Gonorrhoea infection

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

The main goal of treatment for gonorrhoea is to reduce morbidity and mortality, and to interrupt transmission, thereby preventing further infections. Presumptive treatment can be provided to those at risk with symptoms and signs (e.g., mucopurulent discharge) consistent with gonorrhoea and those at high risk who are unlikely to return for follow-up. Asymptomatic people or those with mild symptoms and signs (dysuria) should await definitive diagnosis.

Therapy is based on the latest Centers for Disease Control and Prevention (CDC) STD guidelines from the US, which are subject to periodic updates.[26] Other guidelines may be used in some countries.[3][51] The CDC STD guidelines previously recommended dual antibiotic therapy (i.e., two antimicrobials with different mechanisms of action), because patients infected with Neisseria gonorrhoeae are frequently co-infected with Chlamydia trachomatis and the regimen covered both organisms. However, the CDC has re-evaluated the recommendations on the basis of increasing concern about antimicrobial stewardship, in particular the impact of antimicrobial use on the microbiome and changes in azithromycin susceptibility for gonorrhoea and other organisms. Therefore, the CDC now recommends ceftriaxone monotherapy because N gonorrhoeae remains highly susceptible to ceftriaxone, azithromycin resistance is increasing, and prudent use of antimicrobial agents supports limiting their use. Treatment with 7 days of oral doxycycline (or a single dose of azithromycin in pregnant women) is recommended for co-infection with C trachomatis or when chlamydial infection has not been excluded.[26] Metronidazole is added to the recommended drug regimen for women if there is a history of sexual abuse.[26] Treatment recommendations may vary in different countries, and more recent guidelines from the British Association for Sexual Health and HIV recommended monotherapy.[51]

For all patients with gonorrhoea, every effort should be made to ensure that the patients' sex partners from the preceding 60 days (or the last partner before 60 days if no recent partners are reported) are evaluated and treated for N gonorrhoeae with a recommended regimen.[26] [ ] In some US states the law permits expedited partner therapy, which is the practice of treating the sex partners of persons with sexually transmitted infections without an intervening medical evaluation or professional prevention counselling. CDC: expedited partner therapy Opens in new window[70] This approach should be considered for heterosexual patients with gonorrhoea if it cannot be ensured that all of a patient's sex partners from the prior 60 days will be evaluated and treated.

Uncomplicated gonococcal infection

Uncomplicated infections of the cervix, urethra, rectum, or pharynx

First-line treatment is a single dose of intramuscular ceftriaxone.[26] One meta-analysis found that ceftriaxone had better efficacy for uncomplicated gonorrhoea compared with other antibiotics.[71] If chlamydial infection has not been excluded, patients should receive oral doxycycline for 7 days in addition to the cephalosporin.[26]

In patients with urogenital or anorectal gonorrhoea who have a cephalosporin allergy, a single dose of intramuscular gentamicin plus oral azithromycin may be considered; however, gastrointestinal adverse effects may limit the use of this regimen.[26] In an asymptomatic person, a single dose of ciprofloxacin could be used if the provider is able to perform gyrase A (gyrA) testing to identify ciprofloxacin susceptibility (wild type).[26][72] An infectious disease specialist should be consulted if there is known penicillin/cephalosporin allergy.
Systemic fluoroquinolone antibiotics, such as ciprofloxacin, may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to, tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycaemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behaviour.[73]
- Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability).
- Consult your local guidelines and drug formulary for more information on suitability, contraindications, and precautions.
A single dose of oral cefixime is a suitable alternative regimen if ceftriaxone is not available.[26] However, cefixime has a lower response rate and reduced susceptibility compared with ceftriaxone when used for non-genital sites.[26] If chlamydial infection has not been excluded, patients should receive oral doxycycline for 7 days in addition to the cephalosporin.[26]

Pharyngeal infections are more difficult to treat than urogenital or anorectal infections. Cefixime has limited efficacy against pharyngeal gonorrhoea, and no reliable alternative treatments are available. An infectious disease specialist should be consulted for an alternative treatment recommendation if there is an anaphylactic reaction to ceftriaxone. If chlamydial infection is also identified, patients should receive oral doxycycline for 7 days in addition to ceftriaxone.[26] A test-of-cure is recommended 7-14 days after treatment regardless of the treatment regimen used for pharyngeal infections.[26] Use of an antiseptic mouthwash may help with clearance of pharyngeal infections.[74] In people previously treated for gonorrhoea, re-infection within 12 months ranges from 7% to 12%, and so they should be re-tested 3 months after treatment regardless of whether they believe their sex partners were treated.[75][76] If re-testing at 3 months is not possible, re-testing should be performed within 12 months of initial treatment.[26]

Intramuscular injection animated demonstration

Demonstration of an intramuscular injection into the ventrogluteal site, using a Z-track technique.

