Acute Cystitis

Acute cystitis is a condition involving an infectious inflammation of the lower urinary tract, namely the urinary bladder.

The disease is related to the following processes:  infectious and has an incidence of about  50 / 100.000.

Overview

Infections can occur to any segment of the urinary tract. Acute cystitis is the most common type of urinary tract infection (UTI) [1] and affects the lower part of the tract, as opposed to the kidneys, which constitute the upper urinary tract.

Women are particularly susceptible to UTIs, due to anatomical differences in contradistinction to men; almost 1 out of 5 women will be affected by an infection of the urinary bladder at least once in their life.

Infections are caused by various bacteria and primarily by the gram negative Escherichia coli. Klebsiella pneumonia, Proteus mirabilis and Enterococcus faecalis are the next most common pathogens leading to an UTI. Acute cystitis with no complications is diagnosed with a careful clinical examination and urinalysis, which should display a significant pathogen load in the urine alongside typical symptomatology reported by the patient [2]. Treatment is carried out with antibiotics. First-choice antibiotics against acute cystitis are drugs that target gram negative pathogens, since most cases of cystitis are a result of infection with bacterial strains of microorganisms normally found in the human digestive tract and, subsequently, in excrement.

Etiology

Acute cystitis is an infection of the lower urinary tract. The most common pathogens are:

  • E. coli. It is responsible for up to 90% of bladder infections.
  • Klebsiella spp.
  • Proteus spp.
  • Staphylococcus saprophyticus
  • Enterococcus faecalis
  • Candida albicans
  • Any gram negative bacterium that exhibits resistance to a multitude of drugs, which is found in the hospital setting. Each facility has its own specific pathogens that display an increased antimicrobial resistance [3]; the exact prevalence is important for the planning of the treatment.

In addition to the pathogens responsible for most cases of acute cystitis, various other circumstances increase the possibility of a patient sustaining such an infection. Catheterization is a standard risk factor for the development of cystitis, as they constitute fertile ground for the adhesion of pathogens [4]. A catheter can also be the means through which bacteria originally infect the cyst. Other risk factors include spermicide and diaphragm used as a contraceptive measure, as well as sexual activity. Another factor that has been proposed as increasing the possibility of a urinary tract infection is a gynecological pelvic exam, which can contribute to a bladder infection even in seven weeks after the test [5]. Pregnancy, senior age or congenital structural defects of the urinary tract also render an individual more susceptible to infection.

Renal transplantation is also a risk factor for the development of a UTI. Subsequent immunosuppression and the vesicoureteral reflex are the pathophysiological mechanisms leading to such a manifestation. Patients who have undergone a renal transplantation run a higher risk of infection with Corynebacterium urealyticum for the 2-month period following the surgery.

With regard to acute cystitis caused by candidiasis, risk factors include urinary catheters, antibiotics and diabetes mellitus.

Epidemiology

Acute cystitis frequently affects female patients and particularly younger women who are sexually active. The incidence has been calculated as amounting to approximately 1 infection per year amongst those women [6]. Spermicide use for contraceptive purposes, a medical history of prior UTIs and recent sexual activity all contribute to the infection. Apart from younger women, however, women who have already experienced menopause are also at a risk for cystitis, although the incidence is much lower in this particular subgroup, when compared to younger female patients.

Sex distribution
Age distribution

Pathophysiology

Acute cystitis involves the presence of bacterial load within the bladder, which causes infection accompanied by typical symptomatology. The urinary tract contains no bacteria in healthy individuals. In some cases, various pathogens may be present in the region of the cyst; they invade the mucosa of the cyst and establish a bladder infection.

There are 3 pathophysiological mechanisms which lead to a urinary tract infection and, more specifically, an acute cystitis. Pathogens may enter the cyst from the urethra, following an ascending route or they may be translocated into the bladder from the perineal region. These two mechanisms are the most prominent; a third route of bladder microbial infestation is the hematogenous dissemination type. This mechanism is less often observed and involves pathogens entering the cyst via the blood.

Women tend to be affected by acute cystitis more often than men do. This is attributed to the female urethra, which is shorter in length, allowing for the entrance of microorganisms. Once the pathogens have entered the cyst and attached themselves to the epithelium, they reproduce rapidly; the highest bacterial load has been observed 2 days before the onset of symptomatology [7].

A plethora of pathogens can be potential culprits for a urinary tract infection, but the ones most commonly isolated are gram negative bacteria of the fecal flora. Apart from their being naturally found in the perineal area, which is in close proximity to the urethra, those bacterial strains have specific properties that enable them to establish acute cystitis. Particular structures, such as fimbriae and proteins of the external membrane in E.coli strains, enable the bacteria to attach themselves to glycolipids of the cyst's epithelium, thus causing an acute infection. Other characteristics that promote bacterial adhesion in the urinary tract epithelium include hemolysins, cytotoxic necrotizing factor (CNF) protein and polysaccharides ; pathogens containing these products are more likely to initiate a urinary tract infection than others. Finally there are also other bacterial traits that render some strains more capable of establishing acute cystitis: Proteus mirabilis possesses genes that are activated whenever the microorganism is attached to a solid surface, such as a catheter. This activation leads to mass mobilization of the bacteria which travel towards the cyst, following the catheter's route.

