2.5.4 Non-specific Urethritis

Unspecific urethritis is probably underreported or not correctly diagnosed and thus there is no consistent epidemiologic data available.

The most prevalent pathogens causing urethritis are Neisseria gonorrhea and Chlamydia trachomatis. The term non-specific urethritis (NSU) applies to non-gonococcal, non-chlamydial urethritis (NGNCU). Urethritis is the inflammation of the urethra. Patients complain of discharge, dysuria and urethral discomfort, but can be asymptomatic. Most of the cases are sexually acquired.

In many men with acute urethritis, a known pathogen is not detected.

• The most common organism detected is Mycoplasma genitalium, which accounts for approximately 15-40% of cases and there is a high concordance of infection in sexual partners.

• Ureaplasma urealyticum or Ureaplasma parvum can also cause urethritis in some men. However, detection of the pathogen by nucleic acid amplification tests (NAATs) cannot distinguish between asymptomatic carriage and possible causality.

• The isolation of Trichomonas vaginalis is dependent on the prevalence of the organism in the community.

• Adenoviruses or herpes simplex virus types 1 and 2 (HSV1-2) may account for 2–4% of symptomatic patients.

• There is also evidence that bacterial vaginosis (BV)-associated bacteria may cause urethritis.

• Neisseria meningitidis, Haemophilus sp., Candida sp., and other bacteria (staphylococci, streptococci, enterococci, E.coli) probably account for a small proportion of urethritis.

The etiology of persistent urethritis is multifactorial, with an infectious agent being identified only in less than half of the cases.

Patients complain of urethral discharge, dysuria, penile tip irritation, urethral discomfort or itch, but can be asymptomatic, too. Clinical signs are often modest or missing, the presence of a mucopurulent or purulent urethral discharge or penile tip erythema can be detected on examination. Herpes simplex infection can cause dysuria without signs outside the urethra.

• The diagnosis of urethritis can be confirmed by demonstrating ≥ 5 polymorphonuclear leukocytes (PMNLs) per high power microscopic field from the urethral smear. After taking the sample from the meatus with a cotton tip swab it can be Gram-or methylene blue-stained.

• A leukocyte esterase dipstick of the first-voided urine (FVU) specimen can also be used in detecting urethritis in symptomatic men with a negative urethral smear. The sensitivity and specificity of other methods for diagnosing urethritis are imperfect compared with a urethral smear.

• Patients with urethritis should be tested using NAATs for C. trachomatis, N. gonorrhoeae and M. genitalium (with screening for macrolide resistance).

• Trichomonas vaginalis testing should be considered if it is prevalent (>2% in symptomatic women) in the local population. Urological investigation is usually normal and is not recommended.

• In men with symptoms suggestive of a urinary tract infection (severe dysuria, haematuria, urinary frequency or urgency) a urine analysis should be considered. If urinary tract infection is found, young men should be investigated for urinary tract abnormalities. Symptomatic patients should be reassured and advised to re-attend the clinic for an early morning smear if his symptoms do not settle.

Chlamydia, gonorrhoea. The chronic pelvic pain syndrome should be considered in the differential diagnosis. Urethral stricture and foreign bodies.

Infection should be treated according to the etiological findings.

• According to the current European guideline azithromycin for five days (500 mg stat then 250 mg od for four days) in eradicating macrolide- susceptible M. genitalium infection. Macrolide antimicrobial resistance in M. genitalium is >40% in the majority of countries.

• If macrolide-resistant M. genitalium is detected, moxifloxacin 400 mg orally once daily for 7-14 days is recommended. Also, fluoroquinolone resistance is increasing.

• In many countries resistance-guided therapy is recommended for symptomatic patients, involving initial treatment with doxycycline to reduce organism load followed by azithromycin for macrolide-sensitive infections or moxifloxacin for macrolide-resistant infections.

• Sex partners should be tested and offered treatment. The patient shall be advised not to be sexually active until all parties have completed the treatment. A test of cure >3 weeks after treatment should be performed.

• Empirical treatment of symptomatic urethritis patients with a negative urethral smear is not recommended according to the European guidelines. For those with positive smear, a recommended regimen is doxycycline 100 mg twice daily (bd) or 200 mg once daily (od) orally for seven days, which is effective (70-80%) in men who are U. urealyticum-positive. Second line regimens include azithromycin 500 mg single dose (stat), then 250 mg od for four days or lymecycline 300 mg bd for 10 days or tetracycline hydrochloride 500 mg bd for 10 days. All sexual partners of the last 4 weeks the patient had before the symptoms started should be assessed and offered epidemiological treatment. Current partners should be tested and treated and the patient advised not to be sexually active until all parties have completed treatment.

• Persistent urethritis can result from both treatment failure and re-infection. Recurrent urethritis is defined as the recurrence of symptomatic urethritis occurring 30-90 days following treatment of acute urethritis and occurs in 10-20% of patients. Any treatment of persistent/ recurrent urethritis should cover M. genitalium, T. vaginalis and probably BV-associated bacteria (metronidazole 400 mg twice daily for five days). Re-treatment of the sexual partner will be beneficial.