Gonorrhoea
Gonorrhoea - Summary
Uncomplicated gonorrhoea is caused by localized infection with Neisseria gonorrhoeae. It primarily affects the mucous membranes of the urethra, endocervix, rectum, pharynx, and conjunctiva.
Disseminated gonorrhoea is much less common (occurring in <1% of people).
The prevalence of gonorrhoeal infection is related to sexual activity.
Uncomplicated gonorrhoea is most common in young adults (15–25 years of age) and in men who have sex with men of any age.
In men, acute complications are rare and include epididymitis and penile lymphangitis.
In women, complications include Bartholin’s abscess and pelvic inflammatory disease (PID). Gonorrhoea in pregnancy is associated with spontaneous abortion and other complications.
A diagnosis of gonorrhoea may be suspected on the basis of history, symptoms, and examination.
In men, symptoms (such as urethral discharge and dysuria) usually develop 2–5 days after exposure, although they may appear after 10 days or more. Examination commonly reveals a mucopurulent or purulent urethral discharge, and less commonly epididymal tenderness or swelling, or balanitis.
Uncomplicated urogenital infection is asymptomatic in up to 50% of women. Where present, symptoms (such as dysuria and increased or altered vaginal discharge) usually develop within 10 days. No abnormal findings are present on examination.
Ideally, all people with suspected gonorrhoea should be referred to a genito-urinary (GUM) clinic or other local specialist sexual health service for confirmation of diagnosis.
If the person is unwilling or unable to attend, local guidelines for testing for gonorrhoea should be followed.
Partner notification is essential for all people with newly diagnosed gonorrhoea.
Referral is particularly important in:
Men who have complications such as epididymitis.
Pregnant women.
Women with suspected ascending infection.
Admission to hospital is required for:
People with suspected disseminated gonorrhoea (fever, malaise, joint pain and swelling, and rash may be present).
Women with severe or complicated PID.
Gonorrhoea should be treated in primary care only if specialist services cannot be accessed within a reasonable time, or if the person is unwilling to attend despite receiving appropriate information and advice.
Treatment is indicated following a positive identification of Neisseria gonorrhoeae by microscopy, culture, or nucleic acid amplification testing (NAAT).
Empirical treatment is indicated for people with suspected gonorrhoea (whilst waiting for laboratory confirmation of the diagnosis) and recent sexual partner(s) of people with confirmed gonococcal infection.
For confirmed or suspected uncomplicated anogenital or pharyngeal gonorrhoea, intramuscular ceftriaxone plus azithromycin first line should be prescribed.
Follow up is recommended for all people with gonorrhoea about 1 week after treatment to:
Confirm adherence to treatment and resolution of symptoms.
Confirm that partner notification has been carried out.
Ask about recent sexual history (and the possibility of re-infection), and reinforce advice about safe sexual practice.
A test of cure is recommended for all people who have been treated for gonorrhoea. However, if it is not possible to test everyone, prioritize people:
With persistent signs or symptoms.
With pharyngeal infection.
Who have been treated with anything other than the first-line recommendation.
Have I got the right topic?
This CKS topic covers the diagnosis and management of gonorrhoea infection in men and women.
This CKS topic does not cover the empirical treatment of urethritis or vaginal discharge or the management of disseminated gonorrhoea, complications of gonorrhoea (for example epididymitis), gonorrhoea infection of the eyes, or gonorrhoea in children.
There are separate CKS topics on Bacterial vaginosis, Candida - female genital, Chlamydia - uncomplicated genital, Pelvic inflammatory disease, Scrotal swellings, Trichomoniasis, Urethritis - male, and Vaginal discharge.
The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary health care.
How up-to-date is this topic?
How up-to-date is this topic?
Changes
February 2013 — minor update. The 2013 QIPP options for local implementation have been added to this topic [NICE, 2013].
January 2013 — minor update. Typographical error corrected in the prescribing information section on cephalosporins.
October 2012 — minor update. The 2012 QIPP options for local implementation have been added to this topic [NPC, 2012].
September 2011 — updated to reflect the revised UK National Guideline for the Management of Gonorrhoea in Adults 2011, published by the British Association for Sexual Health and HIV (BASHH) [BASHH, 2011b]. Issued in November 2011.
The main changes to recommendations include:
First-line treatment for gonorrhoea is now ceftriaxone 500 mg by intramuscular injection plus azithromycin 1 g orally.
A test of cure is now recommended for all people after treatment for gonorrhoea.
Previous changes
May 2011 — minor update. The 2010/2011 QIPP options for local implementation have been added to this topic [NPC, 2011]. Issued in June 2011.
September 2010 — minor update. The figures for new diagnoses of gonorrhoea in 2008/9 have been added [HPA, 2010], and the lower age limit for quinolone prescriptions has been raised from 16 to 18 years. Issued in September 2010.
October 2009 — minor update. Minor change to wording of basis regarding amoxicillin use in pregnant and breastfeeding women. Issued in October 2009.
October 2009 — minor update. Recommendations from the National Institute of Health and Clinical Excellence on when to suspect sexual abuse has been added to the Diagnosis section [NICE, 2009]. Issued in October 2009.
July to September 2009 — this is a new CKS topic. The evidence-base has been reviewed in detail, and recommendations are clearly justified and transparently linked to the supporting evidence.
Update
New evidence
Evidence-based guidelines
Guidelines published since the last revision of this topic:
BASHH (2012) UK national guideline for gonorrhoea testing 2012. British Association for Sexual Health and HIV. www.bashh.org [Free full-text (pdf)]
HTAs (Health Technology Assessments)
No new HTAs since 1 November 2011.
Economic appraisals
No new economic appraisals relevant to England since 1 November 2011.
Systematic reviews and meta-analyses
Systematic reviews published since the last revision of this topic:
Dowell, D., and Kirkcaldy, R.D. (2012) Effectiveness of gentamicin for gonorrhoea treatment: systematic review and meta-analysis. Sexually Transmitted Infections 88(8), 589-594. [Abstract]
Primary evidence
Randomized controlled trials published since the last revision of this topic:
Bai, Z.G., Bao, X.J., Cheng, W.D., et al. (2012) Efficacy and safety of ceftriaxone for uncomplicated gonorrhoea: a meta-analysis of randomized controlled trials. International Journal of STD and AIDS 23(2), 126-132. [Abstract]
A diagnostic accuracy study has been published since the last revision of this topic:
Stewart, C.M.W., Schoeman, S.A., Booth, R.A., et al. (2012) Assessment of self taken swabs versus clinical taken swab cultures for diagnosing gonorrhoea in women: single centre, diagnostic accuracy study. BMJ 345, e8017. [Abstract] [Free Full-text]
New policies
No new national policies or guidelines since 1 November 2011.
New safety alerts
No new safety alerts since 1 November 2011.
Changes in product availability
No changes in product availability since 1 November 2011.
Goals and outcome measures
Goals
To refer all people with gonorrhoea (suspected or confirmed) to a genito-urinary medicine (GUM) clinic or other local specialist sexual health service, where possible.
When referral is not possible:
To treat laboratory-confirmed gonorrhoea
To swab and treat empirically people with suspected gonorrhoea
To give information and advice about gonorrhoea and sexual health
To notify and manage the person's sexual partners
To follow up people after treatment for gonorrhoea
QIPP — Options for local implementation
QIPP — Options for local implementation
Antibiotic prescribing — especially quinolones and cephalosporins
Review and, where appropriate, revise current prescribing practice and use implementation techniques to ensure prescribing is in line with Health Protection Agency (HPA) guidance.
