Recurrent cystitis in women - Treatment

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

Cystitis is an infectious disease, and therefore, without a pathogen there is no infection.

Currently, pathogenetically substantiated algorithms for 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 disorders.

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

If dystopia of the urethra is detected, surgical correction of the position of the urethra is recommended in the amount of transposition of the urethra and dissection of the urethrohymenal adhesions.

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Antibacterial treatment of recurrent cystitis in women

Etiological treatment of recurrent cystitis in women is antibacterial therapy.

The choice of antimicrobial drug should be based on the data of microbiological research. If in acute uncomplicated cystitis preference should be given to short courses of antibacterial therapy (3-5 days), then in chronic recurrent 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 Urological Associations for the treatment of urinary tract infections, the standard empirical antibacterial therapy for adult non-pregnant women with acute cystitis includes co-trimoxazole (sulfamethoxazole + trimethoprim) or trimethoprim (in the absence of resistance of more than 10-20% in the region). In the presence of resistance to these drugs, the drugs of choice are fluoroquinolones for oral administration, prescribed for three days, nitrofurantoin (for seven days), fosfomycin and trometamol (in a single dose of 3 g). Children are prescribed inhibitor-protected penicillins and first- to third-generation cephalosporins (orally), pregnant women - first- to third-generation cephalosporins, fosfomycin trometamol (single dose), nitrofurantoin (in the second trimester of pregnancy). All of the above drugs are prescribed orally in outpatient settings. In case of recurrent urinary tract infections, antibacterial therapy is prescribed taking into account the pathogen isolated during bacteriological examination and its sensitivity to antibiotics.

In the international ARESC study, fosfomycin, trometamol, nitrofurantoin and ciprofloxacin are considered to be the drugs to which the sensitivity of pathogens is more than 90%. Thus, according to the latest studies, fosfomycin and trometamol in a dose of 3 g, nitrofurantoin (for five days), fluoroquinolones (ciprofloxacin, norfloxacin for three days) are used for empirical therapy. 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, creating a high concentration in tissues and blood serum.

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

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

If an STI is detected, a course of antibacterial therapy is prescribed, including macrolides, tetracyclines and fluoroquinolones, aimed at eradicating the pathogen. A control bacteriological study is then carried out.

Despite the use of modern antibacterial and chemotherapeutic drugs that allow for rapid and effective suppression of urinary tract infection recurrences and reduction of their frequency by prescribing low prophylactic doses of drugs for a long period, antimicrobial therapy is associated with a number of problems. An alternative approach to the treatment of urinary tract infections is stimulation of the patient's own immune mechanisms directed against pathogenic microflora by oral administration of immunotherapeutic drugs. One of them is a lyophilized protein extract obtained by fractionation of alkaline hydrolysate of some E. coli strains. E. coli bacterial lysate (uro-Vaxom) is available in capsules, each containing 6 mg of standardized fractions. Stimulation of nonspecific immune defense mechanisms with this agent is an acceptable alternative, as effective as low-dose long-term chemoprophylaxis, which is considered a generally accepted method for preventing urinary tract infections. The drug is used one capsule per day on an empty stomach for 3 months, then one capsule per day on an empty stomach for 10 days each month (course duration - 6 months). Taking the drug is recommended after specific therapy.

When 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 polyvalent allergy to antibacterial drugs or the presence of multiresistant pathogens. Despite the lack of placebo-controlled studies of the use of pyobacteriophages, the clinical effectiveness of these drugs is beyond doubt.

Herbal diuretics are used as a method of preventing recurrence of urinary tract infections and at the stage of outpatient follow-up treatment. Canephron H1 is a combined herbal medicinal product, which includes centaury (Gentianaceae), lovage (Apiaceae), rosemary (Lamiaceae). It has a complex effect: diuretic, antispasmodic, anti-inflammatory, antioxidant, antimicrobial and nephroprotective. The drug increases the effectiveness of antibacterial therapy and increases the relapse-free period of chronic urinary tract infections. Apply 50 drops or two dragees three times a day for 2-3 months.

Along with general treatment methods, it is possible to perform instillations of hydrocortisone suspension, sodium heparin and other mucopolysaccharides similar in structure to the glycosaminoglycans of the bladder wall, which help restore its integrity and stabilize mast cells.

