Gonorrhoea & Chlamydia — Viva

Q1: A 24-year-old man presents with purulent urethral discharge and dysuria. Discuss the diagnosis, the likely organisms and the laboratory approach. (2 min)

This is urethritis, and in a sexually active young man the commonest causes are Neisseria gonorrhoeae (typically purulent discharge, 2 to 5 day incubation) and Chlamydia trachomatis serovars D-K (milder, mucoid, 1 to 3 week incubation); other causes of non-gonococcal urethritis (NGU) include Mycoplasma genitalium, Ureaplasma, Trichomonas vaginalis, HSV and adenovirus. Co-infection is common (10 to 30 percent). First-line diagnosis is NAAT (nucleic acid amplification test — PCR) on a first-catch urine (first 10 to 20 mL) — sensitivity above 95 percent for both organisms. A Gram stain of the urethral discharge showing intracellular Gram-negative diplococci within polymorphs is highly specific (above 95 percent) for gonorrhoea in a symptomatic man, allowing immediate diagnosis at the bedside; a negative Gram stain does NOT exclude gonorrhoea. I would also send site-specific swabs if he reports oral or anal exposure (NAAT is site-specific), and screen for co-infections — HIV, syphilis, hepatitis B and C. Because co-infection is so common, I treat for both gonorrhoea and chlamydia empirically.^[1][3]

Q2: What is your treatment for uncomplicated gonococcal urethritis, and why has the regimen changed from dual therapy? (2 min)

CDC 2021 first-line: ceftriaxone 500 mg intramuscularly as a single dose (1 g IM if body weight over 150 kg), PLUS doxycycline 100 mg orally twice daily for 7 days to cover co-existent chlamydia. This replaced the older ceftriaxone + azithromycin dual therapy for two reasons. First, surveillance showed azithromycin resistance emerging in N. gonorrhoeae itself. Second — and more importantly — each azithromycin dose selects macrolide-resistant Mycoplasma genitalium, a rising co-pathogen that causes NGU and PID and is increasingly macrolide-resistant; using azithromycin as routine 'cover' in gonorrhoea was therefore accelerating resistance in a related organism without a clear benefit. The global trend is toward ceftriaxone monotherapy plus chlamydia cover with doxycycline. If the patient has a severe cephalosporin allergy, alternatives are gemifloxacin 320 mg orally or gentamicin 240 mg IM, plus azithromycin 2 g orally (single doses); fluoroquinolones are no longer first-line because of near-universal resistance. I would treat the partners of the last 60 days, advise abstinence for 7 days, and re-test at 3 months for re-infection.^[1][3]

Q3: Describe the pathogenesis and life cycle of Chlamydia trachomatis. Why are beta-lactams ineffective against it? (2 min)

Chlamydia trachomatis is an obligate intracellular Gram-negative bacterium with a unique biphasic developmental cycle. The elementary body (EB) is the infectious, extracellular, metabolically inert, electron-dense form; it attaches to a non-cornified columnar epithelial cell and enters by clathrin-mediated endocytosis. Inside the host cell, the EB differentiates into the reticulate body (RB) — large, metabolically active, non-infectious — which replicates by binary fission inside a membrane-bound inclusion. The crucial immune-evasion feature is that the inclusion does NOT fuse with lysosomes, mediated by type III secretion effectors (Inc proteins). RBs re-differentiate back into EBs, the inclusion ruptures or is exocytosed, and EBs infect neighbouring cells. Beta-lactams are ineffective because the chlamydial cell wall is atypical — it lacks peptidoglycan (muramic acid), so there is no target for penicillin-binding proteins; beta-lactams may inhibit EB-to-RB differentiation but do NOT kill the replicating RB. Effective agents therefore target protein synthesis (doxycycline — 30S ribosomal) or DNA gyrase / topoisomerase (fluoroquinolones) or macrolides (50S ribosomal). Persistent infection with heat-shock protein 60 expression drives a Th1/IFN-gamma fibrotic response that causes tubal scarring — the basis of PID, infertility and the trachoma pannus.^[1][3]

Q4: A young adult presents with migratory polyarthralgia, tenosynovitis and a pustular rash. Discuss the diagnosis, the organism, and how you distinguish it from reactive arthritis. (3 min)