Review the total volume of antibiotic prescribing against local and national data.
Review the use of quinolones and cephalosporin prescribing against local and national data.
Background information
Definition
What is it?
Uncomplicated gonorrhoea is caused by localized infection with the diplococcus bacterium Neisseria gonorrhoeae. It primarily affects the mucous membranes of the urethra, endocervix, rectum, pharynx, and conjunctiva.
Disseminated gonorrhoea may present as septic arthritis or dermatitis. It is much less common than uncomplicated gonorrhoea, occurring in less than 1% of people.
Gonorrhoea is almost always sexually transmitted in adults. It is transmitted by direct inoculation of secretions from one mucous membrane to another, through genital–genital, genital–anorectal, orogenital, or oro–anal contact. Infection of the eye most commonly results from autoinoculation.
Prevalence
How common is it?
Uncomplicated gonorrhoea is most common in young adults (15–25 years of age) and affects a disproportionate amount of people from ethnic minority groups [Bignell, 2009].
In 2010, the Gonococcal Resistance to Antimicrobials Surveillance Programme indicated that the prevalence of gonorrhoeal infection was related to sexual activity [HPA, 2011].
Men who have sex with men accounted for most cases of infection; most of these men were white, and just less than a third had coexisting HIV infection.
Co-infection with chlamydia was identified in 38% of heterosexual men and 40% of women. Overall, 29% of people reported previously being infected with gonorrhoea.
Recent sex abroad was reported by 14% of people, and over half of people reported two or more sexual partners in the preceding 3 months.
In 2010, the Health Protection Agency reported on the incidence of gonorrhoea in 2008–2009 [HPA, 2010].
The incidence of newly diagnosed gonorrhoea in the UK increased by 6%, from 16,629 cases in 2008 to 17,385 cases in 2009.
Young people, aged less than 25 years, experience the highest rates of sexually transmitted infections. In those attending GUM clinics in 2009, 50% of gonorrhoea diagnoses were in those aged less than 25 years.
In contrast to heterosexual men, sexually transmitted infections are common in men who have sex with men of any age; 36% of gonorrhoea diagnoses in 2009 were in men who have sex with men.
Complications and prognosis
What are the complications and prognosis?
Men
Acute complications that may rarely occur include epididymitis, penile lymphangitis, peri-urethral abscess, acute prostatitis, seminal vesiculitis, and infection of Tyson's and Cowper's glands.
Urethral stricture is now considered a rare complication of gonococcal urethritis.
Women
The natural history of gonorrhoeal infection is less understood than in men. As gonorrhoea is often asymptomatic in women, it may remain undiagnosed for long periods (along with coexisting infections of Chlamydia trachomatis and Trichomonas vaginalis).
Bartholin's abscess may present as a local complication of infection, although it is usually caused by more than one pathogen.
Pelvic inflammatory disease is thought to occur in 10–20% of women who contract gonorrhoea. The main concerns of pelvic inflammatory disease are infertility and peri-hepatitis caused by ascending infection.
See the CKS topic on Pelvic inflammatory disease for further information.
Gonorrhoea in pregnancy is associated with spontaneous abortion, premature labour, early rupture of fetal membranes, perinatal mortality, and gonococcal conjunctivitis in the newborn.
Disseminated gonorrhoea is a rare but potentially serious complication of gonococcal infection and may result in arthritis-dermatitis syndrome, gonococcal bacteraemia, and gonococcal endocarditis.
Diagnosis
Diagnosis of gonorrhoea
Suspected diagnosis in men
When should I suspect gonorrhoea in a man?
A diagnosis of gonorrhoea may be suspected on the basis of history, symptoms, and examination.
History
Sexual intercourse with an infected person.
Symptoms
Genital infection is usually symptomatic in men.
Symptoms usually develop 2–5 days after exposure, although they may appear after 10 days or more.
Major symptoms include:
Urethral discharge in 80% of men. Initially it is often scant and mucoid, becoming overtly purulent after 1–2 days.
Pain or difficulty urinating (dysuria) in about 50% of men. Usually there is no effect on frequency or urgency of urination.
Genital infection is asymptomatic in a small proportion (less than 10%) of men.
Rectal infection is asymptomatic in most men (about 75%), but may cause acute proctitis. This presents as anal pruritus, pain and spasm of the anal sphincter (tenesmus), purulent discharge, or bleeding.
Pharyngeal infection is asymptomatic in 90% of men, but may cause overt pharyngitis.
Examination
Examination commonly reveals a mucopurulent or purulent urethral discharge. Less commonly, there may be epididymal tenderness or swelling, or balanitis.
Basis for recommendation
Basis for recommendation
Sexual intercourse with an infected person is the over-riding risk factor for acquiring gonorrhoea [Marrazzo et al, 2010].
The risk of transmission from an infected woman to her male partner is about 20% per episode of unprotected intercourse.
The risk of transmission from an infected man to his female partner is between 50–70% per episode.
The risk of transmission by anal intercourse has not been formally quantified but is thought to be high.
The description of symptoms and examination in men is taken from the UK national guideline for the management of gonorrhoea [BASHH, 2011b] and from expert opinion in a textbook [Marrazzo et al, 2010].
Suspected diagnosis in women
When should I suspect gonorrhoea in a woman?
Gonorrhoea may be suspected on the basis of history, symptoms, and examination.
History
Sexual intercourse with an infected person.
Symptoms
Uncomplicated urogenital infection causes no symptoms in up to 50% of women.
Where present, symptoms usually develop within 10 days and include:
Increased or altered vaginal discharge in up to 50% of women.
Pain or difficulty urinating (dysuria) in 12% of women. Usually there is no effect on urgency or frequency of urination.
Intermenstrual bleeding and, less commonly, postcoital bleeding.
Pelvic or abdominal pain, with possible pain on intercourse (dyspareunia), if there is ascending infection (see the CKS topic on Pelvic inflammatory disease).
Rectal gonorrhoea may occur, but tends to cause symptoms (anal pruritus, pain and spasm of the anal sphincter [tenesmus], purulent discharge, or bleeding) that are less severe than in men.
Pharyngeal infection is asymptomatic in 90% of women, but it may cause overt pharyngitis.
Examination
In most women, no abnormal findings are present on examination.
Examination may show:
Most commonly, purulent or mucopurulent endocervical discharge, or easily induced endocervical bleeding. However, this is not a sensitive predictor of cervical infection (occurring in less than 50% of women).
Less commonly, purulent discharge from the urethra.
Abdominal tenderness if pelvic inflammatory disease is present.
Basis for recommendation
Basis for recommendation
Sexual intercourse with an infected person is the over-riding risk factor for acquiring gonorrhoea [Marrazzo et al, 2010].
The risk of transmission from an infected woman to her male partner is about 20% per episode of unprotected intercourse.
The risk of transmission from an infected man to his female partner is between 50–70% per episode.
The risk of transmission by anal intercourse has not been formally quantified but is thought to be high.
The description of symptoms and examinations in women is taken from the UK national guideline for the management of gonorrhoea [BASHH, 2011b] and from expert opinion in a textbook [Marrazzo et al, 2010].
Confirmation of diagnosis
How do I confirm a diagnosis of gonorrhoea?
Ideally, refer all people with suspected gonorrhoea to a genito-urinary medicine (GUM) clinic or other local specialist sexual health service for confirmation of diagnosis.
If the person is unwilling or unable to attend a GUM clinic or other local specialist sexual health service, follow local guidelines for testing for gonorrhoea.
In men this may include:
A first pass urine sample.
A urethral swab.
