Recurrent cystitis in women: treatment

Treatment of recurrent cystitis in women should be complex (etiological and pathogenetic) and directed primarily at eliminating the causes of frequent recurrence of infection of the lower urinary tract.

Cystitis is an infectious disease, and, consequently, without an agent, there is no infection.

At present, pathogenetically substantiated algorithms of conservative treatment of recurrent cystitis in women have been developed. Pathogenetic methods of therapy include surgical treatment of recurrent cystitis in women, aimed at correcting anatomical changes and eliminating the causes of urodynamic disturbances.

With gross hyperplastic changes in the bladder neck, it is necessary to carry out operative treatment of recurrent cystitis in women, aimed at eliminating obstruction and restoring normal anatomy: meatotomy, TUR of the neck of the bladder. The combination of internal urethrotomy and TUR of the neck of the bladder before the start of medication helps improve its results. In the presence of pseudopolyposis of the neck of the bladder and the proximal urethra in the background of chronic cystitis, the transurethral electrovaporization of the neck of the bladder and the proximal part of the urethra is considered a method of choice, eliminating the cause of the disease and being the most important component of complex therapy, which increased the effectiveness of treatment by 1.98 times.

When a dystopia of the urethra is detected, an operative correction of the location of the urethra in the volume of the transposition of the urethra and the dissection of the urethro-menial adhesions is recommended.

[1], [2], [3], [4], [5], [6], [7], [8], [9], [10]

Antibacterial treatment of recurrent cystitis in women

Etiological treatment of recurrent cystitis in women - antibacterial therapy.

The choice of an antimicrobial agent should be based on microbiological examination data. If in acute uncomplicated cystitis, preference should be given to short courses of antibiotic therapy (3-5 days), then for a chronic relapsing disease for complete eradication of the pathogen, the duration of antibiotic therapy should be at least 7-10 days.

According to the recommendations of the European and American Association of Urologists for the treatment of urinary tract infections, non-pregnant women with acute cystitis include co-trimoxazole (sulfamethoxazole + trimethoprim) or trimethoprim (in the absence of resistance more than 10-20% in the region) for drugs of standard empirical antibacterial therapy. In the presence of resistance to these drugs, the choice of fluoroquinolones for oral administration, prescribed for three days, nitrofurantoin (for seven days), phosphomycin and trometamol (at a dose of 3 g once) is considered a choice drug. Children are prescribed inhibitor-protected penicillins and cephalosporins of the first and third generation (inside), pregnant women - cephalosporins of the first and third generation, phosphomycin trometamol (once), nitrofurantoin (in the second trimester of pregnancy). All specified preparations in out-patient conditions appoint or nominate inside. With recurrent infections of the urinary tract, antibacterial therapy is prescribed taking into account the pathogen isolated during bacteriological examination and its sensitivity to antibiotics.

In the international study ARESC for drugs, the sensitivity of pathogens to which is more than 90%, include phosphomycin, trometamol, nitrofurantoin and ciprofloxacin. Thus, according to recent studies, for empirical therapy, phosphomycin and trometamol are used at a dose of 3 g, nitrofurantoin (for five days), fluoroquinolones (ciprofloxacin, norfloxacin for three days). Systemic fluoroquinolones (ciprofloxacin, ofloxacin, levofloxacin, lomefloxacin) are considered the drugs of choice in the treatment of recurrent urinary tract infections. They have very high activity against E. Coli and other gram-negative pathogens of urological infections, they create a high concentration in tissues and blood serum.

In studies of UTIAP-1 and UTIAP-11 (2004), high resistance of E. Coli to ampicillin and co-trimoxazole was found, which does not allow to recommend these drugs for the treatment of urinary tract infections. The use of co-trimoxazole is considered acceptable only in those regions where the frequency of resistance of E. Coli does not exceed 20%. If there is no information about local resistance to antibiotics, then the drug should not be used.

Non-fluorinated quinolones - pipemidic acid and oxolinic acid have lost their leading importance due to the high resistance of pathogens. They are given the role of drugs, the use of which is possible at the stage of reconvalescence in uncomplicated urinary tract infections.

When an STI is detected, a course of antibacterial therapy with the inclusion of macrolides, tetracyclines and fluoroquinolones, aimed at eradicating the pathogen, is prescribed. In the future, a control bacteriological study is carried out.