Treatment failure

Persistent infection after treatment may be due to re-infection or resistance/treatment failure. Patients who have persistent symptoms after treatment should be re-tested by culture (preferably with simultaneous NAAT). If these cultures are positive for gonococcus, isolates should be submitted for resistance testing.[26]

Persistent infections should be retreated with a single dose of intramuscular ceftriaxone, and an infectious disease specialist should be consulted. If chlamydial infection has not been excluded, patients should receive oral doxycycline for 7 days in addition to the cephalosporin.[26]

A single-dose of intramuscular gentamicin plus oral azithromycin can be used as an alternative regimen for urogenital and rectal gonorrhoea, particularly if resistance to cephalosporins is suspected.[26] No reliable alternative treatments are available for pharyngeal gonorrhoea.[26]
Patients with treatment failure after receiving an alternative regimen (cefixime or gentamicin plus azithromycin) should be retreated with a single dose of ceftriaxone, with or without doxycycline if chlamydial infection has not been excluded.[26]
Sex partners from the preceding 60 days should be identified and treated with the same regimen.[26]

A test-of-cure should be done 7-14 days after retreatment. Treatment failures are generally required to be reported to the relevant health authority within 24 hours of diagnosis.[26]

Complicated gonococcal infection

Pelvic inflammatory disease (PID)

PID is the most important complication of gonorrhoea in women. It may develop in up to one third of women with gonorrhoea and can lead to long-term sequelae even after resolution of infection.[44][45] The most common sequelae of PID are chronic pelvic pain (40%), tubal infertility (10.8%), and ectopic pregnancy (9.1%).[46][47] For further details of management, see Pelvic inflammatory disease.

Mild to moderate PID:

The recommended regimen is dual therapy with single-dose intramuscular ceftriaxone plus oral doxycycline for 14 days.[26]
Cefoxitin (plus probenecid) may be used instead of ceftriaxone. Other parenteral third-generation cephalosporins may also be used.[26]
Metronidazole should be used in combination with doxycycline to provide extended coverage against anaerobic bacteria.[26]
Outpatient treatment with intramuscular and oral agents can be considered because they may be as efficacious as inpatient parenteral treatment in mild to moderate PID, but reassessment after 72 hours is recommended.[26][84]
A Cochrane review assessing CDC-recommended antibiotic regimens for PID found no conclusive evidence that one antibiotic regimen is safer or more effective than another.[85]

Severe PID:

Signs and symptoms of severe infection include: surgical abdomen; tubo-ovarian abscess; severe illness with nausea, vomiting, and fever; inability to take oral regimen; and no response from outpatient therapy.
Hospitalisation and intravenous antibiotic therapy is required. Intravenous therapy with a cephalosporin (ceftriaxone, cefotetan, or cefoxitin) plus doxycycline is the recommended first-line regimen.[26] Ampicillin/sulbactam plus doxycycline or clindamycin plus gentamicin are suitable alternatives.[26]
If the patient can take oral medication, oral doxycycline may be preferred to intravenous doxycycline to minimise pain associated with intravenous infusion.
Metronidazole is added if there is a tubo-ovarian abscess, or suspicion of any anaerobic organism or trichomonas involvement. Metronidazole should be used with ceftriaxone as ceftriaxone is less active against anaerobic bacteria than cefotetan or cefoxitin.
Reassessment can be made at 24 to 48 hours as to whether to discontinue intravenous therapy and continue with suitable oral therapy to complete 14 days of treatment if there is clinical improvement.[26] Parenteral therapy can be discontinued 24-48 hours after clinical improvement; ongoing oral therapy after the parenteral cephalosporin regimen should consist of doxycycline plus metronidazole to complete a total of 14 days of therapy. Oral clindamycin or oral doxycycline can be used after the alternative parenteral clindamycin/gentamicin regimen.[26] If tubo-ovarian abscess is present, oral clindamycin or oral metronidazole should be used with doxycycline as this provides better anaerobic coverage.[26]

Epididymitis

Epididymitis occurs in <5% of men with gonorrhoea.[43] Hospital admission is required for severe cases. Rarely epididymitis can lead to infertility or chronic inflammation. Diagnosis of the offending organism should be pursued because gram-negative rods can also be a causative agent.

