Gonorrhoea & Non-gonococcal Urethritis

Urethritis is inflammation of the urethra presenting with discharge and dysuria, classically split into gonococcal (caused by Neisseria gonorrhoeae) and non-gonococcal urethritis (NGU) (predominantly Chlamydia trachomatis). For NEET PG, this is a high-density topic where microbiology, smear/culture findings, neonatal disease, complications, and the WHO syndromic protocol all converge.

Definition & classification

Urethritis is the symptomatic inflammation of the urethra, usually sexually transmitted. It is divided on the basis of the causative organism:

• Gonococcal urethritis (GU) — caused by Neisseria gonorrhoeae, a Gram-negative intracellular diplococcus. Incubation is short (2–7 days), discharge is typically profuse and purulent.
• Non-gonococcal urethritis (NGU) — diagnosed when gonococci are not demonstrated. The commonest cause is Chlamydia trachomatis (serovars D–K), accounting for 30–50%. Other causes: Mycoplasma genitalium (increasingly recognised, second most common), Ureaplasma urealyticum, Trichomonas vaginalis, HSV, adenovirus.
• Post-gonococcal urethritis (PGU) — urethritis persisting after adequate treatment of gonorrhoea, almost always due to a co-existing chlamydial infection that was not covered. This is the classic reason dual therapy is mandated.

High-yield: Neisseria gonorrhoeae is a Gram-negative, oxidase-positive, kidney/coffee-bean-shaped intracellular diplococcus. Demonstration of these organisms within neutrophils (polymorphs) on a urethral smear is diagnostic in symptomatic men.

Feature	Gonococcal urethritis	Non-gonococcal urethritis
Organism	Neisseria gonorrhoeae	Chlamydia trachomatis (commonest)
Incubation period	2–7 days (short)	7–21 days (longer)
Discharge	Profuse, purulent, yellow-green	Scanty, mucoid/clear, often morning
Dysuria	Marked	Mild to moderate
Onset	Acute	Insidious/subacute
Gram stain	GNID inside polymorphs	Polymorphs only, no organisms
Investigation of choice	NAAT (culture for resistance)	NAAT

Etiology & microbiology

Neisseria gonorrhoeae is a fastidious, non-motile, non-spore-forming Gram-negative diplococcus. Key microbiological facts:

• Oxidase positive, ferments glucose only (gonococcus = "glucose only"; meningococcus ferments glucose AND maltose — classic differentiating point).
• Capnophilic — requires 5–10% CO₂ for growth.
• Grows on chocolate agar and selective Thayer-Martin medium (and modified New York City medium). Thayer-Martin contains antibiotics — VCN: Vancomycin, Colistin, Nystatin (plus trimethoprim in modified versions) — to suppress contaminating flora.
• Virulence factors: pili (attachment & antigenic/phase variation), Opa proteins, IgA1 protease, lipooligosaccharide (LOS), and Por (PorB) protein. Antigenic variation of pili is why no lasting immunity develops and reinfection is common.
• Humans are the only natural host; transmission is almost exclusively sexual (or perinatal).

High-yield mnemonic: "NG = No vaccine, No immunity" — because of antigenic/phase variation of pili and Opa proteins. Repeated infections are the rule, not the exception.

Chlamydia trachomatis (NGU) is an obligate intracellular bacterium with a biphasic life cycle: the elementary body (EB) is the infectious, extracellular form, and the reticulate body (RB) is the intracellular, metabolically active replicating form. Serovars D–K cause urethritis/cervicitis and neonatal disease; A, B, Ba, C cause trachoma; L1–L3 cause lymphogranuloma venereum (LGV).

Pathophysiology

Gonococci attach to columnar/transitional epithelium of the urethra, endocervix, rectum, pharynx and conjunctiva via pili and Opa proteins. They invade epithelial cells, trigger a brisk neutrophilic response producing the purulent discharge, and can ascend to cause epididymitis (men) or PID (women). LOS endotoxin contributes to tissue damage (e.g., ciliary damage in fallopian tubes → tubal scarring → infertility/ectopic pregnancy). Disseminated infection arises from bacteraemic spread.

