Gonorrhoea is caused by the Gram-negative diplococcus Neisseria gonorrhoeae. The primary sites of infection are the columnar epithelium-lined mucous membranes of the urethra, endocervix, rectum, pharynx and conjunctiva.

Transmission is by direct inoculation of infected secretions from one mucous membrane to another. Secondary infection to other anatomical sites, through systemic or transluminal spread, can also occur.

Symptoms and signs of infection with gonorrhoea depend, in part, on the site of infection.

 

• Penile urethral infection

Symptoms occur in over 90% of individuals, with discharge and/or dysuria appearing two to five days following exposure. A mucopurulent urethral discharge is often present on examination. Rarely, individuals may complain of testicular and epididymal pain with tenderness and swelling present on examination.

 

• Female urethral infection

Urethral infection may present with dysuria without urinary frequency.

 

• Endocervical infection

The most common symptom, occurring in about 50% of individuals, is an increased or altered vaginal discharge. In about a quarter of individuals, lower abdominal pain is present. Gonorrhoea rarely causes intermenstrual bleeding and menorrhagia. On examination, a mucopurulent endocervical discharge may be seen and easily induced endocervical bleeding may be present. 

 

• Rectal infection

Most cases are asymptomatic but symptoms may include anal discharge and perianal/ anal pain or discomfort. Rectal infection in cisgender women is present in up to a third of cases of urogenital infection, and individuals may not report a history of anal sex. 

 

• Pharyngeal infection

This is predominantly asymptomatic but is occasionally associated with a sore throat.

 

• Complicated infection

Transluminal spread of N. gonorrhoeae from the urethra or endocervix may occur and cause epididymo-orchitis, prostatitis or pelvic inflammatory disease (PID). Haematogenous dissemination may occur from infected mucous membranes to cause skin lesions, arthralgia, arthritis and tenosynovitis (disseminated gonococcal infection). 

This section should be read in conjunction with Public Health England Guidance for the Detection of Gonorrhoea in England Aug 2014

The diagnosis of gonorrhoea is established by the detection of N. gonorrhoeae at an infected site, either by nucleic acid amplification tests (NAATs) or by culture. The approach and method used to test for gonorrhoea will be influenced by the clinical setting, storage and transport system to the laboratory, local prevalence of infection and the range of tests available in the laboratory. No test for gonorrhoea offers 100% sensitivity and specificity.

 

Microscopy

Microscopy of Gram-stained genital specimens allows direct visualisation of N. gonorrhoeae as monomorphic Gram-negative diplococci within polymorphonuclear leukocytes.

Penile urethra

• Microscopy of urethral or meatal swab smears has good sensitivity (90–95%) in people with discharge from the penile urethra and is recommended to facilitate immediate presumptive diagnosis in these individuals (Grade 1C)
• Microscopy of penile urethral smears in those without symptoms is less sensitive (50–75%) therefore, it is not recommended in asymptomatic individuals (Grade 1C)

Female urethra and endocervix

• Microscopy has only 37–50% and 20% sensitivity compared with culture for detecting gonorrhoea from endocervical and female urethral smears, respectively
• The sensitivity of cervical microscopy compared to NAATs in a more recent study was only 16%
• Female urethral and cervical microscopy is therefore not routinely recommended (Grade 1C)

Rectum and pharynx

• Ano-rectal smears and microscopy should be offered if rectal symptoms are present (Grade 1C)
• The sensitivity of microscopy for detecting asymptomatic rectal infection is low and is not recommended (Grade 1C)
• Microscopy of pharyngeal specimens is not recommended (Grade 1C)

 

Nucleic acid amplification tests

NAATs are more sensitive than culture, particularly for oropharyngeal and rectal sites.NAATs show high sensitivity (>95%) in both symptomatic and asymptomatic infection. Therefore, although NAATs are not licensed for use at extra-genital sites, their use is recommended. Commercially available NAATs differ in their cross-reactivity to commensal Neisseria species which may be present at significant levels, particularly in the pharynx. 

It is recommended that laboratories confirm any reactive test with an alternative molecular target if the positive predictive value of the initial test for the population tested is less than 90% (Grade 1B)

Penile urethra

• NAATs show equivalent sensitivity in urine and urethral swab specimens from cisgender men although a first-pass urine is the preferred sample. 

