EAU Guidelines on Urological Infections

Overview

This Guidelines summary includes evidence-based information and recommendations for the prevention and treatment of urinary tract infections (UTIs) and male accessory gland infections from the European Association of Urology (EAU) guideline on urological infections.

This summary covers information relevant to primary care. For recommendations on complicated UTIs, catheter-associated UTIs, urosepsis, Fournier's gangrene, and peri-procedural antibiotic prophylaxis, refer to the full guideline.

The adaptation of this guideline has been carried out and supervised by Medscape UK. The EAU Guidelines Office will not assume any responsibility for the accuracy of this summary.

Strength of Recommendations

For each recommendation there is an accompanying strength rating. The strength rating forms draw on the guiding principles of the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology but do not purport to be GRADE.

The strength of each recommendation is represented by the words [strong recommendation] or [weak recommendation]. The strength of each recommendation is determined by the balance between desirable and undesirable consequences of alternative management strategies, the quality of the evidence (including certainty of estimates), and nature and variability of patient values and preferences. 

Reflecting on your Learnings

Reflection is important for continuous learning and development, and a critical part of the revalidation process for UK healthcare professionals. Click here to access the Guidelines Reflection Record.

Asymptomatic Bacteriuria in Adults

• Urinary growth of bacteria in an asymptomatic individual is common and corresponds to a commensal colonisation. Treatment of asymptomatic bacteriuria (ABU) should be performed only in cases of proven benefit for the patient to avoid the risk of selecting antimicrobial resistance and eradicating a potentially protective ABU strain.

Diagnostic Evaluation

• Asymptomatic bacteriuria in an individual without urinary tract symptoms is defined by a mid-stream sample of urine showing bacterial growth ≥10⁵ cfu/ml in two consecutive samples in women and in one single sample in men. In a single catheterised sample, bacterial growth may be as low as 10² cfu/ml to be considered representing true bacteriuria in both men and women
• Cystoscopy and/or imaging of the upper urinary tract is not mandatory if the medical history is otherwise without remark
• If persistent growth of urease-producing bacteria is detected, for example, Proteus mirabilias, stone formation in the urinary tract must be excluded. In men, a digital rectal examination must be performed to investigate the possibility of prostate diseases.

Recommendations

• Do not screen or treat asymptomatic bacteriuria in the following conditions: [strong recommendation]
  • women without risk factors
  • patients with well-regulated diabetes
  • postmenopausal women
  • elderly institutionalised patients
  • patients with dysfunctional and/or reconstructed lower urinary tracts
  • patients with renal transplants
  • patients prior to arthroplasty surgeries
  • patients with recurrent UTIs
• Screen for and treat asymptomatic bacteriuria prior to urological procedures breaching the mucosa [strong recommendation]
• Screen for and treat asymptomatic bacteriuria in pregnant women with standard short course treatment. [weak recommendation]

Uncomplicated Cystitis

Uncomplicated cystitis is defined as acute, sporadic, or recurrent cystitis limited to nonpregnant women with no known relevant anatomical and functional abnormalities within the urinary tract or comorbidities.

Diagnostic Evaluation

Clinical Diagnosis

• The diagnosis of uncomplicated cystitis can be made with a high probability based on a focused history of lower urinary tract symptoms (dysuria, frequency, and urgency) and the absence of vaginal discharge
• In elderly women genitourinary symptoms are not necessarily related to cystitis.

Recommendations

• Diagnose uncomplicated cystitis in women who have no other risk factors for complicated UTIs based on: [strong recommendation]
  • a focused history of lower urinary tract symptoms (dysuria, frequency, and urgency)
  • the absence of vaginal discharge
• Use urine dipstick testing for diagnosis of acute uncomplicated cystitis [weak recommendation]
• Urine cultures should be done in the following situations:
  • suspected acute pyelonephritis
  • symptoms that do not resolve or recur within 4 weeks after completion of treatment
  • women who present with atypical symptoms
  • pregnant women. [strong recommendation]

Cystitis in Pregnancy

• Short courses of antimicrobial therapy can also be considered for treatment of cystitis in pregnancy, but not all antimicrobials are suitable during pregnancy
• In general, penicillins, cephalosporins, fosfomycin, nitrofurantoin (not in case of glucose-6-phosphate dehydrogenase deficiency and during the end of pregnancy), trimethoprim (not in the first trimenon), and sulfonamides (not in the last trimenon), can be considered.

