[Rationale for choosing an antibiotic for the treatment of cystitis: recommendations of clinical pharmacologists: A review].

In recent years, the harmonization of domestic and foreign clinical recommendations for the treatment of cystitis has been achieved. Nitrofurans and fosfomycin trometamol are recommended as first line therapy antibiotics, and oral 3rd generation of cephalosporins are recommended as alternative antibiotics; fluoroquinolones are excluded from the recommended medications due to an unfavorable safety profile. The main rationale for inclusion of antibiotics in the recommendations as a first line therapy of cystitis is the level of resistance of uropathogens to antibiotics, primarily Escherichia coli. Stable low level of resistance of E. coli in Russia was noted to nitrofurans and fosfomycin (5%), higher to cephalosporins. Among nitrofurans, furazidine is characterized by higher activity against E. coli compared to nitrofurantoin. The potassium salt of furazidine in dosage form with magnesium carbonate is preferred, since it is characterized by higher bioavailability and provides a therapeutic level of concentrations in urine above the MIC during the entire dosing period. Due to the global increase in the resistance of uropathogens observed in recent years, experts have begun to pay more and more attention to the ecological safety of antimicrobial therapy in order to minimize the risk of concomitant (collateral) damage, contributing to the selection of multi-drug resistant strains of microorganisms. In the latest WHO document of 2021, experts divided antibiotics into three groups (ACCESS, WATCH, RESERVE) according to the priority of choice. The ACCESS group of drugs for the treatment of cystitis includes nitrofurantoin and furazidine as agents with minimal collateral effect, while fosfomycin trometamol and cephalosporins are listed in the WATCH group. Thus, from the standpoint of ecological safety, WHO experts recommend prescribing nitrofurans in the treatment of cystitis in the first line of therapy.

[Rationale for the choice of an antibiotic for urinary tract infections with an emphasis on the environmental safety of therapy].

Difficulties in prescribing antibiotics for lower urinary tract infections (UTI) are associated with a fact that such patients can be treated not only by urologists, but also by general practitioners, internists, pediatricians, and gynecologists. Therefore, it is important to adapt the practical recommendations for the treatment of cystitis for different medical disciplines. When creating clinical guidelines, experts take into account the different factors in choosing antibiotic therapy. First of all, pharmacokinetics is of importance and drugs with renal excretion should be preferred. Secondly, the natural activity of the antibiotic against the pathogens, which cause cystitis, has to be considered. In uncomplicated infections, E. coli predominates, while in complicated and recurrent infections E. coli and other enterobacteria are commonly isolated, as well as Enterococci. In addition, local resistance pattern is reviewed. In the Russian Federation E. coli has minimal resistance to nitrofurans and fosfomycin. Lastly, antibiotics can negatively affect the gastrointestinal and urinary tract microbiota and contribute to the increase of antibiotic resistance and the selection of antibiotic-resistant strains, therefore the environmental safety of therapy should be considered. The effect of antibiotics on the resident flora of the gastrointestinal tract, urinary tract and vagina is called collateral effect, or concomitant (parallel) damage, and it may exceed the therapeutic effect of some antibiotics. Cephalosporins and fluoroquinolones can cause ecologically unfavorable effects with the risk of selection of resistant strains; therefore, these drugs are currently considered as second-line agents for UTI. When choosing an antibiotic, preference should be given to drugs with the narrow spectrum and minimal collateral damage, i.e., the principle of "minimum sufficiency" is of importance. Nitrofurans and fosfomycin trometamol are the optimal drugs in terms of efficiency and environmental safety in UTI. WHO experts consider nitrofurans as the most environmentally safe antibiotics with a minimally sufficient spectrum of activity. The environmental safety of antimicrobial therapy is an important component of preventing antibiotic resistance at the global and local levels.

ANALYSIS OF PSYCHOLOGICAL, SOCIAL, AND LEGAL MEDICAL ASPECTS IN EVALUATING THE QUALITY OF PEDIATRIC ASSISTANCE.

