Exacerbation of chronic cystitis

Infectious and inflammatory disease of the bladder mucosa suddenly begins with frequent urination, cramps and burning during urination, pain in the lower abdomen, and other ailments. This condition requires a response. The absence of therapy or its insufficiency leads to the flow of cystitis into a chronic condition in which periodic exacerbations are possible.

Recurrent urinary tract infection (RUTI) is three episodes of exacerbation with three positive urine cultures over a 12-month period or two infections over the previous 6 months. [1]

Epidemiology

Urinary tract infections are more common in women than in men, in a ratio of 8: 1. [2] Recurrent UTIs (RUTIs) are mainly caused by re-infection of the same pathogen. 

According to statistics, in a third of all cases of cystitis, it goes into a chronic form. Most exacerbations occur in the first 3 months after the acute form. Every sixth man and every second woman are relapsed. 

The survey data show that 1 out of 3 women will have a diagnosis and treatment of UTI by the age of 24, and more than half of them will be sick during their lifetime. [3]In one 6-month study, it was shown that 27% of cases of chronic cystitis recur once and 3% two or more times.[4]

Causes of the exacerbations of chronic cystitis

Chronic cystitis has both periods of calm and relapse. What are the causes of exacerbations? The following can be distinguished:

• insufficient personal hygiene leading to infection in the urethra;
• uncontrolled long-term use of medications that provoke irritation of the walls of the organ;
• stagnation of fluid in the bladder (you can not restrain the urge to empty);
• constipation
• wearing tight underwear and trousers, causing stagnation of blood in the pelvic organs;
  • bladder injuries;
• hypothermia and other factors that reduce immunity;
• allergy to intimate hygiene products;
• kidney disease, the presence of stones in them;
• genital infections.

Risk factors

The main risk factors that predispose to recurring uncomplicated UTIs include menopause, family history, sexual activity, spermicide use, and recent use of antimicrobials. [5]

Exacerbation of cystitis can contribute to intense sexual activity. This does not always indicate a genital infection. Physical impact, friction of the external genitalia leads to inflammation of their tissues, which affects the urethra. In a woman, an exacerbation can provoke the ingress of strains of microorganisms foreign to her immunity.

A significant role in the development of the disease is played by the age of the patient. In older people, such phenomena occur more often due to a slowdown in the process of epithelial regeneration. In postmenopausal women, the incidence of UTI is higher due to pelvic prolapse, a lack of estrogen, a decrease in the number of lactobacilli in the vaginal flora, increased periurethral colonization of Escherichia coli (E. Coli), and a higher incidence of diseases such as diabetes. [6] 

A risk factor for an outbreak is the period before menstruation. This is due to hormonal jumps characteristic of the cycle, and may be a manifestation of such pathologies as uterine fibroids, endometriosis.

Chronic infections of other organs also lead to exacerbations of inflammation of the bladder, a lack of vitamins in the body.

There is a large group of patients with painful bladder syndrome, or interstitial cystitis, whose symptoms are aggravated by eating certain foods. The most common foods are coffee, tea, soda, alcohol, citrus fruits and juices, artificial sweeteners and hot peppers. [7]

In the treatment of chronic cystitis, the Urolife dietary supplement in the instillation solution is often used to restore the protective layer of the bladder or in the form of oral capsules (they act as a protector and maintain a constant concentration of active substances in the epithelium of the organ). With hypersensitivity to the components of the drug, exacerbations are also possible.

Pregnancy, diabetes mellitus and immunosuppression increase the risk of exacerbation of chronic cystitis (RUTI) in women, facilitating access to uropathogens, overcoming the normal protective mechanisms of the body. [8]Patients with diabetes have a higher risk of developing asymptomatic bacteriuria, UTI, and pyelonephritis.

Pathogenesis

Intact urothelium of the walls of the bladder is able to protect itself by synthesis of phagocytes, whose action is aimed at suppressing the growth of pathogenic bacteria. The occurrence due to the listed reasons of a damaging factor leading to hypoxia, transient dysfunction of the immune system, leads to an exacerbation of pathology.

The repeated infectious process results from the impossibility of tissue regeneration. It is believed that ascending infection is caused by bacterial virulence factors that improve adhesion, infection, and colonization by uropathogens. Common uropathogens include Escherichia coli, Staphylococcus saprophyticus, Klebsiella pneumoniae, and Proteus mirabilis. [9]

The pathogenesis of recurrent UTI or exacerbation of chronic cystitis includes bacterial reinfection or bacterial persistence, the former being much more common. [10]When bacteria are resistant, the same bacteria can be cultured in urine 2 weeks after the start of sensitivity-adjusted therapy. Re-infection is a relapse by another organism, the same organism 2 weeks after treatment or a sterile intermediate culture.[11]

Symptoms of the exacerbations of chronic cystitis

The first signs of the pathology are difficult to miss, because its symptoms cause pain, discomfort when the bladder is empty, especially pesters the frequency of urges.

