Gonorrhoea is the second most common bacterial sexually transmitted infection (STI) in the UK, after chlamydia. Neisseria gonorrhoeae is a Gram-negative diplococcus infecting mucous membranes of the urethra, endocervix, rectum, pharynx and conjunctiva.

Transmission occurs by the direct inoculation of infected secretions from one mucous membrane to another, usually sexually and less commonly perinatally. The incubation period is usually taken as being between 2 and 5 days but may be up to 10 days.¹ Virulence varies as does the tendency to develop disseminated disease. The latter is conferred by the antigenic variation between subtypes. One study found that co-infection with chlamydia in women is associated with higher gonococcal organism loads, potentially increasing chances of transmission.²

Resistance to antibiotics also varies and can be spread rapidly by plasmid transfer of antibiotic resistance genes. Mortality associated with disseminated gonorrhoea is rare but morbidity, primarily associated with pelvic inflammatory disease, is a common sequela worldwide.

Epidemiology

The incidence of gonorrhoea in the UK has fallen over the period of a decade, bucking the upward trend for STIs in general. A small increase of 6% was however seen in the UK between 2008-2009 with more than 17,000 new cases diagnosed that year³ and a 3% rise was reported in England between 2009 and 2010.⁴ The highest rates of gonorrhoea are amongst the young and 50% cases of gonorrhoea were diagnosed in under 25 year-olds. Unlike chlamydia and genital warts, which are widely present, it is unevenly distributed and highly concentrated in particular groups, determined by sexual risk and patterns of sexual mixing.⁵ For example, higher rates are found in men who have sex with men (MSMs) and in certain ethnic groupings.⁶ Geographical clusters tend to occur within urban, inner-city populations.

Uncomplicated gonorrhoea (affecting the lower genital tract) is a reasonably common infection but complicated disease (affecting the upper genital tract) is rarer: in 2008, only 348 cases of complicated gonorrhoeal infection were seen in genitourinary medicine (GUM) clinics, compared with over ten times more of complicated chlamydial infections.⁷

Most cases of gonorrhoea are diagnosed by GUM clinics. In 2000, only 5.7% of female cases and 2.9% of male cases were diagnosed in primary care⁸ although there is increasing emphasis placed on the provision of sexual health services within this sector.

Risk factors^1,6

• Young age.
• History of previous STI.
• Co-existent STIs - a third of MSMs with gonorrhoea had co-existing HIV infection; co-infection with chlamydia was seen in 35% of heterosexual men and 41% of women. ¹
• New or multiple sexual partners.
• Recent sexual activity abroad.
• Homosexual activity (unprotected anal intercourse, frequent insertive oral sex).
• Inconsistent condom use.
• History of drug use or commercial sex work.

Presentation⁶

Gonorrhoea is believed to be symptomatic in most men (90-95%) and asymptomatic in half of women.⁷

Symptoms

Men:

• Urethral infection - discharge (>80%) and/or dysuria (>50%), asymptomatic (<10%).
• Rectal infection - usually asymptomatic; may cause anal discharge (12%) or perianal/anal pain, pruritus or bleeding (7%).
• Pharyngeal infection - usually asymptomatic (>90%).

• Endocervical infection - frequently asymptomatic (up to 50%); increased or altered vaginal discharge is the most common symptom (up to 50%), although lower abdominal pain may also be present (up to 25%); a rare cause of intermenstrual bleeding or menorrhagia.
• Urethral infection - cause of dysuria (12%) without frequency.
• Rectal infection (in women, may develop by spread of infected genital secretions or anal intercourse) - usually asymptomatic.
• Pharyngeal infection - usually asymptomatic (>90%).

Signs

Men:

• Mucopurulent or purulent urethral discharge.
• Epididymal tenderness/swelling or balanitis (rare).

• Mucopurulent endocervical discharge (not a sensitive predictor of infection).
• Easily induced contact bleeding of the endocervix.
• Pelvic/lower abdominal tenderness (uncommon, 5%).
• Normal examination (very common).

• Acute conjunctivitis in association with purulent discharge, usually bilateral, <48 hours of birth, often accompanied by chemosis and lid oedema.
• Vaginal discharge and vulval erythema (prepubertal vulvovaginal epithelium is more susceptible to infection compared with that of adult women).

Differential diagnosis

• Other causes of penile or vaginal discharge, e.g. chlamydia.
• Other causes of pelvic pain, e.g. endometriosis, appendicitis.
• Other causes of pharyngitis, arthritis.

