Cystitis, acuteN30.0

In 1808 Philip Syng described cystitis as "an inflammatory condition of the bladder with an ulcer producing the same symptoms as a bladder stone". In 1836, Joseph Parrish referred to cystitis as: "A painful tic of the urinary bladder." (Bschleipfer 2018)

Acute cystitis is the acute onset of dolent inflammation of the urinary bladder (Herold 2020).

Acute cystitis is divided into an uncomplicated and a complicated form.

The following cases are called complicated cystitis:

• any cystitis in
  • Children
  • men
  • pregnant women
• with anatomical peculiarities
• in case of functional peculiarities
• if within the last 14 days:
  • a discharge from the hospital or nursing home has taken place
  • a urinary catheter was inserted
  • antibiotics have been administered

In all other cases, it is an uncomplicated cystitis (Kuhlmann 2015).

However, the terms "complicated" and "uncomplicated" are not treated consistently in the literature (Schmelz 2014).

Although acute cystitis is one of the frequent reasons for a visit to the doctor, there have been no reliable data on its frequency until now.

From 2012 to 2013, extensive analyses were carried out in this regard by a health insurance company, which included female insured persons from the age of 12. The highest prevalence was found in the group of people over 80 years of age (Wagenlehner 2017).

There is a significant gender bias in acute cystitis: up to the age of 50, it occurs almost exclusively in women, with prevalence increasing with age. From the age of 50, however, men are also increasingly affected (Kuhlmann 2015).

Among adult women, between 20 % - 30 % develop acute cystitis ≥ 1 x per year (Schmelz 2014).

Several peaks of disease are found:

1. in infancy and early childhood

2. during the honeymoon (so-called honeymoon cystitis)

3. during pregnancy

4. in the postpartum phase

5. in patients after kidney transplantation (Herold 2020).

Cystitis is the most common bacterial infection in patients with Z. n. kidney trans plantation with 45% - 72% (Guberina 2016) (Keller 2010). In the 1st year after transplantation - especially in the first 3 - 6 months - urinary tract infections occur frequently (Kuhlmann 2015).

For more details see. Urinary tract infection

In women, causal anatomical conditions play a major role such as:

• short urethra in direct localization to the anal region
• Cleaning of the intimate region from back to front instead of from front to back (Herold 2020).

In men, there is some protection against cystitis due to:

• longer urethra
• ingredients of the prostate secretion have an antibacterial effect
• the dry meatus urethrae is only slightly colonised with germs (Keller 2010).

The cause of acute cystitis is in about 50 % bacteria:

• gram-negative pathogens (Escherichia coli in 77 %)
• Gram-positive pathogens (between < 1 % - 4 %) (for more details see urinary tract infection ) (Manski 2020)
• Trichomonads (rare)
• thrush (rare)

Uncomplicated cystitis: Uncomplicated cystitis is caused by E. coli in up to 80% of cases.

Complicated cystitis: In complicated cystitis, 30% of cases are caused by enterococci, 20% each by E. coli and staphylococci, 10% by Pseudomonas aeruginosa and < 5% each by Proteus mirabilis, Klebsiella and other germs.

Cystitis in patients after kidney transplantation: Here, predominantly Gram-negative pathogens and enterococci are found (Kuhlmann 2015).

Nosocomial cystitis: In nosocomial cystitis, there is usually a mixed infection with problem germs such as: Enterococci, Pseudomonas, Proteus, Enterobacter, Citrobacter.

In patients with permanent catheters, 50 % of them have a urinary tract infection after only 1 week, and almost 100 % after 1 month. These are predominantly mixed infections. Candida is found in the urine in approx. 20 %, but there are predominantly no symptoms.

(For more details see urinary tract infection).

Risk factors are primarily:

• recent sexual intercourse
• new sexual partners
• use of spermicides
• history of urinary tract infections
• history of urinary tract infections in first-degree female relatives
• Prostate disease

All other factors, such as pre- or post-coital urination, use of tampons, warm baths, showering behaviour, frequency of micturition, amount of drinking, type of underwear, etc., have not yet been proven in studies (Kuhlmann 2015).

