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Antibiot Khimioter = Antibiotics and Chemotherapy

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Vol 62, No 7-8 (2017)
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ORIGINAL PAPERS

3-7 895
Abstract
It has been shown that using the cytometric method lipopolysaccharide (LPS) and extracellular polysaccharide (EPS) isolated from marine bacteria Pseudoalteromonas nigrifaciens increase the relative amount of monocytes synthesizing IL-12. LPS and EPS enhance the cytotoxic potential of NK cells, enhancing their degranulation (expression of membrane CD107a), intracellular synthesis of IFN-y and increasing the expression of CD25, CD69, HLA-DR, CD11b, and CD54 molecules.
8-12 466
Abstract
The present study was conducted to investigate the antioxidant properties of water-soluble polysaccharides and ethanolic extracts of submerged mycelium of basidiomycetes Ganoderma lucidum (Curtis) P. Karst, Flammulina velutipes (Curtis) Singer and Hericium erinaceus (Bull) Persoon. For this purpose, DPPH radical-scavenging activity assay, ferrous ions chelating assay and oleic acid peroxidation assay were applied. The last method was used only to investigate the antioxidant properties of ethanolic extracts. Water-soluble endo-polysaccharides and ethanol-soluble low molecular compounds of G.lucidum and F.velutipes mycelium showed high chelating capacity which was comparable to the EDTA-Na2 (control group). All ethanolic extracts proved to have antiradical activity and oleic acid peroxidation capacity. Ethanolic extract of H.erinaceus mycelium showed maximum DPPH free radical-scavenging activity and could decompose hydroperoxides. Antiradical activity of water-soluble polysaccharides was not detected.
13-16 359
Abstract
The pharmacokinetics of olivamide, a semisynthetic antitumor derivate of olivomycin A, were studied in rats and rabbits after bolus administration. Plasma concentrations of olivamide were determined by an HPLC assay. The decrease in olivamide levels in blood plasma was biphasic in both rats and rabbits. Olivamide levels declined slowly for up to 24 hours after a sharp drop in drug concentration during the first 15 minutes due to the rapid redistribution of olivamide between blood and peripheral tissues. The tissue availability of olivamide in rats ranged from 5700% (spleen) to 450% (liver). Eight-hour cumulative renal excretion of unchanged olivamide in rats was 18% of the dose. A three-exponential equation was used to describe pharmacokinetic profiles of olivamide in rat and rabbit plasma. The total clearance and steady-state volume of distribution in rats were higher than in rabbits (17.9-22.0 vs. 16.2 ml/(minXkg) and 7.8-8.7 vs. 5.1 l/kg, respectively). The mean retention time of olivamide in rabbits was less than in rats (5.3 vs 6.3-7.3 h). Olivamide pharmacokinetics in rats were linear.

