Urethritis

Urethritis is inflammation of the urethra, most commonly caused by sexually transmissible infections (STIs). It is one of the most frequently diagnosed STI syndromes in Australia, presenting predominantly in young, sexually active males, though females may also be affected. Urethritis is classified as gonococcal (GU) when caused by Neisseria gonorrhoeae, or non-gonococcal urethritis (NGU) when caused by other pathogens. Prompt diagnosis and treatment are essential to prevent complications, onward transmission, and antimicrobial resistance.

In Australia, gonorrhoea notifications have increased substantially over the past decade. The Kirby Institute's 2023 Annual Surveillance Report documents over 30,000 gonorrhoea notifications annually, with rates highest in men who have sex with men (MSM), Aboriginal and Torres Strait Islander people, and young heterosexual adults aged 15–29 years. Chlamydia remains the most commonly notified STI in Australia, with over 85,000 notifications annually — Chlamydia trachomatis is the leading cause of NGU. Antimicrobial resistance in N. gonorrhoeae is a critical public health concern; multidrug-resistant strains are documented in Australia.

Urethritis results from mucosal infection of the urethral epithelium following sexual contact with an infected partner. Transmission is via direct mucosal contact with infected secretions during vaginal, anal, or oral sex. The incubation period varies by pathogen: 1–14 days for gonorrhoea, 1–3 weeks for chlamydia, and 1–5 weeks for Mycoplasma genitalium.

Causative Organisms

• Gonococcal urethritis (GU): Neisseria gonorrhoeae — Gram-negative intracellular diplococcus. In males, causes purulent urethral discharge in ~80% of symptomatic infections. Females often asymptomatic. Multidrug resistance is an emerging crisis.
• Chlamydial urethritis (NGU): Chlamydia trachomatis serovars D–K — obligate intracellular organism. Most common cause of NGU (~40–50%). Frequently asymptomatic, especially in females.
• Mycoplasma genitalium (NGU): Second most common cause of NGU (~15–25%). Associated with persistent and recurrent urethritis. Significant macrolide and fluoroquinolone resistance documented in Australia. Requires targeted treatment based on resistance testing.
• Other NGU causes: Trichomonas vaginalis (especially in men from endemic regions), Ureaplasma urealyticum, herpes simplex virus (HSV), adenovirus, enteric pathogens after insertive anal sex.
• Idiopathic NGU: No pathogen identified in ~30–40% of NGU cases even with comprehensive testing.

Symptoms

• Urethral discharge: Mucopurulent or purulent in GU; mucoid or clear in NGU. Discharge may be first noticed on underwear.
• Dysuria: Burning or pain on urination — more pronounced in GU.
• Urethral irritation/pruritus: Discomfort at the urethral meatus.
• Asymptomatic infection: Common — particularly with chlamydia (up to 50% of males) and gonorrhoea at extragenital sites. All MSM and at-risk individuals should be screened regardless of symptoms.

Signs

• Urethral meatal erythema: May be present in both GU and NGU.
• Discharge expression: Gently milk the urethra to express discharge for sampling if not spontaneous.
• Gonococcal discharge: Typically profuse, yellow-green, creamy — though presentation varies.
• NGU discharge: Often scant, mucoid, or clear. May only be visible in the morning.

Complications

• Epididymo-orchitis: Unilateral testicular pain and swelling — ascending infection, most commonly chlamydial or gonococcal in sexually active men under 35.
• Reactive arthritis (Reiter's syndrome): Urethritis, arthritis, and uveitis — associated with chlamydial and other NGU pathogens.
• Urethral stricture: Complication of recurrent gonococcal urethritis.
• Disseminated gonococcal infection (DGI): Rare — septicaemia, septic arthritis, tenosynovitis, dermatitis. Requires IV penicillin.
• Female complications: Pelvic inflammatory disease, tubal infertility, ectopic pregnancy — from ascending chlamydial or gonococcal infection.