Female urethra and endocervix

• Self-collected or clinician-collected vulvovaginal swabs perform better than endocervical swabs and significantly better than urine for cisgender women. Vulvovaginal swabs are therefore recommended as the optimal specimen (Grade 1A)

 Rectum and pharynx

• Rectal and pharyngeal sampling should be routine in all men who have sex with men (MSM), considered in women who are sexual contacts of gonorrhoea and be guided by an assessment of risk and symptoms in everyone else.
• Oropharyngeal infection is more difficult to treat. Therefore, anyone with genital gonorrhoea (regardless of gender or reported sexual behaviour) should have pharyngeal sampling if either of the following apply (Grade 1D):
  1. Susceptibility results are not available and the infection may have been acquired in the Asia-Pacific region. This is because of high levels of antimicrobial resistance in that region which may lead to treatment failure
  2. Genital infection with a confirmed ceftriaxone resistant strain

 

Culture

• The primary role of culture is for antimicrobial susceptibility testing, which is of increasing importance as antimicrobial resistance in gonorrhoeaecontinues to evolve and spread.
• Specimens for culture (urethral, endocervical, neovaginal, anorectal and pharyngeal swabs) should be taken alongside NAATs from people suspected clinically of having gonorrhoea, and from sexual contacts.
• All individuals with gonorrhoea diagnosed by NAAT should have cultures taken for susceptibility testing prior to treatment (Grade 1D)

 

Considerations for people following genital reconstructive surgery (GRS)

• Please see the full guideline for details

 

Timing of testing

Infection cannot be ruled out in individuals who test within two weeks of sexual contact with an infected partner. Therefore, it is recommended that patients return for repeat testing after this window period if epidemiological treatment is not given (Grade 1D)

 

General advice

Patients should be given a detailed explanation of their condition with particular emphasis on the implications for the health of themselves and their partner(s). This should be reinforced, if necessary, with clear and accurate written information (Grade 1D). Patients should be advised to abstain from sexual intercourse until seven days after they and their partner(s) have completed treatment (Grade 1D)

 

Treatment

Indications for therapy:

1. Identification of intracellular Gram-negative diplococci on microscopy
2. A positive culture for gonorrhoeae
3. A confirmed positive NAAT for gonorrhoeae
4. Sexual partner of confirmed case of gonococcal infection (See section below on Sexual Partners)

 

Treatment of uncomplicated ano-genital and pharyngeal infection in adults

When antimicrobial susceptibility is not known prior to treatment:

• Ceftriaxone 1g intramuscularly as a single dose (Grade 1C)

When antimicrobial susceptibility is known prior to treatment:

• Ciprofloxacin 500mg orally as a single dose (Grade 1A) (See below)

 

The prevalence of ciprofloxacin resistance in the UK is high (36.4% in 2017). Therefore, we only recommend considering ciprofloxacin as first-line treatment if phenotypic or genotypic antimicrobial susceptibility data indicates susceptibility to ciprofloxacin at all suspected sites of infection. 

The move to ceftriaxone monotherapy represents a major change from the 2011 guideline. For a detailed explanation of the considerations underpinning this change, please see the full guideline. A high level of vigilance through use of culture, follow up of patients and test of cure coupled with maintenance of strong surveillance is vital in order to monitor the impact of this approach.

 

Alternative regimens

The following options have all been associated with treatment failure when used as monotherapy particularly when used for pharyngeal infection, therefore it is recommended to use dual therapy with azithromycin 2g where possible (Grade 2C).

Alternative regimens may be given because of allergy, needle phobia or other absolute or relative contraindications. In patients with pencillin allergy there is ample evidence to allow the safe use of all but a few early-generation cephalosporins (e.g. cephalexin, cefaclor and cefadroxil), and third-generation cephalosporins such as cefixime and ceftriaxone show negligible cross-allergy with penicillins

• Cefixime 400mg orally as a single dose plus azithromycin 2g orally (Grade 1B)
  • Only advisable if an intramuscular injection is contraindicated or refused by the patient. Resistance to cefixime is currently low in the UK.

• Gentamicin 240mg intramuscularly as a single dose plus azithromycin 2g orally (Grade 1A)

• Spectinomycin 2g intramuscularly as a single dose plus azithromycin 2g orally (Grade 1B)
  • Spectinomycin is not recommended for pharyngeal infection because of poor efficacy.

