Oxford Handbook of Genitourinary Medicine, HIV, and Sexual
Health (2 edn)
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Introduction
Non-specific genital infection (NSGI) refers to ♂ urethritis in the absence of gonorrhoea, non-gonococcal or non-specific urethritis (NGU or NSU), and the equivalent but less well-defined condition in ♀, mucopurulent cervicitis (MPC). Chlamydia trachomatis is the cause in 30–50% of NGU and 25–45% of MPC. Non-chlamydial NSGI has been attributed to several causes supported by variable evidence.
Aetiology
Non-chlamydial NGU
Microorganisms
Mycoplasma genitalium—up to 20% of NGU (Box 9.1).
Ureaplasma urealyticum—association with non-chlamydial NGU in up to 52% (similar prevalence in the absence of NGU). Serovar 4 more likely to play a role in NGU.
Bacterial vaginosis (BV)—30% of ♂ with NGU have ♀ partners with BV which may be implicated in an undetermined proportion.
Bacteria causing urinary tract infections (UTIs)—up to 6% of NGU seen in GUM clinic is due to UTI. Coliform bacteria may be associated with NGU in ♂ practising insertive anal sex.
Trichomonas vaginalis—up to 15% of NGU in high-prevalence areas.
Herpes simplex virus (HSV)—up to 2% of NGU without external genital ulcers. 30% of primary genital HSV episodes in ♂ include NGU.
Adenovirus—types 8, 19, and 37 (subgenus D) isolated from 0.4% of ♂ attending GUM clinics. 75% of isolates associated with NGU, often with conjunctivitis, pharyngitis, and constitutional symptoms. Transmission probably by oral sex.
A bacterium:
discovered in 1980 in the urethra of 2 ♂ with NGU
classified as belonging to the family Mycoplasmateles
1 of 14 mycoplasmas of human origin
long flask shape with a narrow terminal rod binding to eukaryotic cells
fastidious and slow growing (difficult to isolate)
forms fried-egg-like colonies within agar medium incubated in nitrogen and 5% carbon dioxide
genome—580 kilobase, smallest of any self-replicating bacterium.
Urogenital tract—preferred site of colonization where it may invade epithelial cells.
Sexual transmission—causal role in NGU/MPC and possibly pelvic inflammatory disease (PID)/epididymitis. Identified in:
18–45% of non-chlamydial NGU (odds ratio 7.1)
up to 10% of MPC
16% of endometritis
15% of PID.
~7% of tubal factor infertility (by serology) (odds ratio 4.5)
Sensitive to tetracyclines (except when the tetM gene is present), macrolides, ketolides, and fluoroquinolones, and resistant to penicillins, sulphonamides, and rifampicin. Antibiotics only suppress growth and a competent immune system is necessary for eradication.
The following organisms show a possible or occasional causal role:
Neisseria meningitidis
Candida species (rarely): if present usually associated with balanitis (possible reaction to partner’s candidal infection)
Haemophilus influenzae and parainfluenzae
Staphylococcus saprophyticus
Corynebacterium genitalium
Bacteroides urealyticus
Mycobacterium tuberculosis.
Non-microbial
Congenital anomalies, e.g. urethral stricture
Physical irritation—trauma related to sex, manipulation, or foreign body (e.g. urinary catheter)
Chemical irritation
Reactive urethritis (e.g. reactive arthritis, allergens)
Stevens–Johnson syndrome.
Non-gonococcal non-chlamydial MPC
M.genitalium implicated in up to 10%
HSV infection
Possibly other as yet unidentified causes
Clinical features
Male—NGU
| Symptoms | Signs |
|---|---|
• Urethral discharge • Dysuria • Penile irritation • None (asymptomatic) | • Urethral discharge—varyingamounts, clear to yellow, spontaneous, or expressed • None (subclinical) |
| Symptoms | Signs |
|---|---|
• Urethral discharge • Dysuria • Penile irritation • None (asymptomatic) | • Urethral discharge—varyingamounts, clear to yellow, spontaneous, or expressed • None (subclinical) |
Up to 20% of ♂ with observable discharge have no symptoms. NGU without symptoms and signs (in ~25%) is less likely to be due to C.trachomatis or M.genitalium.
Female—MPC
Usually asymptomatic, but if severe may cause vaginal discharge and vulval irritation. Dysuria unusual.
Cervix appears inflamed, oedematous, and friable with an overlying mucopurulent discharge.
Complications
Epididymo-orchitis (
Chapter 12)
Sexually acquired reactive arthritis ( Chapter 13).
Pelvic inflammatory disease ( Chapter 10).
Diagnosis
NGU
Urethral specimen using a 5mm plastic loop or cotton-tipped swab (better quality if bladder not emptied in preceding 3 hours). If no urethral material check first voided urine (FVU).