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Principles of treatment of recurrent cystitis in women

Patients with frequently recurring uncomplicated urinary tract infections (more than two exacerbations within 6 months and more than three exacerbations within one year) are prescribed prophylactic treatment. There are 4 main approaches to prophylactic antibacterial therapy:

• Long-term prophylactic administration of low doses of one of the fluoroquinolones (norfloxacin 200 mg, ciprofloxacin 125 mg, pefloxacin 800 mg/week), or nitrofurantoin (50-100 mg), or co-trimoxazole (240 mg), or fosfomycin and trometamol (3 g) every ten days for 3 months. During pregnancy, cephalexin (125 mg/day) or cefaclor (250 mg/day) are prescribed.
• Patients with recurrent uncomplicated urinary tract infections associated with sexual intercourse are recommended to take the drug after coitus. This preventive regimen reduces the drug dose, the incidence of adverse reactions, and the selection of resistant strains.
• Patients with rare recurrences of uncomplicated urinary tract infections who are unable to see a doctor may be advised to take an antibacterial drug on their own. To confirm the elimination of the pathogen, it is advisable to conduct a bacteriological examination of urine 1-2 weeks after the end of taking the drug.
• For postmenopausal women, in the absence of contraindications (the presence of hormone-dependent tumors), periurethral or intravaginal use of hormonal creams containing estrogens is recommended. Treatment of this group of patients should include the use of local hormonal drugs (after excluding hormone-dependent tumors of the internal genital organs), such as estriol (per vaginum), to normalize the estrogen background. Suppositories or cream are prescribed daily for weeks, then one suppository at night every other day for a week, followed by a transition to a maintenance course (twice a week for a long time - from a year or more). Dynamic observation is carried out for timely diagnosis of hormonally active diseases of the internal genital organs.
• Strict adherence to indications for invasive urological procedures and mandatory use of antibiotic prophylaxis before performing them.

Medicinal postcoital prophylaxis of cystitis is effective when such risk factors as STIs, inflammatory diseases of the genitals, and abnormalities in the location of the external opening of the urethra are excluded.

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

Leukoplakia is a whitish spot on the visible mucous membranes (oral cavity, urinary organs, cervix, etc.). Morphological examination of leukoplakia areas reveals metaplasia of transitional epithelium into stratified squamous epithelium (sometimes with keratinization). Since the first description of leukoplakia of the bladder, various theories have been proposed for its origin: defects in embryonic development, the influence of a specific infection (tuberculosis, syphilis), vitamin A deficiency. These assumptions have now been refuted. For a long time, the inflammatory theory of the origin of leukoplakia of the bladder was accepted, in favor of which P.A. Herzen (1910) spoke out. However, in the works of foreign morphologists it has been shown that epithelial metaplasia is accompanied by edema of the underlying tissue and vasodilation, but not by pronounced inflammation. By analogy with lesions of other localizations, many authors considered leukoplakia of the bladder as a precancerous condition, however, there is not a single reliable observation of the transition of leukoplakia of the bladder to cancer. In the light of modern research, leukoplakia is a pathological process characterized by a violation of the main functions of the stratified squamous epithelium (absence of glycogen formation and the occurrence of keratinization, which are absent in the norm).

The data presented above confirm 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. At the same time, it has been shown that the causative agents of urogenital infections cause unusual inflammatory damage to the tissues of the urinary tract, different from that caused by nonspecific microflora (E. coli, etc.). Scientific papers have shown that in response to infection penetration into the urothelium, various forms of dystrophic damage constantly occur: vacuolar, ballooning and reticular dystrophy of the cells of the spinous layer, small foci of acantholysis with the formation of spongiform vesicles. Foci of squamous cell metaplasia are often combined with transitional epithelium without signs of proliferation, but more often with hyperplastic urothelium. In proliferating and non-proliferating transitional epithelium, dissociation and desquamation of the umbrella cells of the superficial layer are observed. It has been shown that in patients with persistent dysuria and urgency with or without bacteriuria, squamous cell metaplasia with submucous fibrosis of varying severity is detected during cystoscopy with biopsy. Interestingly, bacteriuria was absent with pronounced morphological changes. Infection is an etiologic factor in urothelium damage and metaplasia formation, while further alteration occurs independently of it and leads to persistent dysuria. In patients with squamous cell metaplasia, increased permeability of the epithelium is noted, adaptive restructuring of the urothelium is impossible with physiological filling of the bladder, which leads to diffusion of urine components into the interstitium and the development of frequent painful urination, the occurrence of pain above the pubis, in the urethra, etc. The main stage of the pathogenesis of leukoplakia of the bladder is considered to be 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, given the ever-increasing proportion of primary uncomplicated urinary tract infections and chronic processes with frequent relapses in the structure of inflammatory urological diseases occurring 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 data, 70 female patients aged 16 to 40 years with recurrent urinary tract infections and persistent dysuria were examined from 2005 to 2007. All of them underwent general analysis and bacteriological examination of urine. For the diagnosis of STIs, a study was performed using PCR serological diagnostics in two biotopes - from the cervical and urethral canals. All patients underwent a vaginal examination and O'Donnell test. Cystoscopy was performed in 54 women with a disease duration of more than two years. Microflora growth was detected in bacteriological examination of urine in 44 (63%) patients, with E. coli isolated in 30 (43%) samples. The presence of STI pathogens was detected by the PCR method in 51 (73%) patients: Ureaplasma urealyticum (biovar Parvo) - in 24 (34%) Chlamydia trachomatis, Herpes simplex type I, II - in 16 (23%); the remaining patients were found to have a mixed infection. During vaginal examination, vaginal ectopia of the external opening of the urethra was detected in 24 women with recurrent urinary tract infections. Among the patients who underwent cystoscopy, 4) 26 were diagnosed with leukoplakia of the bladder neck and vesical triangle with a morphological picture of squamous cell metaplasia of the epithelium and destruction of the glycosaminoglycan layer. Squamous cell papilloma was detected in two women, pseudopolyposis of the bladder neck was found in three examined women.

