Antibiotiki i Khimioterapiya最新文献

The effects of extracts from the mycelium of Lecanicilium lecaniiNo.169, Beauveria fellina No.7 and Beauveria bassianaNo.15 on the activity of 15-lpoxygenase (15-LO) recovered from rat reticulocytes was investigated. The activity of 15-LO was determined by oxidation of linolic acid. The extract from the mycelium of the fungal complex was shown to inhibit 15-LO (IC50 of 12 mcg/ml). The inhibitory effect of the combined extract on 15-LO was due to the substances recovered from Lecanicilium lecanii No.169. The extract fractions responsible for the activity were determined and the compounds containing the fractions were identified. They proved to be 10 - 4-hydroxybenzoic acid and 4-hydroxybenzyl alcohol and genistein, a flavonoid from fraction 11. The possible role of the inhibitory effect of the compounds on 15-LO in the antiatherosclerotic activity of the fungal extract is discussed.

Klebsiellapneumoniae is a significant pathogen associated with hospital infections. Its was isolated in intensive care units (ICU) at two pediatric hospitals in Moscow in 2012-2014 from 41% (387/935) of the patients. The rate of carbapenem-nonsusceptibility (Carba-NS) amounted to 25% for imipenem and 27% for meropenem. For further analyses, 67 isolates were selected, including 57 Carba-NS and 10 Carba-susceptible (Carba-S). Among the isolates, 100% was nonsusceptible to the III-IV generation cephalosporins, 50-84% was resistant to aminoglycosides. The rate of nonsusceptibility to ciprofloxacin and phosphomycin exceeded 90%. All the tested Carba-S Kpneumoniae isolates were susceptible to tigecycline, whereas 25% of the Carba-NS isolates was tigecycline-NS. The prevalence of the colistin-NS isolates was the same in Carba-S (20%) and Carba-NS (26%) bacteria. The blamrx_ gene was carried by 100% of the Carba-S isolates, combining with the blaTEM gene in 60% of the isolates. In 89% of the Carba-NS isolates the OXA-48 carbapenemase was detected, which was combined with CTX-M and/or TEM in all but 1 isolate. Thus, over the last decade, the rate of Carba-NS among nosocomial Kpneuynoniae increased and the OXA-48 carbapenemase was shown to be dominating in the mechanism of Carba-NS in the pediatric ICUs in Moscow.

To establish the relationships between the enrichment of resistant Staphylococcus aureus mutants and the ratio of daily area under the concentration - time curve (AUC24) to the MIC of linezolid, a mixed inoculum of linezolid-susceptible and -resistant cells of three strains of S.aureus was exposed to twice daily linezolid in an in vitro dynamic model. Simulated pharmacokinetic profiles mimicked five-day treatments with linezolid dosing over a 32-fold range of the AUC24/MIC ratio. Population analysis of linezolid-exposed staphylococci was performed daily over 120 h after the start of the treatments. Minor if any enrichment of mutants resistant to 2X, 4X and 8XMIC of antibiotic was observed at the lowest and the highest AUC24/MIC ratios in contrast to pro- nounced enrichment of resistant mutants at the intermediate AUC24/MICs. An integral parameter AUBCm, the area under the time course of resistance mutants, was shown to be a more appropriate endpoint to establish AUC24/MIC relationships with resistance than postexposure number of mutants (NM).

Ceftaroline is a unique cephalosporin with activity against methicillin resistant Staphylococcus aureus (MRSA). It was approved for clinical use in the USA, Europe and Russian Federation since 2010 for the treatment of the skin and soft tissue infection and community-acquired pneumoniae. In the present study there was used molecular typing of 24 isolates of MRSA with reduced susceptibility to ceftaroline. For 8 isolates belonging to different genetic lines (ST8, ST239 and ST228) and requiring MICs there were determined antibiotic concentrations preventing formation of resistant mutants (mutant prevention concentration) and the ranges of the mutant selection window (MSW). The last majority of the isolates with reduced susceptibility to ceftaroline (MIC of 2 mcg/ml) belonged to the clonal line ST228. The whole genome sequencing of two isolates of ST228 showed that they belonged to the epidemic South Germany genetic line and were characterized by the presence of mutations in PBP2a (N146K) and PBP2 (C197Y) responsible for reduced susceptibility. The highest rates of MPC (32 mcg/ml) and MSW (2-16 mcg/ml) were observed in the clinical isolates belonging to the genetic line ST8. The isolates of ST239 and ST228 had the selection window within 2-4 mcg/ml. No dependence of the MIC and MPC/MSW levels was detected.

Under the conditions of emergence of microbial strains with new properties, including antibiotic resistance, in human and animal populations the search for new antimicrobial substances with improved pharmacological properties and new mechanisms of action from natural objects, in particular from aquatic organisms, is continued. This review presents extensive data on antibacterial, antiviral and antifungal properties of biologically active substances (BAS) of different chemical nature, recovered from representatives of the class of cephalopods (squid, octopus, cuttlefish, nautilus). Analysis of the literature shows that antibacterial activity of some BAS is not inferior, but in some cases is even superior to that of the available antibiotics. The authors note that the review includes the results, mainly of the in vitro studies. Adequate extrapolation of these data to the in vivo conditions is required, that could serve as foundation for development of new generations of medicinal compounds, functional foods and biologically active food supplements.

