Chapter 13, ‘Epididymo-orchitis’, pp. 193–200)Non-specific genital infection, NSU, and NGU are all terms that have been used to describe inflammation of the ♂ urethra in the absence of Neisseria gonorrhoeae; NGU is the preferred term. 11–50% of cases are caused by Chlamydia trachomatis, and Mycoplasma genitalium is increasingly being recognized with increasing access to standardized testing assays. The less well defined ♀ equivalent mucopurulent cervicitis (MPC) is more problematic to diagnose; 20–40% are caused by C. trachomatis.
Most commonly caused by C. trachomatis and Mycoplasma genitalium, especially in younger patients and those with urethral discharge or dysuria. M. genitalium may also be associated with balanoposthitis.
See Table 10.1.
Table 10.1 Non-gonococcal urethritis: commonest causative organisms
| Chlamydia trachomatis | 11–50% |
| Mycoplasma genitalium | 6–50% |
| Ureaplasmas | 5–26% |
| Trichomonas vaginalis | 1–20% |
| Adenovirus | 2–4% |
| Herpes simplex virus | 2–3% |
• The rate of TV as a cause of NGU depends on prevalence in the community, and is more common in ♂ aged >30.
• Adenovirus; often with accompanying pharyngitis, conjunctivitis, and constitutional symptoms, probably transmitted via oral sex.
• EBV, N. meningitidis, Candida sp., Haemophilus sp. have also been reported causes.
• BV is seen in 30% of ♀ partners.
• Organism negative NGU is poorly understood. Urethral strictures, urethral foreign body, trauma, manipulation, chemical irritation, allergens, and Stevens–Johnson syndrome have all been implicated.
See Table 10.2 for non-gonococcal urethritis.
Table 10.2 Symptoms and signs of non-gonococcal urethritis
| Symptoms | Signs |
|
• Urethral discharge—varying amount, clear to yellow, spontaneous or expressed |
Up to 20% of ♂ with observable discharge have no symptoms. NGU without symptoms and signs is less likely to be due to C. trachomatis or M. genitalium.
• usually asymptomatic, but if severe may cause vaginal discharge and vulval irritation
• cervix appears inflamed, oedematous, and friable with an overlying mucopurulent discharge.
• epididymo-orchitis ( Chapter 13, ‘Epididymo-orchitis’, pp. 193–200)
• SARA/Reiter’s syndrome, occurs in <1% ( Chapter 14, ‘Sexually-acquired reactive arthritis’, pp. 201–212)
• PID ( Chapter 11, ‘Pelvic inflammatory disease’, pp. 169–179)
Only those with active symptoms or visible signs should be assessed for NGU/MPC.
Urethral specimen, using a 5-mm plastic loop or cotton-tipped swab (after holding urine for 2–4 hours to improve sensitivity). If no urethral material, check FVU.
Urethritis diagnosed by high-power (×1000) microscopy of Gram-stained material and the presence of PMNLs, in the absence of intracellular gonococci:
• ≥5 PMNL/field of urethral smear in ≥5 fields
• ≥10 PMNL/field of threads or deposits from FVU.
Where microscopy is not available, diagnosis can be made based on:
• mucopurulent discharge on examination
• ≥1+ leucocyte esterase on FVU dipstick (poor sensitivity)
• presence of threads on FVU (may be physiological, e.g. semen).
Symptomatic ♂, without evidence of urethritis after holding urine for 2–4 hours, may be re-assessed after holding urine overnight.
No definitive microscopic criteria for diagnosis as the number of cervical PMNLs varies physiologically. Diagnosis based on a friable cervix +/– mucopurulent cervical discharge on examination and microscopic finding of >30 PMNLs/HPF may be used.
• N .gonorrhoeae and C. trachomatis NAAT as routine.
• M. genitalium NAAT if available, with macrolide resistance testing.
• initiate treatment as soon as diagnosis made
• avoid sex until index patient and partner completed treatment
• give patient information regarding causes, health implications, treatment, importance of compliance, contact tracing, and treatment
• avoid over-examination/over-washing
• follow-up indicated if symptoms persist.
Both first line treatments are <85% effective. If infection is caused by M. genitalium treatment failures of <68% with doxycycline 100 mg bd for 7 days and <33% with azithromycin 1 g stat, although the latter is associated with inducing macrolide resistance mutations.