Notably, certain terminal complement deficiencies (C5–C9, the membrane attack complex) and properdin deficiency predispose to recurrent Neisseria (both gonococcal and meningococcal) infections — a favourite single-best-answer link.

Clinical features

Men (gonococcal): Profuse purulent urethral discharge with marked dysuria 2–7 days after exposure. Untreated → acute epididymo-orchitis, prostatitis, urethral stricture (late). Up to 10% of men may be asymptomatic.

Women (gonococcal): Often asymptomatic or mild (endocervicitis with vaginal discharge, dysuria, intermenstrual bleeding). This silent carriage drives transmission and complications. Ascending infection → PID.

Extragenital:

• Pharyngeal gonorrhoea — usually asymptomatic; relevant in MSM and important because pharyngeal infection responds poorly to many oral regimens.
• Anorectal gonorrhoea — proctitis with discharge, tenesmus.
• Gonococcal conjunctivitis in adults — hyperacute, copious purulent, sight-threatening.

Disseminated gonococcal infection (DGI) / Arthritis-dermatitis syndrome: Triad of tenosynovitis + dermatitis (pustular/haemorrhagic skin lesions) + migratory polyarthralgia, often without purulent joint fluid; may progress to a true purulent monoarthritis. DGI is the commonest cause of septic arthritis in young, sexually active adults.

High-yield: Fitz-Hugh-Curtis syndrome = perihepatitis (RUQ pain, "violin-string" fibrous adhesions between liver capsule and anterior abdominal wall/diaphragm) complicating PID due to N. gonorrhoeae or C. trachomatis. Frequently asked as a single-line clue.

NGU clinical features: more insidious, scanty mucoid discharge often noticed only in the morning ("morning drop"), mild dysuria. Chlamydia in women causes cervicitis and is a major cause of tubal factor infertility. Reactive arthritis (Reiter syndrome) — "can't see, can't pee, can't climb a tree" (conjunctivitis + urethritis + arthritis) — follows chlamydial NGU, classically in HLA-B27 positive individuals.

Ophthalmia neonatorum

Neonatal conjunctivitis acquired during passage through an infected birth canal. Timing distinguishes the cause:

Cause	Onset after birth	Features
Chemical (silver nitrate)	<24 hours	Self-limiting irritation
Gonococcal	2–5 days	Hyperacute, copious purulent, corneal ulceration/perforation risk — ophthalmic emergency
Chlamydial	5–14 days	Mucopurulent; risk of neonatal pneumonia (staccato cough, afebrile, eosinophilia) at 1–3 months

High-yield: Gonococcal ophthalmia neonatorum can perforate the cornea and cause blindness — treat with a single dose of IV/IM ceftriaxone (25–50 mg/kg, max 125 mg) plus saline lavage, NOT just topical. Prophylaxis is with topical erythromycin 0.5% eye ointment (silver nitrate/Credé's method is largely abandoned because it causes chemical conjunctivitis and does not cover chlamydia).

Diagnosis & investigation of choice

Approach (men with discharge): Discharge present → Gram-stained urethral smear → GNID within polymorphs = gonorrhoea; polymorphs without organisms = NGU. Confirm and detect co-infection with NAAT on first-void urine or urethral swab. ➜ Smear screens, NAAT confirms, culture for resistance.

