An alternative approach to therapy of infections of the lower urinary tract
Urinary tract infection (UTI) takes the first place among all urological diseases [5, 9, 12-14]. They occur in outpatient and hospital practice, and their share in the structure of nosocomial infections is approaching 40%. On localization distinguish between infections of the upper and lower (INN) of the urinary tract. In outpatient practice often there are cases of uncomplicated UTI. In addition, isolated asymptomatic bacteriuria when patients detect leukocytes and bacteria 2 in urine culture in the titer of 105, and the clinical manifestations of the disease are absent.
In connection with the resistance of most uropathogens to existing antibiotics, currently, special attention is paid to the relationship between the prescription of antibiotics, their collateral damage effects and development of antibiotic resistance bacteria. Thus, in regions with a high frequency of prescribing fluoroquinolones are associated with higher levels of resistance to these drugs in comparison with regions where the drugs in this group are assigned to less frequently .
The number of new antibiotics annually endorse Food and Drug Administration (FDA) for use in medical practice has been steadily decreasing (Fig. 1) .
In the United States annually register up to 2 million cases of diseases caused of antibiotic-resistant bacteria. The resulting additional costs are about $ 20 billion. According to estimates of the European Medicines Agency and European Centre for Disease Prevention and Control, 25 thousand deaths in Europe annually are a direct consequence of antibiotic resistance of bacteria, and the total cost for treatment can reach 1.5 billion euros .
One of the leading mechanisms of development of antibiotic resistance is recognized as the ability of some bacteria to form biofilms. For example, Escherichia coli is the main causative agent of UTI in in vitro studies in 63% of cases demonstrated the capacity to form biofilm .
Biofilm is a source of infection, consisting of a single species of microorganisms or communities of different species that have their own structure, principles of life and life support systems and protection from adverse defense mechanisms of the host and antimicrobial agents . In the deeper layers of biofilms, the microbes survive doses of antibiotics that tens or hundreds of times higher than therapeutic concentrations .
Despite the approved guidelines for treatment of UTI, studies conducted in different countries show the incorrect prescription of antibiotics both in hospital and in ambulatory practice.
Currently, the need for an integrated approach to pharmacotherapy of urological diseases is reflected in the recommendations morethe rational use of antimicrobial drugs, limiting their use in recurrent, INN, treatment and prevention of urological diseases using herbal medicines.
The problem of the use of antimicrobial agents in UTI are suitable more balanced. The results of the pilot study J. Bleidorn et al. (2010) showed that in uncomplicated UTI, the effectiveness of antibiotics and ibuprofen are comparable . That is, in some cases enough to remove marked inflammation, giving the body the ability to fight infection.
In the European guidelines (European Guidelines) for the treatment of infections in urology (2014) in the Chapter "antimicrobial prophylaxis of recurrent infections of the lower urinary tract in women," continuous or postcoital antimicrobial prophylaxis to prevent recurrent UTI are recommended for use only after elimination of behavioral risk factors and measures neinteresno prevention have been ineffective. Screening and treatment of asymptomatic bacteriuria should now be used only in pregnant women and patients who have invasive surgery on the urogenital tract .
By analogy with the European Guidelines in Russian national recommendations of antimicrobial therapy and prevention of infections of the kidneys, urinary tract and male genital organs" in the section "Alternative methods of treatment of recurrent urinary tract infections" also listed drugs for the treatment and prevention of UTI, non-antibiotics .
The herbal remedies that can be applied for the treatment of recurrent UTIS is Kanefron® H ("Bionorica SE, Germany). It is a drug with an optimal integrated action for the treatment and prevention of chronic recurrent UTIS (cystitis, pyelonephritis) and kidney stones. The kanefron® H also effectively used for the rehabilitation of patients who have had surgery on the urinary tract. In the product contains a special extract of centaury, lovage and rosemary, which provide anti-inflammatory, antispasmodic, anti-adhesive, antimicrobial and diuretic effects.
Clinically proven Kanefron® H helps to reduce pain and sharp pains when urinating, reduces the number of repeated exacerbations, improves the effectiveness of antibiotic therapy [2, 7, 9]. The drug is recommended for metaphylaxis of urolithiasis, promotes discharge of stones and prevents their formation [1, 2], significantly reduces irritative symptoms in the postoperative period .
With the required proven in clinical studies of efficacy conducted a pilot studyaimed at validating the use of the drug Kanefron® H as monotherapy in acute uncomplicated cystitis. The study included 125 women who took Kanefron® H for 7 days. At any time at the request of each of the participants could start the antibiotic therapy. After 7 days therapy with the drug was stopped. The patients continued for another 30 days. The severity of symptoms was assessed according to the developed scale, also evaluated the results of the General analysis of urine and blood.
The primary endpoint was frequency of adverse reactions to the drug for 7-day therapy drug Kanefron® H. Secondary end points were the percentage of patients who required treatment with antibiotics until the 7th day and the proportion of patients on 7th day was absent, INN symptoms (dysuria, pollakiuria and urgent need) with a severity greater than average degree (i.e., patients responding to treatment).
None of the 125 patients was not reported side effects associated with the drug. 97.6% of women did not require treatment with antibiotics to the 7th day, and the overall proportion of patients responding to treatment was 71.2%. Thus was demonstrated the possibility of application of the drug Kanefron® H as monotherapy in acute uncomplicated INN. However, to confirm the obtained result, further research is needed, including larger sample volume .
The kanefron® H is used successfully to prevent recurrent UTIS. In the observational study of Maria Sinyakova L. A., in 91% of patients with a diagnosis of "acute pyelonephritis" and "chronic cystitis" in the background of sexually transmitted infections after an adequate etiological and pathogenetic treatment found no relapses of the disease within 1 year if prophylactic drug Kanefron® H .
Under the auspices of the Russian society of obstetricians and gynecologists (President – academician, Professor V. N. Serov was conducted a multicenter retrospective observational study "Evaluation of experience with the herbal drug Kanefron® H in pregnant women". The work evaluated the medical records of 550 pregnant women, of whom 480 are women along with standard antibiotic therapy cystitis, exacerbation of chronic cystitis or pyelonephritis or gestational pyelonephritis took Kanefron® H. 70 women were assigned to only antibiotic therapy (comparison group). The results of the study showed that the dynamics of the dysuric phenomena of acute cystitis and chronic cystitis was statistically significantly better in the group of women who received Kanefron® H (Fig. 2) .
The safety of the drugas proven in animal studies and clinically. The results of the analysis of 19 studies, which included 3327 patients taking Kanefron® H, including 2270 pregnant women confirmed the high safety profile of the drug .
Thus, given the increase of resistance of uropathogens to antimicrobial resistance on a global scale it is necessary to search alternative and synergistic treatment. The kanefron® N, herbal medicine with proven efficacy may be used for the treatment and prevention of a number of uncomplicated UTIS.
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