Showing papers in "Kliničeskaâ mikrobiologiâ i antimikrobnaâ himioterapiâ in 2023"

AMRexpert – online platform for interpretation, verification and validation of antimicrobial susceptibility testing

Abstract: Objective. To review the key principles and functionality of AMRexpert online platform. Materials and Methods. The information part of the platform is comprised of rules based on the EUCAST recommendations and various standards for interpreting the results of antimicrobial susceptibility testing (EUCAST, CLSI versions 2020-2022). The technical part of the platform was developed using C# programming language, Angular and Bootstrap frameworks. AST results of Serratia marcescens, Pseudomonas aeruginosa, Staphylococcus saprophyticus, Enterococcus faecium specific isolates were analyzed for practical testing of the platform using EUCAST v.12.0, 2022 interpretation criteria. Results. The developed platform for the evaluation of microbiological reports includes a wide list of expert rules, various standards for the interpretation of the AST results. Consistent data input, the ability to switch forms between several microorganisms, and the presentation of evaluation results in the form of blocks allows all necessary information to be structured. Practical use of the platform is available for various infectious pathogens. Fast and efficient interaction between users is provided by different options for sharing and saving the results. Conclusions. The web-based application evaluates microbiological reports in a comprehensive approach, with the ability to apply the results later to prescribe antimicrobial therapy. The platform for the interpretation, verification and validation of the AST results – AMRexpert can be accessed at https://amrexpert.ru.

Infective endocarditis caused by Klebsiella pneumoniae in a patient with non ST elevation myocardial infarction

Abstract: A rare clinical case of native aortic valve infective endocarditis (IE) caused by Klebsiella pneumoniae in a 56-year old man without known risk factors predisposing to the development of IE is presented. Diagnosis of IE in this patient was a challenge due to the lack of recent interventions that could be considered as a source of bacteremia, scarce clinical manifestation and absence of typical complications. Aortic valve vegetation was detected by transesophageal echocardiography. K. pneumoniae isolate was susceptible to all antibiotics tested. Antibacterial therapy (cefepime 6 g/day IV for 2 weeks in the hospital followed by ceftriaxone 4 g/day IM and cefixime 400 mg/day PO, a total of 4 weeks as an outpatient) resulted in a complete resolution of IE signs and symptoms, laboratory abnormalities as well as vegetation size decrease. Surgical treatment was not required in this patient.

Adverse drug reactions of macrolide therapy: analysis of spontaneous reports according to the Pharmacovigilance system

Abstract: Objective. To perform pharmacoepidemiological analysis of spontaneous reports of adverse drug reactions (ADRs) occurred during macrolide group antibiotics prescription and registered in the “Pharmacovigilance 2.0” subsystem of the Federal Service for Surveillance in Healthcare. Materials and Methods. A retrospective pharmacoepidemiological analysis of spontaneous reports of ADRs arising from the use of all macrolide and azalide antibiotics registered in Russia and registered in the electronic database of the “Pharmacovigilance 2.0” subsystem of the Federal Service for Surveillance in Healthcare for the period from 01.04.2019 to 30.11.2022 was performed. Results. Analysis of the number of spontaneous reports of ADRs, their structure, outcomes and severity criteria was performed. The most clinically significant ADRs were identified, the occurrence of which was reported to pharmacovigilance bodies. The results of a retrospective pharmacoepidemiological analysis showed that the development of complications of pharmacotherapy in most cases was associated with the use of azithromycin and clarithromycin. The main clinical manifestations of adverse drug reactions were skin and subcutaneous tissue disorders, gastrointestinal disorders, as well as general disorders and injection site reactions. Conclusions. It was found that the reported events generally corresponded to the general spectrum of ADRs typical for individual representatives of macrolide and azalide antibiotics.

Report of the Russian database on adverse drug reactions for COVID-19-related drugs with a focus on favipiravir

Abstract: Objective. The purpose of this study is to systematize and comprehensively evaluate safety data on the drug favipiravir using the national pharmacovigilance database of the Russian Federation. Materials and Methods. The report is based on spontaneous reports in the national automated information system of pharmacovigilance of the Russian Federation for the reporting period from 01.01.2020 – 04.07.2022. To identify safety signals we used disproportionality analysis, to estimate consumption of favipiravir – indicator of the number of consumed DDDs, we additionally performed review of concomitant therapy as a risk factor for serious adverse reactions. Results. A total of 412 reports of 585 adverse reactions was included in the analytic phase. The largest number of reports referred to liver and biliary tract disorders – 166 (38%), gastrointestinal disorders – 93 (16%), changes in laboratory and instrumental data – 53 (9%), and immune system disorders – 44 (7%). A total consumption of oral favipiravir expressed in the number of maintenance daily doses for 2021 was 46,417,274.87, i.e. 30 times the consumption of remdesivir and 6 times the consumption of hydroxychloroquine. One potential statistical safety signal such as hypercreatininemia was identified. Conclusions. Development of hypercreatininemia is a potential statistical safety signal of favipiravir, which requires further validation.