A rectal swab if rectal symptoms are present, or in men who have sex with men (MSM).
A pharyngeal swab if pharyngeal symptoms are present, or in MSM.
For more information, see the section on Assessment in the CKS topic on Urethritis - male.
In women this may include:
Endocervical and urethral swabs.
A rectal swab if rectal symptoms are present, or in women who are sexual contacts of me with confirmed infection.
A pharyngeal swab if pharyngeal symptoms are present.
See the CKS topic on Vaginal discharge for further information.
Sexual contacts of people with confirmed infection should be offered testing as above and empirical treatment for gonorrhoea (see Scenario: Management).
If empirical treatment is not given, a second set of tests should be performed in people who present within 3 days of sexual contact. These tests should usually be done 14 days after contact.
Basis for recommendation
Basis for recommendation
Genito-urinary medicine clinics and specialist sexual health services have the resources to ensure effective diagnosis and treatment of gonorrhoea, as well as screening for other sexually transmitted infections (including HIV), counselling, follow up, and contact tracing (partner notification).
Investigations in primary care
Recommendations for testing for Neisseria gonorrhoeae are based on the UK national guideline for the management of gonorrhoea [BASHH, 2011b] and supported by Guidance for gonorrhoea testing in England and Wales [BASHH and HPA, 2010] and a review article in the medical literature [Bignell et al, 2006].
Diagnosis of gonorrhoea is confirmed by detection of N gonorrhoeae at an infected site.
Investigations will be guided by the clinical setting, storage and transport to the laboratory, local prevalence of infection, and the range of tests available locally. Therefore CKS recommends that practitioners confirm which testing methods are used locally.
Microscopy of gram-stained genital specimens offers 90–95% sensitivity in men with urethral discharge, enabling immediate diagnosis in men with symptomatic genital infection. In men with no symptoms, sensitivity is reduced to 50–75%. Microscopy has poor sensitivity in women (37–50% for endocervical samples and 20% for urethral samples), and is not usually recommended for urethral samples in women. Microscopy is not generally recommended for diagnosing rectal or pharyngeal infection.
Culture allows identification of N gonorrhoeae and antimicrobial susceptibility testing, which is important as antibiotic resistance increases. It is a relatively inexpensive, specific, and sensitive test at genital sites in both men and women. In women, culture ideally requires endocervical and urethral swabs for maximum sensitivity. However, this may not always be possible in primary care. Culture is the only widely validated diagnostic test for rectal and pharyngeal infection.
Nucleic acid amplification testing (NAAT) offers high sensitivity (greater than 96%) in both symptomatic and asymptomatic infection.
In men, first pass urine and urethral swabs show similar sensitivity for detecting N gonorrhoeae.
In women, vaginal and endocervical swabs show similar sensitivity for detecting N gonorrhoeae. The sensitivity for a urine specimen is lower in women, and NAAT testing of urine in women is therefore not recommended.
Possible sexual abuse
When should I suspect sexual abuse?
Consider the possibility of sexual abuse in any child or young person with gonorrhoea, particularly in the following circumstances:
The child is younger than 13 years of age, unless there is clear evidence of mother-to-child transmission during birth, or of blood contamination.
The young person is 13 to 15 years of age, unless there is clear evidence of mother-to-child transmission during birth, blood contamination, or that the sexually transmitted infection (STI) was acquired from consensual sexual activity with a peer.
The young person is 16 to 17 years of age and there is no clear evidence of blood contamination or that the STI was acquired from consensual sexual activity, and there is a clear difference in power or mental capacity between the young person and their sexual partner, in particular when the relationship is incestuous or with a person in a position of trust (such as a teacher, sports coach, minister of religion) or there is concern that the young person is being exploited.
Follow appropriate child protection procedures and refer to a paediatrician if necessary.
Basis for recommendation
Basis for recommendation
These recommendations are based on the National Institute for Health and Clinical Excellence (NICE) guideline When to suspect child maltreatment [NICE, 2009].
Differential diagnosis
What else might it be?
Men
Other causes of penile discharge include:
Non-gonococcal urethritis caused by Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma genitalium, or Trichomonas vaginalis (see the CKS topic on Urethritis - male).
Physiological discharge (small amounts of clear or mucoid discharge upon sexual excitement).
Subpreputial infection (for example candidiasis).
Acute prostatitis — may present with: blood-tinged urethral discharge; dysuria, frequency, and urgency; fever; or penile, perineal, and rectal pain. The prostate is swollen and tender.
Herpes simplex virus infection — can present with herpetic lesions on the urethral meatus.
Women
Chlamydia. It is not possible to distinguish gonorrhoeal infection from chlamydia in women by clinical features alone, and the infections coexist in about a third of women.
See the CKS topic on Chlamydia - uncomplicated genital for further information.
Other causes of vaginal discharge.
See the CKS topics on Vaginal discharge, Candida - female genital, Bacterial vaginosis, Trichomoniasis, and Pelvic inflammatory disease.
Basis for recommendation
Basis for recommendation
Information on differential diagnoses is based on expert opinion in a review article [Adler, 2004] and on the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) [HPA, 2011].
Management
Management
Scenario: Management: covers the management of people with suspected or confirmed gonorrhoea infection.
Scenario: Management
Scenario: Management of gonorrhoea
Management in primary care
How should I manage a person with gonorrhoea in primary care?
Ideally, refer all people with confirmed or suspected gonorrhoea to a genito-urinary medicine (GUM) clinic or other local specialist sexual health service.
If these services cannot be accessed within a reasonable time, or if the person is unwilling to attend despite receiving appropriate information and advice:
Treat for gonorrhoea:
Following a positive identification of Neisseria gonorrhoeae by microscopy, culture, or nucleic acid amplification testing (NAAT) (see Diagnosis).
If a diagnosis of gonorrhoea is suspected from symptoms and examination (see Diagnosis) — treat empirically whilst waiting for laboratory confirmation.
If the person is a recent sexual partner(s) of someone with confirmed gonococcal infection.
If possible, take swabs for culture before giving antibiotics if gonorrhoea was diagnosed by NAAT. This will enable sensitivity testing and identification of resistant strains.
Offer screening for other sexually transmitted infections (STIs) and for HIV.
Encourage patient-led partner notification.
Partners should be screened for STIs and treated empirically for gonorrhoea whilst awaiting results.
Advise the person to abstain from sex until they and any partners have completed treatment; if azithromycin is used, this will be 7 days after treatment is given.
Follow-up after 1 week to verify the success of treatment.
Test of cure is recommended for all people who have been treated for gonorrhoea.
Advise the person to practice safe sex in the future.
Basis for recommendation
Basis for recommendation
These recommendations are based on the British Association for Sexual Health and HIV UK National Guideline for the Management of Gonorrhoea in Adults [BASHH, 2011b].
Admission and referral
When should I refer or admit a person with gonorrhoea?
Ideally, refer all people with suspected or confirmed gonorrhoea to a genito-urinary medicine (GUM) clinic or other local specialist sexual health service.
Referral is particularly important in:
Men who have complications caused by gonorrhoea (such as epididymitis or prostatitis).
Women who are pregnant.
Women with suspected ascending infection (see the CKS topic on Pelvic inflammatory disease).
Admit:
People with suspected disseminated gonorrhoea (systemic symptoms may be present, such as fever, malaise, joint pain and swelling, and rash).
Women with pelvic inflammatory disease if it is severe or there are complications.
Basis for recommendation
Basis for recommendation
Referral
Genito-urinary medicine clinics and other specialist sexual health services have the resources to ensure effective diagnosis and treatment of gonorrhoea, as well as screening for other sexually transmitted infections (including HIV), counselling, follow up, and contact tracing (partner notification).
