[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.

[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.

[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.

[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.

[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.

[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.

[Effectiveness of cefmetazole in the treatment of infectious-inflammatory urologic diseases]. / Effektivnost' tsefmetazola pri lechenii infektsionno-vospalitel'nykh urologicheskikh zabolevanii.

An open non-comparative clinical trial of cefmetazole in the treatment of 40 patients with infections of the lower and upper urinary tracts was performed. The clinical results were excellent and good in 100 per cent of the cases. In 75 per cent of the cases the efficacy was bacteriological (complete eradication of the pathogen). No patients showed any adverse reactions to the treatment with cefmetazole. The general estimate of the results was indicative of the cefmetazole high efficacy in the treatment of the infections of the upper and lower urinary tracts.

[Sulbactam/ampicillin in the treatment and prevention of urologic diseases]. / Sul'baktam/ampitsillin v lechenii i profilaktike urologicheskikh zabolevanii.

Efficacy and safety of unasyn, a combination of sulbactam and ampicillin, was studied in the treatment of 66 patients with infections of the urogenital organs. The drug was administered intramuscularly, intravenously and orally. The treatment course averaged 7-14 days. The dose of the drug for the intravenous and intramuscular administration was 1.5-3 g 4 times a day and that for the oral administration was 0.75 g 2 times a day. The strains of gram-positive cocci, Escherichia coli and Proteus spp. proved to be highly sensitive to the drug: 80-83, 43 and 53 per cent of the sensitive strains respectively. 25-75 per cent of the strains showed beta-lactamase activity that was most frequently detected in Proteus spp. and Staphylococcus spp. The maximum concentrations of ampicillin and sulbactam determined by liquid chromatography were respectively 18 +/- 5.7 and 11 +/- 2.42 micrograms/ml in the blood and 700 and 350 micrograms/ml in the urine. A satisfactory bacteriological effect of the treatment was observed in 93 per cent of the cases. A complete elimination of the initial pathogens was stated in 57-73 per cent of the cases. No side effects were recorded.

[The use of ampicillin/sulbactam (Unasyn) in treating inflammatory urological diseases]. / Ispol'zovanie ampitsillin/sul'baktama (unazina) pri lechenii vospalitel'nykh urologicheskikh zabolevanii.

Unasyn is a combination of ampicillin, a bactericidal antibiotic, and sulbactam, an inhibitor of beta-lactamases. It was used in treatment of 36 patients with urogenital infections. The combination was administered intravenously and in the main intramuscularly. The treatment course amounted to 7-10 days. The average daily dose was 6 to 9 g. 22 patients with acute nonocclusive pyelonephritis were treated with the combination and its clinical and bacteriological efficacy was stated in 95 per cent of the cases. An excellent clinical effect of the combination was observed in 6 patients with acute epididymitis. A clinical improvement was also observed in the treatment of the patients with acute prostatitis and chronic renal infections. Unasyn proved to be a highly efficient antibacterial combination with regard to gram-positive flora and colon bacilli as representatives of gram-negative organisms. Satisfactory results were also stated in the treatment of infections caused by Proteus spp. Complete elimination of the pathogen was achieved in 57.7 per cent of the cases. No adverse reactions to Unasyn except pain in the site of the injection were recorded.

[New quinolones in urological diseases of an inflammatory nature]. / Novye khinolony pri urologicheskikh zabolevaniiakh vospalitel'noi prirody.

New drugs of the group of the 3rd generation fluoroquinolones i. e. norfloxacin, ciprofloxacin, ofloxacin and pefloxacin possess a high antibacterial activity against the majority of the problem causative agents of urinary infections. This was confirmed by the studies on sensitivity of 950 clinical strains of the pathogens isolated from inpatients of an urological department. Sensitivity of the majority of the pathogens to the fluoroquinolones was the following: 80.3 to 100 per cent among enteric bacteria, 80.2 to 89.6 per cent among Pseudomonas spp. and 94.7 to 100 per cent among Staphylococci, 288 patients were treated with the fluoroquinolones. The patients were divided into 3 groups according to the urinary infection i. e. acute inflammatory diseases, chronic pyelonephritis and chronic inflammatory diseases of the genital tract. The results of the studies estimated by complex clinico-laboratory indices revealed a close efficacy of the drugs in the patients. This was due to their analogous antibacterial spectra and similar pharmacokinetic characteristics investigated in 23 patients after the drug administration by various routes: intravenous and oral. No differences in tolerance of the fluoroquinolones were observed.