Investigations^7,9

Follow local protocols:

• Traditionally, culture has been the first-line diagnostic test, confirming diagnosis and allowing for antimicrobial sensitivity testing. It remains necessary in patients with signs and symptoms consistent with gonorrhoea or a positive nucleic acid amplification test (NAAT) result to ensure resistant strains can be identified. Rapid diagnosis can be undertaken where facilities exist - use light microscopy of Gram-stained genital specimens to look for Gram-negative diplococci.
• Increasingly, NAATs are being used in the diagnosis of gonorrhoea. These can be taken from a range of genital samples - invasive, e.g. urethral, endocervical and non-invasive, e.g. first pass urine - so are frequently more acceptable. However, urine testing in women is inferior to endocervical or vulvovaginal swab-based methods. NAATs are superior to culture for extragenital sites such as the rectum or pharynx. Supplementary NAAT testing is required to prevent false positive results.
• Specimens should be sent to the laboratory as soon as possible. If there is likely to be considerable delay getting swabs from primary care to the laboratory, it may be preferable to ask the patient to attend a GUM clinic.¹⁰
• It should be noted that the concentration of organisms can be site-dependent. In men who have sex with men, far higher concentrations were seen in rectal specimens than in pharyngeal samples, particularly where proctitis was a feature.¹¹

Management^1,9

General

• Where a patient has tested positive for gonorrhoea, or where an individual has suggestive symptoms/is at high risk, referral to a GUM clinic or service offering an enhanced sexual health service is strongly encouraged.
• Emergency medical admission may be required if there is evidence of disseminated gonorrhoea or severe pelvic inflammatory disease.
• Allow time to provide a detailed explanation of the condition and its long-term implications for the patient and their partner's/partners' health, reinforced with written information. Advise on safer sexual practices for the future.
• Advise patients to avoid unprotected sexual intercourse until both they and their partner(s) have completed treatment.
• Advise routine screening for other STIs in all patients with or at risk of gonorrhoea. Co-infection with other STIs, particularly chlamydia, is common.
• Partner notification should preferably be performed by a trained health adviser. For male patients with symptomatic urethral infection, all partners with whom they have had sexual contact in the previous two weeks or their last partner (if longer than two weeks). With asymptomatic infection or infection at other sites, sexual partners of the preceding three months should be notified. These partners should receive a full STI screen and receive empirical treatment for gonorrhoea and chlamydia in advance of results.
• Patients should be followed up to check compliance with treatment, to make sure symptoms have resolved, to explore the risk of re-infection and to further partner notification and health promotion.

Drug

• Recommended treatment for confirmed, uncomplicated gonococcal anogenital infection in adults is ceftriaxone 500 mg IM stat plus azithromycin 1 g orally stat.
• National guidance is informed by the Gonococcal Resistance to Antimicrobials Programme (GRASP) which monitors emerging patterns of resistance in the UK.¹²
• Treatment failures to cephalosporins should be reported to the Health Protection Agency.

A test of cure (with culture >72 hours or with nucleic acid amplification testing (NAAT) >2 weeks following antibiotic treatment) is recommended in all cases

Resistance to antimicrobial therapy is an ongoing issue with widespread resistance to penicillins, tetracyclines and ciprofloxacin in in the UK and worldwide.^13,14 Resistance to third-generation cephalosporins is emerging in England and Wales. Whilst most resistant infections are acquired at home, sex abroad carries a higher risk of acquiring a resistant strain. Use local guidelines which should take account of local patterns of antimicrobial sensitivity to N. gonorrhoeae.

Alternative options may be required in some circumstances.

• Cefixime 400 mg single oral dose - this is only indicated if IM treatment is contra-indicated or refused by the patient.
• Cefotaxime 500 mg IM as a single dose or cefoxitin 2 g IM as a single dose plus probenecid 1 g orally are suitable single-dose options.
• Spectinomycin 2 g IM as a single dose - occasionally used for the treatment of gonorrhoea in beta-lactam allergic patients (off-licence).
• It is difficult to obtain but may be available from a small number of UK suppliers.¹⁵
• Cefpodoxime can be given orally at a single dose of 200 mg. It is licensed in the treatment of uncomplicated gonorrhoea but is less effective in pharyngeal infection.
• Quinolones are no longer recommended as first-line treatment but may be considered in patients whose infection has previously responded to them. In such cases, ciprofloxacin 500 mg orally as a single dose or ofloxacin 400 mg orally as a single dose is generally used.
• High-dose azithromycin (2 g as a single dose) is effective but has a high incidence of gastrointestinal side-effects. Resistance can also be a problem.
• This list is not exhaustive but reflects current UK practice.

Pregnancy and breast-feeding

• Ceftriaxone 500 mg IM stat with azithromycin 1g orally as a single dose.
• Spectinomycin 2 g IM as a single dose with azithromycin 1g orally as a single dose can be used as an alternative.