Urethritis diagnosed by high-power (1000×) microscopy of Gram-stained material:
≥5PMNL)/field of urethral smear
≥10PMNL/field of threads or deposits from FVU.
Symptomatic ♂ without evidence of urethritis may be re-assessed after retaining urine overnight (or for at least 3 hours).
MPC
No clear microscopic criteria for diagnosis as the number of cervical polymorphonuclear leucocytes (PMNLs) varies physiologically. Diagnosis based on the cervical appearance possibly supported by microscopy (>30PMNLs/high-power field).
Other investigations
N.gonorrhoeae and C.trachomatis—as routine.
Midstream sample of urine (MSSU)—positive dipstick for leucocyte esterase, nitrites, and blood suggests UTI. Confirm with microscopy and culture.
M.genitalium—culture difficult and not readily available. Polymerase chain reaction ↑ sensitivity but not yet available for routine use.
Management
► Advise avoidance of sexual intercourse, including with condoms, until the patient and partner(s) have completed treatment and symptoms have resolved. Discourage repeated self-examination and advise that other factors (e.g. spicy food) may aggravate or prolong symptoms. Standard anti-chlamydial regimens are generally effective against non-chlamydial NSGI (except if 2° to UTI/coliforms).
Recommended treatment regimens
Doxycycline 100mg twice daily for 7 days.
Azithromycin 1g—single dose. 87% effective in M.genitalium infection with failures likely to be associated with resistance due to mutation in region V of 23S rRNA. Azithromycin 500mg followed by 250mg daily for 4–6 days is 97% effective and less likely to induce the mutation.
Alternative regimens
Tetracyclines
Tetracycline 500mg 4 times a day for 7 days
Minocycline 100mg once daily for 7 days
Macrolides
Erythromycin 500mg twice daily for 14 days
Clarithromycin 400mg twice daily for 7 days
Fluoroquinolones
Ofloxacin 200mg twice daily or 400mg once daily for 7 days.
Moxifloxacin 400mg daily for 10 days if resistant M.genitalium and no response to other treatments because of risk of serious side-effects.
↑ risk
of life-threatening liver reactions, cardiac
arrhythmias with QTc prolongation, rhabdomyolysis,
and tendon rupture.
Epidemiological treatment regimens
As for uncomplicated infection.
Partner notification
Assessment of sexual partners may reveal possible causes (e.g. trichomoniasis) which could affect overall management. Epidemiological treatment of sexual partners of ♂ with chlamydia-negative NGU may ↓ recurrence and possibly↓ ♀ morbidity. Suggested ‘look-back’ periods: 4 weeks for symptomatic ♂; up to 6 months for asymptomatic ♀.
Similarly, sexual partners of ♂ with MPC should be offered epidemiological treatment and routine screening for STIs.
Follow-up
May be by telephone to ensure management compliance, resolution of symptoms, and partner notification. If symptoms or signs persist/recur, repeat urethral smear/FVU specimen. Repeat treatment if risk of reinfection.
Persistent, relapsing, and chronic NGU
Persistent NGU—continuing despite treatment of initial episode
Relapsing NGU—recurrence following resolution of initial episode
Chronic NGU—persistent or relapsing NGU ≥30 days post-treatment
All without a risk of re-infection.
Persistent or relapsing NGU occurs in 20–60% of ♂ treated for acute NGU and half of these may become chronic with U.urealyticum and M.genitalium of possible importance. A continuing inflammatory response following eradication of active chlamydial infection has also been suggested. In this situation there is no ↑ risk of PID in ♀ partners.
Recommended treatment regimen
Azithromycin 500mg stat followed by 250mg daily for 4 days plus metronidazole 400mg twice a day for 5 days.
Erythromycin 500mg 4 times a day for 3 weeks plus metronidazole 400mg twice a day for 5 days.
Repeat epidemiological treatment of partner using erythromycin if doxycycline used initially.
Moxifloxacin 400mg daily if resistant M.genitalium for 10 days.
↑ risk
of life-threatening liver reactions and other
serious risks. Use only if no alternative
suitable.
Continuing symptoms
Microscopic urethritis with no signs or symptoms after two courses of treatment is of little clinical significance. Further re-treatment of sexual partners is not beneficial. Limited evidence on how best to manage patients who either remain symptomatic or have frequent relapses following a 2nd course of treatment. Consider:
urological investigations—usually normal unless the patient has urinary flow problems
chronic abacterial prostatitis
psychosexual causes.
M.genitalium may enhance transmission of HIV. Impaired immune function hampers its eradication (detection rate in urethra—56% with AIDS compared with 12% without AIDS).