Despite the use of modern antibacterial and chemotherapeutic drugs that can quickly and effectively stop the recurrence of urinary tract infections, as well as reduce their frequency by prescribing low preventive doses of medicines for a long period of time, antimicrobial therapy is associated with a number of problems. An alternative approach to the treatment of urinary tract infections is the stimulation of the patient's own immune mechanisms directed against pathogenic microflora by the ingestion of immunotherapeutic drugs. One of them is a lyophilized protein extract obtained by fractionating an alkaline hydrolyzate of some strains of E. Coli. Lysate of E. Coli bacteria (uro-Vax) is released in capsules, each containing 6 mg of standardized fractions. Stimulation of nonspecific immune defense mechanisms with this drug is an acceptable alternative, as effective as low-dose long-term chemoprophylaxis, which is considered a common method of preventing urinary tract infections. The drug is applied one capsule per day on an empty stomach for 3 months, then - one capsule per day on an empty stomach for 10 days of each month (duration of the course is 6 months). The drug is recommended after specific therapy.

Considering the treatment of recurrent cystitis in women, it is necessary to pay attention to the use of polyvalent bacteriophages, which is especially important for patients with a polyvalent allergy to antibacterial drugs or the presence of multiresistant pathogens. Despite the absence of placebo-controlled studies on the use of piobacteriophages, the clinical efficacy of these drugs is undeniable.

Plant diuretics are used as a method of preventing recurrence of urinary tract infections and in the stage of outpatient care. Kanefron H1 - a combined herbal medicine, which includes a centiparous (Gentianaceae), lovage (Apiaceae), rosemary (Lamiaceae). It has a complex action: diuretic, spasmolytic. Anti-inflammatory, antioxidant, antimicrobial and nephroprotective. The drug increases the effectiveness of antibiotic therapy and increases the relapse-free period of chronic infections of the urinary tract. Apply 50 drops or two pills three times a day for 2-3 months.

Along with the general methods of treatment, it is possible to carry out installations with a suspension of hydrocortisone, sodium heparin and other mucopolysaccharides. Similar in structure to glycosaminoglycans, the walls of the bladder, contributing to the restoration of its integrity and stabilizing mast cells.

[11], [12], [13], [14], [15]

Principles of treatment of recurrent cystitis in women

Patients with frequently recurrent uncomplicated urinary tract infections (more than two exacerbations within 6 months and more than 3 exacerbations within one year) are prescribed preventive treatment. There are 4 main approaches to conducting preventive antibiotic therapy:

• Prolonged prophylactic intake of low doses of one of the fluoroquinolones (norfloxacin at 200 mg, ciprofloxacin 125 mg, pefloxacin 800 mg / week), or nitrofurantoin (50-100 mg), or co-trimoxazole (240 mg each), or phosphomycin and trometamol (3 g) every ten days for 3 months. During pregnancy, prescribe cephalexin (125 mg / day) or cefaclor (250 mg / day).
• Patients with relapses of uncomplicated urinary tract infections associated with sexual intercourse are recommended to take the drug after coition. With this mode of prevention, the dose of the drug decreases, the frequency of development of unwanted reactions, the selection of resistant strains.
• Patients with rare relapses of uncomplicated urinary tract infections who do not have the opportunity to see a doctor can be recommended to take an antibacterial drug alone. To confirm the elimination of the pathogen, it is desirable to conduct a bacteriological study of urine 1-2 weeks after the end of the drug intake.
• Women in the postmenopausal period in the absence of contraindications (the presence of hormone-dependent tumors) is recommended periurethral or intravaginal application of hormonal creams containing estrogens. Treatment of this group of patients should include the use of local hormonal drugs (after exclusion of hormone-dependent tumors of the internal genital organs), for example estriol (per vaginum), for the normalization of the estrogen background. Suppositories or cream are prescribed daily for a week, then one suppository per night every other day for a week, followed by a transition to a supportive course (twice a week for a long time, for a year or more). For timely diagnosis of hormonal-active diseases of internal genital organs, dynamic monitoring is carried out.
• Strict adherence to indications for invasive urological manipulation and mandatory use of antibiotic prophylaxis before their administration.

Medication postcoital prophylaxis of cystitis is effective in eliminating such risk factors as STI, inflammatory diseases of the genital organs, anomalies of the location of the external opening of the urethra.

Chronic cystitis is rarely an independent disease. That is why there is a need for a comprehensive approach to diagnosis (with the establishment of the cause of the disease), treatment (should be etiological and pathogenetic) and prevention.

