to treat patients with COVID-19. In the period from April to May 2020, City Clinical Hospital No. 52 obtained clinical experience of baricitinib clinical use in the therapy of 113 patients with COVID-19: 58 (51%) women and 55 (49%) men, whose average age was 57±12.6 years old. Analysis of the results of using baricitinib showed that therapy with baricitinib against the background of standard pathogenetic therapy was found to be effective in 95 (84%) patients and ineffective in 18 (16%). Significant positive changes were shown in comparison with the baseline level of the following indicators: body temperature (from 37.2±0.8˚C to 36, ±0.68˚C, P=0.000), blood oxygen saturation (from 95.5±3.0% to 96.5±2.2%, P=0.011), C-reactive protein (from 46.1±48.0 mg/L to 33.5±43.7 mg/L, P=0.010 ), National Early Warning Score (NEWS) (from 1.7±1.3 to 1.1±1.2, p=0.001). From the safety point of view, patients showed a slight decrease in the average value of the number of neutrophils — from (3.1±1.4)×109 to (3.0±2.0)×109 and lymphocytes — from (1.8±0,9)×109 to (1.7±0.9)×109, as well as minimal multidirectional changes in the mean values of transaminase activity — alanine aminotransferase changed from 33.9±23.6 U/L to 34.9±47.5 U/L, aspartate aminotransferase — from 40.6±49.0 U/L to 38.5±25.5 U/L. In general, the results obtained within the experience of the clinical use of baricitinib in 113 Russian patients with COVID-19 are consistent with the available data from foreign clinical studies and confirm the efficacy and safety of baricitinib.
REVIEWS
The MCR-type polymyxin resistance gene localized on a mobile genetic element was described was described in 2015 for the first time. Publications, following the first description, demonstrated the global distribution of MCR-type genes and the role of animal husbandry in this process. At the same time, practical importance of polymyxins is growing, considering spread of genes of acquired resistance to carbapenem antibiotics. This review briefly summarizes the principal data on this issue.
The aim of the work was the search for materials from experimental and clinical studies reflecting the pathogenetic role of the possible use of succinates for the correction of hypoxia in COVID-19.
Materials and methods. 79 foreign and domestic literature sources were analyzed concerning the pathogenesis of COVID-19 and the pathogenetic role of succinates in hypoxia under conditions of COVID-19, oxidative stress, and diaphragmatic dysfunction were analyzed. The literature search was carried out using Pubmed and ELIBRARY.ru databases.
Results. As the analysis of the literature has shown, tissue hypoxia is the basis of COVID-19 pathogenesis, triggering the entire cascade of pathomorphological events leading to the development of multiple organ failure. A number of experimental and clinical studies (on a fairly large number of patients) reflect the positive effect of tissue hypoxia correction
using succinates, both in adult patients and in children with a different spectrum of pathology associated with acute respiratory failure syndrome.
Conclusion. Analysis of literature data allows to substantiate the prospect of using preparations containing succinate (reamberin, cytoflavin) in the complex therapy of severe cases of COVID-19.
ANNIVERSARY