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Antibiot Khimioter = Antibiotics and Chemotherapy

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Vol 67, No 11-12 (2022)
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EXPERIMENTAL STUDIES

4-9 323
Abstract

The aim  of the work was to study the biological activity  of modifiers and carbon  sorbent samples modified by them  in relation to some types of microorganisms.

Material and  methods. The carbon  sorbent under  study  and the modified samples were obtained at the Center of New Chemical Technologies BIC. Glycolic acid, lactic acid, glycine, and glutamic acid were used as modifiers. Strains of Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae 418, Esherichia coli ATCC 25922, Candida albicans (clinical strain) were used as test cultures. The test sample was placed in the wells of a sterile plate, then a working suspension of the test culture was added in the amount of 2.0 ml until completely wet 1:1. The survival of microorganisms was determined by quantitative inoculation from each well of the «sample — microorganism» mixture on Petri dishes with simple nutrient agar using the sector crop method (Gold). The culture species were confirmed by studying their cultural, morphological, and biochemical properties.

Results. The conducted studies have demonstrated high antibacterial and antimycotic activity of carbon  sorbent samples modified with hydroxyl acids  in relation to the most  common opportunistic pathogens of pyoinflammatory diseases of bacterial and fungal  nature  in comparison with the initial  sorbent sample. The carbon  sorbent modified with lactic  acid oligomer showed the highest antibacterial and antimycotic activity.

Conclusion. High antibacterial and antimycotic activity  of carbon  sorbent samples modified with hydroxy  acids  and amino acids in relation to the most common opportunistic pathogens of pyoinflammatory diseases of bacterial and fungal nature  was established in comparison with the initial  sample of the sorbent. The carbon  sorbent sample modified with amino acids has a pronounced antibacterial effect against all studied bacterial test strains, but exhibits weak antimycotic properties. The use of modified carbon  sorbents is a promising direction for the application therapy of pyoinflammatory infections.

10-15 321
Abstract

Сhikungunya  virus (CHIKV) is a member of the Flavivirus genus, Flaviviridae family. It belongs to the zoonotic arbovirus infections transmitted by mosquitoes of the genus Aedes. In humans, this flavivirus causes a disease known as Сhikungunya fever, etymologically related to yellow fever, dengue, West Nile, and Zika. There is no specific treatment for Сhikungunya fever, as there is no vaccine or preventive measures to date. A comparative analysis of the effectiveness of chemotherapy drugs, interferon inducers and two classes of interferon α-, β-, and γ-showed that interferon drugs effectively inhibit the reproduction of CHIKV in the Vero cell culture in a wide range of concentrations. Chemotherapy drugs Triazavirin® and Ingavirin®  did not affect the reproduction of CHIKV strain FN198/66 in Vero cell culture. Ribavirin® at a concentration of 100 µg/ml almost completely suppressed the reproduction of the CHIKV virus when the drug was introduced into the culture medium both before and after infection.

16-21 686
Abstract

Background. The spread of extensive drug-resistance among gram-negative bacteria calls for the search for antimicrobics with new mechanisms of actions.

The aim was to assess susceptibility of extensively drug-resistant K. pneumoniae strains to cefiderocol and other new inhibitor-protected β-lactams, and to determine genetic mechanisms of antibiotic resistance.

Methods. This study included 30 extensively drug-resistant K. pneumoniae strains collected in 2016–2021 from 4 regions of Belarus. Carbapenemase genes were detected by real-time PCR. Minimum inhibitory concentrations (MICs) for cefiderocol and other new antibiotics were assessed by microdilution method using the Sensititre system. Whole genome sequencing was performed for 2 resistant and 3 cefiderocol-susceptible strains. Genome assemblies and annotation were performed using UGENE v. 37.0 software. Nucleotide sequences were translated using CLC  Sequence Viewer v. 8.0 (QIAGEN) package. The PROVEAN software was used to assess amino asides substitutions and their influence on the functional activity of proteins.

Results. KPC carbapenemase-producers were 4 strains, OXA-48 — 17, KPC+OXA-48 — 1, NDM — 7, OXA-48 + NDM — 1. All KPC-producers were susceptible to imipenem/relebactam and meropenem/vaborbactam. Resistance to ceftazidime-avibactam was noted in all NDM  producers and OXA-48+NDM  co-producer. The study has identified 9 cefiderocol-resistant strains. These were NDM and OXA-48-producers isolated from hospitalized patients with COVID-19 infection from 3 regions of Belarus. Resistant strains had functionally significant nonsynonymous  substitutions in the genes of TonB-dependent receptors for catecholate siderophores FepA (F472V, P64S) and Fiu (T92S).

Conclusion. The study has shown high efficacy of new inhibitor-protected carbapenems and cephalosporins against certain types of carbapenemase-producers. Strains with mutational resistance to cefiderocol, an antibiotic not previously used in Belarus, have been identified.