(For further risk factors, see urinary tract infection).

At the beginning of the inflammation, hyperemia, edema and infiltration of the bladder wall occur in the urinary bladder due to neutrophilic granulocytes. In the further course, the mucosa is replaced by an easily injured granulation tissue. Occasionally, shallow ulcers filled with exudate develop there. The inflammation usually affects only the mucosa and submucosa. All layers of the muscularis are rarely affected.

Without treatment, hemorrhages and necrosis of the bladder wall occur in the late stages of the disease.

(Manski 2019)

Acute cystitis usually begins suddenly. The cardinal symptoms are:

• Disorders of micturition such as:
• Dysuria (difficult urination with weakened urinary stream)
• Alguria (pain during urination)
• Pollakisuria (frequent urination with predominantly small amounts of urine)
• nocturia (nocturnal urination)
• Pain in the suprapubic area

In addition, the following symptoms may occur:

• Hematuria
• turbidity of the urine
• change in the smell of the urine
• new or increased incontinence

(Manski 2019 / Keller 2010 / Kuhlmann 2015 / Schmelz 2014)

According to the S3 guideline of the DGU, no further diagnostic measures are required for acute cystitis:

• with typical symptoms(pollakiuria, dysuria)
• WITHOUT genital fluoride
• renal bed NOT palpable
• Otherwise healthy, non-pregnant pre-menopausal women.

(Manski 2019)

In all other cases should be done according to the symptomatology:

• Urine sediment
• Urine culture
• sonography of the kidney and bladder
• vaginal examination (if vaginitis or adnexitis is suspected; in case of confirmation, swabs should be taken for microbacterial examination)
• Urogram
• Cystoscopy
• Micturition cystourethrography (MCU)

(Manski 2019)

It remains open - according to the S3- guideline - whether a complete urological examination should be performed in uncomplicated cystitis in younger men.

In any case, this is recommended in:

• febrile cystitis
• recurrent cystitis
• V. a. complicating factors
• V. a. chronic bacterial prostatitis

(Wagenlehner 2017)

ACSS questionnaire

In 2015, Alidjanov et al. presented the Acute Cystitis Symptom Score (ACSS) questionnaire to validate uncomplicated acute cystitis in women.

Part A of the ACSS includes questions on typical symptoms, differential diagnosis, quality of life and concomitant circumstances and was completed at initial presentation.

Part B contains additional questions on the dynamics and is filled out at the follow-up visit.

Here, only suboptimal discriminatory power with regard to treatment success was found.

This was probably due to an ambiguous wording in the translation and was revised in 2017 for all language versions.

German version s.: https://link.springer.com/article/10.1007/s00120-017-0327-2

Scoring:

A score of ≥ 6 points in the "typical symptoms" category indicates acute cystitis with a sensitivity of 94.7% and a specificity of 82.4%.

Part B indicates a very good discriminatory power between success or non-success of a treatment performed up to that point.

(Alidjanov 2017)

Sonography

According to Manski (Manski 2019), sonography of the urinary bladder and kidneys may reveal:

• anatomical norm variants
• diverticula of the urinary bladder
• urinary bladder stones
• Urinary retention
• Residual urine

Urogram: The performance of a urogram does not play a role in acute cystitis. It is recommended in recurrent cystitis that shows abnormalities on sonography (such as urinary retention, urinary bladder diverticula, infectious stones, ureterocele, etc.) (Manski 2019).

Cystoscopy: Cystoscopy should be performed exclusively in the infection-free interval. Routinely, according to the S3- guideline, it is not recommended in women without other relevant concomitant diseases, even in the case of recurrent urinary tract infections, but it is recommended above a certain age (not further defined) and in the case of complications such as a micro- hematuria, detection of pathogens other than E. coli, etc (Manski 2019).

Contrast-enhanced CT: MRI is indicated in acute cystitis only if sonography has revealed unclear findings (Herold 2020).