• Essential
  NAAT for N. gonorrhoeae and C. trachomatis

  Nucleic acid amplification test (NAAT) on first-void urine (males) or self-collected vaginal swab (females). High sensitivity and specificity. Available at all Australian pathology laboratories. Also test extragenital sites (pharynx, rectum) in MSM and where indicated by sexual history. A positive gonorrhoea NAAT requires culture to guide antibiotic sensitivity.
• Essential
  Gonorrhoea culture and sensitivity

  Urethral swab (or cervical/rectal/pharyngeal swab) plated on Thayer-Martin or GC agar at point of collection. Essential for antimicrobial sensitivity testing given widespread resistance. Culture in addition to NAAT for any presumed gonococcal infection. Specimen transport to lab within 2 hours at 35–36°C.
• Essential
  Urethral smear (Gram stain)

  Urethral smear for Gram stain in symptomatic males: confirms urethritis (≥5 PMNLs/HPF) and may show Gram-negative intracellular diplococci (GNID) indicating GU. Sensitivity for GU in symptomatic males: ~95%. Sensitivity in asymptomatic males and females: lower. Provides immediate management guidance at point of care.
• Available
  NAAT for Mycoplasma genitalium with macrolide resistance testing

  Available at major Australian reference laboratories (e.g., Melbourne Pathology, Sullivan Nicolaides). Test on first-void urine or urethral swab. Resistance-guided testing detects 23S rRNA mutations conferring macrolide resistance. Essential for treatment decisions in persistent/recurrent NGU. Not yet widely available at point-of-care.
• Available
  First-void urine (FVU) microscopy

  ≥10 PMNLs/HPF on first-void urine sediment confirms urethritis in males who cannot undergo urethral swab. Useful where urethral smear is not feasible.
• Essential
  HIV serology and full STI screen

  Offer HIV serology, syphilis serology (RPR + TPPA), hepatitis B surface antigen/antibody, and hepatitis C antibody at every STI presentation. Gonorrhoea and chlamydia at all relevant anatomical sites. Rectal and pharyngeal swabs in MSM.
• Available
  Urine MCS (midstream)

  Midstream urine culture to exclude bacterial urinary tract infection as an alternative diagnosis in male urethritis. MSU bacterial culture is typically negative in STI-associated urethritis.

Gonococcal Urethritis (GU) — First-Line

Non-Gonococcal Urethritis (NGU) — First-Line

Gonorrhoea — Sensitivity-Directed Treatment

• Await culture results: Always obtain culture and sensitivities before de-escalating or changing from first-line ceftriaxone + azithromycin dual therapy.
• Ceftriaxone-sensitive (MIC ≤0.125 mg/L): Standard 500 mg IM single dose + azithromycin 1 g oral as per empirical regimen.
• Reduced susceptibility / resistance: Consult sexual health specialist and refer to the Australian Gonococcal Surveillance Programme (AGSP) recommendations. Options include higher-dose ceftriaxone (1 g) or gentamicin 240 mg IM + azithromycin 2 g oral.
• Penicillin allergy: Cephalosporin allergy is rare (2–8% cross-reactivity with penicillin allergy). If true allergy confirmed, consult sexual health specialist urgently. Spectinomycin 2 g IM (not PBS listed, limited availability) or gentamicin-based regimens may be considered.

Mycoplasma genitalium — Resistance-Guided Treatment

Persistent / Recurrent NGU

• Re-evaluate: Repeat urethral smear to confirm ongoing urethritis. Repeat NAAT for gonorrhoea, chlamydia, and M. genitalium with resistance testing. Test for T. vaginalis.
• Exclude re-infection: Ensure sexual partners have been tested and treated. Advise no sexual activity until patient and partners are treated.
• Extended treatment: Doxycycline 100 mg BD × 21 days (for non-specific persistent NGU) after excluding identifiable causes.
• Specialist referral: Persistent NGU unresponsive to multiple courses requires sexual health specialist review.