Cystitis in Men

• Cystitis in men without involvement of the prostate is uncommon and should be classed as a complicated infection. Therefore, treatment with antimicrobials penetrating into the prostate tissue is needed in males with symptoms of UTI
• A treatment duration of at least 7 days is recommended, preferably with trimethoprim sulphamethoxazole or a fluoroquinolone if in accordance with susceptibility testing.

Renal Insufficiency

• In patients with renal insufficiency the choice of antimicrobials may be influenced by decreased renal excretion; however, most antimicrobials have a wide therapeutic index
• No adjustment of dose is necessary until glomerular filtration rate (GFR) is <20 ml/min, with the exception of antimicrobials with nephrotoxic potential, for example, aminoglycosides. The combination of loop diuretics (for example, furosemide) and a cephalosporin is nephrotoxic
• Nitrofurantoin is contraindicated in patients with an eGFR of <30 ml/min/1.73m² as accumulation of the drug leads to increased side effects as well as reduced urinary tract recovery, with the risk of treatment failure.

Recommendations

• Prescribe fosfomycin trometamol, pivmecillinam, or nitrofurantoin as first-line treatment for uncomplicated cystitis in women [strong recommendation]
• Do not use aminopenicillins or fluoroquinolones to treat uncomplicated cystitis. [strong recommendation]

Table 1: Suggested Regimens for Antimicrobial Therapy in Uncomplicated Cystitis

Follow-up

• Routine post-treatment urinalysis or urine cultures in asymptomatic patients are not indicated
• In women whose symptoms do not resolve by end of treatment, and in those whose symptoms resolve but recur within 2 weeks, urine culture and antimicrobial susceptibility testing should be performed. For therapy in this situation, one should assume that the infecting organism is not susceptible to the agent originally used
• Re-treatment with a 7-day regimen using another agent should be considered.

Recurrent UTIs

• Recurrent UTIs (rUTIs) are recurrences of uncomplicated and/or complicated UTIs, with a frequency of at least three UTIs per year or two UTIs in the last 6 months.

Diagnostic Evaluation

• Initial diagnosis of rUTI should be confirmed by urine culture
• Extensive routine diagnostic investigation including cystoscopy and imaging is not routinely recommended as the diagnostic yield is low. However, it should be performed without delay in atypical cases, for example, if renal calculi, outflow obstruction, interstitial cystitis, or urothelial cancer is suspected.

Behavioural Modifications

• Women with rUTI should be counselled on avoidance of risks (for example, insufficient drinking, habitual and postcoital delayed urination, wiping from back to front after defecation, douching, and wearing occlusive underwear) before initiation of long-term prophylactic drug treatment, although there is limited evidence available regarding these approaches.

Antimicrobials for Preventing rUTI

Continuous Low-dose Antimicrobial Prophylaxis and Postcoital Prophylaxis

• Antimicrobials may be given as continuous low-dose prophylaxis for longer periods, or as postcoital prophylaxis. There is no significant difference in the efficacy of the two approaches
• After discontinuation of the drug, UTIs tend to re-occur, especially among those who have had three or more infections annually
• The choice of agent should be based on the local resistance patterns. Regimens include nitrofurantoin 50 mg or 100 mg once daily, fosfomycin trometamol 3 g every 10 days, trimethoprim 100 mg once daily, and during pregnancy cephalexin 125 mg or 250 mg or cefaclor 250 mg once daily. Postcoital prophylaxis should be considered in pregnant women with a history of frequent UTIs before onset of pregnancy, to reduce their risk of UTI.

Self-diagnosis and Self-treatment

• In patients with good compliance, self-diagnosis and self-treatment with a short course regimen of an antimicrobial agent should be considered. The choice of antimicrobials is the same as for sporadic acute uncomplicated UTI.