Relevance and purpose: The current state of society is characterized by increasing awareness of citizens about their rights and state obligations in all spheres of human activity including healthcare. It is crucial to note the importance of conflict provoking factors, conflict development, and the propositions for its prevention which is impossible without the study of attitude towards various aspects of providing medical assistance to children. The purpose of the study is the identification of the relationship of pediatricians to the importance of juridical and psychological aspects of care. MATERIALS AND METHODS: Analysis legal and psychological aspects of quality of care was carried out on the results of a questionnaire various specialties of pediatric survey among employees of "Regional Children's Clinical Hospital by N.F. Filatov" and several children's clinics in Penza. RESULTS: The most important role in the prevention of conflict plays juridical knowledge and mental preparation, as well as the ability to use them in clinical practice. Formulated for execution and real proposals for the prevention of conflicts between children's doctors, patients and their parents indicate the practical significance of the work. CONCLUSIONS: Conclusions are consistent with that goal; they are based on reliable information obtained in the course of the study. The implementation of the measures proposed by researchers of conflict's prevention in pediatrics will reduce the number of calls to the police, the investigating committee and the courts.

[Fecal microbiota transplantation for graft-versus-host disease in children and adults: methods, clinical effects, safety].

AIM: Was to evaluate clinical efficacy, adverse events and changes in the gut microbiome after fecal microbiota transplantation (FMT) in patients with gastrointestinal (GI) form of graft-versus-host disease (GVHD). MATERIALS AND METHODS: The prospective single-center study in R.M. Gorbacheva institute included 27 patients with GI GVHD after allogeneic stem cell transplantation. 19 patients received FMT, 8 patients received placebo. Clinical scales for GI autoimmune diseases were used to evaluate response. Microbiome alterations were assessed with multiplex PCR. RESULTS: After FMT higher overall bacterial mass (р=0.00088), higher bacterial numbers ofBifidobacteriumspp. (р=0.021),Escherichia coli(р=0.049) andBacteroides fragilisgr. (р=0.000043) compared to placebo group. Also higher bacterial mass was observed in patients with clinical response (р=0.0057). The bacterial mass after procedure in non-responders was compared to the placebo group (р=0.31). Partial response of GVHD was achieved faster in the FMT group compared to placebo (median 4 days vs 48 days,p=0.014). Complete response was observed in 8 (42%), 14 (74%) and 16 (84%) at 30, 60 and 90 days respectively, while in the placebo group only 0%, 1 (13%) and 4 (50%) achieved complete response at the same time points. The incidence and severity of adverse events was comparable between FMT and the placebo group. CONCLUSION: FMT in patients with refractory GI GVHD was associated with favorable clinical outcomes and recovery in certain marker bacterial populations. Multiplex PCR can be used to assess an engraftment of a donor microbiota. FMT in GI GVHD was not associated with life-threatening adverse events, but further studies are required to validate clinical efficacy.

Inactivation of M111 Protein Gene Modifies Streptococcus Pyogenes Interactions with Mouse Macrophages In Vitro.

Immunomodulatory properties of S. pyogenes protein M111 were studied on the model of Gurov strain and its isogenic mutant not expressing M protein. Mouse resident peritoneal macrophages were incubated with bacteria and generation of nitroxide and superoxide anions and production of IL-6, IL-10, and IL-17 were evaluated. Protein M111 modified macrophage response: it exhibited antiphagocytic activity, prevented ROS formation, and stimulated the production of anti-inflammatory cytokine IL-10. The results suggested that this protein could serve in the bacteria as a factor suppressing the host defense forces and promoting the realization of the strategy beneficial for pathogens - escape from the host immune defense.

Multicentre Study of the Prevalence and Clinical Value of Hospital-Acquired Infections in Emergency Hospitals of Russia: ERGINI Study Team.