Men who are suspected of having complications caused by gonorrhoea require specialist management (for example extended courses of antibiotics) [Bignell, 2009; Marrazzo et al, 2010].
Gonorrhoea in pregnancy is associated with spontaneous abortion, premature labour, early rupture of fetal membranes, perinatal mortality, and gonococcal conjunctivitis in the newborn [Marrazzo et al, 2010].
Admission
Admission is required for disseminated gonorrhoea because it can develop into life-threatening infection (for example gonococcal meningitis). Treatment in secondary care will typically involve higher doses of an intramuscular or intravenous cephalosporin for up to a week [Bignell, 2009].
The recommendation to admit a woman with pelvic inflammatory disease that is severe or has complications is based on expert opinion in guidelines from the Royal College of Obstetricians and Gynaecologists and the British Association for Sexual Health and HIV [RCOG, 2009; BASHH, 2011a].
Sexually transmitted infection and HIV screening
Screening for other sexually transmitted infections is in line with guidelines from BASHH and the Health Protection Agency [RCGP and BASHH, 2006; HPA, 2008; BASHH, 2011b].
Treatment
How should I treat a person with gonorrhoea in primary care?
Treat gonorrhoea in primary care only if specialist services cannot be accessed within a reasonable time, or if the person is unwilling to attend despite receiving appropriate information and advice.
Treatment is indicated following a positive identification of Neisseria gonorrhoeae by microscopy, culture, or nucleic acid amplification testing (NAAT) (see Diagnosis).
Empirical treatment is indicated for:
People with suspected gonorrhoea, whilst waiting for laboratory confirmation of the diagnosis.
Recent sexual partner(s) of people with confirmed gonococcal infection.
For confirmed or suspected uncomplicated anogenital gonorrhoea, prescribe:
Ceftriaxone 500 mg intramuscular (IM) injection as a single dose, plus azithromycin 1 g orally as a single dose.
If an IM injection is contraindicated or refused, offer cefixime 400 mg orally as a single dose, plus azithromycin 1 g orally as a single dose.
If cephalosporins are contraindicated (for example the person has a true allergy to penicillin-type antibiotics), consider a fluoroquinolone (ciprofloxacin 500 mg, single oral dose or ofloxacin 400 mg, single oral dose) plus azithromycin 1 g, single oral dose.
Only prescribe a fluoroquinolone if the infection is known to be sensitive to fluoroquinolones (that is, culture and sensitivity results are available for the person or recent sexual partners).
If these regimens are unsuitable or unavailable, contact the local microbiology or genito-urinary medicine clinic for advice.
For confirmed pharyngeal gonorrhoea, prescribe:
Ceftriaxone 500 mg intramuscular (IM) injection as a single dose, plus azithromycin 1 g orally as a single dose.
If an IM injection is contraindicated or refused, offer oral cefixime (400 mg loading dose, followed by 200 mg twice a day for 3 days) plus azithromycin 1 g orally as a single dose.
Note this regimen is off-label and is recommended on the basis of expert opinion rather than trial-based evidence.
If cephalosporins are contraindicated (for example the person has a true allergy to penicillin-type antibiotics), consider a fluoroquinolone (ciprofloxacin 500 mg, single oral dose or ofloxacin 400 mg, single oral dose).
Only prescribe a fluoroquinolone if the infection is known to be sensitive to fluoroquinolones (that is, culture and sensitivity results are available for the person or recent sexual partners).
Basis for recommendation
Basis for recommendation
Treatment recommendations are based on the National guideline on the diagnosis and treatment of gonorrhoea in adults, published by the British Association for Sexual Health and HIV (BASHH) [BASHH, 2011b].
Treatment with antibiotics
Good evidence from several comparative randomized controlled trials (RCTs) supports the use of antibiotics in the treatment of gonorrhoea. Historically, cephalosporins, fluoroquinolones, and macrolides have produced microbiological cure rates in excess of 95% in these trials [Moran and Levine, 1995].
Choice of antibiotics
Since the introduction of sulphonamides in the 1930s, there has been growing evidence of gonococcal resistance to many classes of antibiotics [Workowski et al, 2008]. Therefore, antibiotic recommendations are mainly based on current gonococcal sensitivity to antibiotics, rather than historical evidence of their efficacy from RCTs [Tyson, 2005].
Surveillance data in England and Wales show significant levels of N. gonorrhoeae resistance to penicillin (20% in 2010), tetracyclines (69% in 2010), and ciprofloxacin (36% in 2010) [HPA, 2011].
Cephalosporins are recommended first line because N. gonorrhoeae is largely sensitive to this drug class, although resistance to cefixime is increasing [HPA, 2011]. Ceftriaxone and cefixime are third-generation cephalosporins that have shown evidence of a cure rate greater than 95% in RCTs (the accepted level of effectiveness) [Moran and Levine, 1995].
Confirmed therapeutic failure to cefixime is rare, and is undocumented for ceftriaxone in England and Wales.
In 2010, no isolates were reported as having decreased susceptibility to ceftriaxone, although a trend of increasing MIC drift has been observed [HPA, 2011]. Concerns about increasing resistance to cephalosporins have led to an increase in the recommended dose of ceftriaxone to 500 mg. Ceftriaxone is less convenient than cefixime but was shown to give a 100% cure rate in one trial of people with uncomplicated infection [Zajdowicz et al, 1983], and in one trial which included people with pharyngeal infection [Christophersen et al, 1989].
In 2009, 1.2% of gonococcal isolates demonstrated reduced susceptibility to cefixime at a MIC of 0.25 mg/L or more; in 2010 this rose to 6.3% [HPA, 2011]. In 2011, three cases of failure with cefixime treatment were reported [BASHH, 2011b]. The use of cefixime for the treatment of gonorrhoea is off-label [ABPI Medicines Compendium, 2010b], but one RCT showed it to be effective at a single oral dose of 400 mg (cure rate 96%, 95% CI 94 to 98) [Handsfield, 1991]. Because treatment failure has been reported with cefixime it should only be used if an intramuscular injection is contraindicated or refused.
Alternative injectable or oral cephalosporins offer no advantage over ceftriaxone or cefixime.
Azithromycin (1 g) is recommended by BASHH as add-on therapy for uncomplicated anogenital infection to delay the onset of widespread resistance to cephalosporins [BASHH, 2011b]. Improved eradication of pharyngeal gonorrhoea has been reported with the addition of azithromycin to a cephalosporin.
Ciprofloxacin and ofloxacin are fluoroquinolones that are recommended if cephalosporins are contraindicated, most commonly because of documented beta-lactam allergy (allergy to penicillins, cephalosporins, and associated antibiotics). Between 1% and 10% of people with penicillin allergy are thought to have cross-sensitivity to cephalosporins [Workowski et al, 2008].
Good evidence from RCTs indicates that fluoroquinolones have been effective in the treatment of gonorrhoea [Bignell, 1996]. However, evidence from surveillance data indicates that there is endemic resistance of gonorrhoeal isolates to ciprofloxacin, with a prevalence of around 36% [HPA, 2011]. Therefore, it is important that the sensitivity of the infection is known before treatment with a fluoroquinolone is prescribed.
High-dose azithromycin (2 g as a single dose) was shown to be effective at eradicating N. gonorrhoeae in one open-label randomized controlled trial (98.9% eradication rate). However, it was associated with a high level of gastrointestinal irritation [Handsfield et al, 1994]. A high level of resistance to azithromycin has been observed in the UK [Chisholm et al, 2009]. Because there is no apparent rationale for prescribing high-dose azithromycin in preference to a cephalosporin or a fluoroquinolone, CKS does not recommend this regimen in primary care.