Doxycycline 100 mg bd for 7 days
Azithromycin 1 g once followed by 500 mg od for next 2 days; or ofloxacin 200 mg bd or 400 mg od for 7 days
Recurrent NGU (return of symptoms within 30–90 days) occurs in 10–20%. Re-infection should be considered.
Persistent NGU occurs in 15–25%, is multifactorial and is organism negative in >50%. In 20–40% of those treated with azithromycin 1 g stat M. genitalium is identified and in 10–20% C. trachomatis is found. TV and ureaplasmas may also play a role.
• ensure initial treatment complied with and reinfection considered
• only investigate if symptomatic or clinical evidence of urethritis
• consider TV and M. genitalium PCR testing if available.
• azithromycin 1 g once, followed by 500 mg od next 2 days (to be started within 2 weeks of doxycycline treatment) plus metronidazole 400 mg bd for 5 days.
• moxifloxacin 400 mg od for 10–14 days plus metronidazole 400 mg bd for 5 days.
Risk of life-threatening liver reactions, Steven–Johnson syndrome, and haematological abnormalities with moxifloxacin.
doxycycline 100 mg bd plus metronidazole 400 mg bd 5 days.
Box 10.1 Mycoplasma genitalium
Mycoplasmas are the smallest free-living organisms. M. genitalium was isolated in 1980 from ♂ urethra. It is slow growing and difficult to isolate, preferentially colonizes the urethra, where it can invade epithelial cells.
Largely by genito-genital mucosal contact. Anogenital transmission can occur, but oro-genital transmission is unlikely to be significant as oral carriage is low. Prevalence 10–35% in ♂ with non-chlamydial NGU and 40% in ♂ with persistent NGU. Significant association between M. genitalium and cervicitis, ♀ urethritis, endometritis, PID, tubal infertility, and pre-term birth.
Up to 30% men and 75% women asymptomatic. In women dysuria, discharge, cervicitis, and rarely intermenstrual bleeding (IMB)/post-coital bleeding (PCB), low abdominal pain may be seen. In men, dysuria and urethral discharge, and in one study balano-posthitis may be present. Complications include SARA, epididimo-orchitis, PID, tubal infertility.
Diagnosis is by NAAT, with macrolide resistance probe if positive. Intrinsic resistance to many antimicrobials. Sensitive to tetracyclines (except if tetM gene present), macrolides, and fluoroquinolones. Increasing resistance to macrolides due to widespread use of single dose azithromycin for treatment of NGU. Test for cure ≥3 weeks after treatment started.
Doxycycline 100 mg bd for 7 days followed by azithromycin 1 g once then 500 mg daily for next 2 days or moxifloxacin 400 mg daily 10days.
Doxycycline 100 mg bd 7 days followed by pristinamycin 1 g qds 10 days or doxycycline 100 mg bd 14 days or pristinamycin 1 g qds 14 days or minocycline 100 mg bd 14 days.
Moxifloxacin 400 mg od 14 days.
Azithromycin 1 g single dose followed by 500 mg daily for 2 days (in pregnancy and breastfeeding moxifloxacin is contraindicated, and doxycycline and pristinamycin not advised)
• Limited evidence for management.
• Urological investigation recommended if urinary flow symptoms.
• Consider abacterial prostatitis, chronic pelvic pain syndrome, and psychosexual causes ( Chapter 12, ‘Prostatitis/chronic pelvic pain syndrome in men, pp. 181–191).
• Consider retreatment of index and partner concurrently with same antimicrobials.
• Erythromycin 500 mg qds for 3 weeks or clarithromycin 500 mg bd for 3 weeks has been tried with success.
If high risk of STI, presumptive treatment should be considered, alternatively awaiting results is an option. Follow-up to ensure resolution is advised.
Doxycycline 100 mg bd for 7 days.
Azithromycin 500 mg stat, then 250 mg daily for next 4 days.
Management as for recurrent/persistent NGU.
PN should be carried out with epidemiological treatment and testing for all contacts within the last 4 weeks of symptomatic patients with NGU and 8 weeks for contacts of MPC.
Provide epidemiological treatment with the same antimicrobials that resulted in cure in the index case.
Further information
British Association for Sexual Health and HIV guidelines for NGU and Mycoplasma Genitalium 
https://www.bashh.org/guidelines