Recommendations

• Diagnose rUTI by urine culture [strong recommendation]
• Do not perform an extensive routine diagnostic investigation (for example, cystoscopy, full abdominal ultrasound) in women younger than 40 years of age with rUTI and no risk factors [weak recommendation]
• Advise premenopausal women regarding increased fluid intake as it might reduce the risk of rUTI [weak recommendation]
• Use vaginal oestrogen replacement in postmenopausal women to prevent rUTI [strong recommendation]
• Use immunoactive prophylaxis to reduce rUTI in all age groups [strong recommendation]
• Advise patients on the use of local or oral probiotic containing strains of proven efficacy for vaginal flora regeneration to prevent UTIs [weak recommendation]
• Advise patients on the use of cranberry products to reduce rUTI episodes; however, patients should be informed that the quality of evidence underpinning this is low with contradictory findings [weak recommendation]
• Use D-mannose to reduce rUTI episodes, but patients should be informed of the overall weak and contradictory evidence of its effectiveness [weak recommendation]
• Use methenamine hippurate to reduce rUTI episodes in women without abnormalities of the urinary tract [strong recommendation]
• Use continuous or postcoital antimicrobial prophylaxis to prevent rUTI when non-antimicrobial interventions have failed. Counsel patients regarding possible side effects [strong recommendation]
• For patients with good compliance, self-administered short-term antimicrobial therapy should be considered. [strong recommendation]

Uncomplicated Pyelonephritis

Uncomplicated pyelonephritis is defined as pyelonephritis limited to nonpregnant, premenopausal women with no known relevant urological abnormalities or comorbidities.

Diagnostic Evaluation

Clinical Diagnosis

• Pyelonephritis is suggested by fever (>38°C), chills, flank pain, nausea, vomiting, or costovertebral angle tenderness, with or without the typical symptoms of cystitis
• Pregnant women with acute pyelonephritis need special attention, as this kind of infection may not only have an adverse effect on the mother with anaemia, renal and respiratory insufficiency, but also on the unborn child with more frequent preterm labour and birth.

Differential Diagnosis

• It is vital to differentiate as soon as possible between uncomplicated and complicated mostly obstructive pyelonephritis, as the latter can rapidly lead to urosepsis. This differential diagnosis should be made by the appropriate imaging technique.

Recommendations

• Perform urinalysis (for example, using the dipstick method), including the assessment of white and red blood cells and nitrite, for routine diagnosis [strong recommendation]
• Perform urine culture and antimicrobial susceptibility testing in patients with pyelonephritis [strong recommendation]
• Perform imaging of the urinary tract to exclude urgent urological disorders [strong recommendation]
• Treat patients with uncomplicated pyelonephritis not requiring hospitalisation with short-course fluoroquinolones as first-line treatment [strong recommendation]
• Do not use nitrofurantoin, oral fosfomycin, and pivmecillinam to treat uncomplicated pyelonephritis. [strong recommendation]

Urethritis

• Urethritis can be of either infectious or non-infectious origin. Inflammation of the urethra presents usually with lower urinary tract symptoms and must be distinguished from other infections of the lower urinary tract
• Urethral infection is typically spread by sexual contact.

Diagnostic Evaluation

• In symptomatic patients, the diagnosis of urethritis can be made based on the presence of any of the following criteria:
  • mucoid, mucopurulent, or purulent urethral discharge
  • Gram or methylene-blue stain of urethral secretions demonstrating inflammation
  • the presence of >10 polymorphonuclear leukocyte/high power field in the sediment from a spun first-void urine sample or a positive leukocyte esterase test in first-void urine.