Acute cystitis is not only established when a bacterial strain capable of infection is present in the cyst. The defensive mechanisms of the urinary tract itself play an equally important role. Frequent urination is a simple and effective measure which helps to "flush" the cyst of any pathogens that may be present within, thus diminishing the cyst's bacterial load. Vaginal lactobacilli also prevent from bacterial colonization in women who have not yet entered the menopausal period; the disruption of the vaginal flora, induced by almost all antibiotics, may frequently lead to acute cystitis. Another factor that protects the urinary tract from infection is IgA immunoglobulin: ABH blood antigen non-secretors are more susceptible to cystitis compared to secretors. Finally, urine acidity, osmolality and urea additionally help to eradicate bacteria that are found in the bladder.

Given the aforementioned mechanisms, risk factors for the development of acute cystitis are:

  • Failure to urinate frequently
  • Catheter use
  • Sexual intercourse
  • Obstruction of the urinary tract
  • Vesicoureteral reflux

The basic pathophysiology of acute cystitis can be summarized to an increased bacterial virulence and decreased defensive mechanisms of any individual.

Prognosis

Acute cystitis is a frequent urinary tract infection with excellent prognosis after appropriate antibiotic treatment is administered [8].

Presentation

Acute cystitis with no subsequent complications causes typical symptomatology that may even be diagnosed without a visit to the doctor [9]. Symptoms include:

  • Dysuria
  • Frequent need of urination
  • Urgency
  • Hematuria, altered smell.

The presence of complications is diagnosed if other symptoms are present, such as fever and nausea, chills, abdominal or back pain and vaginal discharge.

Workup

The diagnosis of acute cystitis is accomplished primarily via the patient's symptom reporting and a dipstick testing. Patients are expected to report dysuria, urgency and frequent urination, whereas the physical examination reveals no abnormal findings, apart from 15% of the cases, which present with tenderness in the suprapubic area [10]. A dipstick testing is the first choice to confirm a suspected uncomplicated cystitis and should reveal leukocyte esterase and nitrites. The usual procedure involves urine collected after washing of the urogenital area and specifically urine from the middle of the stream; however, studies have shown that even if the procedure is not followed, i.e. in emergency cases, there is no contamination that would render the results falsely positive [11].

Further assessment with a urine culture and imaging is not necessary and is reserved from patients who suffer from recurrent cystitis, those who do not respond to treatment and for patients with a suspected complicated acute cystitis.  

Treatment

The treatment of acute, uncomplicated cystitis in women of any age is usually empirical. Possible antibiotic choices include [12]:

  • Nitrofurantoin monohydrate. It should not be administered if the patient is suspected to suffer from complications such as pyelonephritis or if the patient exhibits creatinine clearance less than 60 mL per min.
  • TMP-SMX (Trimethoprim-sulfamethoxazole). If the patient has already been treated with the agent, its use is not recommended, unless the bacterial strain responsible for the cystitis is known to be sensitive to TMP-SMX. Trimethoprim may be used as an equivalent drug [13].
  • Fosfomycin. Should not be administered if the patient is suspected to suffer from pyelonephritis.
  • Fluoroquinolones. They are used when the aforementioned antibiotics are contraindicated but should be reserved for severer infections.
  • Pivmecillinam. An antibiotic of the penicillin class, it is less effective than fluoroquinolones or TMP-SMX but it has low rates of resistance [14].

There are various criteria that a physician should bear in mind before making the choice of an appropriate antibiotic treatment. Antimicrobials are chosen based on studies concerning local resistance prevalence, cost, previous treatments, hypersensitivity and the ability to adhere to a treatment plan. Fosfomycin, nitrofurantoin and pivmecillinam are unable to reach a therapeutic concentration in the kidneys and are therefore rejected when a patient is suspected to be suffering from pyelonephritis.

Prevention

There are many suggestions that can considerably reduce a woman's chance of developing acute cystitis and include:

  • Urination before and after sexual intercourse
  • Wiping from the front to the back to avoid dispersion of fecal bacteria
  • Frequent urination
  • Avoidance of spermicide
  • Non-barrier contraception

In general, a patient receives antibiotic treatment when they report cystitis-related symptoms. Treatment of asymptomatic bacteriuria is recommended only in pregnant individuals, in order to prevent complications such as pyelonephritis, which cause a preterm labor or even pregnancy termination.