BASHH also recommends intramuscular spectinomycin (2 g as a single dose) plus azithromycin as an alternative regimen. However, CKS does not recommend this regimen for use in primary care because spectinomycin is not currently being manufactured in the UK and may be difficult to obtain.
Pharyngeal gonorrhoea
In general, single-dose antimicrobials have demonstrated lower efficacy in pharyngeal infection than in anogenital infection. Failure has been reported with ceftriaxone.
For treatment of pharyngeal gonorrhoea, BASHH recommends ceftriaxone plus azithromycin first line [BASHH, 2011b]. However, because ceftriaxone may not be readily available in primary care, some experts recommend an alternative 3-day regimen of cefixime (plus azithromycin) on the basis of pharmacokinetic principles [Horner, Personal Communication, 2009]. This is reasonable, as a test of cure is always recommended for pharyngeal gonorrhoea (see Follow-up).
Because of widespread quinolone resistance, treatment with ciprofloxacin or ofloxacin is only recommended if N. gonorrhoeae is known to be quinolone sensitive. In this case supplementary azithromycin is not necessary, unless additional antibiotics are needed to cover for Chlamydia trachomatis.
Empirical treatment
As it is not possible to accurately differentiate between infection with N. gonorrhoeae and Chlamydia trachomatis by clinical features alone, and the infections often coexist, empirical treatment aims to cover both organisms [RCGP and BASHH, 2006].
As the recommended regimens for empirical treatment now include azithromycin 1 g, which will also treat C. trachomatis, further additional empirical treatment for chlamydia is no longer necessary.
For more information, see the CKS topic on Chlamydia - uncomplicated genital.
Pregnancy and breastfeeding
What treatment should I prescribe for a pregnant or breastfeeding woman with gonorrhoea in primary care?
For confirmed or suspected uncomplicated gonorrhoea, prescribe:
Ceftriaxone 500 mg intramuscular (IM) injection as a single dose, plus azithromycin 1 g orally as a single dose.
If IM ceftriaxone is unavailable or unsuitable, offer cefixime 400 mg as a single oral dose plus azithromycin.
Do not prescribe a fluoroquinolone for a woman who is pregnant or breastfeeding. Seek specialist advice if a cephalosporin is contraindicated, for example if the woman has a true allergy to penicillin.
Basis for recommendation
Basis for recommendation
Treatment recommendations for women who are pregnant or breastfeeding are based on the National guideline on the diagnosis and treatment of gonorrhoea in adults, published by the British Association for Sexual Health and HIV (BASHH) [BASHH, 2011b].
Treatment with antibiotics
Good evidence from several comparative randomized controlled trials (RCTs) supports the use of antibiotics in the treatment of gonorrhoea. Historically, cephalosporins, fluoroquinolones, and macrolides have produced microbiological cure rates in excess of 95% in these trials [Moran and Levine, 1995].
Choice of antibiotics
Since the introduction of sulphonamides in the 1930s, there has been growing evidence of gonococcal resistance to many classes of antibiotics [Workowski et al, 2008]. Therefore, antibiotic recommendations are mainly based on current gonococcal sensitivity to antibiotics, rather than historical evidence of their efficacy from RCTs [Tyson, 2005].
Surveillance data in England and Wales shows significant levels of N. gonorrhoeae resistance to penicillin (20% in 2010), tetracyclines (69% in 2010), and ciprofloxacin (36% in 2010) [HPA, 2011].
Cephalosporins are recommended first line because N. gonorrhoeae is largely sensitive to this drug class, although resistance to cefixime is increasing [HPA, 2011]. There is evidence from a meta-analysis of two comparative randomized controlled trials that cefixime and ceftriaxone are effective in the treatment of confirmed gonorrhoea in pregnant women [Brocklehurst, 2002].
Confirmed therapeutic failure to cefixime is rare, and is undocumented for ceftriaxone in England and Wales.
In 2010, no isolates were reported as having decreased susceptibility to ceftriaxone, although a trend of increasing MIC drift has been observed [HPA, 2011]. Concerns about increasing resistance to cephalosporins have led to an increase in the recommended dose of ceftriaxone to 500 mg. Ceftriaxone is less convenient than cefixime but was shown to give a 100% cure rate in one trial of people with uncomplicated infection [Zajdowicz et al, 1983], and in one trial which included people with pharyngeal infection [Christophersen et al, 1989].
In 2009, 1.2% of gonococcal isolates demonstrated reduced susceptibility to cefixime at a MIC of 0.25 mg/L or more; in 2010 this rose to 6.3% [HPA, 2011]. In 2011, three cases of failure with cefixime treatment were reported [BASHH, 2011b]. The use of cefixime for the treatment of gonorrhoea is off-label [ABPI Medicines Compendium, 2010b], but one RCT showed it to be effective at a single oral dose of 400 mg (cure rate 96%, 95% CI 94 to 98) [Handsfield, 1991]. Because treatment failure has been reported with cefixime it should only be used if an intramuscular injection is contraindicated or refused.
Alternative injectable or oral cephalosporins offer no advantage over ceftriaxone or cefixime.
Azithromycin (1 g) is recommended by BASHH as add-on therapy for uncomplicated anogenital infection to delay the onset of widespread resistance of cephalosporins [BASHH, 2011b]. Improved eradication of pharyngeal gonorrhoea has been reported with the addition of azithromycin to a cephalosporin.
BASHH also recommends intramuscular spectinomycin (2 g as a single dose) plus azithromycin as an alternative regimen for women who are pregnant or breastfeeding. However, CKS does not recommend this regimen for use in primary care because spectinomycin is not currently being manufactured in the UK and may be difficult to obtain.
Safety of antibiotics in pregnancy
The benefits of antibiotics for gonorrhoea outweigh the risks in pregnancy.
Left untreated, gonorrhoea in pregnancy is associated with spontaneous abortion, premature labour, early rupture of fetal membranes, perinatal mortality, and gonococcal conjunctivitis in the newborn [Marrazzo et al, 2010].
Cefixime and ceftriaxone are not specifically licensed in pregnancy but 'are not known to be harmful' [BNF 61, 2011]. Although cephalosporins cross the placenta, there is no evidence from animal studies to indicate that they are toxic to the embryo or the fetus, and no harms have been shown in observational studies of pregnant women who have been exposed to cephalosporins [Schaefer et al, 2007; NTIS, 2008d].
Macrolides are considered to be suitable treatment options in pregnancy where indicated [NTIS, 2008c].
Erythromycin is generally preferred because there is more experience with it than with other macrolides [NTIS, 2008b]. However, it is probably not as effective as azithromycin in the treatment of chlamydia [Brocklehurst and Rooney, 1998].
Animal studies and limited observational data have not indicated an increased risk of congenital malformations with the use of azithromycin in pregnancy [NTIS, 2008a]. The manufacturer advises that azithromycin tablets should only be used in pregnancy if definitely indicated, and that breastfeeding should be discontinued during treatment with azithromycin and for 2 days after stopping treatment (breast milk should be discarded during this period) [ABPI Medicines Compendium, 2011].
Fluoroquinolones are not recommended in pregnancy or breastfeeding except 'for the treatment of serious or life-threatening conditions unresponsive to standard antibiotic therapy', because there is a theoretical risk of arthropathy in the child [Schaefer et al, 2007; NTIS, 2008c].
Information and advice
What information and advice should I give someone with gonorrhoea?