GUIDELINES FOR PRACTITIONERS

17-23 333
Abstract
At the initiative of the St. Petersburg's Territorial Fund for Mandatory Medical Insurance a retrospective cross-sectional observational study of the structure and adequacy of antibiotic use was initiated in four multi-specialty hospitals in the city (with a total bed capacity of more than 4 thousand) in 2014. In total, 18,250 medical records of the inpatients were analyzed, of which 2008 cards of the patients receiving antibiotics were selected, the CRFs were filled in according to the selected cards. Subsequently, 1978 of the 2008 CRFs were included in the detailed analysis after the final verification of the electronic database. Of the 1978 antibiotic prescriptions, a microbiological study was assigned in 585 (28%). Each patient received an average of 1.9 courses of antibiotics. In general, the therapy duration was up to two weeks. Short courses (from 1 to 5 days) were prescribed in 51% of cases, in 40% of cases the duration of therapy ranged from 6 to 14 days. Only 9% had to take antibiotics for more than 2 weeks. A total of 60 different antibiotics were used. Ceftriaxone, metronidazole, ciprofloxacin, cefazolin, and cefotaxime accounted for 78% of prescriptions. The most commonly prescribed combination therapy used 2 antibacterial drugs. Perioperative prophylaxis in surgery accounted for 22% of prescriptions, antibiotics were prescribed for the purpose of empirical therapy in 67% of cases. Targeted therapy accounted for only 7% of the total number of medical prescriptions. The duration of primary antibiotic prophylaxis in surgery was up to 24 hours only in 14% of the cases. Adequate antibiotic therapy was prescribed in 26% of the cases of acute pyelonephritis and in 31% of the cases of community-acquired pneumonia. Antibiotics were prescribed in the absence of the signs of bacterial infection documented in the medical history in 35% of the cases. There is an obvious need to take urgent measures to optimize the practice of antibiotic therapy in hospitals of St. Petersburg.
24-29 574
Abstract
4324 patients with a basic diagnosis of urolithiasis were examined from 2010 to 2015. 2372 strains were isolated, the leading uropathogens were the bacteria of the genus Enterococcus and Escherichia coii. The high activity of phosphomycin against both gram-positive and gram-negative cultures was noted, which makes it possible to recommend this drug as prophylaxis, in particular for endoscopic procedures. Because of the high resistance of most uropathogens (29% and more), as well as the possible selection of multiresistant pathogens, fluoroquinolones should not be routinely prescribed and should be used in the presence of confirmed sensitivity to them, as well as for suspected infections of the upper urinary tract.
30-35 1084
Abstract
The article presents the data on determination of sensitivity of Salmonella strains in vitro by the method of serial dilutions in broth with the determination of the minimum inhibitory concentrations (MIC) to antimicrobial agents in accordance with the 2015 EUCAST (European Committee on Antimicrobial Susceptibility Testing European Committee for determination of sensitivity to antimicrobial agents) criteria and national clinical guidelines. The study demonstrated a high pharmacodynamic activity of the III generation cephalosporins (Cefotaxime, cefepime), azithromycin, co-trimoxazole and the presence of Salmonella with resistance to ciprofloxacin (24.3%).

DRUG STANDARDIZATION AND CONTROL

36-41 1488
Abstract
The article presents the results of the study of the possibility of using the method of electrosensitive zones (Coulter's method) to evaluate the indicator «Particulate matter (invisible)» in domestic medicinal human blood-derived products. The studies were carried out on suspensions of latex particles, the size and quantity of which corresponded to those normalized for parenteral preparations. Suspensions simulated human blood-derived products, which can presumably contain some invisible particles. Factors that can influence the reliability of test results conducted using the method of electrosensitive zones are determined: the electrical conductivity of the test sample, the volume of the analytical sample, the degree of dilution of the sample.
42-47 1025
Abstract
The use of the LAL test as a method for determining bacterial endotoxins (BE) allows us to normalize the content of impurities causing a pyrogenic reaction in patients. Increasing the reliability and reproducibility of this method is promoted by validation procedures, which are an integral part of the methods for determining BE and are based on the construction of a «model experiment» where the test and control samples are compared. Depending on the test procedure (gel-clot or photometric tests) for determining the presence of BE, appropriate validation procedures are used to assess the necessary parameters. The purpose of the study: to prove the possibility of interchangeability of the methods for determining BE with the help of validation procedures on the example of the drug «Ceftriaxone powder for intramuscular injection 500 mg». Research techniques: Gel-clot and Kinetic Chromogenic tests. The results of the conducted tests confirm the reproducibility and specificity of the LAL test methods. The sensitivity of the LAL reagent used is confirmed. In the experiments of the gel-clot test for Ceftriaxone, a dilution of 1:160 of the base solution in the concentration of 100 mg/ml was validated. The parameters of the calibration curve in the Kinetic Chromogenic test corresponded to the validation requirements (CV<10% and r>0.98). Determination of the bacterial endotoxin content in Ceftriaxone by the photometric method is possible at the same 1:160 dilution, where the accuracy of determination of the BE in the test sample is <20%, the degree of extraction of the added endotoxin is 108%. Conclusions. The conducted studies proved the possibility of interchangeability of the methods for determining the BE on the example of the Ceftriaxon drug, which is confirmed by the necessary validation procedures.

