Within the interstitium, soluble factors, such as the AMP cathelicidin LL , form an important component of the response to pathogens like UPEC by targeting virulence factors. Immune cells are also present in both the epithelium and interstitium. In the upper urinary tract, dendritic cells, macrophages, neutrophils, and lymphocytes interact to defend against microorganisms. In the lower tract, mast cells, macrophages, neutrophils, and, in particular, natural killer NK cells act to combat colonization.
In addition to their barrier function, epithelial cells express TLRs which trigger responses to pathogens. Both macrophages and NK cells release cytokines to promote this process, while mast-cell derived factors e. As in all immune responses, the stimulus-dependent portions of the immune system in the urinary tract should balance between potency of response and excessive inflammation.
An imbalance may result in bacteria persisting, causing subsequent infection, or inflammatory damage to the urothelium. In the latter stage of infection, mast cells take on an inhibitory role, keeping dendritic cells in an immature T-cell inhibitory state and reducing inflammation though interleukin IL production.
In addition, neutrophils are capable of producing anti-inflammatory meta-protease enzymes. Vaccines remain the gold standard for preventive infectious-disease control. While E. Despite these challenges data from animal models showing that antibody titers correlate with bacterial load and infection duration suggest that vaccine-based prophylaxis can be effective.
Several bacterial lysate therapies are available for UTI prevention. OM has a dual mechanism, acting as an immunostimulator increasing both the innate and adaptive response, and also as an immunoregulator acting on dendritic cells and promoting Treg cells.
This dual immunomodulatory mechanism begins with nonspecific activation of dendritic cells in the gut-associated lymphoid tissue. The integrated mucosal immune system allows cell migration and the mounting of an immune response in the urothelium and other mucosal tissue.
Acute uncomplicated cystitis and pyelonephritis of a complicated or uncomplicated nature form the two major subdivisions in guidelines dealing with UTIs. The heterogeneous group of nosocomially acquired UTIs and complicated UTIs excluding pyelonephritis , each require separate guideline classification.
These complicated infections are often related to comorbid disease or urological conditions. In addition, guidelines define treatment strategies for potentially life-threatening urosepsis and site-specific infections including urethritis, prostatitis, and epididymitis.
Definitions of uncomplicated cystitis vary between guidelines. The European Association of Urology EAU guidelines define uncomplicated UTI as acute, sporadic, or recurrent cystitis limited to nonpregnant, premenopausal women with no relevant anatomical or functional abnormalities in the urinary tract.
When treating acute uncomplicated cystitis, physicians should target rapid resolution of symptoms, reduction of morbidity, and prophylaxis against reinfection. Treatment goals can be achieved via short-term antibiotic therapy without a focus on eliminating the presence of potentially pathogenic microbes in the urinary tract.
The advantages of short-term therapy include: good compliance; low costs; fewer adverse events; and low impact on periurethral, vaginal, and rectal flora. Current EAU and German S3 guidelines recommend short courses of older antibiotics fosfomycin trometamol, nitrofurantoin, nitroxoline, or pivmecillinam for uncomplicated cystitis. Guidelines state that co-trimoxazole, fluoroquinolones, or cephalosporins should not be considered as first-line antibiotics for uncomplicated cystitis both due to the rise of resistance in the urinary tract, and collateral damage such as selecting for resistance in other compartments including the skin and fecal flora.
So, how should physicians treat asymptomatic bacteriuria ABU? The weight of evidence suggests that ABU is benign in the majority of cases and may in fact be protective. Studies have demonstrated that treatment of ABU has no beneficial effect in patients with diabetes, and antibiotic therapy has a detrimental effect on recurrent UTI, likely due to disruption of the urinary tract microbiota. Classical diagnostics in acute uncomplicated cystitis involve: taking history to determine experience of recurrence and complicating factors; determining symptoms including frequency, urgency, and dysuria; physical examination of the genitals and assessment of suprapubic and flank pain; urinalysis using test strips, flow cytometry or microscopy; and urine culture.
The delay involved in urine culture generally makes the test impractical, resulting in empirical treatment of most acute uncomplicated cystitis cases. Novel data on the sensitivity and specificity of uranalysis and an increased understanding of the benign nature of ABU have led to a refocusing on symptoms scoring as a measure of diagnosis and treatment success. Recent data show that targeting symptoms and underlying inflammation using ibuprofen can be almost as effective as antimicrobial therapy.
However, cases of pyelonephritis were somewhat higher in the ibuprofen group. Diagnostic tests that can differentiate between patients who need therapy directed at the host response and those who need antimicrobial therapy could ameliorate the risk of patients developing pyelonephritis.
There are three tiers of prophylactic measures for recurrent UTI: behavioral modification and counseling should be the first tactics employed to reduce recurrence, followed by nonantibiotic prophylaxis, and finally by low-dose continuous or postcoital antibiotic prophylaxis as a last resort. However, rare but serious hepatic and pulmonary adverse reactions during long-term prophylaxis with nitrofurantoin must be taken into account and have led to its contraindication in some European countries.
Effective alternative strategies should avoid the side effects associated with antimicrobial use, avoid collateral damage, prevent resistance, and spare the limited antibiotic armament.
In postmenopausal women with a history of recurrent UTI, data from a randomized controlled trial indicates that use of topical estrogen estriol 0. Topical use is recommended once or twice weekly for prophylaxis, and daily use of oral products containing these strains can restore the vaginal lactobacilli. Competition of Lactobacilli with urogenital pathogens leads to a reduction in bacterial vaginosis, a condition that increases the risk of UTIs. In a randomized placebo-controlled trial of women, those receiving intravaginal capsules containing L.