Advise the person to attend a genito-urinary medicine clinic or other local specialist sexual health service if possible.
Inform the person that these services have the resources to ensure effective management and partner notification, and that they are confidential and non-judgemental.
Discuss the long-term implications if gonorrhoea is left untreated for the health of the person and their partners.
Reinforce this information with clear and accurate written material where available (see the patient information from the Family Planning Association on Gonorrhoea (fpa)).
Advise the person to abstain from sex until they and any partners have completed treatment; if azithromycin is used, this will be 7 days after treatment is given.
Advise the person regarding safe sexual practice in the future.
Basis for recommendation
Basis for recommendation
Recommendations for providing information and advice are based on expert opinion from the National guideline on the diagnosis and treatment of gonorrhoea in adults, published by the British Association for Sexual Health and HIV [BASHH, 2011b].
Partner notification
When and how should sexual partners be notified?
Partner notification is essential for all people with newly diagnosed gonorrhoea. Ideally this should be done by a trained health adviser in genito-urinary medicine (GUM).
For people with symptomatic anogenital gonorrhoea, all partners within the preceding 2 weeks should be notified, or their most recent partner, if this was longer than 2 weeks ago.
For people with asymptomatic gonorrhoea, or gonorrhoea at other sites, all partners within the preceding 3 months should be notified.
Three methods of partner notification are used. For each method, the healthcare professional should document all actions and outcomes.
Patient referral: the person with gonorrhoea is encouraged to notify their past and present partners. This is the usual method used in primary care and the only practical option if provider referral is not available.
Provider referral: the healthcare professional notifies the person's partners on their behalf. This option is recommended, but is often not available in primary care. Ideally, provider referral should be facilitated by a trained health adviser in a GUM clinic (see Admission and referral). If referral to a GUM clinic is not possible, a primary healthcare professional who has undergone appropriate training and has support from healthcare advisers in GUM is the next best option.
Contract referral: the person with gonorrhoea is encouraged to notify their partners, with the understanding that a healthcare professional will later notify those partners who do not visit the health service within an allotted time. This option is not usually suitable in a primary care setting.
Notified partners should be screened for sexually transmitted infections (prior to giving antibiotics if possible) and treated empirically whilst waiting for results.
Basis for recommendation
Basis for recommendation
Recommendations for partner notification are based on expert opinion from the National guideline on the diagnosis and treatment of gonorrhoea in adults, published by the British Association for Sexual Health and HIV [BASHH, 2011b].
Partner notification in primary care
There is expert consensus that if referral to a GUM clinic (or to a general practice providing an enhanced sexual health service) is not possible, contact tracing should be undertaken in primary care, and this should be documented [Fitzgerald et al, 1996].
Period of partner notification
The recommended periods for notification are consistent with what is known about the natural course of symptomatic infection with gonorrhoea [Marrazzo et al, 2010]. However, there is less certainty about the natural course of asymptomatic infection or infection at sites other than the genitals and rectum, and a period of 3 months is therefore advised as a precautionary measure [BASHH, 2011b].
Method of partner notification
A Cochrane systematic review (search date: around 2001) found evidence that both provider and contract referral methods result in more partners presenting for medical evaluation compared with patient referral [Mathews et al, 2001]. However, in practice, provider referral can be difficult to organize, and most GUM clinics in the UK use patient referral as the contact method of first choice [Stokes and Schober, 1999].
Follow-up
How should I follow up someone with gonorrhoea?
Follow up all people with gonorrhoea about 1 week after treatment.
Confirm that the person has adhered to treatment and symptoms have resolved.
Confirm that partner notification has been carried out (if patient or contract referral was used).
Ask about recent sexual history (and the possibility of re-infection), and reinforce advice about safe sexual practice.
A test of cure (TOC) is recommended for all people who have been treated for gonorrhoea.
If signs or symptoms persist, test with culture, performed at least 3 days after completion of treatment.
If the person is asymptomatic, test with nucleic acid amplification testing (NAAT) where available (followed by culture if positive), at least 2 weeks after completion of treatment.
If it is not possible or practical to perform a test of cure in all people treated for gonorrhoea, the following groups of people should be prioritized for a TOC:
People with persistent signs or symptoms.
People with pharyngeal infection.
People who have been treated with anything other than the first-line recommendation.
Basis for recommendation
Basis for recommendation
Recommendations on follow up are based on the National guideline on the diagnosis and treatment of gonorrhoea in adults, published by the British Association for Sexual Health and HIV [BASHH, 2011b].
A test of cure (TOC) is now recommended in all people treated for gonorrhoea to identify patterns of emerging resistance.
The recommendations for the method and timing of TOC are based on expert opinion and pragmatic considerations.
Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC) (http://medicines.org.uk/emc), or the British National Formulary (BNF) (www.bnf.org).
Cephalosporins (ceftriaxone or cefixime)
What issues should I consider before prescribing a cephalosporin?
Intramuscular (IM) ceftriaxone is the cephalosporin of choice for treating gonorrhoea. If an IM injection is contraindicated or refused, oral cefixime is recommended. Both ceftriaxone and cefixime are third generation cephalosporins.
Contraindications and precautions
Cephalosporins should not be taken by people who have a true penicillin allergy. Note that gastrointestinal adverse effects alone (e.g. nausea, vomiting, or diarrhoea) do not constitute an allergy to penicillin.
Adverse effects
Gastrointestinal effects such as diarrhoea, nausea and vomiting are common with cephalosporins.
Rarely, cephalosporins can cause antibiotic-associated colitis — consider the possibility of this in anyone who presents with diarrhoea after treatment with ceftriaxone or cefixime.
Drug interactions
Oral hormonal contraception — additional contraceptive precautions are not required during or after a course of ceftriaxone or cefixime.
However, women should be advised about the importance of correct contraceptive practice if they experience vomiting or diarrhoea. For further information, see the section on Antibiotics in the CKS topic on Contraception - assessment.
Basis for recommendation
Contraindications and precautions
Between 0.5% and 6.5% of people with a true penicillin allergy will also be allergic to cephalosporins [BNF 61, 2011]. Although this cross-sensitivity is thought to be negligible with third generation cephalosporins, it is recommended that all people with a history of true penicillin allergy should avoid taking any cephalosporin [ABPI Medicines Compendium, 2009b; BASHH, 2011b; BNF 61, 2011].
Adverse effects
Gastrointestinal effects including diarrhoea, nausea, and vomiting are reported to occur in 1–10% of people taking ceftriaxone [ABPI Medicines Compendium, 2009b]. Pseudomembranous colitis (caused by infection with Clostridium difficile) is reported to be very rare (less than 0.01%), however, the manufacturers recommend that this should be considered in people who develop diarrhoea after a course of ceftriaxone or cefixime [ABPI Medicines Compendium, 2009b; ABPI Medicines Compendium, 2010b].
Drug interactions
Although the UKMEC criteria advise additional precautions with antibiotics that do not induce enzymes [FSRH, 2009], this was an interim measure until the evidence could be reviewed in detail by the FSRH clinical effectiveness unit.
Having reviewed the available evidence, the FSRH no longer advises that additional precautions are required to maintain contraceptive efficacy when using antibiotics that are not enzyme inducers with combined hormonal methods for durations of 3 weeks or less, unless the antibiotics (or the illness) cause vomiting or diarrhoea.
Azithromycin
What issues should I consider before prescribing azithromycin?
Cautions and precautions
Use azithromycin with caution in people who may be predisposed to prolongation of the QT interval. This includes people:
With congenital or documented acquired QT prolongation.