REVIEWS

56-68 432
Abstract
Members of the genus Streptomyces are mycelial bacteria that undergo a complex life cycle that makes them similar to multicellular organisms. Streptomycetes are important industrial microorganisms, as they produce a plethora of medically relevant natural products, including the majority of clinically important antibiotics. This review addresses the morphogenesis of streptomycetes in submerged growth conditions in connection with the biosynthesis of antibiotics, as well as the events of programmed cell death in the course of the producer's development.
69-79 853
Abstract
The increase in the growth rate of MRSA as an etiologic factor has been recorded worldwide in recent years. The main problem of antibiotic resistance in Staphylococcus aureus is its resistance to beta-lactam antibiotics. Previously, MRSA has traditionally been considered as an exclusively nosocomial pathogen, but in recent years it has become prominent in patients with community-acquired infections, mainly of skin and soft tissues. The proportion of infections caused by MRSA in hospitalized patients is steadily increasing, and the antibiotic drugs most often used in clinical practice with anti-MRSA activity have certain usability limitations due to the safety profile, the need for therapeutic drug monitoring or intensive laboratory monitoring during therapy. The appearance of a new representative of oxazolidinone class of antibiotics - tedizolid - is important for the treatment of infections caused by MRSA. Tedisolid is 4-32 times more active against staphylococci, enterococci and streptococci in vitro than linezolid. It is potentially important that many strains resistant to line-zolid maintain in vitro susceptibility to tedizolid. Two Phase 3 studies in patients with acute bacterial skin and soft tissues infections have shown that a relatively short course of therapy with tedizolid at a dose of 200 mg once daily for 6 days is not inferior in effectiveness and safety to the standard long-term linezolid course at a dose of 600 mg 2 times per day for 10 days. In general, the number of clinical studies of tedizolid is limited, but the available data allow to consider it as an effective drug with a favorable safety profile, registered for the treatment of complicated skin and soft tissue infections, including the ones caused by G(+) pathogens resistant to other antibiotics.
80-88 785
Abstract
Antibiotics occupy a leading position among drugs that cause adverse drug reaction (ADR), in Russia as well. Drug-induced pulmonary disease (DIPD), which is the least studied, takes a special place among ADR in antibiotic therapy. There are difficulties in diagnosing such complications of antibiotic therapy, especially in patients with chronic bronchopulmonary pathology and receiving antibiotics due to an infection of the respiratory tract. Antibiotics occupy the third place (4.4%), after antitumor (53%) and antirheumatic (15%) drugs, among other groups of drugs that cause lung damage. Clinical options for DIPD are diverse. Antibiotics, which cause DIPD, are represented (in order of descending risk) by nitrofurans, daptomycin, tetracyclines (minocycline), cephalosporins (ceftaroline, ceftriaxone, cefotaxime, cefepime), fluoroquinolones (ciprofloxacin, levofloxacin). The forms of DIPD are extremely diverse when using nitrofurans (mainly nitrofurantoin) - from acute eosinophilic pneumonia (EP) to chronic interstitial pneumonitis and fibrosis («nitrofuran lung»). DIPD during treatment with lipotetic antibiotic daptomycin are well studied and are clinically presented by EP with a favorable outcome after discontinuation of the drug and the appointment of glucocorticoids; the risk of DIPD development directly depends on the total dose of daptomycin. Numerous clinical variants of DIPD have been observed with the use of tetracyclines (mainly minocycline, to a lesser extent doxycycline): EP, obliterating bronchiolitis with organizing pneumonia, pleurisy, pericarditis. With the use of certain cephalosporin antibiotics (cefotaxime, ceftriaxone, cefepime, ceftarolin), development of EP and hypersensitive pneumonitis has been noted; the development of the latter is associated with a genetic predisposition, since it is found predominantly among the inhabitants of Japan. Extremely rare cases of DIPD due to fluoroquinolones (ciprofloxacin, levofloxacin) are represented by hypersensitive pneumonitis. According to the classification of ADR, most DIPD belong to type B reactions (unpredictable, dose-independent, unrelated to pharmacological action); at the same time, lung damage due to daptomycin can be attributed to type C reactions (association with cumulation and dose of the drug, but not related to pharmacological action). The following clinical data allow to suspect DIPD in a patient receiving antibiotics: antimicrobial treatment, for which the development of lung damage is possible; the appearance of pulmonary symptoms in a patient receiving antibiotics due to infection of other localization, or exacerbation of pulmonary symptoms, despite the conduct of adequate antibiotic therapy; bilateral and interstitial nature of pulmonary lesions and the presence of systemic manifestations; eosinophilia of blood and BAL fluid. For the diagnosis of DIPD, a high-resolution CT scan, a dynamic study of eosinophils in the blood, a cytology of BAL fluid, and, in particularly difficult situations, a targeted fine needle biopsy of the lung are recommended.


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ISSN 0235-2990 (Print)