This is the arthritis-dermatitis syndrome of disseminated gonococcal infection (DGI), complicating an often asymptomatic mucosal gonococcal infection. The triad is migratory polyarthralgia, tenosynovitis (inflamed tendon sheaths of wrists, fingers, ankles, knees) and a pustular skin rash — typically a few (5 to 40) tender, haemorrhagic pustules on an erythematous base on the extensor surfaces of distal extremities. DGI occurs in 0.5 to 3 percent of untreated gonorrhoea; the disseminating strains are typically complement-resistant (they bind factor H and sialylate their LOS), of the AHU/IA auxotype and PorB IA serotype. The diagnostic pitfall is that blood, synovial and skin cultures are often negative — the highest-yield test is therefore NAAT of the mucosal sites (urine, rectal, pharyngeal), which detects the primary infection even when disseminated lesions are culture-negative.^[1][3]

Distinguishing DGI from reactive arthritis (Reiter syndrome): both affect young adults and may follow chlamydial infection, but they are mechanistically and clinically distinct. DGI is a septic/bacteraemic process with PAINFUL/TENDER pustules, TENOSYNOVITIS, and the organism recoverable from mucosa or blood; it responds rapidly to IV ceftriaxone. Reactive arthritis is a sterile, post-infectious, HLA-B27-associated autoinflammatory response (1 to 4 weeks after chlamydia or a GI infection such as Campylobacter, Salmonella, Shigella); its lesions are PAINLESS (keratoderma blennorrhagicum, circinate balanitis), the arthritis is an asymmetric oligoarthritis with enthesitis and dactylitis (sausage digit), and there is NO tenosynovitis and NO recoverable organism in the joint. I would treat DGI with ceftriaxone 1 g IV daily for 7 days (longer for septic arthritis, endocarditis or meningitis), and investigate for terminal complement deficiency (C5-C9) if there is a history of recurrent neisserial infection, because complement deficiency markedly increases the risk of recurrent DGI and meningococcaemia.^[1][3]

Q5 (examiner's probe): A 3-day-old neonate presents with hyperacute purulent conjunctivitis. Discuss the differential by day of onset, the emergency treatment, and the prevention.

This is gonococcal ophthalmia neonatorum — onset day 2 to 5, hyperacute, profusely purulent conjunctivitis with marked lid oedema, chemosis and intracellular Gram-negative diplococci on Gram stain; it is sight-threatening, progressing to corneal ulceration, perforation and blindness within hours. The day of onset discriminates the cause: chemical (day 1, silver nitrate prophylaxis, mild, self-limiting); gonococcal (day 2 to 5, hyperacute, emergency); chlamydial (day 5 to 14, mucopurulent, may be followed by neonatal chlamydial pneumonia at 1 to 3 months with staccato cough, afebrile, eosinophilia); HSV (day 6 to 14, vesicles, dendritic keratitis); and other bacteria (Staph, Strep, Haemophilus — day 4+).^[1][3]

Treatment of gonococcal ophthalmia: ceftriaxone 25 to 50 mg/kg IV or IM as a single dose (maximum 125 mg) PLUS frequent saline eye irrigation, with urgent ophthalmology review and fluorescein examination for corneal ulcer. Avoid ceftriaxone in a hyperbilirubinaemic neonate (it displaces bilirubin — use cefotaxime instead). Topical antibiotics alone are insufficient because they do not eradicate systemic colonisation. Treat the mother and her partner, and screen for co-infections.^[1]

Chlamydial ophthalmia/pneumonia is treated with oral erythromycin 50 mg/kg/day in four divided doses for 14 days (azithromycin is an alternative); topical therapy alone is inadequate because it does not eradicate nasopharyngeal carriage.^[1][3]

Prevention: ocular prophylaxis at birth — 1 percent silver nitrate, 0.5 percent erythromycin, or 2.5 percent povidone-iodine — prevents gonococcal ophthalmia (though NOT chlamydial). The most effective prevention is antenatal screening and treatment of the mother: screen ALL pregnant women for chlamydia and gonorrhoea at the first antenatal visit, treat (azithromycin for chlamydia, ceftriaxone for gonorrhoea), do a test of cure at 4 weeks, and re-screen high-risk women in the third trimester.^[1][3]

References3ShowHide

1. [1]Workowski KA, Bachmann LH, Chan PA, et al. Sexually Transmitted Infections Treatment Guidelines, 2021 MMWR Recomm Rep, 2021.PMID 34292926
2. [2]Luckey A, Balasegaram M, Barbee LA, et al. Zoliflodacin versus ceftriaxone plus azithromycin for treatment of uncomplicated urogenital gonorrhoea: an international, randomised, controlled, open-label, phase 3, non-inferiority clinical trial Lancet, 2026.PMID 41391465
3. [3]Peuchant O, Lhomme E, Martinet P, et al. Doxycycline versus azithromycin for the treatment of anorectal Chlamydia trachomatis infection in women concurrent with vaginal infection (CHLAZIDOXY study): a multicentre, open-label, randomised, controlled, superiority trial Lancet Infect Dis, 2022.PMID 35550262