For more details, see. Urinary tract infection

Micturition cystourethrography (MCU): The performance of an MCU also plays no role in the diagnosis of acute cystitis, only in the presence of complications (for more information, see urinary tract infection).

Urine test strip: A positive test strip increases the probability of cystitis. However, as both sensitivity and specificity are insufficient, the test strip is currently not recommended for the diagnosis of cystitis (Wagenlehner 2017).

Urine sediment

• 1. bacteriuria:

Urine should be obtained before starting antibiotic treatment.

Prerequisites for correct collection are spreading of the labia, careful cleaning of the meatus urethrae or glans penis. The midstream urine can then be obtained.

Prerequisites for the correct interpretation of the findings are rapid transport by cold chain, the use of special media or immediate elaboration.

According to Kass, one speaks of significant bacteriuria if a bacterial count of ≥ 105 / ml urine is found in the midstream urine after appropriate processing. Lower bacterial counts indicate contamination.

However, forced diuresis may also result in falsely low bacterial counts.

In treated patients with typical symptoms of cystitis, bacterial counts ≤ 103 to 104 / ml urine are considered pathological (Herold 2020).

In permanent catheter users, a bacterial count of > 104 plus leukocyturia of > 100 / µg is considered a significant infection (unless the urine was collected from the catheter bag) (Manski 2019).

For any significant bacteriuria, an antibiogram should be created for germ differentiation (Herold 2020)

• 2. leukocyturia:
  • leukocyturia is an indication of pyelonephritis
  • Leukocyturia in otherwise sterile urine (so-called sterile leukocyturia) can be caused by:
  • cystitis treated with antibiotics
  • genital contamination (e.g. by fluorine)
  • mycoplasmaurethritis
  • Chlamydial urethritis
  • urogenital tuberculosis
  • Reiter's syndrome (a triad of urethritis, conjunctivitis, arthritis)
  • Gonorrhea
  • Analgesic anphropathy

Urineculture: For a urine culture, medium stream urine is needed (collection see above "Urine sediment": bacteriuria) (Manski 2019). The establishment of a urine culture is recommended in the case of acute cystitis in:

• Men
• pregnant women
• postmenopausal women
• diabetes mellitus
• after unsuccessful antibiosis (Schmelz 2014)
• Urethritis
• Vaginitis

• benign prostatic hypertrophy
• paracytic cystitis due to infection with Schistosoma haematobium
• tuberculous cystitis
• caused by other diseases such as: prostatitis, intestinal diseases, adnexitis
• drug-induced cystitis due to e.g.: ifosfamide, cyclophosphamide, NSAIDs
• caused by other bladder diseases such as lithiasis, tumour, foreign body
• due to radiogenic cystitis
• Heart failure
• genital herpes
• gonorrhoea
• neurogenic bladder disorder
• psychosomatic complaints (Manski 2019)
• Urethritis (insidious onset, vaginal fluor, herpetic lesions, etc.; inflammation here is distal to the sphincter urethrae internus [Herold 2020])
• Vaginitis (vaginal fluoride, itching, odor, etc.) (Schmelz 2014)

• recurrent cystitis (Herold 2020)
• Haematuria up to macrohaematuria (Kasper 2015).
• Pyelonephritis due to ascension of the pathogens. Occurs in < 5% of all patients with acute cystitis (Manski 2019 / Schmelz 2014)
• paranephritic abscess (CT).
• in pregnant women:
  • Pyelonephritis due to ascension of pathogens in up to 23 % . This can be complicated by pre-existing
    • anemia (23 %)
    • renal dysfunction (7 %)
    • respiratory insufficiency (7 %)
  • Pyelonephritis in pregnant women can lead to:
    • Prematurity
    • reduced birth weight
    • increased neonatal mortality
    • pre-eclampsia (Manski 2019)

Acute cystitis in an otherwise healthy premenopausal woman has a high spontaneous healing rate (Kuhlmann 2015). Therefore, these patients can (initially) wait with regard to antibiotics. The patient should be advised to:

• drink plenty of fluids
• warm sitz baths
• analgesics
• anticholinergics

If there is no improvement under this, antibiotic treatment is required (Manski 2019).