BACKGROUND: Hospital-acquired infection (HAI) is a common problem in intensive care units (ICU) and other hospital units. The methodical system of surveillance of hospital-acquired infections (HAI) is not available in Russia and there is no reliable data about the prevalence or epidemiology of HAI. We aimed in this pioneer study to determine the prevalence, epidemiological and microbiological characteristics, risk factors, clinical value and outcomes of HAI in different units of emergency multifields hospitals of Russia. METHODS: This prospective multicentre 1-day prevalence study with 28-days follow-up was realized between January and May 2013. Thirty two emergency hospitals with more than 500-beds from 18 cities participated in this study. The study was conducted separately on 5 different days in ICU, therapeutic, surgical, urology and neurology units. All patients treated in the unit on the day of the study were examined for the presence of HAI according to CDC criterias. Risk factors of HAI, nosological and etiological structure, susceptibility of pathogens were also evaluated. RESULTS: Totally 3809 patients were included in the study during 5 days of investigation in ICU and therapeutic, surgical, urology and neurology units (respectively 449, 1281, 1431, 342 and 306 patients). The total number of registered HAI was 290 and the prevalence of HAI was 7.61% (95% CI 6.81%, 8.50%). The greatest rate of HAI was registered in ICU (26.28%) and neurological unit (13.73%); the rate was lower in therapeutic, surgical and urology units (4.76, 4.12 and 2.92%). The prevalence of HAI.was similar in adult and pediatric hospitals .(7.62 and 7.54%). The prevalence of community-acquired infections was 28.53%. The lower respiratory tract was the most common site of infection, accounting for 42.4%.of HAIs followed by the urinary tract (19.0%), skin and soft tissue (13.4%), abdomen (11.4%) and intravascular (4.8%). 311 pathogens were isolated: 58.8% of isolates were gram-negative, 32.8% gram-positive, and 8.4% Candida spp. The most common bacterial isolates were Klebsiella spp. (19.6%), E.coli (12.2%), S.aureus (11.3%), Acinetobacter spp. (10.9%), E.faecalis (7.4%) and P.aeruginosa (7.1%). The resistance rate of E.coli and Klebsiella spp. to 3rd generation of cephalosporins was 60.5 and 95.1%. Only 26.5% of Acinetobacter isolates and 59,1% of P.aeruginosa isolates were susceptible to imipenem. The MRSA rate was 48.6%; 17,4% of E.faecalis were resistant to ampicillin. The mortality rate was higher in patients with HAI (16.5%) than in patients without HAI (3.0%); the mean length of hospital stay was also higher in patients with HAI (24.6±11,4 vs. 16.2±15,3 days). CONCLUSION: The prevalence of HAI in Russian hospitals is high. According to the prevalence data the estimating annual number of HAI in Russia is approximately 2,300,000 cases. The multi-drug resistant microorganisms were dominated among causative agents of HAI.

[Clinical efficacy of the antimicrobial drug furamag in nosocomial urinary tract infections].