Pneumococcal pneumonia and other diseases caused by pneumococci still remain the main factors of high morbidity and mortality rates throughout the world. Pneumococci as the leading pathogens of community-acquired pneumonia (CAP), acute otitis media and sinusitis also cause a number of other serious systemic disorders including invasive infections with high mortality in spite of the antimicrobial resistance status and adequate antimicrobials choice. Pneumococcal infections are responsible for 5-35% or more of community-acquired pneumonias. The burden of pneumonia (up to 100-200 per thousand) is recorded among military recruits in training centers. Since the specific environment of the soldiers could be carrected, their health protection requires medical surveillance. For these reasons, polysaccharide and more immunogenic conjugated pneumococcal vaccines were developed. There is now an urgent need to understand whether such vaccines are effective in military conscripts. Controversy about the effectiveness and value of the polysaccharide (PPV-23) vaccine as a CAP morbidity restriction measure still persists. There were implemented plenty of metaanalyses of pneumococcal vaccines in adults. Some of them showed that the vaccine was effective against bacteremic pneumococcal pneumonia in 'low risk' healthy adults and elders. There have been a number of poor quality observational studies in Russia where 'all pneumonia cases' were considered as an endpoint. It remains controversial whether these observational studies provide adequate evidence to justify the use of the polysaccharide vaccine in the groups of healthy young men for whom it is being advocated. In our analysis we found weak evidence supporting pneumococcal vaccination with PPV-23 for this group. Nevertheless, favorable tendency was found to immunize. It is the reason for a trail to find pharmacoepidemiological support for vaccination by novel conjugated vaccines with better immunogenicity.

The review includes the analysis of plague incidence throughout the world, in Russia and neighboring countries within the last 25-30 years, as well as the current state of the problem. The historical development of antibacterial therapy, experimental data and clinical observations are presented. The phenomenon of emergence of antibiotic resistance is described along with proposed ways of its prevention. The urgency of the problem nowadays is shown in regard to migration events and bioterrorism threat. Further perspectives are outlined for scientific approaches to solution of the problems of antibacterial therapy of plague infection.

Thionins (NsW1 and NsW2), earlier isolated from the seeds of endemic Middle-Asian black cumin (Aligella sativa L.), showing signilicant inhibitory action on some bacterial and yeast pathogens were investigated for cytotoxic properties against several tumor cell lines (AsPC-1, Colo357, RD and Jukart) in vitro within nano- and micromolar ranges of the active concentrations and as modulators of expression of the genes controlling conversion of normal cells to malignant ones. Suppression of the expression of the genes from MMP, RhoA, miR21 families in human rhabdomyosarcoma (RD) cells was observed, whereas the influence of the molecules on the genes in normal blood cells was not identified. It was shown that the thionins from black cumin induced almost 90% of the cell death in RD and Jukart lines. Moreover, the polypeptides inhibited clinical isolates of Aspergillus ochraceus and A.fimigatus at the level comparable with that of amphotericin B. The data demonstrated that the peptides could be considered as perspective antitumor and antimycotic agents.

In patients under artificial lung ventilation (ALV) there is often observed development of severe ventilator-associated pneumonia (VAP) due to polyresistant hospital pathogens. It should be noted that in the patient described here with the initial diagnosis of community-acquired pneumonia rapidly subjected to prolonged ALV the previous antibacterial therapy by broad spectrum drugs significantly increased the risk of contamination just by multiresistant nosocomial strains, which hampered the starting therapy of nosocomial pneumonia either when there were not available or sometimes there were available microbial cultures. When the treatment of severe pneumonias caused by multiresistant hospital flora resistant to carbapenems is actual, in the alternative therapy it could be used tigecycline, a tetracycline from the group of glycylcyclines. A case of successful treatment of nosocomial VAP by tigecycline based on the results of the bronchoalveolar lavage (BAL) culture is described. The case is of interest because tigecycline was used as off label.

Reliable inhibition of an infectious agent in the wound is an integral part of the therapeutic measures for the diabetic foot syndrome. Because of low immunity in patients with diabetes the use of antibiotics should be based not only on the'systemic but also local signs of the infection. Unfortunately, the antibiotic therapy does not always provide adequate inhibition of the pathogens. Investigation of the microbial landscape of the wound surface and susceptibility of the pathogens to antibiotics in patients with the diabetic foot syndrome showed that the main pathogens were Staphylococcus aureus, Enterococcus faecalis, Enterobacter cloacae and the Acinetobacter baumannii complex. A detailed analysis of the microbiological tests in a particular -department allows to identify the, most significant pathogens, that makes it possible to assign an earlier rational empirical antibiotic therapy for such pathology.