Anti-staphylococcal activity and cytocompatibility of lysostaphin

Abstract: Objective. To study the antibacterial activity of lysostaphin against staphylococci various species, as well as its effect on the viability of Vero cells. Materials and Methods. Lysostaphin was obtained by genetic engineering. Purification of the protein was carried out on SP-sepharose, the purity was determined by electrophoresis in PAGE by Lamley. The susceptibility to lysostaphin of 9 species 175 strains of staphylococci was studied. Identification was performed by MALDI-TOF MS, antibiotic susceptibility by EUCAST (v. 11.0). The MIC of lysostaphin was studied by the method of serial dilutions with concentrations between 0.015 and 512 mg/l. For 72 hours, the viability of Vero cells with lysostaphin at concentrations of 0.5-32.0 mg/l was determined by the MTT method with counting of living cells according to their growth curve. The results were analyzed by ANOVA followed by Dunnett’s test. Results. A kinetic study of S. aureus growth in the presence of revealed an inhibitory effect of endopeptidase (MIC 0.06 mg/l). Lysostaphin was characterized by pronounced activity against clinical methicillinsensitive S. aureus. The MIC ranged between 0.03 and 0.5 mg/l and the MIC50/90 was 0.125⁄0.5 mg/l. For methicillin-resistant S. aureus MIC50/90 0.25⁄0.5 mg/l. The MIC50 for MRSE was 2 times higher than for MSSE – 1 mg/l. The maximum MIC value was determined against isolates of S. warneri and S. hominis – 64 mg/l, the lowest for S. saprophyticus – 0.5 mg/l. MIC50 of lysostaphin against MRSA was 4 times lower than that of vancomycin, MIC90 was 3 times lower. Differences in viable cells depending on the concentration of lysostaphin were not found. Conclusions. Significant activity of lysostaphin against staphylococci was revealed, which is several times higher than vancomycin against MRSA. Lysostaphin was also effective against methicillin-resistant S. aureus. The high anti-staphylococcal activity and cytocompatibility of lysostaphin are promising for its further study in the prevention and treatment of staphylococcal orthopedic infections.

Patterns of antimicrobial dispensing in community pharmacies in Russia during the COVID-19 pandemic

Abstract: Objective. To evaluate the existing patterns of antimicrobials dispensing in community pharmacies during the COVID-19 pandemic. Materials and Methods. In a cross-sectional study conducted from October 2020 to January 2021 it was obtained the data on the major antimicrobials dispensing in community pharmacies in Moscow and four regions of Russian Federation: date of release, customer’s age and gender, drug name and formulation, the reason for the release (symptoms, preliminary or confirmed diagnosis), prescription-based supply or not/emergency releasing. Results. The study included 71 pharmacies, including 41 private and 30 public organizations. During the mentioned period of time 5514 antimicrobials were supplied to 5270 customers. Antibiotics and antiviral drugs for systemic use accounted the largest share in the structure of purchased antimicrobials (60.5% and 26.3% of all sales, respectively). The frequency of non-prescription-based supplies was 28.5%. The greatest demand among antibiotics was registered for macrolides (14.9%), combinations of penicillins with beta-lactamase inhibitors (12.3%) and fluoroquinolones (11.4%). Upper respiratory tract infections were the most frequent reason for antimicrobials releasing – 36,9%. COVID-19 was the reason for 8.4% of antimicrobials sales. Azithromycin and umifenovir were the most frequently used drugs for SARS-CoV-2. Conclusions. Antibiotics for systemic use have still remained the commonly used ones, whereas upper respiratory tract infections are the main indication for their purchase. Nearly a third of antimicrobials, including systemic antibiotics, were dispensed in private pharmacies without prescription. COVID-19 is uncommon cause of outpatient antimicrobial sales, but a common reason for systemic antibiotic prescribing.