AIM: To evaluate the efficacy of the combined drug furamag (furasidine potassium and magnesium hydroxycarbonate) in combination with the third-generation cephalosporin cefotaxime versus cephalosporin monotherapy for nosocomial urinary tract infections (NUTI). SUBJECTS AND METHODS: The randomized open-label comparative parallel group clinical trial enrolled 52 male and female patients aged over 18 years with a documented diagnosis of NUTI. Group 1 (a study group) took oral furamag 300 mg/day in combination with intravenous cefotaxime 6 g/day; Group 2 (a control group) received cefotaxime monotherapy. The duration of therapy in both groups was 7 to 10 days until the efficiency levels were achieved. RESULTS: A final efficiency analysis was made in 24 and 25 patients from Groups 1 and 2 who had different forms of NUTI (catheter-associated NUTI, cystitis, pyelonephritis). On day 3 of treatment, most patients were noted to have a decreased systemic inflammatory response; lower C-reactive protein and procalcitonin levels being in the study group patients. The clinical efficiency of antibacterial therapy, which had been evaluated both immediately after treatment termination and during further control, did not substantially differ in the furamag/cefotaxime combination and control groups although there was an obvious tendency towards the more marked effect of combined therapy 7-14 days after treatment (11.8% efficiency differences; p>0.05). Analysis of bacteriological efficacy revealed its most pronounced and clinically significant differences between the groups: the cefotaxime/furamag combination led to higher pathogen eradication in all follow-up periods: after 3 days of treatment (82.6%) and following a complete therapy cycle (95.8%) versus the cefotaxime monotherapy group (43.5 and 70.8%, respectively; p<0.01). Microbiological results showed that the major NUTI pathogens (Escherichia coli, enterococci) were more susceptible to potassium furasidine (furamag) versus cefotaxime. The in vitro higher activity of furamag versus cefotaxime was attended by the significantly higher eradication of one of the two important NUTI pathogens - Enterococcus faecalis. CONCLUSION: Furamag used in combination with the third-generation cephalosporin cefotaxime showed a higher bacteriological efficacy and a rapider reduction in the symptoms of a systemic inflammatory response in patients with NUTI. On the basis of the findings, the above combination of furamag and cefotaxime may be recommended as first-line therapy for NUTI when multidrug- resistant nosocomial infection pathogens are widely distributed now.

[Humoral and cell-mediated immune responses in humans to the A/California/07/ 2009 (H1N1) virus, A(H1N1)pdm2009].

During the twentieth century the world faced four influenza A pandemics: A (H1N1) in 1918, A (H2N2) in 1957, A (H3N2) in 1957 and A (H1N1) recirculation in 1977. In the beginning of 2009 the global spread of A(H1N1)pdm2009 virus was detected. In consideration of clinical evidences and genetic data analysis WHO declared as the novel pandemic of 21th century. However, the fact of exceedingly prolonged previous worldwide circulation of A (H1N1) influenza viruses was not taken into account. Further development showed epidemiological prognosis not to be accurate enough. The present work is an attempt to analyze this question from the immunological standpoint based on our studies of antibody and cellular immunity to A(H1N1)pdm2009 virus in vaccinated and non-vaccinated persons of different ages. The study results allow concluding that A(H1N1)pdm2009 is the drift variant of A (H1N1) viruses antigenically close to A/Swine/1976/1931 (H1N1). It was shown that the significant of persons have cross-reactive B and T cell immunological memory to A(H1N1)pdm2009 strain. This could be a reason of decreased A(H1N1)pdm2009 pandemic severity.

[Investigation of the genetic profile of Blastocystis species in Saint Petersburg residents with gastrointestinal tract diseases in different age groups].

A total of 1500 people, including 1273 children with various gastrointestinal tract diseases and 327 patients with chronic viral hepatitis C, were examined. Microscopy and polymerase chain reaction (PCR) were used to determine Blastocystis in the feces. Blastocysts were detected in 33% of the patients with chronic viral hepatitis C and in 4.9% of the children. Genotyping established that Blastocystis species subtype 3 (antroponous) was encountered relatively rarely (25%) in these patients; there were most common Blastocystis species subtypes 5 (36.1%) and 6 (36.1%). Significant intestinal dyspepsia was noted in all the patients with chronic hepatitis C and Blastocystis invasion. Blastocystis species subtype 3 was prevalent (62.3%) among the examined children. The other subtypes were less frequently detected. These were subtype 1 (29.5%), subtype 2 (24.3%), subtype 4 (1.3%), and subtype 7 (3.8%) whereas subtype 5 and subtype 6 were not found in any case. The comparison of clinical symptoms in children could reveal the following tendency: there were digestive disorders and skin allergic reactions with Blastocystis species subtype 1 and subtype 2, respectively.