Currently receiving treatment with other active substances known to prolong the QT interval such as antiarrhythmics of classes IA and III.
With electrolyte disturbance, particularly in cases of hypokalaemia and hypomagnesaemia.
With clinically relevant bradycardia, cardiac arrhythmia, or severe cardiac insufficiency.
Adverse effects
Nausea, vomiting, diarrhoea, and abdominal discomfort are the most common adverse effects of all the macrolides, but are milder and less frequent with azithromycin than with erythromycin.
Drug interactions
Warfarin — rarely, azithromycin can produce a marked increase in the anticoagulant effects of warfarin.
Advise people taking warfarin to seek immediate medical advice if they experience spontaneous bleeding, and the bleeding does not stop or recurs. This includes bruising, bleeding gums, nosebleeds, prolonged bleeding from cuts, and blood in the urine or stools.
Basis for recommendation
Cautions and precautions
Prolonged QT interval or cardiac repolarization have been reported with other macrolides and a similar effect with azithromycin has not been ruled out [ABPI Medicines Compendium, 2011].
Adverse effects
Information regarding the nature and frequency of adverse effects is taken from the British National formulary [BNF 61, 2011].
Drug interactions
Macrolides are generally considered to be inhibitors of the enzyme CYP3A4, however they vary in the strength of their effect and azithromycin only inhibits CYP3A4 to a small, usually clinically insignificant degree [Baxter, 2010].
A marked increase in the effects of warfarin has been noted in a small number of people concomitantly taking azithromycin. Although a causal mechanism has not been established, the manufacturer recommends that prescribers give consideration to the frequency of INR monitoring for people who are already taking warfarin [ABPI Medicines Compendium, 2011]. However, it is unclear how this might be affected by single-dose azithromycin.
Quinolones (ciprofloxacin or ofloxacin)
What issues should I consider before prescribing a quinolone?
Ciprofloxacin or ofloxacin are the quinolones of choice for treating gonorrhoea. However, a quinolone should only be prescribed when an infection is known to be quinolone sensitive before treatment is started.
Contraindications and precautions
Avoid quinolones in:
Children and adolescents younger than 18 years old.
People with epilepsy or conditions that predispose to seizures, and in people taking other medication that may predispose to seizures.
People with a history of tendonitis.
Adverse effects
Musculoskeletal pain is occasionally experienced by people taking quinolones (0.1–1.0%); tendinitis is a very rare adverse effect (less than 0.01%).
Advise the person that if they experience pain or inflammation of a tendon they should urgently consult a healthcare professional.
If tendonitis is suspected (if pain or inflammation of a tendon occurs), treatment should be stopped.
Rarely, quinolones can cause antibiotic-associated colitis — consider the possibility of this in anyone who presents with diarrhoea after treatment with ciprofloxacin or ofloxacin.
Drug interactions
Theophylline — concurrent administration of ciprofloxacin can cause an increase in serum theophylline levels; advise the person to be aware of the signs of increased levels of theophylline, such as nausea, vomiting, tremor, and palpitations.
Phenytoin — concurrent administration of ciprofloxacin can cause an increase or decrease in serum phenytoin levels.
Warfarin — increased anticoagulation has occasionally been reported with concurrent administration of quinolones.
Advise people taking warfarin to seek immediate medical advice if they experience spontaneous bleeding, and the bleeding does not stop or recurs. This includes bruising, bleeding gums, nosebleeds, prolonged bleeding from cuts, and blood in the urine or stools.
Basis for recommendation
Contraindications and precautions
The manufacturers of ciprofloxacin (Ciproxin®) and ofloxacin (Taravid®) state that fluoroquinolones should be avoided in people with tendinitis or epilepsy [ABPI Medicines Compendium, 2009a; ABPI Medicines Compendium, 2010a]. However, the adverse effects of fluoroquinolones are not likely to be significant, as they are given as a single dose for the treatment of gonorrhoea.
Quinolones can lower the seizure threshold and should therefore be avoided in people at increased risk of seizure. Seizures have rarely occurred in people without a previous history of seizures; concurrent use of nonsteroidal anti-inflammatory drugs or theophylline may also increase the risk [CSM, 1991].
Quinolones can very rarely cause tendon damage; the risk of tendon rupture is increased by co-administration of corticosteroids [CSM, 2002].
Adverse effects
Gastrointestinal effects including diarrhoea and nausea are reported to occur in 1–10% of people taking ciprofloxacin [ABPI Medicines Compendium, 2010a], and are slightly less common with ofloxacin [ABPI Medicines Compendium, 2009a]. Pseudomembranous colitis (caused by infection with Clostridium difficile) is reported to be very rare (less than 0.01%), however, the manufacturers recommend that this should be considered in people who develop diarrhoea after a course of ciprofloxacin or ofloxacin [ABPI Medicines Compendium, 2009a; ABPI Medicines Compendium, 2010a].
Interactions
Information on drug interactions is taken from the Summary of Characteristics for ciprofloxacin (Ciproxin®) and ofloxacin (Taravid®) [ABPI Medicines Compendium, 2009a; ABPI Medicines Compendium, 2010a] and from the reference text Stockley's Drug Interactions [Baxter, 2010].
Evidence
Evidence
Supporting evidence
Antibiotics in men and non-pregnant women
Evidence on effectiveness of antibiotics for gonorrhoea in men and women who are not pregnant
Randomized controlled trials (RCTs) have found single-dose antibiotics to be effective in the treatment of uncomplicated genital gonorrhoea, although they are less effective in the treatment of pharyngeal gonorrhoea. Cephalosporins, fluoroquinolones, and macrolides have historically all produced microbiological cure rates in excess of 95%, but recent issues with bacterial resistance have meant that third-generation cephalosporins (cefixime or ceftriaxone) are recommended first line.
Overall effectiveness of antibiotics
A systematic review (search date: 1981 to 1993) investigated the effectiveness of single-dose antibiotics in men and women with confirmed gonorrhoea infection [Moran and Levine, 1995]. In total, 24,383 trial participants receiving 30 different antibiotic regimens (21 antibiotic drugs) were analysed. The main outcome reported was microbiological cure.
Most of the antibiotics were highly effective, with an overall cure rate of 96.7%.
Antibiotics that were effective included cephalosporins, fluoroquinolones, and macrolides (penicillin drugs were not studied, or these trials predated the literature search).
Antibiotics were at least 95% effective for the treatment of gonorrhoea of the male and female urethra, male and female rectum, and cervix. For example, the cure rate for male urethritis was 96.4% (95% CI 96.0 to 96.7).
Antibiotics were less effective in the treatment of pharyngeal gonorrhoea, with a 79.2% cure rate in men (95% CI 73.3 to 85.2) and 83.6% in women (95% CI 78.9 to 88.4).
The investigators found a good correlation between the cure rate and the minimum inhibitory concentration required to inhibit the growth of 90% of organisms (MIC90, calculated from studies in vitro). The authors commented that, ideally, a drug should achieve a plasma concentration of four times its MIC90 for a minimum of 10 hours to be considered fully effective.
The authors concluded that ceftriaxone, cefixime, ciprofloxacin, or ofloxacin was the preferred treatment for people with uncomplicated gonorrhoea. Fluoroquinolones are no longer suitable for empirical treatment because of problems with resistance. See Resistance to antibiotics for more information.
Effectiveness of ceftriaxone and cefixime
CKS identified three comparative RCTs that investigated the effectiveness of intramuscular ceftriaxone and oral cefixime (third-generation cephalosporin antibiotics recommended by UK national guidelines [BASHH, 2011b]).