• Azithromycin 2g as a single oral dose (Grade 1B)
  • The clinical efficacy of azithromycin does not always correlate with in vitro susceptibility testing⁸³and azithromycin resistance is high.

 

COVID-19 Guidance - April 2020

 

Treatment of complicated infections

Gonococcal PID

• Ceftriaxone 1g intramuscularly as a single dose in addition to the regimen chosen to treat PID

 

Gonococcal epididymo-orchitis

• Ceftriaxone 1g intramuscularly as a single dose in addition to the regimen chosen to treat epididymo-orchitis

 

Gonococcal conjunctivitis

• Ceftriaxone 1g intramuscularly as a single dose (Grade 2D)

 

 Disseminated gonococcal infection

• Ceftriaxone 1g intramuscularly or intravenous every 24 hours or
• Cefotaxime 1g intravenous every eight hours or
• Ciprofloxacin 500mg intravenous every 12 hours (if the infection is known to be susceptible) or
• Spectinomycin 2g intramuscularly every 12 hours

Therapy should continue for seven days but may be switched 24–48 hours after symptoms improve to one of the following oral regimens guided by sensitivities:

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

 

Pregnancy and breastfeeding

Pregnant and breastfeeding individuals should not be treated with quinolone or tetracycline antimicrobials. Pregnancy does not diminish treatment efficacy.

• Ceftriaxone 1g intramuscularly as a single dose (Grade 1A) or
• Spectinomycin 2g intramuscularly as a single dose (Grade 1A)
  • Spectinomycin is in the FDA pregnancy category B and therefore not expected to be harmful and can be used if no suitable alternatives. It is not known if it is excreted in breastmilk and should be used with caution in those who are breastfeeding.
• Azithromycin 2g as a single oral dose (Grade 1B)
  • The manufacturer of azithromycin advises use only if adequate alternatives are not available. In addition, azithromycin should only be used if isolate known to be susceptible.

 

HIV-positive individuals

HIV-positive individuals with gonorrhoea should be managed in the same way as HIV-negative individuals.

 

Sexual Partners

Partner notification should be pursued in all patients identified with gonococcal infection. The following partners should be notified:

• All partners within the preceding two weeks (or the last partner if longer than two weeks ago) of male patients with symptomatic urethral infection;
• All partners within the preceding three months of patients with infection at other sites or asymptomatic infection.

Epidemiological treatment is not needed for all sexual contacts, and ideally treatment should only be given to those partners who test positive for gonorrhoea. However, an infection may be missed if a test is performed too soon after a potential exposure. The time between exposure and a positive test result may vary depending on a number of host, pathogen and diagnostic factors. There is a lack of evidence to support recommendations for the optimal time for testing. Therefore, in order to reduce the unnecessary use of antibiotics, we recommend the following as a pragmatic approach:

• For those presenting after 14 days of exposure we recommend treatment only following a positive test for gonorrhoea.
• For those presenting within 14 days of exposure we recommend considering epidemiological treatment based on a clinical risk assessment and following a discussion with the patient. In asymptomatic individuals, it may be appropriate to not give epidemiological treatment, and to repeat testing 2 weeks after exposure.

 

Follow-up and test of cure (TOC)

All patients diagnosed with gonorrhoea should be advised to return for TOC, with extra emphasis given to patients:

1. With persistent symptoms or signs
2. With pharyngeal infection
3. Treated with anything other than first line recommended regimen when antimicrobial susceptibility unknown
4. Who acquired infection in the Asia-Pacific region when antimicrobial susceptibility unknown

A positive TOC could be due to treatment failure, reinfection or residual non-viable organism and should be interpreted in the clinical context.

• Culture, performed at least 72 hours after completion of therapy, should be used if symptoms or signs are present at time of TOC.
• NAAT should be used if asymptomatic, followed by culture if NAAT-positive.
• The time to a negative TOC using NAATs is variable and there are limited data to inform optimum time to TOC. However, most individuals should be negative seven days following treatment where an RNA NAAT is used and 14 days following treatment when using a DNA NAAT.
• We recommend TOC should be performed at an appropriate time depending on the type of NAAT used (Grade 1B).

 

Treatment failures

Cases of possible ceftriaxone treatment failure in England should be reported to Public Health England using the on-line form: https://hivstiwebportal.phe.org.uk/login.aspx