Pharyngeal infection

• Ceftriaxone 500 mg IM with azithromycin 1 g orally as a single dose
• Ciprofloxacin 500 mg orally or ofloxacin 400 mg orally (if N. gonorrhoeae known to be quinolone-sensitive).

Pelvic inflammatory disease

Ceftriaxone 500 mg IM stat followed by oral doxycycline 100 mg twice daily plus metronidazole 400 mg twice daily for 14 days.

Gonococcal epididymo-orchitis

Ceftriaxone 500 mg IM plus doxycycline 100 mg twice daily for 10-14 days.

Gonococcal conjunctivitis

Systemic treatment is recommended as the cornea may be involved and the eye is relatively avascular:

• Wash the eye with saline/water.
• Ceftriaxone 500 mg IM daily for 3 days.
• If there is history of penicillin anaphylaxis use spectinomycin 2 g IM daily for 3 days or azithromycin 2 g orally stat plus doxycycline 100 mg twice daily for 1 week plus ciprofloxacin 250 mg daily for 3 days.

Children

Ophthalmia neonatorum:

• During the first year of life, gonorrhoea can cause ophthalmia neonatorum (neonatal conjunctivitis), pharyngitis, rectal infections and pneumonia. Signs develop within two to five days following birth, because exposure to infection tends to have occurred during delivery.
• Gram-stain conjunctival exudates followed by culture are the investigations of choice. Treatment should be prompt to prevent corneal ulceration and permanent visual loss - usually parenteral benzylpenicillin or cephalosporin, in combination with saline lavage and topical antibiotic (e.g. chloramphenicol, erythromycin).
• Both parents should be screened.
• Prophylaxis is widely used in some parts of the world (although not in the UK) and involves the topical use of silver nitrate or antibiotics.¹⁴ One meta-analysis found that failure rates of universal eye prophylaxis support warranted re-examination of this approach where the prevalence of maternal infection was low.¹⁶

• Ceftriaxone 1 g IM or IV every 24 hours; or
• Cefotaxime 1 g IV every 8 hours; or
• Ciprofloxacin 500 mg IV every 12 hours (if the infection is known to be sensitive); or
• Spectinomycin 2 g IM every 12 hours.

The following oral therapy may be substituted after 24-48 hours:

• Cefixime 400 mg twice daily; or
• Ciprofloxacin 500 mg twice daily; or
• Ofloxacin 400 mg twice daily.

Therapy should continue for a total of seven days.

Allergy

A history of sensitivity to cephalosporins or severe hypersensitivity to a penicillin or other beta-lactam drug may present a problem. In such cases the following may be used:

• Spectinomycin 2 g IM as a single dose with azithromycin 1 g orally as a single dose.
• Azithromycin 2 g orally as a single dose.
• Ciprofloxacin 500 mg orally as a single dose when the infection is known to be quinolone-sensitive.

• Consider the possibility of sexual abuse in the under-age and vulnerable. Follow local child protection guidance and seek expert advice.
• After the neonatal period, it is thought that genital and pharyngeal gonorrhoea are almost always due to sexual abuse by an infected adult,¹⁷ although there are cases, particularly of conjunctivitis, that appear to have been acquired nonsexually.¹⁸ All cases of gonorrhoea post-infancy must be investigated thoroughly.

Complications¹

Men:

• Gonococcal urethritis may cause urethral scarring and stricture, resulting in bladder-outflow obstruction.
• Local spread causing acute epididymitis, prostatitis, seminal vesiculitis, penile lymphangitis, peri-urethral abscess and infection of Tyson's and Cowper's glands.

• Bartholin's abscess (usually multiple pathogens).
• Pelvic inflammatory disease - thought to occur in 10-20%, causing infertility, chronic pelvic pain and ectopic pregnancy.
• Peri-hepatitis (Fitz-Hugh Curtis syndrome).
• In pregnancy it may be associated with premature labour and miscarriage.
• Corneal scarring and blindness from neonatal ophthalmic infection.

• Haematogenous dissemination (uncommon - <1%) causing:
  • Skin lesions (papules, bullae, petechiae and necrotic skin lesions).
  • Arthralgia, arthritis and tenosynovitis of the ankles, wrists, hands and feet (Reiter's syndrome).
  • Meningitis, endocarditis or myocarditis, with risk of death or permanent sequelae (extremely rare).
• Increased risk of acquiring and transmitting HIV infection.

Prognosis⁶

Where treatment is rapidly received for a recently acquired gonorrhoeal infection, prognosis is good with full recovery as normal. Continuing symptoms are more likely to be due to re-infection than persistence of the original infection.¹⁹ The risk of infertility increases with repeated episodes.