Current approaches and prospects for the development of laboratory diagnosis of measles

Abstract: Measles virus causes an acute infectious disease with high contagiousness. It is possible to limit the spread of measles virus only with a sufficiently wide coverage of the population by vaccination. Despite the success of measles elimination programs, many countries have seen an increase in the incidence of measles in recent years, making early diagnosis increasingly important. The importance of laboratory diagnosis is related to the difficulties of clinical differential diagnosis of measles in the early stages of the disease. This review is devoted to an analysis of existing methods for diagnosing measles. It demonstrates the limitations of the most commonly used method, the enzyme immunoassay, and the need to develop and implement alternative diagnostic methods. Particular attention in the review is paid to molecular diagnostic methods, the sensitivity of which is reviewed for different types of biological sampled at different stages of the disease. Characteristics of the measles virus that are of key importance in the development of PCR tests are described. Studies evaluating the significance of introducing PCR in the routine diagnosis of measles are presented. The main advantages of molecular methods are the possibility of early detection of the virus and the possibility of simultaneous detection of several pathogens, which allows differential diagnosis of diseases with a similar clinical presentation. The development and implementation of rapid and accurate approaches based on molecular diagnostic methods into the health care system is an urgent need in the implementation of global and local programs for the elimination of measles.

Pulmonary aspergilloma after previous COVID-19: a case report and a literature review

Abstract: Pulmonary aspergillosis has always been considered as a disease that occurs in patients with certain risk factors for its development. The COVID-19 pandemic has shown that fungal complications are common in patients without aspergillosis risk factors. Thus, invasive aspergillosis is a common complication of COVID-19. There are rare reports of aspergilloma that developed after a severe coronavirus infection in individuals who did not previously have cavitary lesions in the lungs. Development of aspergilloma as an expected long-term complication after COVID-19 may be due to damage of lung structure caused by coronavirus infection, oxygen therapy and mechanical ventilation. This article describes a case report of aspergilloma in a patient with confirmed severe COVID-19 and background chronic diseases without risk factors for fungal infection. A review of publications on the development of aspergilloma in patients following COVID-19 is also presented.

Fusobacterium nucleatum: from a classic periodontal pathogen to a complete participant of carcinogenesis

Abstract: Fusobacterium nucleatum is a component of the oral microflora, and in clinical practice it is associated primarily with periodontal diseases. Since 2011, the scientific community has confirmed the association of F. nucleatum with colorectal cancer (CRC) by seeding it from tumor tissue samples. Research has led to the discovery of mechanisms by which this bacterium may contribute to the development, metastasis of CRC and chemoresistance. With the help of its adhesion proteins (FadA and Fap2) F. nucleatum specifically attaches to colorectal carcinoma cells. Following invasion, F. nucleatum induces inflammation, activates β-catenin signaling, and creates a favorable microenvironment for tumor growth and development. Recently, the role of F. nucleatum in other types of oncological pathology, such as oral cavity cancer, head and neck cancer, gastric cancer, esophageal cancer, pancreatic cancer, cervical cancer and breast cancer, has been confirmed. Understanding the mechanisms of association of F. nucleatum with oncological diseases will help to find new approaches in the treatment, prevention and diagnosis of cancer. Thus, further studies of the correlation between F. nucleatum and carcinogenesis are needed, using a multidisciplinary approach and physicians from other specialties.

COVID-19 risk factors for mortality in hospitalized patients: results of a retrospective study

Abstract: Objective. To identify risk factors for fatal outcome and COVID-19-associated liver damage in hospitalized adult patients with coronavirus infection. Materials and Methods. In a retrospective cohort study, 389 cases of patients with coronavirus infection complicated by bilateral viral pneumonia were studied. Demographic characteristics, clinical features of the course of the disease, anamnestic data, results of laboratory and instrumental methods of examination were analyzed and correlated with mortality. At the time of admission, the following were taken into account: fever, severity of the patient’s condition according to COVID-19 classification of severity, body mass index (BMI), oxygen saturation (SpO2), percentage of lung tissue damage according to computed tomography (CT). Laboratory indices of biochemical blood analysis were assessed in dynamics: alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, total protein, albumin, C-reactive protein (CRP). Data analysis was performed using the R programming language (ver. 4.1.1.). Results. The following risk factors, assessed at the time of hospitalization, increased the likelihood of death: severe and extremely severe condition of the patient (RR = 4.77; 95% CI: 3.33–6.83); SpO2 less than 93% (RR = 3.76; 95% CI: 2.57–5.49); diabetes mellitus (RR = 2.94; 95% CI: 2.01–4.30); lung tissue damage CT-3 and CT-4 (RR = 2.66; 95% CI: 1.79–3.75); concomitant chronic pyelonephritis and chronic kidney disease (CKD) (RR = 2.59; 95% CI: 1.79–3.74); age 65 years and older (RR = 2.50; 95% CI: 1.70–3.67); ischemic heart disease (IHD) (RR = 2.39; 95% CI: 1.42–4.01); an increase in the level of CRP more than 15 mg/l (RR = 2.22; 95% CI: 1.16–4.24); BMI 35 kg/m2 or more (RR = 1.89; 95% CI: 1.28–2.77); AST level more than 2 upper limit of normal (ULN) (RR = 1.75; 95% CI: 1.20–2.55). Risk factors for an increase in AST more than 2 ULN were: SpO2 less than 93% (RR = 1.53; 95% CI: 1.15– 2.03), severe and extremely severe course of coronavirus infection (RR = 1.83; 95% CI: 1.38–2.43), concomitant chronic liver disease (RR = 1.45, 95% CI: 1.08–1.95). Conclusions. Risk factors for fatal COVID-19 in hospitalized patients are: severe and extremely severe initial condition of the patient, oxygen saturation less than 93%, lung tissue damage more than 50%, age older than 65 years, presence of concomitant diabetes mellitus, chronic pyelonephritis and CHD, CHD, obesity, increased CRP level more than 15 mg/l, and AST more than 70 units/l. Elevation of AST over 2 IU/L can be considered as one of the prognostic laboratory markers of adverse prognosis COVID-19.