Recommendations

• Perform a Gram stain of urethral discharge or a urethral smear to preliminarily diagnose gonococcal urethritis [strong recommendation]
• Perform a validated nucleic acid amplification test (NAAT) on a first-void urine sample or urethral smear prior to empirical treatment to diagnose chlamydial and gonococcal infections [strong recommendation]
• Delay treatment until the results of the NAATs are available to guide treatment choice in patients with mild symptoms [strong recommendation]
• Perform a urethral swab culture, prior to initiation of treatment, in patients with a positive NAAT for gonorrhoea to assess the antimicrobial resistance profile of the infective strain [strong recommendation]
• Use a pathogen directed treatment based on local resistance data [strong recommendation]
• Sexual partners should be treated maintaining patient confidentiality. [strong recommendation]

Table 2: Suggested Regimens for Antimicrobial Therapy for Urethritis

Bacterial Prostatitis

Diagnostic Evaluation

History and Symptoms

• Acute bacterial prostatitis usually presents abruptly with voiding symptoms and distressing but poorly localised pain.

Symptom Questionnaires

• In chronic bacterial prostatitis (CBP), symptoms appear to have a strong basis for use as a classification parameter. Prostatitis symptom questionnaires have therefore been developed to assess severity and response to therapy. They include the validated Chronic Prostatitis Symptom Index; however, its usefulness in clinical practice is uncertain.

Recommendations

• Do not perform prostatic massage in acute bacterial prostatitis (ABP) [strong recommendation]
• Take a mid-stream urine dipstick to check nitrite and leukocytes in patients with clinical suspicion of ABP [weak recommendation]
• Take a mid-stream urine culture in patients with ABP symptoms to guide diagnosis and tailor antibiotic treatment [weak recommendation]
• Take a blood culture and a total blood count in patients presenting with ABP [weak recommendation]
• Perform accurate microbiological evaluation for atypical pathogens such as Chlamydia trachomatis or Mycoplasmata in patients with CBP [weak recommendation]
• Perform the Meares and Stamey 2- or 4-glass test in patients with CBP [strong recommendation]
• Perform transrectal ultrasound in selected cases to rule out the presence of prostatic abscess [weak recommendation]
• Do not routinely perform microbiological analysis of the ejaculate alone to diagnose CBP. [weak recommendation]

Table 3: Suggested Regimens for Antimicrobial Therapy for CBP

Follow-up

• In asymptomatic post-treatment patients, routine urinalysis and/or urine culture is not mandatory as there are no validated tests of cure for bacterial prostatitis except for cessation of symptoms
• In patients with persistent symptoms and repeated positive microbiological results for sexually transmitted infectious pathogens, microbiological screening of the patient's partner/s is recommended. Antibiotic treatments may be repeated with a more prolonged course, higher dosage, and/or different compounds.

Acute Infective Epididymitis

• Epididymitis is a common condition and can be acute, chronic, or recurrent. Acute epididymitis is clinically characterised by pain, swelling, and increased temperature of the epididymis, which may involve the testis and scrotal skin.

Recommendations

• Obtain a mid-stream urine and a first voided urine for pathogen identification by culture and NAAT [strong recommendation]
• Initially prescribe a single antibiotic or a combination of two antibiotics active against C. trachomatis and Enterobacterales in young sexually active men; in older men without sexual risk factors, only Enterobacterales have to be considered [strong recommendation]
• If gonorrhoeal infection is likely, give single-dose ceftriaxone 1000 mg intramuscularly or intravenously^[A] in addition to a course of an antibiotic active against C. trachomatis [strong recommendation]
• Adjust antibiotic agent when pathogen has been identified and adjust duration according to clinical response [weak recommendation]
• Follow national policies on reporting and tracing/treatment of contacts for sexually transmitted infections. [strong recommendation]

Management of Human Papillomavirus in Men

Risk Factors

• Risk factors for human papillomavirus (HPV) infection include early age of first sexual intercourse, sexual promiscuity, higher frequency of sexual intercourse, smoking, and poor immune function. Incidence and prevalence of overall HPV was considerably higher in men who have sex with men compared to heterosexuals.

Transmission

• HPV typically spreads by sustained direct skin-to-skin or mucosal contact, with vaginal, oral, and anal sex being the most common transmission route. In addition, HPV has been found on surfaces in medical settings and public environments raising the possibility of object-to-skin/mucosa transmission.

