[Development of clinical recommendations Cystitis in women].

The article is devoted to the stages of developing clinical recommendations on bacterial cystitis in accordance with the order of the Ministry of Health of Russia. Principles of evidence -based medicine (meta-analyses, systematic reviews and randomized clinical trials) are given. The Evidence Validity Level Assessment Scale (TDS) and Recommendation Credibility Level Assessment Scale (TDS) are given. In accordance with these requirements, modern methods for diagnosing bacterial cystitis have been selected, including the Acute Cystitis Symptom Score (ACSS), and the urination diary. Current approaches to treatment of asymptomatic bacteriuria, antimicrobial treatment regimens of acute and recurrent bacterial cystitis are given. Evidence-based methods of cystitis recurrence prevention are presented. Information is also provided for patients, including lifestyle recommendations, water regime, risk factors for cystitis recurrences, and explanations for completing questionnaires and diaries.

[Bacteriophage Therapy of Urological Infections].

A literature review dedicated to the problem of bacteriophage therapy for infectious and inflammatory diseases, including urological infections, is presented. Considering the growth of antibiotic resistance, the search for alternative treatments is relevant. Current data about bacteriophages and mechanism of their action, difference of virulent and temperate phages is given, as well as mechanisms of bacteria resistance to phages and ways of its overcoming. The history of phage therapy for infectious diseases from the beginning of the 20th century to the present days is presented. Pharmacokinetic studies of phages after oral administration are given. Moreover, we described our 30 years experience on of clinical use of bacteriophage cocktails in the treatment and prevention of urological infection. In addition, problems of phage therapy are discussed, including immunological issues and the advantages of bacteriophages over antibiotics.

[Prevention of infectious and inflammatory complications after percutaneous nephrolithotomy].

INTRODUCTION: Given the increase in antibiotic resistance of uropathogens, one of the urgent problems is a development of optimal antimicrobial prophylaxis for surgical interventions, as well as an adequate regimen of antibiotic therapy after percutaneous nephrolithotomy (PCNL). AIM: to determine an effective perioperative antimicrobial prophylaxis for PCNL in patients with kidney stones. MATERIAL AND METHODS: A total of 90 patients with staghorn or multiple large kidney stones who underwent PCNL were included in the study. Before PCNL, urine culture was performed in all patients in order to determine the sensitivity not only to antibiotics, but also to bacteriophages. In addition, urine was taken for additional microbiological studies after the puncture of the collecting system, as well as on the 3rd and 7th day after PCNL. All patients were divided into three groups of 30 patients depending on the regimen of perioperative prophylaxis. In group 1, patients were prescribed ciprofloxacin 1000 mg i.v. intraoperatively, then 1000 mg i.v. q.d. for 3-5 days. In the group 2, patients received one dose of cefotaxime + sulbactam (1.0 g + 0.5 g) 2 hours before PCNL i.m. In the group 3, a polyvalent pyobacteriophage purified was given orally 1 hour before PCNL in a dose of 40 ml and the same dose was used t.i.d. for 3-5 days postoperatively. RESULTS: In all three groups of patients, the following infectious complications were evaluated: acute pyelonephritis, systemic inflammatory response syndrome (SIRS) and urosepsis. There were no serious infectious and inflammatory complications in the early postoperative period among all patients. SIRS developed on days 1-3 after PCNL in 26.6%, 20% and 20% of patients in group 1, 2 and 3, respectively. However, by days 4-7 after PCNL, there was normalization of blood cells count (leukocytes, neutrophil band cells), temperature and general condition. CONCLUSION: Different regimens of antimicrobial prophylaxis for PCNL have the same efficiency. The development of SIRS on days 1-3 after PCNL is correlated not only with the antimicrobial agents used and the route of their administration (intravenously, intramuscularly and orally). Most likely, the development of SIRS is more associated with surgical trauma.

[Current state of antibiotic resistance of pathogens causing community-acquired urinary tract infections in Russia, Belarus and Kazakhstan: results of the international multicenter study Darmis-2018].