Most uncomplicated urethritis is managed entirely with oral or IM therapy. IV treatment is reserved for disseminated gonococcal infection (DGI) or epididymo-orchitis with systemic sepsis.

• Disseminated gonococcal infection (DGI): IV ceftriaxone 1 g daily until 24–48 hours of clinical improvement, then switch to oral cefixime 400 mg BD to complete 7 days total (sensitivity permitting). Alternatively, oral amoxicillin-clavulanate if sensitive.
• Switch criteria: Afebrile, haemodynamically stable, improving inflammatory markers, tolerating oral intake, sensitive organism confirmed.
• Uncomplicated GU/NGU: No IV therapy required — single-dose ceftriaxone IM + oral azithromycin or doxycycline.

🤰 Pregnancy

Gonorrhoea and chlamydia in pregnancy carry significant maternal and neonatal risks including preterm labour, chorioamnionitis, neonatal conjunctivitis (ophthalmia neonatorum), and neonatal pneumonia.

• Screening: Chlamydia NAAT at first antenatal visit for all women <25 years and older women with risk factors. Gonorrhoea NAAT in high-prevalence populations and areas.
• Chlamydia in pregnancy: Azithromycin 1 g stat (preferred — safe in pregnancy) or amoxicillin 500 mg TDS × 7 days. Avoid doxycycline (contraindicated). Test of cure NAAT 4 weeks post-treatment.
• Gonorrhoea in pregnancy: Ceftriaxone 500 mg IM single dose + azithromycin 1 g oral. Test of cure mandatory. Neonatal prophylaxis (erythromycin eye ointment) for all babies born to mothers with gonorrhoea.
• M. genitalium in pregnancy: Limited data; azithromycin (macrolide-sensitive strains only) under specialist guidance. Avoid moxifloxacin (teratogenicity concerns).

👶 Paediatrics

Gonorrhoea or chlamydia in pre-pubertal children is a child protection emergency requiring mandatory notification.

• Neonatal gonococcal ophthalmia: IV/IM ceftriaxone 25–50 mg/kg (max 125 mg) single dose. Eye irrigation with saline. Ophthalmology review.
• Neonatal chlamydial conjunctivitis/pneumonia: Erythromycin ethylsuccinate 12.5 mg/kg QID × 14 days (oral). Test both parents.
• Pre-pubertal child: Any STI diagnosis mandates child protection notification, forensic examination, and specialist review.

🛡️ Immunocompromised / HIV-positive

HIV-positive individuals are at higher risk of STI acquisition and may have atypical presentations. Screen at every HIV clinic visit.

• Treatment regimens: Same as HIV-negative for gonorrhoea and chlamydia. M. genitalium treatment: same resistance-guided approach; consult sexual health specialist for treatment failures.
• Screening frequency: 3-monthly full STI screen (gonorrhoea, chlamydia, syphilis, HIV viral load) for sexually active MSM. More frequent if multiple partners.
• Drug interactions: Check for interactions between azithromycin/moxifloxacin and antiretroviral therapy (particularly QT-prolonging agents).

👴 Elderly Patients

STIs in older adults are under-recognised and under-screened. Sexual activity continues in older age groups; clinicians should not assume patients are not at risk.

• Treatment: Standard regimens. Renal function monitoring for any renally cleared agents if eGFR reduced.
• Comorbidities: Review drug-drug interactions with antiarrhythmics, anticoagulants, and other medications when prescribing azithromycin or moxifloxacin.

• Avoid azithromycin monotherapy for gonorrhoea: Azithromycin monotherapy must NOT be used for gonorrhoea — it drives resistance and treatment failures are documented. Only use as part of dual therapy with ceftriaxone.
• Avoid fluoroquinolones empirically: Ciprofloxacin and other fluoroquinolones should not be used empirically for gonorrhoea due to widespread resistance. Use only if sensitivity confirmed.
• Resistance-guided treatment for M. genitalium: Azithromycin should not be prescribed for M. genitalium without macrolide resistance testing. Empirical azithromycin drives resistance and treatment failure.
• Australian Gonococcal Surveillance Programme (AGSP): Culture isolates should be sent to AGSP reference labs. Antibiogram data informs national treatment guidelines and outbreak monitoring.
• Doxycycline for NGU: First-line doxycycline for NGU is preferred over azithromycin where compliance can be ensured — lower resistance pressure on M. genitalium. Directly observed single-dose azithromycin is an acceptable alternative where adherence is uncertain.
• Mandatory notification: Gonorrhoea must be notified to state/territory health authorities in all Australian jurisdictions.