Uncomplicated acute cystitis in premenopausal women: This can be treated by short-term oral antibiotic therapy.

The S3- guideline primarily recommends agents that show a low resistance rate, do not play a role in severe infections and are sensitive to the typical pathogen spectrum in women in Germany.

The 1st choice agents include:

• Fosfomycin- Trometamol (e.g. Monuril). It shows a sensitivity of 96 % and leads to a development of resistance in 1 %. However, from a GFR of < 20 ml / min / 1.73 m² KOF, fosfomycin- trometamol is contraindicated. Dosage recommendation: 3,000 mg 1 x as a single dose.
• Nitrofurantoin: Nitrofurantoin is contraindicated in renal insufficiency from < 60 ml / min / 1.73 m² KOF.Sensitivity is 86%, resistance development is 5%. Dosage recommendation: 50 mg 4 x / d for 7 days or or nitrofurantoin ret. 100 mg 2 x 1 for 5 days.
• Nitroxolin: Nitroxolin is also contraindicated in severe renal impairment (serum creatinine > 2.0 mg / dl). Dosage recommendation: 250 mg 3 x / d over 5 days (Wagenlehner 2017 / Manski 2019).

(Complicated) acute cystitis in pregnant women: In pregnancy, acute cystitis should be treated immediately with antibiotics, otherwise the risk of complications (see above "Complications") increases.

Antibiotics that can be used are:

• Fosfomycin- Trometamol (e.g. Monuril): It shows a sensitivity of 96 % and leads to a development of resistance in 1 %. However, from a GFR of < 20 ml / min / 1.73 m² KOF, fosfomycin- trometamol is contraindicated. Dosage recommendation: 3,000 mg 1 x as a single dose.
• Pivmecillinam (e.g. X- Systo): From a GFR of < 30 ml / min / 1.73 m² KOF, a dose adjustment is required. Dosage recommendation: 400 mg 3 x / d for 3 days (Manski 2019).

(Complicated) cystitis in postmenopausal women: There are few studies that have investigated the efficacy of short-term therapy in postmenopausal women. The choice and efficacy of each antibiotic is similar to that of uncomplicated premenopausal cystitis, but the duration of therapy should be extended if necessary.

• Fosfomycin- Trometamol (e.g. Monuril): An uncontrolled study of single dose showed viral elimination of 87% and clinical efficacy of 96% in postmenopausal women. However, fosfomycin- trometamol is contraindicated above a GFR of < 20 ml / min / 1.73 m² KOF. Dosage recommendation: 3,000 mg 1 x as a single dose.
• Ciprofloxacin: sensitivity is 92%, resistance development is 7% . Dose adjustment required from a GFR of < 60 ml / min / 1.73 m² KOF Dosage recommendation: 250 mg 2 x / d . In this regard, a study in postmenopausal women demonstrated the equivalence of a 3- or 6-day treatment, with better tolerability in the short therapy (Kuhlmann 2015 / Manski 2019).

(Complicated) acute cystitis in younger men: As this occurs very rarely, few meaningful comparative studies can be found. In symptomatic cystitis, oral drug treatment with the following antibiotics is recommended - after a urine culture has been established:

• Pivmecillinam: The sensitivity is 98% and the development of resistance is 1% (Manski 2019. )Dosage recommendation: 400 mg 2 - 3 x / d for7 - 10 days.
• Nitrofurantoin: Here the sensitivity is 86 % and resistance is 5 % (Manski 2019). Dosage recommendation: 50 mg 4 x / d over 7 - 10 days Nitrofurantoin should not be used if the prostate is involved (Wagenlehner 2017).
• Fluoroquinolones: Fluoroquinolones can be used as long as the resistance rate for local E. coli is still < 10 %. The sensitivity is 92 %, the resistance 7 %. Dose adjustment is required from a GFR of < 50 ml / min / 1.73 m² KOF. Dosage recommendation: e.g. ciprofloxacin 250 mg 2 x / d. Duration of therapy: 7 - 10 days (so far, studies have not been able to prove that a short therapy is as effective in men as in women).