Common symptoms of exacerbation of chronic cystitis are dysuria, frequent urination, suprapubic pain and possible hematuria. Systemic symptoms are usually mild or absent. Urine may have an unpleasant odor and be cloudy. The diagnosis depends on the characteristics of the clinical features, history, three positive urine cultures during the previous 12-month period in patients with symptoms and the presence of neutrophils in the urine (pyuria). [12] Symptoms of urinary dysfunction are present in 25-30% of women with RUTI. The probability of detecting a positive culture in the presence of the above symptoms and the absence of vaginal discharge is about 81%. [13]For complex UTIs, such as pyelonephritis, UTI symptoms will persist for more than a week with systemic symptoms of persistent fever, chills, nausea, and vomiting.[14]

The pain is most often localized in the pubic area or in the depths of the small pelvis. Cramps appear mainly at the end of the act of urination, but can at the beginning. To all this, a general feeling of well-being is mixed, sometimes the body temperature rises.

Urine takes on a cloudy appearance, flakes may float in it, and blood may be mixed.

Exacerbation of cystitis during pregnancy

Often, pregnancy is accompanied by exacerbation of cystitis. This is not an accident. The growing uterus compresses the bladder, ureter. The outflow of urine and blood circulation are disturbed, which leads to the development of infection.

In the early stages of bearing a child, inflammation is promoted by a decrease in immunity due to hormonal changes. During pregnancy, manifestations of pathology cannot be neglected, since this can negatively affect not only the health of the expectant mother, but also the baby, and lead to a miscarriage. [15]

During pregnancy, factors contributing to the risk of exacerbation of chronic cystitis are the expansion of the ureter and renal pelvis; increased urine pH; muscle tone of the ureters and glucosuria is reduced, which contributes to the growth of bacteria. Treatment of asymptomatic bacteriuria in pregnant women reduces the risk of pyelonephritis. Because RUTIs are common during pregnancy, they need preventative treatment. Bacteriuria screening is recommended for all pregnant women at their first antenatal visit, and then in the third trimester. [16]They should then be treated with antibiotics such as nitrofurantoin, sulfisoxazole or cephalexin. [17],  [18]RUTI Antibiotic prophylaxis in pregnant effective when used in continuous or postcoital circuits. The causative agents of UTI during pregnancy are similar to those found in non-pregnant patients, with E. Coli accounting for 80–90% of infections. [19], [20] 

Complications and consequences

Untreated cystitis is dangerous not only by its transition to a chronic form, but also by more serious consequences and complications related to kidney damage, for example, inflammation of the organ - pyelonephritis. If bacteria enter the bloodstream, they can cause serious complications, including septicemia, shock, and, rarely, death. [21]

Diagnostics of the exacerbations of chronic cystitis

Diagnosis of cystitis is carried out according to the clinical picture characteristic of the disease, and also requires laboratory, instrumental studies (including cystoscopy, CT urogram or ultrasound of the abdominal cavity), an analytical approach to the results. [22]Examination of the patient includes a thorough history taking, other existing stages of diagnosis, always taking into account the condition of the genitals and the characteristics of sexual life.

Bacteriological examination of urine - a basic analysis for cystitis. It is also necessary to determine the sensitivity of flora to antibiotics. General urine and blood tests are also done to detect white blood cells. Based on the alleged diagnosis, others are possible, for example, for sexually transmitted diseases.

Of the instrumental methods, they often resort to ultrasound of the pelvic organs, upper urinary tract. An organ x-ray may also be needed. At the final stage, an endoscopic examination is mandatory, but the full picture of the histological changes in the bladder mucosa will be clarified by optical coherence tomography (OCT) and multifocal biopsy.

Differential diagnosis

Exacerbation of cystitis is differentiated with gynecological and venereal diseases, acute appendicitis . Changes in the walls of the organ caused by the chronic course of the pathology are similar to dysplasia, metaplasia, hyperplasia - precancerous conditions. For clarification, OCT is used.

Treatment of the exacerbations of chronic cystitis

Cystitis is treated with antibacterial drugs, herbal diuretics, but to get suitable therapy, you need to see a doctor and take tests.