However, more studies are required before recommendations can be made for D-mannose prophylaxis. Efficacy data for the oral bacterial lysate OM are available from five 6-month randomized controlled trials and one month randomized controlled trial.
The proportion of patients experiencing at least one adverse event was similar in the OM versus the placebo group Furthermore, in higher risk patients there was a greater benefit of OM prophylaxis. Results in terms of safety and antibiotic sparing were similar to individual trials. Tentative positive results for bacteria-derived vaginal suppository Urovac, cranberry, and acupuncture, require further supporting research Figure 3.
Forest plot of the efficacy of different forms of UTI prophylaxis. Nonantibiotic prophylaxis for recurrent urinary tract infections: a systematic review and meta-analysis of randomized controlled trials. A number of open-label studies also suggest that OM is effective in higher risk groups.
The mean incidence of recurrences fell by All the newborns were healthy with normal Apgar Appearance, Pulse, Grimace, Activity, and Respiration scores, however, further studies are necessary before the safety of OM can be confirmed during pregnancy. OM was well tolerated in all trials. The EAU guidelines give a strong recommendation for OM level of evidence: 1a; grade of recommendation: strong. All other previously mentioned prophylactic strategies require more data, except for topical estrogen for postmenopausal women, which received a weak recommendation level of evidence: 1b; grade of recommendation: weak.
The unique ethnic makeup of patients, alongside local variation in the availability of medicines, antibiotic resistance, and health care practices necessitates the creation of regional guidelines on the treatment of UTI.
Prescription of antibiotics for recurrent UTI without consideration of preventive measures is common in many Latin American countries. In a global survey of E. The committee included papers that cover genital prolapse, stress urinary incontinence, overactive bladder, mixed urinary incontinence, painful bladder syndrome, and recurrent UTI.
Guideline sections covering genital prolapse and stress urinary incontinence have been published in the Brazilian Journal of Gynecology and Obstetrics. Although local guidelines from individual countries or regions exist, there is a need for an overarching Latin American consensus. In addition, a database of regional studies is being created to act as a single regional data repository to facilitate multicenter studies and promote high-quality publications.
Following their first meeting, the board defined the parameters of their upcoming consensus statement on the management of recurrent UTI, which will cover diagnostic workup, risk factors and behavioral changes, nonantimicrobial prophylaxis, and antimicrobial prophylaxis. As of summer , the consensus has been drafted, and an English translation is being created in anticipation of publication.
The following section summarizes cases with special features resulting in difficult treatment choices, which, though unusual, are still seen frequently in urological clinics. A year-old woman presented with an acute uncomplicated UTI and a 3-year history of recurrent UTIs six episodes per year. Despite receiving multiple treatments from multiple specialists including behavioral interventions, her quality of life was poor at presentation.
Recurrent UTIs began following an uneventful recovery and normal urine flow without leakage confirmed by computed tomography scan. At presentation, the patient was receiving hormone replacement therapy HRT with oral estrogens and had an abnormal vaginal flora. Her urine culture revealed multi-resistant E. Urine culture showed multi-resistance E. A year-old female patient presented with acute UTI. She had a 4-year history of type 2 diabetes and recurrent vaginal infections caused by Candida spp.
Her glycemic control was poor despite treatment with metformin and a SGLT-2 inhibitor. Her vaginal flora was deficient, and she was using combined topical HRT to control her symptoms. Upon presentation she was found to have a Candida albicans infection resistant to fluconazole and voriconazole. Leukocytes were negative and bacteria were absent.
The patient was referred to an endocrinologist to address the underlying glycosuria. With improved glycemic control, prophylaxis, and acute treatment she presented with one UTI caused by E. The branches of the immune system act in concert to control infection, and under normal circumstances maintain a balance between control of infection and excess inflammation. In the urinary tract, immunomodulatory therapies such as OM have dual modalities, acting both to stimulate the immune response and to regulate excessive inflammation.
The integrated mucosal immune system facilitates the immunomodulatory effect of oral therapies at remote sites including the urinary tract. UTIs are more than just an inconvenience. Untreated, UTI bacteria can enter your bloodstream and cause a serious blood infection known as septicemia. Drinking plenty of water and other fluids increases your urine output, which helps prevent bacterial buildup in your bladder and other urinary tract structures.
Aim for six to eight glasses of liquid daily. This helps flush bacteria out of your urinary tract. Careful wiping can prevent rectal bacteria from entering your urinary tract.
Urinating right after sex can help wash away bacteria. The moisture from baths could help bacteria multiply. If you do take baths, keep them short. Douches, feminine hygiene sprays, and powders can irritate your urinary tract and make it more susceptible to infection.
If you get recurring UTIs, consider avoiding fluids that irritate the bladder, like alcohol and caffeinated drinks. Holding in urine rather than relieving yourself when you feel the urge can contribute to harmful bacteria growth.
Visit the bathroom at least every hours to discourage bacterial growth and flush urine from your system. Urinating before and after having sex can decrease your risk of developing a UTI, too. Sexual intercourse can increase the bacteria around your urethra, but urinating before and after flushes out the area to help prevent a UTI. Whenever you use the toilet, wipe from front to back.
Bacteria that cause UTIs, particularly E. Some types of birth control may contribute to bacterial overgrowth and recurrent UTIs. Diaphragms, spermicidal products, and non-lubricated condoms could cause your UTIs because they change bacteria in your vagina, so talk to our team about other effective options for birth control.
Similarly, irritating feminine products can disrupt the natural balance of bacteria inside your vagina. Avoid using scented pads, tampons, soaps, or powders. When cleaning your genital area, use gentle, unscented cleansers. After menopause , your body makes less estrogen.
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