Diagnosis

• There is currently no approved test for HPV in men and routine testing to check for HPV or HPV-related disease in men is not recommended
• A physical examination to identify HPV lesions should be carried out
• An acetic acid test to diagnose subclinical HPV lesions may be performed. If the diagnosis is uncertain or there is a suspicion of cancer, a biopsy should be carried out.

Treatment of HPV-related Diseases

• Approximately 90% of HPV infections do not cause any problems and are cleared by the body within 2 years. However, treatment is required when HPV infection manifests as anogenital warts to prevent the transmission of HPV-associated anogenital infection and to minimise the discomfort caused to patients.

Recommendations

• Use self-administered imiquimod 5% cream applied to all external warts overnight 3 times a week for 16 weeks for the treatment of anogenital warts [strong recommendation]
• Use self-administered sinecatechins 15% or 10% applied to all external warts 3 times daily until complete clearance, or for up to 16 weeks for the treatment of anogenital warts [strong recommendation]
• Use self-administered podophyllotoxin 0.5% self-applied to lesions twice daily for 3 days, followed by 4 rest days, for up to 4 or 5 weeks for the treatment of anogenital warts. [strong recommendation]

Circumcision for Reduction of HPV Prevalence

• Discuss male circumcision with patients as an additional one-time preventative intervention for HPV-related diseases. [strong recommendation]

Therapeutic Vaccination

• Offer HPV vaccine to males after surgical removal of high-grade anal intraepithelial neoplasia [strong recommendation]
• Offer early HPV vaccination to boys with the goal of establishing optimal vaccine-induced protection before the onset of sexual activity [strong recommendation]
• Apply diverse communication strategies in order to improve HPV vaccination knowledge in young adult males. [strong recommendation]

Genitourinary Tuberculosis

Diagnosis

• The diagnosis of genitourinary tuberculosis (GUTB) is challenging as no single diagnostic test exists
• Diagnosis relies on a high suspicion of infection based on patient history; microbiological, molecular, and histological testing; and imaging findings
• Patients generally present with nonspecific urological complaints for which no obvious cause is identified, including haematuria, increased urinary frequency, difficulty voiding, abdominal, lumbar and suprapubic pain, and in female patients menstrual irregularities and pelvic pain. Patients may also present for infertility issues.

Recommendations

Diagnosis

• Take a full medical history including history of previous tuberculosis infection (pulmonary and extrapulmonary) form all patients presenting with persistent nonspecific genitourinary symptoms and no identifiable cause [strong recommendation]
• Perform smear microscopy on urine, semen, tissue specimens, and discharged or prostatic massage fluid using Ziehl–Neelsen (ZN) or auramine staining in patients with suspected GUTB [weak recommendation]
• Perform acid-fact bacilli culture on three midstream first-void urine samples, on 3 consecutive days for M. tuberculosis isolation in patients with suspected GUTB [strong recommendation]
• Use a recommended polymerase chain reaction (PCR) test system in addition to microbiological reference standard in urine specimens as a diagnostic test in patients with signs and symptoms of GUTB [weak recommendation]
• Use imaging modalities in combination with culture and/or PCR to aid in the diagnosis of GUTB and to assess the location and extent of damage to the genitourinary system. [weak recommendation]

Treatment

• Use medical treatment as first-line treatment for GUTB [strong recommendation]
• Use a daily 6-month regimen for treatment of newly diagnosed GUTB this should include an intensive phase of 2 months with isoniazid, rifampicin, pyrazinamide, and ethambutol, followed by a continuation phase of 4 months with isoniazid and rifampicin [strong recommendation]
• Treat multidrug-resistant TB with an individualised treatment regime, including at least five effective tuberculosis medicines during the intensive phase, including pyrazinamide and four core second-line tuberculosis medicines. [strong recommendation]

For recommendations on complicated UTIs, catheter-associated UTIs, urosepsis, Fournier's gangrene, and peri-procedural antibiotic prophylaxis, refer to the full guideline.

Footnote

[A] Despite the lack of randomised controlled trials, there is increasing evidence that intravenous treatment with ceftriaxone is safe and effective for the treatment of gonorrhoeal infections and avoids the discomfort of an intramuscular injection for patients.