Prospects for the use of statins in antiviral therapy

Abstract: Inhibitors of hydroxymethylglutaryl-CoA reductase, in addition to suppressing cholesterol synthesis, have an antiviral effect. Clinical studies have shown antiviral efficacy of statins against COVID-19, HCV, HBV, RSV, HIV, influenza viruses. The ability of statins to inhibit influenza viruses, COVID-19, RSV, HIV, as well as Ebola, Zika, Dengue, Coxsackie, rotaviruses, ADV, HDV, HHV was experimentally confirmed. Statins can also enhance the effects of antiviral drugs, making them more effective in treating infections. Therefore, the use of statins in the complex therapy of viral infections is promising. In addition, the role of influenza viruses, T-cell leukemia and herpesviruses, HIV, HBV, HCV, HPV in the development of atherosclerosis has been identified, so the use of statins in complex treatment is also necessary to correct endothelial dysfunction that occurs under the influence of viruses. Since the activity of retroelements that are evolutionarily related to exogenous viruses increases with aging, it has been suggested that retrotransposons can also be targets for statins. This is evidenced by a change in the expression of non-coding RNAs under the action of statins, since the key sources of non-coding RNAs are retroelements. This property may be an additional factor in the prescription of statins to increase life expectancy, in addition to the prevention and treatment of atherosclerosis, since pathological activation of retroelements are the causes of aging. Viruses, like retroelements, are involved in the pathogenesis of malignant neoplasms, in the treatment of which statins have shown their effectiveness and the ability to enhance the effect of anticancer drugs, overcoming chemoresistance (similar to the potentiation of antiviral drugs). One of the mechanisms of this activity of statins may be their effect on retroelements and viruses.

The known-unknown: third- and fourth-generation cephalosporins combined with sulbactam

Abstract: Despite the presence of more than 100 different antibacterials in the therapeutic arsenal, beta-lactam antibiotics, in general, and the third-generation cephalosporins, in particular, remain the main option for the treatment of the most of infections in inpatients. At the same time, the widespread and oftentimes inappropriate use of the third-generation cephalosporins in Russian hospitals lead to the emergence and spread of antimicroabial resistance. The review covers the problems of antibiotic resistance to cephalosporins due to the production of beta-lactamases, the role of beta-lactamase inhibitors in overcoming this type of resistance, options for combinations of cephalosporins with beta-lactamase inhibitors, in vitro activity of cefotaxime/sulbactam and cefepime/sulbactam, the results of clinical studies, and the role of the above combinations in the treatment of infections in the hospital.

Aztreonam: clinical and pharmacological characteristics at the present stage

Abstract: One of the urgent problems of modern health care is the growing resistance of microorganisms to antibiotics, including carbapenems, which until recently were considered as the drugs of choice in the treatment of life-threatening infections. Enzymatic inactivation of antibiotics, including through the production of carbapenemase, is the main mechanism of resistance in Gram-negative bacteria. The treatment of these infections presents significant difficulties due to the extremely limited arsenal of effective drugs. Aztreonam is currently the first and only monocyclic beta-lactam antibiotic, monobactam, which is used in clinical practice for the treatment of infections caused by gram-negative bacteria. The data obtained in vitro and clinical observations are presented. These results justify the use of the drug in infections caused by a number of «problem» Gram-negative pathogens, including those resistant to carbapenems. Aztreonam has a high potential and should be used to treat patients with nosocomial infections – the focus of its use is Gram-negative bacteria-producers of metallo-beta-lactamases.