Post-Treatment Follow-Up

Prevention

• Condom use: Consistent use of condoms significantly reduces gonorrhoea and chlamydia transmission. Counsel on correct use including for oral sex.
• Regular STI screening: 3-monthly for MSM with multiple partners; annual for sexually active heterosexuals with risk factors.
• Doxycycline PEP (Doxy-PEP): Post-exposure doxycycline 200 mg within 72 hours of condomless sex reduces chlamydia and gonorrhoea acquisition in MSM. Available through sexual health clinics. Monitor for impact on M. genitalium resistance.
• Pre-exposure prophylaxis (PrEP): HIV PrEP programs provide regular STI screening opportunities — leverage for comprehensive STI prevention.
• Vaccination: No vaccine available for gonorrhoea or chlamydia. Meningococcal B vaccine (4CMenB) has shown modest cross-protection against gonorrhoea in observational studies — discuss with sexual health specialist in very high-risk patients.

• 01
  Australasian Sexual Health Alliance (ASHA). Australian STI Management Guidelines for Use in Primary Care — Urethritis, Gonorrhoea, Chlamydia. Sydney: ASHA; 2023. Available at: stipu.org.au
• 02
  Kirby Institute. HIV, viral hepatitis and sexually transmissible infections in Australia: Annual Surveillance Report 2023. Sydney: UNSW Sydney; 2023.
• 03
  Australian Gonococcal Surveillance Programme (AGSP). Annual Report 2022. Communicable Diseases Intelligence. Canberra: Australian Government Department of Health; 2023.
• 04
  Workowski KA, Bachmann LH, Chan PA, et al. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep. 2021;70(4):1–187.
• 05
  Unemo M, Ross J, Serwin AB, et al. 2020 European guideline for the diagnosis and treatment of gonorrhoea in adults. Int J STD AIDS. 2021;32(6):548–556.
• 06
  Horner PJ, Blee K, Falk L, et al. 2016 European guideline on the management of non-gonococcal urethritis. Int J STD AIDS. 2016;27(11):928–937.
• 07
  Bissessor M, Tabrizi SN, Twin J, et al. Macrolide resistance and azithromycin failure in a Mycoplasma genitalium-infected cohort and response of azithromycin failures to alternative antibiotic regimens. Clin Infect Dis. 2015;60(8):1228–1236.
• 08
  Luetkemeyer AF, Donnell D, Dombrowski JC, et al. Postexposure Doxycycline to Prevent Bacterial Sexually Transmitted Infections. N Engl J Med. 2023;388(14):1296–1306.
• 09
  Manhart LE, Jensen JS, Bradshaw CS, et al. Efficacy of Antimicrobial Therapy for Mycoplasma genitalium Infections. Clin Infect Dis. 2015;61(Suppl 8):S802–S817.
• 10
  Wi T, Lahra MM, Ndowa F, et al. Antimicrobial resistance in Neisseria gonorrhoeae: Global surveillance and a call for international collaborative action. PLoS Med. 2017;14(7):e1002344.
• 11
  Kong FYS, Tabrizi SN, Law M, et al. Azithromycin versus doxycycline for the treatment of genital chlamydia infection. Clin Infect Dis. 2014;59(2):193–205.
• 12
  Australian Government Department of Health. National Aboriginal and Torres Strait Islander Blood Borne Viruses and Sexually Transmissible Infections Strategy 2018–2022. Canberra: DoH; 2018.