Prophylactic antibiotics, taken every day or after sexual intercourse, are also a recommendation for women who experience recurrent urinary tract infections. Proposed antimicrobials include TMP-SMX, nitrofurantoin and methenamine; the latter is reserved for short-term prophylactic treatment [15]. The consumption of cranberry juice can also be encouraged although there is no scientific data to support its beneficial effect.

Patient Information

Acute cystitis is an infection of the bladder caused by various bacteria. Since the urinary tract normally contains no flora, namely bacteria that are located there and serve a purpose, when microorganisms enter the region of the bladder they are expected to cause a reaction. Bladder infections are most commonly caused by bacteria of the fecal flora. Those ascend to the bladder through the urethra, either during sexual intercourse or while wiping oneself in the toilet. Other possible causes for a bladder infection are a weakened immune system, keeping urine in the bladder for too long before urinating, the use of spermicide and a wrong-placed diaphragm. Diabetes is also a risk factor for the development of acute cystitis, as are poor hygiene habits, catheters, pregnancy and immobility. Women are

A bladder infection is simple to diagnose, as the patients present with a typical triad of symptoms: pain during urination, urgency to urinate and the need to urinate abnormally frequently. Blood may be seen in the urine, alongside a different smell. A dipstick testing is quick, noninvasive and fast and is safe to diagnose acute cystitis in an individual. Patients who do not respond to treatment or suffer from recurring infections may need to undergo further assessment in order to establish the diagnosis.

After acute cystitis is diagnosed, it is treated with antibiotics that a physician will prescribe without a culture. Choices include TMP-SMX, nitrofurantoin, beta lactames and other agents. A doctor will ask you for any prior hypersensitivity occurrences, whether you have recently been treated with any of the proposed antibiotics and will proceed to the administration of the medication. The prognosis is excellent. 

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References

  1. Abrahamian FM, Moran GJ, Talan DA. Urinary tract infections in the emergency department. Infect Dis Clin North Am. 2008 Mar; 22(1):73-87, vi.
  2. Little P, Turner S, Rumsby K, et al. Dipsticks and diagnostic algorithms in urinary tract infection: development and validation, randomised trial, economic analysis, observational cohort and qualitative study. Health Technol Assess. 2009 Mar; 13(19):iii-iv, ix-xi, 1-73.
  3. Kanj SS, Kanafani ZA. Current concepts in antimicrobial therapy against resistant gram-negative organisms: extended-spectrum beta-lactamase-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, and multidrug-resistant Pseudomonas aeruginosa. Mayo Clin Proc. 2011 Mar; 86(3):250-9.
  4. Hooton TM, Bradley SF, Cardenas DD, et al. Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin Infect Dis. 2010 Mar 1; 50(5):625-63.
  5. Tiemstra JD, Chico PD, Pela E. Genitourinary infections after a routine pelvic exam. J Am Board Fam Med. 2011 May-Jun; 24(3):296-303.
    Hooton TM, Scholes D, Hughes JP, et al. A prospective study of risk factors for symptomatic urinary tract infection in young women. N Engl J Med. 1996; 335:468.
  6. Czaja CA, Stamm WE, Stapleton AE, et al. Prospective cohort study of microbial and inflammatory events immediately preceding Escherichia coli recurrent urinary tract infection in women. J Infect Dis. 2009 Aug 15; 200(4):528-36.
  7. Foxman B, Barlow R, D'Arcy H, et al. Urinary tract infection: self-reported incidence and associated costs. Ann Epidemiol. 2000; 10:509-515.
  8. Campbell J, Felver M, Kamarei S. 'Telephone treatment' of uncomplicated acute cystitis. Cleve Clin J Med. 1999; 66:495-501.
  9. Stamm WE. Urinary tract infections. In: Root RK, Waldvogel F, Corey L, Stamm WE. Clinical Infectious Diseases: A Practical Approach. New York, NY: Oxford University Press. 1999; 649–656.
  10. Bradbury SM. Collection of urine specimens in general practice: to clean or not to clean? J R Coll Gen Pract. 1988; 38(313):363–365.
  11. Gupta K, Hooton TM, Naber KG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011; 52:e103.
  12. Warren JW, Abrutyn E, Hebel JR, et al. Guidelines for antimicrobial treatment of uncomplicated acute bacterial cystitis and acute pyelonephritis in women. Infectious Diseases Society of America (IDSA). Clin Infect Dis. 1999; 29:745.
  13. Graninger W. Pivmecillinam--therapy of choice for lower urinary tract infection. Int J Antimicrob Agents. 2003; 22 Suppl 2:73.
  14. Lee BS, Bhuta T, Simpson JM, et al. Methenamine hippurate for preventing urinary tract infections. Cochrane Database Syst Rev. 2012; (10):CD003265.
  15. Lee BS, Bhuta T, Simpson JM, et al. Methenamine hippurate for preventing urinary tract infections. Cochrane Database Syst Rev. 2012; (10):CD003265.

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