• Gram stain of urethral discharge: rapid, >95% sensitive and specific in symptomatic men; far less sensitive at the cervix/pharynx/rectum.
• NAAT (nucleic acid amplification test) — the overall investigation of choice for both gonorrhoea and chlamydia owing to highest sensitivity; can be run on first-void urine (non-invasive) and detects both organisms simultaneously. Cannot give antibiotic susceptibility.
• Culture on Thayer-Martin / modified New York City medium — required when antimicrobial resistance testing is needed, in suspected treatment failure, medico-legal/sexual-assault cases, and extragenital sites. Incubate at 35–37 °C in 5–10% CO₂.
• Confirmatory tests on isolate: oxidase positive, sugar fermentation (glucose only), superoxol test.
• In DGI, blood cultures, synovial fluid culture/NAAT, and skin lesion sampling are used (organism recovery is often low-yield, hence NAAT helps).

High-yield: First-void urine NAAT (not midstream) is preferred for urethral chlamydia/gonorrhoea because the organisms reside in the distal urethra and are flushed out first.

Always screen for co-existing STIs — HIV, syphilis (VDRL/RPR), hepatitis B/C — and offer partner notification and treatment.

Management / drug of choice

Dual therapy is the cornerstone

Because of rising cephalosporin resistance and frequent chlamydial co-infection, gonorrhoea is treated with dual therapy:

Ceftriaxone (IM, single dose) + treatment for chlamydia.

• Current (CDC 2020+) preferred regimen: Ceftriaxone 500 mg IM single dose (1 g if body weight ≥150 kg). If chlamydial infection is not excluded, add Doxycycline 100 mg orally twice daily for 7 days.
• Older / WHO-style regimen frequently quoted in Indian texts and MCQs: Ceftriaxone 250 mg IM single dose PLUS Azithromycin 1 g orally single dose. The blurb's "azithromycin plus ceftriaxone dual therapy" reflects this classic answer — recognise both.
• Azithromycin was historically added to cover chlamydia and slow resistance; doxycycline is now favoured for chlamydia (and for M. genitalium, which has high azithromycin resistance — confirm with resistance-guided therapy, often moxifloxacin).

High-yield: Fluoroquinolones and penicillins are NO LONGER recommended for gonorrhoea due to widespread resistance (PPNG — penicillinase-producing N. gonorrhoeae, and quinolone-resistant strains). The single-dose intramuscular third-generation cephalosporin ceftriaxone is the drug of choice.

NGU / chlamydia

• Doxycycline 100 mg BD × 7 days is now the preferred drug for uncomplicated chlamydia (superior for rectal infection); Azithromycin 1 g single dose is the alternative (preferred in pregnancy is azithromycin, as doxycycline and ofloxacin are contraindicated).
• Mycoplasma genitalium: azithromycin extended course or moxifloxacin if macrolide-resistant.

Syndromic management (WHO / NACO)

In resource-limited settings without lab confirmation, the urethral discharge syndrome is treated by covering both gonorrhoea and chlamydia simultaneously:

Urethral/vaginal discharge ➜ treat gonorrhoea (ceftriaxone/cefixime) + chlamydia (azithromycin/doxycycline) in the same visit ➜ counsel + condoms + partner treatment + screen other STIs.

This is the basis of NACO colour-coded STI "kits" (e.g., Kit 1 = grey for urethral discharge/cervicitis containing azithromycin 1 g + cefixime 400 mg).

High-yield: Treat the partner(s) even if asymptomatic; abstain from sex for 7 days after single-dose therapy (or until a 7-day course is completed) and until partners are treated. Test of cure is not routine for genital gonorrhoea except in pharyngeal infection, pregnancy, or persistent symptoms.

Complications

System	Gonorrhoea	Chlamydia/NGU
Male genital	Epididymo-orchitis, prostatitis, urethral stricture	Epididymitis
Female genital	PID, tubo-ovarian abscess	PID, cervicitis
Reproductive	Tubal infertility, ectopic pregnancy	Tubal infertility (major cause)
Systemic	DGI (arthritis-dermatitis), endocarditis, meningitis	Reactive arthritis (Reiter, HLA-B27)
Hepatic	Fitz-Hugh-Curtis perihepatitis	Fitz-Hugh-Curtis perihepatitis
Neonatal	Ophthalmia neonatorum (2–5 d)	Ophthalmia neonatorum (5–14 d), pneumonia

Both organisms enhance HIV transmission/acquisition by causing mucosal inflammation.