After receiving the antibiogram, adjust therapy if necessary (Wagenlehner 2017 / (Manski 2019).

Cystitis in patientsafter kidney transplantation: Patients with kidney transplantation have an increased incidence of urinary tract infections - already due to immunosuppression (Guberina 2016). Pyelonephritis can lead to a significant deterioration in graft function, which is only partially reversed even after successful treatment (Kuhlmann 2015).

If cystitis occurs immediately after transplantation, initial antibiotic treatment appropriate to resistance should be initiated parenterally. Further treatment can be oral and should continue for at least 6 weeks (Keller 2010).

Within the first 3 months after transplantation, 6 weeks of oral therapy is recommended according to the antibiogram. If cystitis occurs later than 6 months after transplantation, a 10-14 day treatment period is usually sufficient (Keller 2010).

• "Essen algorithm for calculated antibiotic treatment of urinary tract infections in renal transplant patients":

The algorithm was first presented in 2011 for the calculated antibiotic treatment of kidney transplant patients. It considers gram-negative germs in addition to enterococci occurring in the early phase.

It recommends the use of quinolones (gyrase inhibitors) in the first two months after transplantation and then cephalosporins from the third month onwards. Treatment should be started parenterally for severe infection and continued orally (Becker 2011).

Acute cystitis with Candida: In susceptible Candida species, treatment should be with:

• Fluconazole 200 mg - 400 mg /d orally for 14 days.
• Amphotericin B: Alternatively, bladder irrigation with 50 mg amphotericin B / l water for 5 - 7 days. In this case, however, the success is unclear (Kuhlmann 2015).

The spontaneous healing rate of uncomplicated acute cystitis is between 30 % - 50 % within one week.

With the exception of pregnant patients, antibiotic treatment only alleviates symptoms and brings about a more rapid improvement in symptoms, as shown in a study conducted in Belgium. The NNT (Number needed to Treet) in this study was 4.4 and after 7 days 2.7 (Kuhlmann 2015).

Cystitis treated with antibiotics should show after 24 h:

• resolution of any fever that may be present
• Improvement of the clinical symptoms

The urine should be sterile again after 3 days. If this is not the case, there are probably complications (see above).

Prophylaxis: Prophylaxis of recurrent cystitis s. Urinary tract infection.

1. Alidjanov J F et al (2017) New questionnaire for German validation of the "Acute Cystitis Symptom Score". Urologist (56) 364 - 366
2. Becker S et al (2011) Urinary tract infections after kidney transplantation. The Urologist (50) 53 - 56
3. Bschleipfer T et al. (2018) Guideline group S2K guideline for interstitial cystitis (IC/BPS) long version, 1st edition, version 1, 2018. AWMF register no: 043/050.
4. Guberina H et al. Infections in immunosuppressed patients. Nephrologist 11 (6) 388 - 395
5. Herold G et al (2020) Internal medicine. Herold Publishers 617 - 622
6. Kasper D L et al (2015) Harrison's Principles of Internal Medicine. Mc Graw Hill Education 294
7. Keller C K et al (2010) Practice of nephrology. Springer Verlag 64 - 66
8. Kuhlmann U et al (2015) Nephrology: pathophysiology - clinic - renal replacement procedures. Thieme Verlag 542 - 548
9. Manski D (2019) The urology textbook. Dirk Manski Publishers 348 - 352
10. Schmelz H U et al. (2014) Specialist examination in urology: 1000 documented examination questions. Georg Thieme Verlag 117 - 120
11. Sökeland J et al (2008) Pocket textbook of urology. Georg Thieme Verlag 7.1.3.1.
12. Wagenlehner F et al. (2017) Interdisciplinary S3 guideline epidemiology, diagnosis, therapy, prevention and management of uncomplicated, bacterial, community-acquired urinary tract infections in adult patients update 2017. AWMF register no. 043/044.