22-28 439
Abstract

The basis for conducting bioequivalence studies is the determination of the bioavailability of the active substance of the drug at its place of action by establishing the concentration of the drug in biological fluids using sensitive analytical techniques. The bioanalytical technique used should provide reliable results which would lead to satisfactory level of interpretation. To investigate the bioequivalence of rivastigmine preparations, an 8 times more sensitive method (compared to the data in the available literature) for the quantitative determination of rivastigmine in human blood plasma by HPLC-MS/MS was developed. Rivastigmine is extracted from plasma by precipitation of plasma proteins with acetonitrile. Chromatographic separation of rivastigmine and the internal standard was carried out on a YMC  Triart C18. 50×2.0 mm (1.9 µm) column in a gradient elution mode with a flow rate of 0.5 ml/min. A 0.1% solution of ammonium  hydroxide and acetonitrile were used as mobile phases. The lower limit of the quantitative determination of the method was 25 pg/ml.

29-35 441
Abstract

The wide prevalence of inflammatory vaginal diseases in women of different ages, a significant deterioration in the quality of life due to their presence, as well as an adverse effect on conception and the course of pregnancy make the search for more efficient and safe therapy of vaginitis an urgent issue. The article presents the results of experimental staphylococcal vaginitis treatment with probiotics and autoprobiotics in rat models, including hormonized animals after ovariectomy. The effectiveness of topical application of the probiotic strain E. faecium L3 in rats has been confirmed. The probiotic proved to be effective both in rats with a hormonized cycle and in rats with preserved ovaries. Among the tested autoprobiotic and homologous (rat) strains, the elimination of staphylococci occurred faster after the introduction of bifidobacterial. However, lactobacilli are more reliable in protection against the recurrence of infection. At the same time, homologous strains of both lactobacilli and bifidobacteria contribute to faster elimination of the pathogen compared to autostamps.

GUIDELINES FOR PRACTITIONERS

36-45 909
Abstract

Background. The difficulties of antibacterial therapy of infections caused by carbapenemase-producing  gram-negative bacteria are associated with limited options for adequate therapy since, in addition to resistance to carbapenems and other beta-lactams, these microorganisms are often characterized by associated resistance to other classes of antibiotics, including polymyxins. In vitro data support the idea of combined use of inhibitor-protected cephalosporins with aztreonam for the treatment of such infections. The aim of the study was to investigate the effectiveness of cefepime/sulbactam (FEP/SB) in combination with aztreonam (ATM) in infections caused by class B and D carbapenemase producers.

Methods. A prospective observational study evaluated the effectiveness of the combination of FEP/SB + ATM in ICU patients with nosocomial infections complicated by sepsis or septic shock caused by carbapenem-resistant pathogens with documented production of class B or D carbapenemase. The ineffectiveness of previous treatment and the absence of other options for adequate therapy were used as inclusion criteria. Microbiological, clinical efficacy, and 30-day mortality were indicators of therapy evaluation.

Results. The study included 25 patients with nosocomial infection (76% of them was VAP), with sepsis (60%) or septic shock (40%) and an average SOFA score of 6 points caused by Klebsiella pneumoniae (23 patients) or Pseudomonas aeruginosa (2) producing carbapenemases OXA-48 (56%), NDM (20%), NDM + OXA-48 (16%), and class B carbapenemase in two strains of P. aeruginosa. The average daily dose of FEP/SB and ATM was 6.6 g, the duration of therapy was 9.9 days. As a result of the treatment, eradication was achieved in 68% of patients, clinical efficacy was 72%, and the 30-day mortality rate was 28%.

Conclusion. Our results show good clinical and bacteriological efficacy of the combination of FEP/SB and ATM in infections caused by extremely resistant K. pneumoniae, non-susceptible to carbapenems and producing class B or D carbapenemase.

46-50 276
Abstract

The aim of the work was to study the effectiveness of remaxol inclusion in treatment regimens designed for patients with comorbid tuberculosis and hepatotoxic response to etiotropic therapy.

Materials and Methods. Case histories of 25 patients (21 men and 4 women) with a confirmed diagnosis of tuberculosis infection and hepatotoxic reactions to etiotropic treatment were analyzed. Of these, 9 patients had a comorbid (TB/HIV) pathology and 16 patients had TB/HIV with concomitant diseases. To stop the signs of hepatotoxicity, all patients were prescribed with remaxol: 400 ml intravenously on alternate days (course No. 5), then 1 time per week (course No. 4). In addition to the standard clinical and laboratory examination, all patients underwent follow-up (before and after the course of remaxol) examination of the levels of aspartate aminotransferase and total bilirubin in the blood, as well as the levels of interleukin production (1β, 4, 6 and 10) and tumor necrosis factors (TNF-α and TNF-γ). Standard regimens were used when conducting anti-tuberculosis chemotherapy.