The influence of probiotic Enterococcus faecium strain L5 on the microbiota and cytokines expression in rats with dysbiosis induced by antibiotics.

The animal model of intestinal dysbiosis induced by antibiotics was created. Dysbiotic condition was confirmed by the changes in titre of the indigenous microbiota (excessive growth of opportunistic microorganisms and reduced number of lactobacilli, bifidobacteria and enterococci) and the appearance of dyspeptic symptoms. Consumption of the fermented milk product with probiotic strain Enterococcus faecium L5 led to the rapid disappearance of dysbiosis symptoms, normalisation of the microbiota, increase in expression of IL-10 and decrease in IL-8 expression.

[Infective endocarditis of staphylococcal etiology: clinical process and antibacterial therapy].

Characteristics of the clinical process of staphylococcal endocarditis in 115 inpatients and the adequacy of various regimens for their antibiotic therapy within a period of 10 years were analysed. Four clinical criteria for prognosis of staphylococcal endocarditis were determined: intravenous narcomania, splenomegalia, leukocytosis and hemorrhagic skin eruption. The analysis of the Russian and foreign findings showed that the use of betalactams (oxacillin, the 1st and 3rd generation cephalosporins) and lincomycin provided the adequate therapy resulting in eradication of the pathogen in case of oxacillin resistant staphylococci, whereas the use of ciprofloxacin and vancomycin was inexpedient. In case of MRSA it was recommended to use vancomycin and in case of endocarditis due to S. aureus with intermediate resistance to vancomycin (VISA, MIC > 0.5 mcg/ml) the use of linezolid was recommended.

[Evaluation of efficacy and safety of josamycin (Vilprafen) in the treatment of patients with community-acquired pneumonia].

Clinical and bacteriological efficacy ofjosamycin (Vilprafen), a macrolide antibiotic, was studied in 30 out- and inpatients at the age of 18 to 68 years (the average of 43.4+/-16.7 years old) with nonsevere (PORT) community-acquired pneumonia in the case histories. Josamycin was administered orally in a dose of 500 mg every 8 hours for 7 to 10 days. The treatment course was 5 to 10 days (the average of 7.7+/-1.3 days). The recovery was stated in 28 (93.3%) patients and the pathogen eradication was recorded in 16 (88.9%) patients. Moderate side effects not requiring discontinuation of the drug use were observed in 3 patients. The results of the treatment were indicative of the josamycin high efficacy in the treatment of the patients with nonsevere community-acquired pneumonia.

Specificity of catechol ortho-cleavage during para-toluate degradation by Rhodococcus opacus 1cp.

Degradation of para-toluate by Rhodococcus opacus 1cp was investigated. Activities of the key enzymes of this process, catechol 1,2-dioxygenase and muconate cycloisomerase, are detected in this microorganism. Growth on p-toluate was accompanied by induction of two catechol 1,2-dioxygenases. The substrate specificity and physicochemical properties of one enzyme are identical to those of chlorocatechol 1,2-dioxygenase; induction of the latter enzyme was observed during R. opacus 1cp growth on 4-chlorophenol. The other enzyme isolated from the biomass grown on p-toluate exhibited lower rate of chlorinated substrate cleavage compared to the catechol substrate. However, this enzyme is not identical to the catechol 1,2-dioxygenase cloned in this strain within the benzoate catabolism operon. This supports the hypothesis on the existence of multiple forms of dioxygenases as adaptive reactions of microorganisms in response to environmental stress.

[Staphylococcal pneumonia]. / Stafilokokkovye pnevmonii.