Leukoplakia - whitish spots on the visible mucous membranes (oral cavity, urinary organs, cervix, etc.). In the morphological investigation of the sites of leukoplakia, metaplasia of the transitional epithelium is revealed in a multilayer flat (sometimes with cornification). Since the first description of bladder leukoplakia, various theories of its occurrence have been proposed: embryonic development defects, the effect of a specific infection (tuberculosis, syphilis), vitamin A deficiency. Currently, these assumptions are disproved. For a long time, an inflammatory theory of the onset of leukoplakia of the bladder was adopted, in favor of which P.A. Herzen (1910). However, foreign morphologists have shown that metaplasia of the epithelium is accompanied by edema of the underlying tissue and vasodilation, but not by marked inflammation. By analogy with the lesion of other localizations of leukoplakia of the bladder, many authors considered it to be a precancerous condition, meanwhile there is not a single reliable observation of the transition of bladder leukoplakia to cancer. In the light of modern research, leukoplakia is a pathological process characterized by a violation of the basic functions of multilayer flat epithelium (absence of glycogen formation and the appearance of keratinization, which are absent in the norm).

The evidence supporting the role of urogenital infections (Chlamidia trachomatis, Ureaplasma urealiticum, N. Gonorrhoeae, M. Genitalium T. Vaginalis, Herpes simplex I, II) in the etiology of urethritis and cystitis in women was presented above. At the same time, it was shown that the causative agents of urogenital infections cause unusual inflammatory damage to the tissues of the urinary tract, different from that caused by exposure to nonspecific microflora (E. Coli, etc.). In scientific works it is shown that in response to the penetration of infection in urothelium, various forms of dystrophic damage constantly arise: vacuolar, ballooning and reticular dystrophy of prickly layer cells, small foci of acantholysis with the formation of spongeiform vesicles. Foci of squamous cell metaplasia are often combined with transitional epithelium without signs of proliferation, but more often with hyperplastic urothelium. In the proliferating and non-proliferating transitional epithelium, uncoupling and desquamation of the umbilical cells of the surface layer are observed. It was shown that in patients with persistent dysuria and urgency with or without bacteriuria, cystoscopy with biopsy shows squamous metaplasia with submucous fibrosis of varying severity. Interestingly, with pronounced morphological changes, bacteriuria was absent. Infection is the etiological factor of urothelial damage and the formation of metaplasia, while further alteration occurs independently of it and leads to persistent dysuria. Patients with squamous metaplasia have increased permeability of the epithelium, adaptive urothelial reconstruction is not possible at physiological filling of the bladder, which leads to diffusion of urine components into interstitium and development of frequent painful urination, the development of pain over the bosom, in the urethra, etc. The main stage of the pathogenesis of urinary leukoplakia Bubble is considered the destruction of the normal glycosaminoglycan layer of the bladder wall under the influence of urogenital infections. Even with eradication of the pathogen after a course of specific antibacterial therapy, clinical symptoms persist.

Thus, considering the increasing specific gravity of primary uncomplicated urinary tract infections and chronic processes with frequent recurrences in the structure of inflammatory urological diseases taking place against the background of asymptomatic urogenital infection, the etiological role of the latter in the pathogenesis of uncomplicated urinary tract infections requires further study and development of treatment tactics for this category of patients.

According to some reports, for the period from 2005 to 2007, 70 patients aged 16 to 40 years with recurrent urinary tract infections and persistent dysuria were examined. A general analysis and a bacteriological study of urine were conducted. For the diagnosis of STIs, a serum diagnostic study was carried out using PCR in two biotopes, from the cervical and urethra. All patients underwent a vaginal examination and O'Donnel test. 54 women with a duration of disease for more than two years performed cystoscopy. Growth of microflora in a bacteriological study of urine was found in 44 (63%) patients, while E. Coli was isolated in 30 (43%) samples. The presence of STI agents by PCR was detected in 51 (73%) patients: Ureaplasma urealyticum (Parvo biovar) - in 24 (34%) Chlamydia trachomatis, Herpes simplex I, type II in 16 (23%); the remaining patients were found to have a mixed infection. During vaginal examination, 24 women with recurrent urinary tract infections were found to have a vaginal ectopy of the external opening of the urethra. Among patients who underwent cystoscopy "4) in 26 diagnosed leukoplakia of the neck of the bladder and the urinary bladder triangle with a morphological picture of squamous cell metaplasia of the epithelium and destruction of the glycosaminoglycan layer. Two women were diagnosed with squamous cell papilloma, three of them had pseudopolyposis of the neck of the bladder.