If you grabbed at the wrong time or place, then what should I do? What emergency assistance can be used?

Patients should be advised and advised to drink plenty of fluids (two to three liters per day) and urinate frequently to help flush bacteria from the bladder. Prolonged retention of urine allows bacteria to multiply in the urinary tract, which leads to cystitis.

Women are advised to avoid spermicidal contraceptives, diaphragms, and vaginal douching, which can irritate the vagina and urethra and facilitate the penetration and colonization of bacteria in the urinary tract. It is better to avoid skin allergens introduced into the genital area, such as bath foams, bath oils, vaginal creams and lotions, deodorizing sprays or soaps, as they can alter the vaginal microflora and ultimately lead to UTI. [23]

On the lower abdomen or between the legs, you can put a warm heating pad, take a painkiller, antispasmodic, non-steroidal anti-inflammatory drug.

Medication

Continuous low-dose antibiotic prophylaxis is effective in preventing UTI. A systematic review of the 2008 Cochrane Database brought together 10 studies in which 430 women participated to evaluate continuous antibiotic prophylaxis compared to placebo. A meta-analysis of these trials showed that the relative risk of clinical relapse per patient per year (CRPY) was 0.15 (95% CI 0.08–0.28) in favor of antibiotics. The relative risk of severe side effects (requiring discontinuation of treatment) was 1.58 (95% CI 0.47–5.28), and other side effects were 1.78 (95% CI 1.06–3.00) in placebo. Side effects included vaginal and oral candidiasis, as well as gastrointestinal symptoms. Severe side effects were most often a skin rash and severe nausea. No additional trials have been identified that refute this systematic review. [24]

Since the optimal prophylactic antibiotic is unknown, the choice of antibiotic should be determined by allergies, previous susceptibility, the nature of local resistance, cost, and side effects. Nitrofurantoin and cephalexin show the highest efficacy. Before prophylaxis, patients should understand the common side effects and the fact that serious side effects are rare.[25]

Ampicillin, amoxicillin and sulfonamides are no longer the drugs of choice for empirical treatment because of the widespread resistance in 15–20% of Escherichia coli. [26], [27]Nitrofurantoin or amoxicillin / clavulanic acid remains effective in terms of bacterial sensitivity, but nitrofurantoin should be avoided in patients with pyelonephritis due to its low level in serum and tissues. Less than 5% of E. Coli strains are resistant to nitrofurantoin, while other strains are often resistant to it. 

Penicillins and cephalosporins are considered safe during pregnancy, but trimethoprim, sulfonamides, and fluoroquinolones should be avoided. Oral antibiotic therapy resolves 94% of uncomplicated UTIs, although relapse is not uncommon. The recently published International Clinical Guidelines for the Treatment of Acute Cystitis recommends a 3-day regimen of trimethoprim-sulfamethoxazole (TMP-SMX) and a 5-day course of nitrofurantoin as a first-line therapy for the treatment of uncomplicated UTIs. A 5-day course of nitrofurantoin has a high efficacy equivalent to a 3-day course of TMP-SMX. [28],  [29]3-7 days Mode for beta-lactams such as cefaclor or amoxicillin / clavulanic acid is suitable when you can not use first-line therapy. Although a 3-day course of fluoroquinolones can be quite effective, it is usually not recommended as first-line therapy because of the emerging resistance to them and their potential side effects, as well as because of the high cost; however, fluoroquinolones are the drug of choice for women who experience low tolerance or allergic reactions after empirical therapy. [30]A meta-analysis showed that a single-dose regimen of tromethamol fosfomycin is a safe and effective alternative for treating UTI in both pregnant and non-pregnant women, as well as the elderly and children. Due to its low effectiveness, amoxicillin and ampicillin should not be used for empirical treatment of UTI.

In the presence of chronic cystitis, you need to have several medicines in your home medicine cabinet that can help in case of a sudden exacerbation. Among them, a monural, urolesan.

• Monural is a broad-spectrum antibiotic that prevents the attachment of bacteria to the epithelium of the walls of the organ. It is taken on an empty stomach at bedtime once after dissolving the powder in half a glass of water.

It is not prescribed for children under 12 years old, women during breastfeeding. Pregnant women can take the drug on the advice of a doctor in case of urgent need. When conducting animal tests, no harmful effects on the fetus were detected. Of the side effects, heartburn, diarrhea, dizziness, and fatigue are possible.

Monural is contraindicated in people with hypersensitivity to its components, with severe renal failure, undergoing hemodialysis.

