Non specific urethritis persistent or recurrent NSU

Non-specific urethritis (NSU) has a very broad meaning. It used to apply to any urethritis, which is not gonococcal in origin (also referred to as non-gonococcal urethritis [NGU]). However, since chlamydia and mycoplasma can now be diagnosed specifically, NSU, in these guidelines, refers to chronic or persistent urethritis where gonorrhoea, chlamydia, mycoplasma and other infections have been excluded, and where there are > 5 WBC/HPF on microscopy.

It is assumed that the patient presenting with a discharge has already had treatment for gonorrhoea and/or chlamydia as per the management of discharge. If the patient is no longer symptomatic following treatment no further treatment is required at follow-up.

For the management of men with a discharge at first presentation, see Urethral discharge dysuria.

It is important that the partner is also tested and treated.

It is important to exclude the following possibilities before diagnosing NSU:

• gonorrhoea and/or chlamydia infection or re-infection from a new or untreated partner
• non-compliance with treatment
• chronic checking for discharge by an anxious patient can result in an often clear discharge due to mechanical irritation after inflammation of the urethra
• antibiotic therapy prior to initial testing which may have resulted in a false negative test.

If Chlamydia trachomatis and Neisseria gonorrhoeae have been satisfactorily excluded consider:

• Mycoplasma genitalium (thought to be responsible for around 30% of NSU in Aus.)
• Trichomonas vaginalis
• HSV
• Adenovirus (often associated with URTI in partner and oral sex)
• Meatal candidiasis

If chlamydia and gonorrhoea have not been completely excluded re-test for both, and consider the need for testing at other sites, e.g. MSM and rectal and pharyngeal testing.

See below for discussion of ureaplasmas as possible pathogen in NSU.

Symptoms:

• a clear or muco-purulent scanty to copious discharge from the penis, which can range from persistent to intermittent
• pain on passing urine
• discomfort or irritation at the meatus.

History:

• non-compliance with treatment
• any sexual contact since treatment:
• new infection with new sexual partner
• reinfection – partners not investigated and/or treated 
• squeezing – ongoing mechanical irritation of the urethra any symptoms at other extra-genital sites.

STI Atlas (external site)

• Urethral M,C, & S to confirm the diagnosis i.e. > 5 WBC/HPF on microscopy
• Consider whether re-testing for Chlamydia trachomatis and Neisseria gonorrhoeae is appropriate (NAAT FVU +/- urethral swab [no transport medium])

The following infective causes of urethritis should be excluded before making a diagnosis of NSU:

• Mycoplasma genitalium FVU +/- urethral NAAT (no transport medium)
• Trichomonas vaginalis FVU +/- urethral NAAT  (no transport medium)
• Herpes FVU +/- urethral NAAT  (no transport medium)
• Adenovirus urethral NAAT  (no transport medium) where available.

Treatment depends upon what treatment has been given previously.

• Doxycycline 100 mg orally, 12-hourly for 2 weeks

        or

• roxithromycin 300 mg orally, daily for 2 weeks (second-line)

        plus

• metronidazole 2 g orally, as a single dose

        or

• tinidazole 2 g orally, as a single dose.

Provide herpes treatment if appropriate.

Patients may require longer therapy.

Advise avoidance of alcohol with either metronidazole or tinidazole treatment.

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• Non-specific urethritis (Healthy WA)

No sexual contact for 7 days after treatment and avoid sexual contact with prior partners until 7days after they have been tested and treated.

Female sexual partners should be tested and treated for presumed cervicitis – the female equivalent of NSU. The term non-specific genital infection, which applies to both these conditions, is rarely used.

Recent studies have shown up to 70% of female partners of NSU have either:

• symptoms of infection
• signs of infection OR
• an infection is detected

• Patients need to be reviewed to ensure symptoms have resolved, preferably one week after treatment has concluded.
• Review after treatment for management of any causative organisms that have been identified. 
• If possible, also review partners' management if the index case remains symptomatic with no cause evident.
• Consider referral to or review by a sexual health physician in persistent cases.

Until post-treatment review, ask patients to avoid:

• squeezing of the penis and self-examination.

This is not a notifiable disease.

Contact tracing and further counselling are important.

Always test for other STIs.

NAAT tests exist for both U. urealyticum and U. parvum.

Testing for Ureaplasma species is a contentious issue. There is an opinion that more research is required before generalized STI testing occurs both in terms of pathogenicity and treatment.

Ureaplasmas can be found in 30% of men as a commensal. Rarely, it may result in a urethritis and be a cause of NSU. Therefore, detection in NSU does not confirm it as the causative organism (often a causative organism is not found in NSU).

Effective antibiotic treatment has yet to be established. Doxycycline [100mg BD for 14 days] is used with some effect in treating the symptoms, but often does not eradicate the organism.

This highlights the dilemma, if NSU is already being treated with doxycycline, what benefit is conferred by testing for ureaplasmas as their presence does not necessarily indicate causality for the NSU?  More research is required before the use of these tests can be widely recommended.

The Royal College of Physicians have made the following recommendations:

“Ureaplasma species are part of the normal genital microbiota and there are typically high rates of colonisation of the organism in sexually active adults. Testing or screening for genital infection with ureaplasma species is not recommended outside specialist or research settings as they have not been established as a cause of lower genital tract disease.”