[Clinical effectiveness of pefloxacin (abaktal)in the treatment of inflammatory diseases of the kidneys, urinary tracts and genital organs]. / Klinicheskaia éffektivnost' pefloksatsina (abaktal*) v lechenii vospalitel'nykh zabolevanii pochek, mochevyvodiashchikh putei i polovykh organov.

Pefloxacin (Abaktal) was used in treatment of 83 patients: 14 patients with acute pyelonephritis, 5 patients with carbuncle of the kidney, 17 patients with postoperative acute pyelonephritis, 3 patients with urosepsis, 7 patients with acute prostatitis, 18 patients with chronic pyelonephritis in the phase of active inflammation, 9 patients with exacerbation of chronic prostatitis, 3 patients with acute cystitis, 2 patients with acute urethritis and 5 patients with epididymo-orchitis. Two dosage forms of pefloxacin were used i.e. tablets of 400 mg and ampoules of 5 ml containing 400 mg of the active substance. The treatment course amounted to 7-14 days. In the patients with inflammatory infectious diseases of the lower urinary tracts (cystitis and urethritis) the treatment course amounted up to 5 days. The results of the treatment with the ampoule solutions were good and satisfactory. With the use of the tablets the results were unsatisfactory in 3 patients (8.1 per cent). Satisfactory bacteriological efficacy of the treatment was stated in 89.5 per cent of the cases. The adverse reactions such as nausea, vomiting, diarrhea and skin eruption were recorded in 5 patients (6 per cent).

[Ligenten--a combination drug with anesthetic and antibacterial action for local use in urology and gynecology]. / Ligenten--kombinirovannyi preparat s anesteziruiushchim i antibakterial'nym deistviem dlia mestnogo primeneniia.

Ligenten gel is a combined dosage form containing gentamicin (a broad spectrum antibiotic), lidocaine (an anesthetic) and ethonium (an antiseptic). The hydrogel sodium carboxymethylcellulose in combination with polyvinylpyrrolidone is used as the ligenten base. The clinical trials in urologic and gynecologic patients showed that ligenten had a high therapeutic efficacy in the treatment of inflammatory diseases, as well as an anesthetic action in instrumental examinations and surgical endoscopic manipulations.

[Gentacycol--a delayed-action form of gentamicin in the treatment of suppurative infection]. / Gentatsikol--prolongirovannaia lekarstvennaia forma gentamitsina v lechenii gnoinoi inferktsii.

Efficacy of gentacycol was studied in the treatment of various purulent infections. It was used in therapy of hematogenic and traumatic osteomyelitis, wound infections, soft tissue abscesses, purulent diffuse peritonitis as a complication of comissural ileus or appendectomy, pyothorax, destructive pneumonia and mediastinitis. Gentacycol ++ was also used for the prophylaxis in cholecystectomy, herniotomy and other conditions. The favourable results were stated in 93 per cent of the cases.

[Sulacillin (a combination of ampicillin and sulbactam)--a new combined drug form for treatment of bacterial infections]. / Sulatsillin (sochetanie ampitsillina s sul'baktamom)--novaia kombinirovannaia lekarstvennaia forma dlia lecheniia bakterial'nykh infektsii.

The results of the cooperated clinical trial of sulacillin, a formulation including sodium ampicillin and sulbactam (2:1), are presented. The trial was carried out in different hospitals of Moscow and Smolensk. Rapid development of the favourable time course and recovery were stated in 93.7 per cent of the cases with upper and lower respiratory tract infections, urinary and biliferous tract infections, infections of the skin and soft tissues, gynecological infections and severe suppurative complications after surgical operations. Sulacillin is useful in the empirical therapy of purulent inflammatory diseases before the pathogen isolation and identification.

[The efficacy of Ligenten gel in the prevention and treatment of infectious-inflammatory diseases of the urogenital organs]. / Effektivnost' gelia Ligentena pri profilaktike i lecheniia infektsionno-vospalitel'nykh zabolevanii mochepolovykh organov.

A new therapeutic in the form of a gel named ligenten was studied. The gel active components are lidocain, gentamicin and ethonium. Ligenten was shown to have a marked local anesthetic action when administered transurethrally. As a prophylactic agent the gel was highly active against the majority of the causative agents of renal infections due to cystoscopy, catheterization and bougienage of the urethra. Ligenten provided a sufficient anesthetic effect in transurethral operations but did not prevent superinfection due to the hospital strains. Marked antiinflammatory and reparative actions of the gel especially in the treatment of ulcerous cystitis were observed.