Results. It was noted that the presence of a comorbidity aggravates the course of tuberculosis and reduces the effectiveness of etiotropic therapy due to the development of hepatotoxicity. The inclusion of remaxol contributed to a decrease in the severity of hepatotoxic reactions and made it possible to avoid the correction of the main treatment course. The revealed positive dynamic in cytokine profile indicators can be regarded as a mediated immunological effect of the drug and requires further research.

REVIEWS

51-55 366
Abstract

The article discusses the issues of terminology, epidemiology, etiopathogenesis, clinical manifestations, approaches to the diagnosis and treatment of post-covid syndrome (PCS). It has been shown that the incidence of PCS in people who had COVID-19 is 10–35%; there are no generally accepted approaches to defining the term PCS. Clinical manifestations of PCS include more than 50 symptoms that occur in both children and adults, regardless of their place of residence. The damage caused by metabolites of the systemic inflammatory response of the central nervous system with the formation of a syndrome of autonomic dysfunction,  cognitive  impairment,  and affective disorders is of critical importance  in the genesis of PCS.  Antipsychotics, antidepressants, and benzodiazepine drugs are used in the correction of PCS. However, they have limitations, in particular — when used in children with comorbid disorders. The use of aminoacetic acid (glycine), which has a wide range of safety,anxiolytic, anti-inflammatory, and nootropic effects in the correction of PCS, can become an effective therapeutic strategy.

56-63 472
Abstract

Healthcare-associated infections (HAIs) are a global medical and socioeconomic problem. Nosocomial infections occupy one of the leading places among the causes of death in the Russian Federation. About 60–70% of all nosocomial infections are associated with the use of medical implants of various profiles. Pseudomonas aeruginosa, various types of streptococci, staphylococci, Escherichia coli, enterococci (Enterococcus faecalis), Klebsiella pneumoniae, Proteus mirabilis, and representatives of the genus Acinetobacter are highly  likely to be found  in biofilms of medical supplies. A distinctive feature of microbes that cause  HAIs is poly- or even  pan-resistance of microbes to recommended antimicrobials. The search  for methods and means to overcome is a priority task of modern medicine. Phage therapy seems to be one of the logical and promising ways to combat bacteria that are resistant to conventional therapy. The article outlines the advantages and disadvantages of phage therapy, provides an overview of the successful use of mono- and combined preparations of bacteriophages in the experiment and clinic, as well as modern directions for the use of bacteriophages not only for therapeutic, but also for prophylactic purposes, based on the latest achievements of genetic engineering and biotechnology.

64-78 344
Abstract

Over the past two years, the SARS-CoV-2 pandemic has dominated all aspects of health care around the world, often leaving other long-term public health problems in the background. Despite the fact that COVID-19 is a viral disease, the use of antibiotics in these patients was common practice, especially at the beginning of the pandemic. The use of antibiotics (ABs) in patients with the novel coronavirus infection (NCI) reaches over 70% cases. Suspected concomitant bacterial infection, lack of effective means of treating NCI, terminological problems associated with the definition of «pneumonia» may have been the motivating factor for such widespread use. The data of the conducted studies indicate that there is currently insufficient evidence for the widespread empirical use of antibiotics in the majority of hospitalized patients, as the total proportion of bacterial infections in COVID-19 is quite low. Thus, according to most researchers, combined bacterial infection is rare and is less than 10%. Unjustified prescription of ABs to patients with COVID-19 can lead to complications that could otherwise have been avoided, including increased bacterial resistance, Clostridioides dicile infection, kidney failure, and much more. The article provides information on the frequency of AB therapy at various stages of medical care. The analysis of data on the nature of antibiotics prescribed to inpatients and outpatients with COVID-19 in different countries was carried out. Recommendations from different countries on AB therapy in patients with COVID-19 are presented. Conclusion. The data reviewed confirm the discrepancy between the unjustified and excessive prescribing of antibiotics to patients with COVID-19 and the small number of evidence of associated bacterial infections.

79-90 1504
Abstract

Aminoglycosides are broad-spectrum antibacterial agents used  in the treatment of urinary  tract infections, tuberculosis, visceral leishmaniasis, sepsis in newborns, as well as cystic fibrosis. However, the use of aminoglycosides is limited due to their ototoxicity — the risk of developing serious adverse  reactions, in particular, persistent irreversible hearing loss and vestibular disorders associated with the death of hair cells in the inner ear. The review analyzes scientific data on the possible mechanisms of aminoglycosides’ damaging effect  on the hair cells  of the inner  ear. Genetically determined causes contributing to the manifestation of ototoxic properties of drugs of this group are described. The necessity of genetic screening for the carriage  of mutations m.1555A>G  and m.1494C>T in the MT-RNR1 gene  of mitochondrial DNA is substantiated in order to minimize the risk of hearing disorders in patients with hereditary predisposition. Understanding the mechanisms of ototoxicity of aminoglycosides will make it possible to find ways to prevent and correct hearing loss after their use.



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ISSN 0235-2990 (Print)