One study randomized 128 men with confirmed gonococcal urethritis to receive either ceftriaxone 250 mg or cefoxitin 2 g (both delivered intramuscularly) [Zajdowicz et al, 1983]. Both drugs were highly effective at curing the infection, with ceftriaxone having a 100% success rate and cefoxitin having a 99% success rate (one person with penicillin-resistant gonorrhoea relapsed).
One study in 393 people with uncomplicated and/or pharyngeal gonorrhoea randomized them to receive a single 250 mg dose of ceftriaxone or pivampicillin (1.2 grams with probenecid, unavailable in the UK) [Christophersen et al, 1989]. Ceftriaxone was found to have a 100% cure rate for both sites of infection (70 people had pharyngeal infection).
One study randomized 209 men and 124 women with uncomplicated gonorrhoea to receive one of three interventions: oral cefixime 400 mg or 800 mg, or intramuscular ceftriaxone 250 mg [Handsfield, 1991].
The overall microbiological cure rates were similar in men and women: 96% (95% CI 94 to 98) for cefixime 400 mg, 98% (95% CI 95 to 100) for cefixime 800 mg, and 98% (95% CI 95 to 100) for ceftriaxone.
However, only 91% of people presenting with pharyngeal gonorrhoea were successfully treated, and about 50% of people who presented with coexisting chlamydia had persistent chlamydial infection.
Antibiotics in pregnant women
Evidence on effectiveness of antibiotics for gonorrhoea in pregnant women
Evidence from two comparative randomized controlled trials (RCTs) indicates that amoxicillin (combined with probenecid), ceftriaxone, and cefixime are effective in the treatment of gonorrhoea in pregnant women. However, amoxicillin is no longer recommended for empirical treatment because of the emergence of gonococcal resistance to penicillins.
A Cochrane systematic review (search date: January 2007) identified two comparative RCTs with 346 participants that investigated the effectiveness of antibiotics in pregnant women with microbiologically confirmed gonorrhoea [Brocklehurst, 2002].
All the antibiotics were considered effective, with microbiological cure rates between 89% and 97%. Failure to achieve microbiological cure was similar for each regimen.
Amoxicillin (plus probenecid) compared with spectinomycin — favoured spectinomycin, but this was not significant (odds ratio [OR] of treatment failure 2.29, 95% CI 0.74 to 7.08).
Amoxicillin (plus probenecid) compared with ceftriaxone — favoured ceftriaxone, but this was not significant (OR 2.29, 95% CI 0.74 to 7.08).
Ceftriaxone was of similar effectiveness to cefixime (OR 1.22, 95% CI 0.16 to 9.01).
The author commented that the small number of participants limited their ability to detect modest but important differences between the regimens.
Amoxicillin is no longer recommended for the empirical treatment of gonorrhoea because of the emergence of bacterial resistance (see Resistance to antibiotics for more information).
Resistance to antibiotics
Evidence on gonococcal resistance to antibiotics
Historical evidence has shown that the organism that causes gonorrhoea has become increasingly resistant to antibiotics, including sulphonylureas, penicillins, tetracyclines, macrolides, and quinolones. Currently, cephalosporins are the only commonly prescribed drug class that does not have significant resistance issues, although some evidence indicates that resistance is emerging.
Gonorrhoea is caused by the Gram-negative diplococcus bacterium Neisseria gonorrhoeae, which is capable of chromosomal and plasmid-mediated genetic change through selection pressure. Consequently, gonorrhoea has become increasingly resistant to modern antibiotics.
Gonorrhoea was first treated successfully with the discovery of sulphonamides in the 1930s, but their efficacy was short-lived because of the development of resistance in the mid-1940s [Workowski et al, 2008].
Penicillin was introduced in the 1940s and remained an effective treatment for gonorrhoea for several decades. However, resistance became increasingly prevalent in the 1980s, and its use as a first-line antibiotic was no longer recommended by the 1990s [Tyson, 2005]. Resistance to tetracyclines also precluded these as an effective option by this time [Bignell et al, 2006].
The fluoroquinolone ciprofloxacin was first patented in 1983, and initially the fluoroquinolones were a highly effective treatment for gonorrhoea. However, case reports of resistance rapidly emerged from the Far East and Pacific regions, and by the mid-2000s, fluoroquinolones were no longer regarded as a suitable option for the empirical treatment of gonorrhoea [CDC, 2007].
The Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) was established in June 2000 with the remit of monitoring gonococcal resistance to antibiotics in the UK. In 2010 GRASP collected 1425 isolates and performed antimicrobial susceptibility testing on those which proved positive to N. gonorrhoeae. The following is a summary of their findings [HPA, 2011]:
Penicillin resistance in genito-urinary medicine (GUM) clinics remained relatively stable at 20%.
Tetracycline resistance in GUM clinics remained relatively stable at 69%.
Ciprofloxacin resistance remained endemic in GUM clinics at 36%.
Azithromycin resistance decreased from 1.2% in 2009 to 0.5% in 2010 in GUM clinic isolates.
Cefixime resistance rose from 1.2% of gonococcal isolates in 2009 to 6.3% in 2010. Worryingly, there is also evidence of a drift towards higher minimum inhibitory concentrations for ceftriaxone and cefixime in recent years. However, confirmed therapeutic failure to cefixime is rare, and is undocumented for ceftriaxone in England and Wales.
No isolates showed resistance to ceftriaxone in 2010.
Current recommendations for the management of gonorrhoea reflect the fact that cephalosporins (ceftriaxone and cefixime) have less resistance associated with them compared with other antibiotics [BASHH, 2011b]. However, surveillance of antibiotic resistance is an ongoing process and is likely to affect the appropriate antibiotic selection for gonorrhoea in the future.
Search strategy
Scope of search
A full literature search was not required as this CKS topic is primarily based on the British Association for Sexual Health and HIV guideline UK national guideline on the management of gonorrhoea in adults 2011 [BASHH, 2011b].
Sources of guidelines
National Institute for Health and Clinical Excellence (NICE)
Scottish Intercollegiate Guidelines Network (SIGN)
Royal College of General Practitioners
National Guidelines Clearinghouse
Guidelines International Network
NHS Scotland National Patient Pathways
Agency for Healthcare Research and Quality
Institute for Clinical Systems Improvement
National Health and Medical Research Council (Australia)
Royal Australian College of General Practitioners
British Columbia Medical Association
University of Michigan Medical School
Michigan Quality Improvement Consortium
National Resource for Infection Control
UK Ambulance Service Clinical Practice Guidelines
RefHELP NHS Lothian Referral Guidelines
Medline (with guideline filter)
Driver and Vehicle Licensing Agency
NHS Health at Work (occupational health practice)
Sources of systematic reviews and meta-analyses
Systematic reviews
Protocols
Database of Abstracts of Reviews of Effects
Medline (with systematic review filter)
EMBASE (with systematic review filter)
Sources of health technology assessments and economic appraisals
NIHR Health Technology Assessment programme
NHS Economic Evaluations
Health Technology Assessments
Canadian Agency for Drugs and Technologies in Health
International Network of Agencies for Health Technology Assessment
Sources of randomized controlled trials
Central Register of Controlled Trials
Medline (with randomized controlled trial filter)
EMBASE (with randomized controlled trial filter)
Sources of evidence based reviews and evidence summaries
Central Services Agency COMPASS Therapeutic Notes
Sources of national policy
Health Management Information Consortium (HMIC)
Sources of medicines information
The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.
British National Formulary (BNF)
electronic Medicines Compendium (eMC)
European Medicines Agency (EMEA)
References
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