• Urolesan - has 3 release forms: capsules, drops, syrup. It contains a combination of many extracts and oils of medicinal plants. Take the drug before meals in doses: 8-10 drops for sugar for adults, for children 7-14 years old - 5-6 drops; syrup: 5ml and 2-4ml, respectively; capsules: after 14 years - 1 pc. Reception three times a day.

Side effects are possible in the form of nausea, belching, skin rashes, itching, headache, and slow heartbeat. Contraindicated in children up to the above age, pregnant and lactating, people with ulcers, erosion, stones more than 3 mm in the kidneys.

Of other antibacterial agents, fluoroquinolones are used: ofloxacin, norfloxacin, lomefloxacin.

As a rule, patients with chronic cystitis have deviations in their immune status. To stimulate the immune mechanisms, immunotherapeutic drugs are used, one of which is the uro-vaccine.

• Uro-vaccine - in acute situations, drink one capsule daily in the morning before meals for at least 10 days in combination with another treatment. Children can be treated from 4 years old by mixing the contents of the capsule with juice or water. The effects on pregnancy and during breastfeeding have not been investigated.

The drug can cause discomfort in the abdomen, swelling in the mouth, skin rash, itching, and sometimes fever.

To treat urogenital diseases in women, they resort to sex hormones - estrogen. An example of it is the drug ovestin.

• Ovestin is its active substance estriol. Assign for replacement therapy with atrophy of the mucous layer of the lower parts of the genitourinary system. The suppository is injected into the vagina once a day. Do not use for thrombosis, tumors of the mammary glands and genitals, bleeding, diabetes mellitus, cholelithiasis, pancreatitis, epilepsy, asthma. May cause local reactions: itching, vaginal irritation, and breast tenderness.

The use of estrogen stimulates the proliferation of lactobacilli in the vaginal epithelium, lowers pH and prevents vaginal colonization by uropathogens. After menopause, estrogen levels and the number of lactobacilli fall; this plays an important role in the development of bacteriuria and makes postmenopausal women susceptible to UTI. Vaginal use of estrogen reduces RUTI by 36–75% and has minimal systemic absorption. Based on the Cochrane review, postmenopausal women with RUTI versus placebo found that vaginal estrogens prevent RUTI, but estrogen does not have the same effect orally. [31], [32]Topical estrogen creams twice a week and a vaginal ring releasing estradiol are both effective in reducing RUTI attacks. [33], [34]They restore the microflora of the vagina, lower pH and, therefore, reduce UTI; However, the reappearance of vaginal lactobacilli takes at least 12 weeks when using an estrogenic vaginal ring. [35]Although evidence does not support the use of a particular type or form of vaginal estrogen, topical creams are cheaper than the estradiol-releasing vaginal ring, but have more side effects. 

Probiotics are beneficial microorganisms that can protect against UTIs. Lactobacillus strains are the most famous probiotics and are found in fermented milk products, mainly in yogurt. Other probiotics include Lactobacilli bifidobacteria, rhamnosus, casei, bulgaricus and salivarius; Streptococcus thermophiles and Enterococcus faecium. Reid et al. Showed in vitro that lactobacillus can prevent uropathogenic infections. [36]Other studies have shown that L. Rhamnosus gr-1 and L. Fermentum rc-14 can colonize the vagina, which could subsequently prevent UTI. However, more clinical trials are needed to determine their role in the prevention of RUTI.[37]

Vitamins

Since exacerbations of cystitis often occur from a lack of vitamins, a decrease in the body's defenses, they must be included in the complex treatment of pathology. Multivitamin complexes, which contain vitamins A, C, E, B, as well as foods rich in them, with the exception of citrus fruits, tomatoes, are considered beneficial in influencing the genitourinary organs.

Physiotherapeutic treatment

A very effective method in the treatment of cystitis belongs to hydrotherapy. Well-proven in this mineral water "Naftusya".

Recent studies show that cystitis among cystitis-prone women who received acupuncture was one-third less than among untreated women, and half that among women who were treated with false acupuncture. Thus, acupuncture can prevent RUTI in healthy adult women. [38],  [39], [40]

Alternative treatment

Alternative recipes can alleviate the condition of the patient, accelerate recovery, but not replace it. Abundant drinking of cranberry and lingonberry fruit drinks, rosehip broth, aronia, containing a large amount of vitamins C, remove pathogens, increase immunity. The Cochrane review showed that there is little evidence of the benefits of cranberry juice in the prevention of UTI; Thus, cranberry juice cannot be recommended for the prevention of UTI. [41]

Herbal medicine is effective for repeated urinary tract infections. [42]Warm baths with decoctions of soothing, anti-inflammatory, disinfecting herbs: string,  [43]chamomile,  [44]calendula,  [45]eucalyptus leaves,  [46]will reduce the symptoms of the disease.