Despite the fact that the endoscopic picture of leukoplakia of the bladder is very characteristic (the picture of "melting snow"), a histological confirmation of the diagnosis is necessary. Differential diagnosis should be carried out with squamous cell papilloma and in rare cases with bladder cancer.

After morphological confirmation of the diagnosis, treatment can be carried out. Pathogenetically justified treatment of leukoplakia is considered eradication of STD pathogens.

Unfortunately, only with the use of antibacterial therapy, the restoration of damaged urothelium and regression of the clinical picture does not occur. It is probably necessary to continue treatment aimed at the restoration of the destroyed glycosaminoglycan layer. At present, clinical studies on intravesical administration of exogenous glycosaminoglycan analogues (heparin sodium, hyaluronic acid, chondroitin sulfate, pentosan sodium polysulphate, etc.) are underway in this category of patients. Preliminary data demonstrate the high effectiveness of this method of treatment. TUR is performed only if the treatment is ineffective or in the presence of pseudopolips.

Treatment of recurrent urinary tract infections

• Pathogenetic treatment of recurrent cystitis in women.
  • Correction of anatomical disorders. Patients in whom chronic cystitis developed against the background of "vaginalization" of the external opening of the urethra, transposition of the urethra, dissection of urethrogimenal adhesions outside the exacerbation of the chronic process is recommended.
  • Treatment of STIs. Drugs of choice: macrolides (josamycin, azithromycin, midecamycin), tetracyclines (doxycycline), fluoroquinolones (mok-sifloxacin, levofloxacin, ofloxacin).
  • Postcoital prevention.
  • Treatment of inflammatory and dysbiotic gynecological diseases.
  • Correction of hygiene and sexual factors.
  • Correction of immune disorders. Apply nonspecific immunomodulators (dioxomethyltetrahydropyrimidine for 0.5 g 3 times a day for 20-40 days).
  • Local treatment of recurrent cystitis in women. Intravesical infusions of mucopolysaccharides (25,000 units of sodium heparin once a day for 10 days), structurally similar to glycosaminoglycans of the bladder wall, contributing to the restoration of its integrity and stabilizing mast cells.
  • Diuretics and drugs of complex action of plant origin (Kanefron) are used as a method of preventing recurrences of urinary tract infections and at the stage of outpatient care.
• Etiological treatment of recurrent cystitis in women - antibacterial therapy.
  • Duration up to 7-10 days.
  • Choose a drug is necessary in view of the sensitivity of the selected pathogen to antibacterial drugs.
  • Assign antibiotics with bactericidal action:
    • in uncomplicated infections of the lower urinary tract (in the case of the exclusion of STIs), phosphomycin, trometamol, fluoroquinolones (norfloxacin), nitrofurantoin;
    • In the presence of STIs, macrolides (josamycin, azithromycin, midecamycin), tetracyclines (doxycycline), fluoroquinolones (moxifloxacin, levofloxacin, ofloxacin) are considered to be the drugs of choice.
  • Antiviral treatment of recurrent cystitis in women with the detection of genital herpes: acyclovir, valaciclovir, famciclovir.
  • Immunobiotherapy uro-vacc.

One of the most promising drugs is Lavomax (tilorone), a synthetic low-molecular inducer of interferon, effective for oral administration. The drug has an immunomodulatory and antiviral effect. Data on immunomodulatory effects of Lavomax testify to the advisability of its use in various infectious and non-infectious diseases accompanied by immunodeficiency states, in particular, in chronic recurrent cystitis. The immunomodulating activity of the drug is also manifested by an increase in the activity of the cellular immune link.

In the complex therapy, the drug Lavomax contributes to a faster disappearance of clinical signs of cystitis.

The inclusion of Lavomax in the treatment of chronic cystitis contributes to a decrease in the frequency of relapses.

The drug is not biotransformation, does not accumulate in the body.

Lavomax with cystitis is prescribed according to the following scheme: the first day of 0.125 g 2 times, then 0.125 g at 48 h. The course of treatment is 1.25 g (10 tablets). Next, the drug is prescribed for prophylaxis by 0,125 g once a week for 6 weeks. The course of preventive treatment is 0.75 g.

To treat herpetic infection, Lavomax is prescribed according to the following scheme: the first two days of 0.125 g then 48 h to 0.125 g.

In the treatment of chlamydial infection apply according to the scheme: 0.125 g per day for the first two days, then after 48 hours. For the course of 1.25 g.