[The results of phase III multicenter open randomized controlled study REM-Chol-III-16 in patients with intrahepatic cholestasis syndrome caused by chronic diffuse liver diseases].

AIM: To assess the safety and efficacy of Remaxol, solution for infusion, compared with parenteral form of S-adenosyl-L-methionine, in the treatment of patients with intrahepatic cholestasis syndrome accompanying chronic diffuse liver diseases of various etiology. MATERIALS AND METHODS: In a multicenter open-label comparative study of the safety and efficacy of Remaxol (inosine + meglumine + methionine + nicotinamide + succinic acid) 317 patients aged 18 to 65 years were randomized into 2 groups: patients of the experimental group (n=168) received intravenous Remaxol, solution for infusion, 400 ml, and patients of the control group (n=149) Heptral (S-adenosyl-L-methionine) 800 mg. The duration of treatment was 10 days. The primary efficacy endpoint was the proportion of patients who responded to therapy, as demonstrated by dynamics of laboratory parameters of liver functional status: decrease in gamma glutamyl transpeptidase level by 40%, and/or alkaline phosphatase level by 30%, and/or decrease total bilirubin level by 30% from baseline by the end of the treatment course. RESULTS: The proportion of responders was 51% in the Remaxol group vs. 44.9% in the Heptral group (p=0.303); the lower limit of the one-sided 95% confidence interval for the difference in the proportions of responders was -4.01%, which exceeds the non-inferiority margin pre-defined by the study protocol, thus, the non-inferiority hypothesis was proven, i.e. Remaxol at a dose of 400 ml/day demonstrates similar efficacy to Heptral at a dose of 800 mg/day in patients with intrahepatic cholestasis syndrome associated with chronic diffuse liver diseases. Similar positive trends in the levels of transaminases, total bilirubin and the severity of pruritus were revealed in both treatment groups. We did not reveal statistically significant between-group differences in the frequency of adverse events definitely related to the study treatment. CONCLUSION: Administration of Remaxol as a part of the pathogenetic therapy of patients with intrahepatic cholestasis syndrome who need hepatoprotection is justified.

[Resistance of pathogens of community-acquired urinary tract infections: lessons from Russian multicenter microbiological studies. Part II].

The choice of antimicrobials for the treatment of urinary tract infections (UTIs) is determined by many factors, however, at present, population antibiotic resistance of uropathogens is used as one of the most important criteria. At the same time, there are cases when the clinical efficacy of an antimicrobial drug does not correlate with in vitro activity, in particular, such discordance was found for fosfomycin trometamol. Comparison of data from microbiological studies of UTI pathogens performed at different times is of great practical and scientific interest. At the same time, such comparisons have limitations, such as the use of different criteria for interpreting the sensitivity of microorganisms, the peculiarities of the formation of the studied patient population, and collection of strains in different geographical areas. Therefore, for all the seeming simplicity and clarity of the data on the sensitivity of uropathogens, their use to substantiate rational antimicrobial therapy is associated with numerous nuances that can significantly distort their objective assessment. In this connection, it is important to conduct not only microbiological, but also clinical studies to obtain data on the comparative effectiveness of the antimicrobials used.

[Resistance of pathogens of community-acquired urinary tract infections: lessons from russian multicenter microbiological studies].

The review describes large-scale microbiological studies performed in Russia over the past 20 years to study urinary tract infections (UTIs). The article analyzes data on the structure of UTI pathogens, as well as on the antibiotic resistance of the main uropathogens, compares the data with similar foreign studies. From 1999 year, 7 large multicenter microbiological studies were carried out in Russia to obtain the data of the antimicrobial resistance of uropathogens caused community-acquired UTIs. An analysis of the data allows described trends in antimicrobial resistance - high level of resistance of uropathogens to aminopenicillins, co-trimoxazole, fluoroquinolones, an increase antimicrobial resistance to amoxicillin / clavulanate, and third generation cephalosporins. In review discussed a critical assessment of various approaches to the use of data on the sensitivity of uropathogens to antimicrobial drugs when antimicrobial therapy is provided. The necessity of comparing not only microbiological data obtained from different sources, but also clinical data, characteristics of pharmacodynamics and pharmacokinetics of antimicrobial drugs is discussed. The review discusses the difficulties associated with the clinical interpretation of data on the sensitivity of microorganisms, primarily in the limited objective information describing the correlation of in vitro data with the clinical efficacy of therapy. The publication substantiates the need for a wider conduct of not only microbiological, but also clinical studies to obtain data on the comparative efficacy of the used antimicrobial drugs.

[Resistance of urinary tract pathogens and the choice of antimicrobial therapy: deceptive simplicity].

Urinary tract infection (UTI) is one of the most common reasons for prescribing antibiotics in outpatient and inpatient settings. One of the main criteria for selecting antimicrobial drugs for treating UTI is data on the antibiotic resistance of uropathogens. The article discusses the difficulties in interpreting the results of antimicrobial sensitivity testing of uropathogens and the impact of antibiotic resistance of uropathogens on the clinical effectiveness of managing UTI.