Key differentials

• Gonococcal vs non-gonococcal urethritis — distinguish by Gram stain (GNID vs none), incubation, discharge character (see table above).
• DGI vs reactive arthritis — DGI is a true infection (pustular skin lesions, tenosynovitis, positive cultures/NAAT, responds to ceftriaxone); reactive arthritis is post-infectious, sterile, HLA-B27 linked, with the urethritis-conjunctivitis-arthritis triad.
• Genital ulcer vs urethritis — gonorrhoea/chlamydia cause discharge, NOT ulcers. Painful ulcer = chancroid (Haemophilus ducreyi); painless = syphilis (chancre); ragged painful + bubo = chancroid; LGV = small painless ulcer + painful matted inguinal nodes ("groove sign").
• Neisseria gonorrhoeae vs N. meningitidis — both Gram-negative diplococci, oxidase positive; gonococcus ferments glucose only, meningococcus ferments glucose + maltose; meningococcus has a polysaccharide capsule and a vaccine, gonococcus does not.

Recently asked / exam angle

• Image-based: Photomicrograph of polymorph with intracellular Gram-negative diplococci ➜ identify N. gonorrhoeae; "diagnostic specimen/medium?" ➜ Thayer-Martin / chocolate agar.
• Single-line clues: "Violin-string adhesions over liver" ➜ Fitz-Hugh-Curtis; "young sexually active adult with migratory polyarthralgia, tenosynovitis and pustular rash" ➜ DGI; "neonatal conjunctivitis at day 3, copious pus" ➜ gonococcal ophthalmia (treat IM ceftriaxone).
• Pharmacology: Drug of choice for gonorrhoea ➜ ceftriaxone (dual therapy with azithromycin/doxycycline); why dual therapy ➜ chlamydial co-infection / PGU + resistance.
• Microbiology: Difference between gonococcus and meningococcus (maltose fermentation); VCN antibiotics in Thayer-Martin; investigation of choice = NAAT; sample = first-void urine.
• Immunology: Recurrent neisserial infections ➜ terminal complement (C5–C9, MAC) / properdin deficiency.
• Public health: NACO syndromic kits and the principle of treating both organisms + partner.
• Ophthalmia neonatorum prophylaxis: topical erythromycin (not silver nitrate now); timing-based differential of neonatal conjunctivitis.

Rapid revision

1. N. gonorrhoeae = Gram-negative, oxidase-positive, intracellular diplococcus; diagnostic = organisms inside polymorphs.
2. Ferments glucose only; meningococcus ferments glucose and maltose.
3. Selective medium = Thayer-Martin (VCN — Vancomycin, Colistin, Nystatin); needs 5–10% CO₂.
4. Investigation of choice = NAAT (first-void urine); culture reserved for resistance testing and medico-legal cases.
5. Drug of choice = IM ceftriaxone; give dual therapy (+ azithromycin or doxycycline) for chlamydial co-infection.
6. No fluoroquinolones/penicillins — resistance (PPNG, quinolone-resistant strains).
7. NGU commonest cause = Chlamydia trachomatis serovars D–K; second = Mycoplasma genitalium.
8. Fitz-Hugh-Curtis = perihepatitis with violin-string adhesions (gonococcus/chlamydia).
9. DGI = tenosynovitis + dermatitis + polyarthralgia; commonest septic arthritis in young adults.
10. Gonococcal ophthalmia neonatorum day 2–5, chlamydial day 5–14; prophylaxis = topical erythromycin.
11. Recurrent neisserial infection ➜ terminal complement (C5–C9)/properdin deficiency.
12. Reactive arthritis after chlamydial NGU is HLA-B27-linked: "can't see, can't pee, can't climb a tree."