OBJECTIVE: To study in vitro activity of antimicrobials against clinical isolates from patients with community-acquired urinary tract infections (UTIs) in different regions of Russia, Belarus and Kazakhstan in 2017-2018. MATERIALS AND METHODS: A total of 1260 isolates collectedin the Russian Federation, Belarus and Kazakhstanas a part of the international multicenter prospective epidemiological study of the dynamics of antimicrobial resistance of uropathogens causing community-acquired urinary tract infections in different subsets of patients ("DARMIS-2018") were included in the analysis. 1124 strains represented the Enterobacterales order. Uropathogenswere isolated from children and adults of both sexes of all age groups with acute (and recurrences of chronic) community-acquired UTIs including pregnant women with asymptomatic bacteriuriain 34 centers of 26 cities of Russia, Kazakhstan and Belarus in 2017-2018. RESULTS: Enterobacterales jointly comprised a total of 89,2% of all isolated bacterial pathogens (88,9% in the adult subset; 89,3% in the subset of pregnant women and 91,4% in the subset of children and adolescents under 18). The most prevalent species were Escherichia coli (69,4% in the adult subset; 73,6% in the subset of pregnant women and 77,1% in the subset of children and adolescents under 18) and Klebsiella pneumoniae (11,5% in the subset of adults; 10,4% in the subset of pregnant women and 7,1% in the subset of children and adolescents under 18 years of age). The maximum activity against E. coli among oral drugs demonstrated fosfomycin (97,9% in the adult subset; 95,9% in the subset of pregnant women and 99,1% in the subset of children and adolescents under 18) and nitrofurantoin (97,9% in adult subset; 100% in the subset of pregnant women and 96,3% in the subset of children and adolescents under 18). Out of the parenteral drugs meropenem (out of carbapenems) and amikacin showed the highest activity (99,5% and 97,7% in the adult subset; 99,5% and 99,1% in the subset of pregnant women; 100% and 97,2% in the subset of children and adolescents under 18 years of age, respectively). Ampicillin, amoxicillin/clavulanic acid and trimethoprim/sulfamethoxazole demonstrated the lowest in vitro activity against Escherichia coli (less than 80% for everypatient subset). The susceptibility of E. colito ciprofloxacin was 60,4% in the adult subset; 80,0% in the subset of pregnant women and 80,6% in the subset of children and adolescents under 18. The rate of production of extended spectrum beta-lactamases among E. coli isolates based on the results of phenotypic tests was 21,9%. CONCLUSIONS: Results of this study indicate the increase of resistance of community-acquired isolates of Enterobacterales and in particular E. coli to the most of antimicrobials in Russia, Belarus and Kazakhstan.

[The 2015 Federal Clinical Guidelines for Antimicrobial Therapy and Prevention of Infections of the Kidney, Urinary Tract, and Male Genitals]. / Federal'nye klinicheskie rekomendatsii «Antimikrobnaya terapiya i profilaktika infektsii pochek, mochevyvodyashchikh putei i muzhskikh polovykh organov - 2015 g.¼.

This paper reviews the latest federal guidelines published in 2015. Emphasis is placed on the etiology and pathogenesis of uncomplicated lower urinary tract infection (uLUTI). There are data of the last Russian Darmis-2011 study of urinary tract infection pathogens and their resistance to essential antibiotics. The paper reveals the causes of persistence of uropathogenic Escherichia coli, the main pathogen of uLUTI, and shows the occurrence of intracellular bacterial communities in the superficial layer of the bladder mucosa, which are characteristic of recurrent cystitis. There are justified treatment and prevention regimens using both first-line and alternative drugs for uLUTI and recurrent iLUTI.

[Search for new modes of antibiotic prophylaxis of septic complications after percutaneous nephrolithotripsy].

The risk of infectious and inflammatory complications after PNL is based on presence of microorganisms in the form of biofilms inside the stone. Destruction of stones during surgery or lithotripsy may be a trigger for the growth of microorganisms that are integrated into the biofilms, and the migration of bacteria and their toxins in the blood flow under pressure of irrigation fluid can cause septic complications. The danger of infectious and inflammatory complications after percutaneous interventions for kidney stones requires a search for specific antibiotics for antimicrobial prophylaxis and efficient modes of their administration. The results of a comparative study of pharmacokinetic parameters of ciprofloxacin, and the effectiveness of two modes of administration (bolus dosing and prolonged intravenous administration) at a dose of 1000 mg are presented.