Prevention⁷

• Promotion of safer sex methods.
• Consistent use of condoms reduces the risk of acquiring gonorrhoea and other STIs.
• Testing for those sexually active and at risk of acquiring gonorrhoea - in the UK there is no current evidence base to support widespread unselected screening for gonorrhoea and only very limited evidence for selective community screening. Localised interventions targeted on high-risk groups (inner-city residents, GUM attendees, military personnel, prisoners and men who have sex with men (MSMs) are more likely to be cost-effective and beneficial than unselected screening.
• Prompt treatment with an advised regime, partner tracing and treatment of contacts and follow-up is important.²⁰

National guidelines recommend that:⁹

• Male patients with symptomatic urethral infection should notify all sexual partners within the preceding two weeks or their last partner if longer than two weeks.
• People with infection at other sites or asymptomatic infection should contact all partners within the preceding three months.
• Partners should be offered testing and treatment.

Document references

1. Gonorrhoea, Prodigy (September 2009)
2. Stupiansky NW, Van Der Pol B, Williams JA, et al; The natural history of incident gonococcal infection in adolescent women. Sex Transm Dis. 2011 Aug;38(8):750-4. [abstract]
3. Health Protection Report, Weekly Report, Volume 4 Number 34, Health Protection Agency, Aug 2010
4. Health Protection Report, Weekly Report, Volume 5 Number 24, Health Protection Agency, June 2011
5. Fenton KA, Mercer CH, Johnson AM, et al; Reported sexually transmitted disease clinic attendance and sexually transmitted infections in britain: prevalence, risk factors, and proportionate population burden. J Infect Dis. 2005 Feb 1;191 Suppl 1:S127-38. [abstract]
6. Gonorrhoea, Health Protection Agency
7. Guidance for gonorrhoea testing in England and Wales, British Association for Sexual Health and HIV (2010)
8. Cassell JA, Mercer CH, Sutcliffe L, et al; Trends in sexually transmitted infections in general practice 1990-2000: population based study using data from the UK general practice research database. BMJ. 2006 Feb 11;332(7537):332-4. Epub 2006 Jan 26. [abstract]
9. Management of Gonorrhoea, British Association for Sexual Health and HIV (2011)
10. Standards Unit, Evaluations and Standards Laboratory, 2005; Investigation of gential tract and associated specimens: BSOP 28
11. Bissessor M, Tabrizi SN, Fairley CK, et al; Differing Neisseria gonorrhoeae bacterial loads in the pharynx and rectum in men J Clin Microbiol. 2011 Sep 28. [abstract]
12. GRASP: The Gonococcal Resistance to Antimicrobials Surveillance Programme, Health Protection Agency
13. Kirkcaldy RD, Ballard RC, Dowell D; Gonococcal resistance: are cephalosporins next? Curr Infect Dis Rep. 2011 Apr;13(2):196-204. [abstract]
14. Cole MJ, Chisholm SA, Hoffmann S, et al; European surveillance of antimicrobial resistance in Neisseria gonorrhoeae. Sex Transm Infect. 2010 Nov;86(6):427-32. [abstract]
15. British Association for Sexual Health and HIV; Spectinomycin for Treatment of Gonorrhoea 2011; Link to Word document
16. Darling EK, McDonald H; A meta-analysis of the efficacy of ocular prophylactic agents used for the J Midwifery Womens Health. 2010 Jul;55(4):319-27. [abstract]
17. Whaitiri S, Kelly P; Genital gonorrhoea in children: determining the source and mode of infection. Arch Dis Child. 2011 Mar;96(3):247-51. Epub 2010 Jun 3. [abstract]
18. Goodyear-Smith F; What is the evidence for non-sexual transmission of gonorrhoea in children after the neonatal period? A systematic review. J Forensic Leg Med. 2007 Nov;14(8):489-502. Epub 2007 Jul 30. [abstract]
19. Fowler T, Caley M, Johal R, et al; Previous history of gonococcal infection as a risk factor in patients presenting Int J STD AIDS. 2010 Apr;21(4):277-8. [abstract]
20. Mehta SD, Erbelding EJ, Zenilman JM, et al; Gonorrhoea reinfection in heterosexual STD clinic attendees: longitudinal analysis of risks for first reinfection. Sex Transm Infect. 2003 Apr;79(2):124-8. [abstract]

Internet and further reading

• Walker CK, Sweet RL; Gonorrhea infection in women: prevalence, effects, screening, and management. Int J Womens Health. 2011;3:197-206. Epub 2011 Jul 19. [abstract]
• Ohneck EA, Zalucki YM, Johnson PJ, et al; A Novel Mechanism of High-Level, Broad-Spectrum Antibiotic Resistance Caused by a MBio. 2011 Sep 20;2(5). pii: e00187-11. doi: 10.1128/mBio.00187-11. Print 2011. [abstract]