A large role in the treatment of exacerbations of cystitis belongs to the ingestion of potions from herbs. The leader in this is the mountaineer bird, bearberry, half a half, corn stigmas, parsley seeds, a shepherd’s bag.

Homeopathy

In pharmacies, you can buy homeopathic medicines, the parallel use of which with the main treatment will accelerate recovery. So, the Arnica-Heel complex remedy is indicated for acute and chronic diseases of bacterial and viral origin. Drops are dissolved in water (10 ml per 10 drops) and drunk 3 times a day 20 minutes before meals or an hour after. Not prescribed for pregnant women and children. Cases of side effects are very rare and manifest as allergies or intestinal disorders.

Berberis-Homacord - a herbal preparation relieves pain and inflammation of the genitourinary tract. Applies to children from 12 years old. Ten drops of the solution are combined with water or immediately under the tongue and lingers there for a while before swallowing. Contraindicated for allergies to components and in the first trimester of pregnancy.

Gentos - tablets, relieve inflammation, edema, improve blood circulation in the pelvic organs, reduce congestion. Children 5-12 years old are recommended half a tablet 2 times a day, adolescents and adults kiss. In the acute stage of cystitis in the first 2 days, you can increase the frequency of administration up to 4 times. Side effects are possible: skin rashes, itching.

Kalium Floratum Dr. Schussler’s salt No. 4 - tablets, is applied to the smallest patients: up to one year, 1 tablet 2 times, 1-5 years - 3 r., 6-11 years - 4 r., After 12 years - 6 times throughout the day. The drug is contraindicated for allergies to wheat. There is also a primary temporary exacerbation of the pathology, which requires the cessation of treatment and treatment to the doctor.

Diet for exacerbation of cystitis

Chronic cystitis, especially its exacerbation, requires a special diet. From food it is necessary to exclude spicy, salty, smoked, spicy, alcohol. The menu should have no more acidic vegetables and fruits (fresh cucumbers, zucchini, cauliflower, melons, watermelons, pears, peaches), as well as cottage cheese, dairy products. From drinks compotes, juices, weak tea.

Prevention

There is no convincing evidence of conservative measures to prevent recurrence of UTI. Modifiable predisposing factors for UTIs, including sexual activity and the use of spermicides, may be recommended for patients. [47], [48]

With cystitis, as a preventive measure, proper hygiene of the genitourinary organs, anus after defecation, dressing in accordance with the weather, not sitting on cold surfaces, maintaining your immunity with good and proper nutrition, vitamin complexes should be observed. Sufficient daily drinking is another way to avoid exacerbations.

The evidence underlying the probiotic lactobacilli in the prevention of UTI is also inconclusive. [49], [50]

Preventive measures against recurring uncomplicated urinary tract infections: 

• Conservative measures, including restricting the use of spermicides and post-coital urination, have no evidence of their effectiveness, but are unlikely to be harmful (evidence level 4, grade C recommendation).
• Cranberry products have conflicting data on their effectiveness (Level 1 evidence, Class D recommendation).
• Continuous antibiotic prophylaxis is [51]effective for the prevention of UTI. (Level 1 evidence, level A recommendation).
• Postcoital antibiotic prophylaxis within 2 hours after sexual intercourse is also effective in preventing UTI (level of evidence: 1, grade A recommendation).
• Self-administration of antibiotic therapy using a 3-day dose of antibiotic for treatment when symptoms occur is another safe option for treating recurring uncomplicated UTIs (level of evidence: 1, grade A recommendation).

Oral immunoprophylaxis may be an effective alternative to antibiotics in the prevention of exacerbations of chronic cystitis. A meta-analysis of 5 studies showed that the oral preparation for the prevention of Uro-Vax ® with Escherichia coli extract (Terra-Lab, Zagreb, Croatia) taken for 3 months was effective in preventing exacerbations of chronic cystitis for 6 months. [52]Another double-blind study confirmed that E. Coli extracts are effective and well tolerated in the treatment of UTIs, reducing the need for antibiotics and preventing UTIs. [53]

Forecast

Timely treatment, the recommended course even with the disappearance of symptoms (usually internal processes are longer than external manifestations) gives a favorable prognosis for recovery. Ignoring the problem threatens kidney damage.