[Infectious genesis of nephroliths (electron-microscopic study)].

Scanning electron microscopy and x-ray microstructural analysis were employed in the study of nephroliths from patients suffering from nephrolithiasis. Bacterial biofilms, urease producing microorganisms, alkaline reaction of the urine are basic factors for local urine crystallization, formation of the base of the nephroliths and its rigid fixation to the pelvic mucosa. Mechanic trauma of the pelvic tissues by the concrement results in destruction of the pelvic mucosa epithelium at the site of the nephrolith. Subsequent inflammation in the underlying connective tissue contributes to formation of connective tissue commissures fixing the conrement in the kidney. It is shown that bacteria as a part of a biofilm are capable to persist in nephroliths for a long time. Destruction of the stones during operation or lithotripsy can trigger activation of growth of bacteria integrated in the biofilm and cause septic complications. Preservation of commissures with elements of the destroyed stone after lithotripsy or surgical removal is one of the leading causes of recurrent nephrolithiasis.

[Choice of antibacterial drugs in urinary infection].

A rise in efficacy of the treatment of acute infection affecting the lower urinary tract (LUTI) and prolongation of recurrence-free interval in chronic LUTI can be achieved only by an optimal antibacterial treatment. The study was made of 987 community-acquired strains of uropathogens from the patients living in 20 cities of the Russian Federation, Belarus and Kazakhstan (of them, 903 strains were from Russia). Enterobacteriaceae comprised 83.5%. E. coli infection of LUTI was found in 63.5% patients. The incidence of this infection was about the same both in uncomplicated and complicated cases (64.6 and 62.1%, respectively). Most active oral drugs against E.coli were phosphomycin (98.4%), furasidin (95.7%), nitrofurantoin (94.1%) and oralcefalosporins of the third generation (ceftibuten and cefixim). As to Enterobacteriaceae, only phosphomycin had activity against these bacteria above 90%, i.e. 91.5%. Furasidin and nitrofurantoin activity was 86.3 and 76.8%, respectively. From parenteral drugs, most active against E. coli were carbapenems (ertapenem, meropenem, imipenem. Strains resistant to them were not isolated. High in vitro activity was demonstrated also by cefoperason/sulbactam (97.4%), piperacillin/tasobactam (95.7%), cefalosporins of the third/fourth generation and amikacin (98.9%). Carbapenems were also highly active against Enterobacteroaceae. Empiric treatment of uncomplicated urinary infection should be performed with medicines which are not used for other indications.

[Russian results of the international epidemiological study of clinical aspects and resistance to antimicrobial medicines of cystitis uropathogens in females (ARESC): significance of empiric therapy].

A total of 656 female patients from Russia aged between 18 to 65 years with uncomplicated cystitis entered the international ARESC trial, of them 647 were eligible for final analysis. Positive cultural urine tests ( > 10(4) CFU/ml) were in 419 (64.7%) patients, 393 (93.8%) patients had monoinfection. The central laboratory of Genoa (to which the isolated samples were sent) has tested 416 uropathogens from 399 patients. The following pathogens were isolated: E. coli (72.6%), enterococcus (7.0%), Klebsiella pneumoniae (4.6%), Staphylococcus saprophyticus (3.6%), Proteus mirabilis (2.4%) and Staphylococcus aureus (1.7%). E. coli was most sensitive to phosphomycin (99.3%), mecillinam (97.3%), nitrofurantoin (94.7%), ciprofloxacin (87.4%). The lowest sensitivity was to ampicillin (42.1%) and cotrimoxasol (69.4%). As to the whole bacterial spectrum, the highest sensitivity was found to phosphomycin (96.5%), nitrofurantoin (85.6%) and citrofloxacin (82.8%), the less sensitivity--to ampicyllin (44.3%) and co-trimoxasol (70.1%). Phosphomycin, mecillinam (not registered in Russia) and nitrofurantoin showed activity in vitro and can be considered as drugs of choice for empiric therapy of cystitis. Because of high resistance of pathogens, co-trimoxasol (trimetoprim) and fluoroquinalones are not recommended as first-line treatment for uncomplicated cystitis in females.