Despite the fact that the endoscopic picture of leukoplakia of the bladder is quite characteristic (the picture of "melting snow"), histological confirmation of the diagnosis is necessary. Differential diagnostics 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 based treatment of leukoplakia is considered to be eradication of STI pathogens.

Unfortunately, the damaged urothelium is not restored and the clinical picture does not regress with antibacterial therapy alone. It is likely that continued treatment aimed at restoring the destroyed glycosaminoglycan layer is necessary. Clinical trials are currently underway on the intravesical administration of exogenous glycosaminoglycan analogues (sodium heparin, hyaluronic acid, chondroitin sulfate, sodium pentosan polysulfate, etc.) in this category of patients. Preliminary data demonstrate the high efficiency of this treatment method. TUR is performed only if the treatment is ineffective or in the presence of pseudopolyps.

Treatment of recurrent urinary tract infections

• Pathogenetic treatment of recurrent cystitis in women.
  • Correction of anatomical disorders. For patients who have developed chronic cystitis against the background of "vaginalization" of the external opening of the urethra, transposition of the urethra and dissection of urethrohymenal adhesions outside of an exacerbation of the chronic process are recommended.
  • Treatment of STIs. Drugs of choice: macrolides (josamycin, azithromycin, midecamycin), tetracyclines (doxycycline), fluoroquinolones (moxifloxacin, levofloxacin, ofloxacin).
  • Postcoital prophylaxis.
  • Treatment of inflammatory and dysbiotic gynecological diseases.
  • Correction of hygienic and sexual factors.
  • Correction of immune disorders. Non-specific immunomodulators are used (dioxomethyltetrahydropyrimidine 0.5 g 3 times a day for 20-40 days).
  • Local treatment of recurrent cystitis in women. Intravesical infusions of mucopolysaccharides (25,000 U of sodium heparin once a day for 10 days), structurally similar to glycosaminoglycans of the bladder wall, helping to restore its integrity and stabilizing mast cells.
  • Diuretics and herbal combination drugs (Kanefron) are used as a method for preventing recurrence of urinary tract infections and at the stage of outpatient follow-up treatment.
• Etiological treatment of recurrent cystitis in women is antibacterial therapy.
  • Duration up to 7-10 days.
  • The drug must be selected taking into account the sensitivity of the isolated pathogen to antibacterial drugs.
  • Antibiotics with bactericidal action are prescribed:
    • for uncomplicated lower urinary tract infections (if STIs are excluded), fosfomycin, trometamol, fluoroquinolones (norfloxacin), and nitrofurantoin are used;
    • In the presence of STIs, the drugs of choice are macrolides (josamycin, azithromycin, midecamycin), tetracyclines (doxycycline), fluoroquinolones (moxifloxacin, levofloxacin, ofloxacin).
  • Antiviral treatment of recurrent cystitis in women when genital herpes is detected: acyclovir, valacyclovir, famciclovir.
  • Immunobiotherapy with Uro-Vaxom.

One of the most promising drugs is Lavomaks (tilorone), a synthetic low-molecular interferon inducer effective when taken orally. The drug has an immunomodulatory and antiviral effect. Data on the immunomodulatory effects of Lavomaks indicate the advisability of its use in various infectious and non-infectious diseases accompanied by immunodeficiency states, in particular, chronic recurrent cystitis. The immunomodulatory activity of the drug is also manifested by an increase in the activity of the cellular link of immunity.

As part of complex therapy, the drug Lavomaks promotes a more rapid disappearance of clinical signs of cystitis.

The inclusion of the drug Lavomaks in the therapy of chronic cystitis helps to reduce the frequency of relapses.

The drug does not undergo biotransformation and does not accumulate in the body.

Lavomaks for cystitis is prescribed according to the following scheme: the first day, 0.125 g 2 times, then 0.125 g every 48 hours. The course of treatment is 1.25 g (10 tablets). Then the drug is prescribed for prophylactic purposes, 0.125 g once a week for 6 weeks. The course of prophylactic treatment is 0.75 g.

For the treatment of herpes infection, Lavomaks is prescribed according to the following scheme: 0.125 g for the first two days, then 0.125 g after 48 hours. The course dose is 2.5 g.

For the treatment of chlamydial infection, use the following regimen: 0.125 g per day for the first two days, then after 48 hours. The course is 1.25 g.