In January to December 2000, a total of 15 (8.8%) patients with staphylococcal community-acquired pneumonia (CAP), 13 (27.7%) patients with staphyloccocal nosocomial pneumonia (NP) that occurred at general units (GU), and 9 (50%) patients with GU that occurred under artificial ventilation (AV) at intensive care units (ICU) were followed up. Meticillin-resistant S. aureus strains were isolated in 6.7, 38.5, and 55.6% of cases, respectively. As compared with pneumococcal CAP, staphyloccocal CAP were more frequently characterized by the severe course of the disease (46.7% versus 15.4%), bilateral lesion (33.3% versus 5.1%), and the presence of complications (66.7% versus 30.8%). Staphyloccocal NP that had occurred at GU, as compared to that at ICU also showed the severe course of the disease (46.2% versus 2.9%), bilateral lesion (30.7% versus 0%), and developed complications (75% versus 25%). Staphylococcal NP developed under AV at ICU had no specific features as compared with NP of another etiology. Oxacillin and first-second-generation cephalosporins remain to be the drugs of choice when meticillin-sensitive S. aureus strains are isolated; lincomycin and erythromycin being alternative agents against these strains. Glycopeptides are the drugs of choice when meticillin-resistant S. aureus strains are isolated, its alernatives are linesolide or rifampicin. High mortality rates due to staphylococcal pneumonia are preserved. These are 7.1% in CAP, 7.7 and 66.7 in staphylococcal NP occurring at GU and under AV at ICU, respectively.

[Etiology and microbiological diagnosis of nosocomial pneumonia in newborns]. / Etiologiia i mikrobiologicheskaia diagnostika nozokomial'nykh pnevmonii u novorozhdennykh.

A comparative analysis of the cases of ventilator-associated pneumonia (VAP) among premature infants in intensive care units and premature infant nurseries in 1994 (group I) and 1999 (group II) is presented. It was shown that the number of the cases of ventilator-associated pneumonia in the premature infants of group. I was 2,4 times higher than that in the group II (45.8 and 19.2 per cent respectively). A marked difference in the species pattern of the pathogens isolated from the endobronchial aspirate in 1994 and 1999 was observed. The species pattern of the isolates from the respiratory tract (Pseudomonas aeruginosa--40 per cent; Klebsiella pneumoniae--31 per cent; Staphylococcus epidermidis and Enterococcus--rare) showed that the pneumonia were nosocomial. The revealed similarity of the species patterns of the microflora in various parts of the respiratory tract and the throat posterior wall made it possible to consider the isolates of the throat posterior wall as a relative guide for confirming the etiological diagnosis of nosocomial pneumonia.

[Program of empirical antibacterial therapy of community-acquired pneumonia]. / Razrabotka programmy émpiricheskoi antibakterial'noi terapii vnebol'nichnoi pnevmonii.

Clinical and bacteriological efficacies of some antibacterial agents were estimated with their differential use in the management of various groups of patients with community-acquired pneumonia. Group 1 included young and middle-aged patients with mild pneumonia. Group 2 included young and middle-aged patients with moderate pneumonia. Group 3 included elderly patients with pneumonia and/or patients with concomitant diseases or certain factors complicating the main process. The patients of group 1 were treated with roxithromycin and spiramycin and showed a rapid clinical effect in 100 and 86 per cent of the cases and a rapid bacteriological effect in 84 and 75 per cent of the cases respectively. The patients of group 2 were treated with parenteral cefuroxime with positive clinical and bacteriological effects in 68 and 78 per cent of the cases respectively. The patients of group 3 were treated with ceftibuten and pefloxacin which provided a clinical effect in 91 and 70 per cent of the cases and a bacteriological effect in 72 and 100 per cent of the cases respectively. The results of the treatment with an account of the differences in the pathogen spectra made it possible to recommend as the 1st order agents for the empirical therapy of community-acquired pneumonia (1) macrolide antibiotics for young and middle-aged patients with mild pneumonia without concomitant diseases, (2) 2nd generation cephalosporins for patients with moderate pneumonia without severe concomitant diseases and (3) 3rd generation cephalosporins or fluoroquinolones for elderly patients with pneumonia and the patients with complicating factors.