[Significance of detection of genomic markers of pathogenicity islands in Escherichia coli in urological practice].

Examinations of 86 (100%) patients aged 16 to 68 years who had urinary tract infection could isolate 67 Escherichia coli cultures, 32 of them in acute pyelonephritis with marked destructive changes, 24 during an exacerbation of chronic cystitis, 11 in asymptomatic bacteriuria. Twenty E. coli strains isolated from feces of apparently healthy individuals were used as a control. The genetic determinants associated with nucleotide sequences of pathogenicity islands (PI) known for enterobacteria: hlyA, hlyB, cnf-1, papC, fimA, and irp-2 were determined in bacteria, by using polymerase chain reaction. There was an association of the frequency of PI determinants in E. coli with the severity of the clinical course of urinary tract infection. The high frequency of 2 PI determinants or more was ascertained in highly pathogenic E. coli strains as compared with the cultures isolated from apparently healthy individuals.

[Clinical implications of E. coli pathogenic factors in patients with urinary infection].

The authors show perspectives of using primers detecting nucleotide gene sequences in isolated E. coli strains; pathogenic factors of E. coli, fimbrial adhesive (type I and type P); alpha-hemolysin (hly); cytotoxic necrotising factor I (cnf-1); iron-regulated proteins for predicting the course of the inflammatory process in urological patients with bacterial infection.

[Economic profitability: current aspects of X-ray contrast diagnosis in urology].

A diversity of X-ray contrast diagnostic techniques used in urology provides a way of using different groups of X-ray contrast materials (XCMs) in accordance of the set tasks. Many years' experience in handling water-soluble triiodinated XCMs while examining the kidneys and urinary tract provides evidence for their diagnostic effectiveness and safety. The new Triombrast (OAO "Farmac", Kiev) synthesized on the basis of the Spanish substance (Justesa Imagen SA) has successfully undergone clinical trials and meets the high requirements made by the specialized urological facilities is economically profitable. The paper has been prepared, by using the reports on the results of preclinical studies of the agent and the experience of its use in the clinic of the Research Institute of Urology and City Clinical Hospital No. 47, Moscow.

[Doksazozin "Cardura" in acute urinary retention caused by benign prostatic hyperplasia]. / Doksazozin "Kardura" pri ostroi zaderzhke mocheispuskaniia, obuslovlennoi dobrokachestvennoi giperplaziei prostaty.

Drug treatment of acute ischuria (AI) caused by benign prostatic hyperplasia (BPH) is discussed. Catheterization of the urinary bladder is the main treatment for AI. AI is caused by anatomical obstruction, hypertone of smooth myocytes, and energy imbalance of detrusor. Use of alpha 1-adrenoblockers in AI is pathogenetically justified, as the development of stable spasm of smooth-muscle structures of the prostate, vesical cervix, and prostatic compartment of the urethra resultant from increased functional activity of alpha 1-adrenoreceptors underlies the dynamic component of obstruction. alpha 1-Adrenoblocker doxazosin (cardura) was used for arresting AI caused by BPH after 12-h randomization and catheterization of the bladder. A prospective randomized placebo-controlled study was carried out on 36 patients. Spontaneous urination was restored in 55.5% patients, in 63.3% of these after doxazosin and in 16.6% after placebo. 37.9% of patients from the doxazosin group were discharged from hospital for outpatient therapy with alpha-blockers and the rest were operated on. Hence, doxazosin increases the chance of recovery of spontaneous urination for patients with AI caused by BPH and allows time and conditions for preparation of patients to surgery. Therapy with alpha 1-adrenoblockers after resolution of AI in patients with BPH can be effective and should be further investigated.

[Experience in the use of doxazosin in patients with benign hyperplasia of the prostate]. / Oøyt primeneniia doksazozina u bol'nykh dobrokachestvennoi giperplaziei prostaty.

Selective alpha-1-adrenoblockers are thought promising in current conservative treatment of benign prostatic hyperplasia (BPH). The trial of doxazosin (cardura)--a selective alpha-blocker--included 78 BPH patients with obstructive urination. All the patients received a single daily dose of doxazosin 4-8 mg (mean 5.7 mg). 60 patients on placebo served as control. The comparison of the effects observed in the study vs control group has demonstrated that doxazosin has a favourable effect on BPH: it improved quality of life, relieved obstructive symptoms, reduced amount of residual urine. There is objective urodynamic evidence on decreased infravesical obstruction.

[A clinical trial of the treatment of patients with benign prostatic hyperplasia using the alpha 1-adrenoblocker alfuzosin]. / Klinicheskii opyt lecheniia bol'nykh dobrokachestvennoi giperplaziei predstatel'noi zhelezy al'fa 1-adrenoblokatorom al'fuzozinom.

Alfuzosin (dalphaz) has been tried in 32 patients with benign prostatic hyperplasia (BPH). The treatment lasted for 14 weeks: 2 weeks of placebo and 12 weeks of alfuzosin. The drug was given in a daily dose of 10 mg (5 mg twice a day). The response was registered in 87.5% of cases. Improvement of urination occurred by all the parameters of IPSS scale (the overall IPSS dropped by 10.5 scores). Dalphaz had a good hypotensive effect: high blood pressure lowered to normal, normal pressure did not change. Dalphaz was well tolerated in all the cases except one when an allergic eruption broke out.

[The rapid microbiological control of the efficacy of the antibacterial therapy of bacteremia and septicemia]. / Mikrobiologicheskii ékspress-kontrol' éffektivnosti antibakterial'noi terapii bakteriemii i septitsemii.

No previous isolation of the agent on the media is needed in using a new microbiological express-method of automatic control over antibacterial therapy of bacteremia and septicemia. The method is efficient in determination of sensitivity to the drug of the whole heterogeneous population of bacteria. It does not predict efficacy of antibacterial therapy but states the presence or absence of the effect in vivo. The method is integral, evaluates antibacterial plasma titer suggesting adequate correction. The duration of the test is maximum 12 h that is 3-4 times less than other methods.

[The efficacy of bacteriophage preparations in treating inflammatory urologic diseases]. / Effektivnost' preparatov bakteriofagov pri lechenii vospalitel'nykh urologicheskikh zabolevanii.

Urinary infection is the most commonly encountered hospital infection. Antibacterial therapy promotes selection and dissemination of polyresistant microorganism strains, development of intestinal dysbacteriosis, reduction of intestinal contamination resistance. Clinical and bacteriological efficacy of urinary infection treatment with bacteriophage preparations (pyocyanic, proteus, staphylococcal, coliphage, combined pyobacteriophage) was studied. Sensitivity of the infective agent phage isolated from urological patients was tested before treatment. The preparations were adapted to recently isolated agents from urological patients to raise phage sensitivity of the strains. A total of 293 strains were studied. Phage sensitivity made up 68.9%. Bacteriophage preparations were used both locally and orally in 46 patients with acute and chronic urogenital inflammation. Bacteriological efficacy amounted to 84%, clinical one to 92%. It is inferred that phagotherapy is effective and safe therapeutic modality in the treatment of urinary infection in monotherapy and in combination with antibiotics.

[The use of cephmetazon in treating infectious inflammatory diseases of the upper and lower urinary tract]. / Primenenie tsefmetazona pri lechenii infektsionno-vospalitel'nykh zabolevanii verkhnikh i nizhnikh mochevyvodiashchikh putei.

A clinical trial of cephmethasone (Sankyo, Japan) has been performed in 40 patients with pyelonephritis. 3 patients with chronic cystitis. 19 patients with chronic prostatitis. Cephmethasone, cephalosporin of the second generation, is active against gram-positive and gram-negative agents, hospital infection. The treatment course consists of 4-14 daily doses of 2-4 g. Bacterial elimination was reached in 79.5% of the cases with a complete response in 70% and partial one in 30% of patients. Side effects were not registered. As a highly active wide-spectrum antibiotic, cephmethasone is offered for treatment of urinary infections. Cephmethasone monotherapy provides a rapid relief of cystitis, prostatitis and pyelonephritis symptoms.