Due to the high rate of fluoroquinolone resistance, intramuscular ceftriaxone plus oral doxycycline is recommended for 10 days if epididymitis infection is suspected to be sexually transmitted (i.e., gonorrhoea or chlamydia).[26] Chlamydia will be covered by doxycycline.

Reassessment should be made after 48 hours.

If the patient is suspected to have epididymitis due to an enteric organism, then fluoroquinolone therapy could be used, but it is important to rule out gonorrhoea and chlamydia first.

For further details of management, see Acute epididymitis.

Gonococcal conjunctivitis

First-line treatment is intramuscular ceftriaxone.[26] Clinical studies have used a higher dose of ceftriaxone for gonococcal conjunctivitis than that used in other types of gonococcal infections.[86] There are no data for the use of oral cephalosporins in gonococcal conjunctivitis.
As gonococcal conjunctivitis is uncommon and data on treatment in adults are limited, an infectious disease specialist should be consulted.

Disseminated gonococcal infection (DGI)

DGI occurs in <3% of gonorrhoea infections.[48] Women are thought to be more likely to develop DGI than men, possibly related to menses. Fever occurs in 60% of DGI. The most common features are skin rash (75%) followed by tenosynovitis (68%), polyarthralgias (52%), and monoarticular arthritis (48%). Septic arthritis may develop without any of the other features of DGI. Joint aspiration will reveal a high leukocyte count of predominantly polymorphonuclear cells, and Neisseria gonorrhoeae should be detectable in the joint fluid. Rarer manifestations of DGI include endocarditis, meningitis, and epidural abscess.

It is recommended that patients with DGI be hospitalised for initial therapy.[26] Treatment of DGI should be undertaken with an infectious disease specialist. In cases of penicillin/cephalosporin allergy, desensitisation may be required.

DGI (excluding meningitis and endocarditis):

The recommended first-line regimen is intravenous or intramuscular ceftriaxone.[26] Cefotaxime is a suitable alternative regimen.
Parenteral therapy should be continued for 24 to 48 hours after substantial clinical improvement, and then the patient switched to a suitable oral regimen for at least 7 days guided by antimicrobial sensitivity testing.[26]
If chlamydial infection has not been excluded, patients should receive oral doxycycline for 7 days in addition to the cephalosporin.[26]

DGI (meningitis and endocarditis):

The recommended first-line regimen is intravenous ceftriaxone.[26]
Treatment for meningitis is continued for 10 to 14 days, and for endocarditis treatment is continued for at least 4 weeks.[26]
If chlamydial infection has not been excluded, patients should receive oral doxycycline for 7 days in addition to the cephalosporin.[26]

Pregnant women

Intramuscular ceftriaxone monotherapy is the recommended first-line regimen in pregnant women, preferably given under direct observation.[26] Consultation with an infectious disease specialist is recommended if the patient has a cephalosporin allergy or there are any other considerations that preclude treatment with this regimen. A single dose of azithromycin may be added to treat chlamydia, if chlamydial infection has not been excluded.[26]

Pharyngeal infections are more difficult to treat than urogenital or anorectal infections. The CDC recommends a test-of-cure 7-14 days after treatment regardless of the treatment regimen used for pharyngeal infections.[26]

Complicated infection in pregnant women requires hospitalisation and management by an experienced clinician.

Mothers of newborns with ophthalmia neonatorum, scalp abscesses or DGI caused by gonococcal infections, and their sex partners, should be treated presumptively.[26]

Neonates, infants, and children

Neonates who are born to women with untreated gonococcal infections are at high risk of infections and should be treated presumptively in the absence of signs of gonococcal infection.[26]

Neonates with ophthalmia neonatorum should receive a single dose of intravenous/intramuscular ceftriaxone.[26] Neonates with scalp abscesses or DGI (i.e., bacteraemia, arthritis, or meningitis) should receive intravenous/intramuscular ceftriaxone or cefotaxime for 7 days (bacteraemia, arthritis) or 10-14 days (meningitis).[26] An infectious disease specialist should be consulted for advice on management if there is known penicillin/cephalosporin allergy.

Infants and children with uncomplicated vulvovaginitis, cervicitis, urethritis, pharyngitis, or proctitis who weigh ≤45 kg should be treated with a single dose of intravenous/intramuscular ceftriaxone.[26] Those with complicated gonococcal infection should be treated with intravenous/intramuscular ceftriaxone for 7 days (bacteraemia, arthritis), 10-14 days (meningitis), or at least 4 weeks (endocarditis).[26]

Children who weigh >45 kg should be treated with adult regimens; however, the one difference is that children with bacteraemia or arthritis should continue parenteral therapy for 7 days.[26]

It is important to consider the possibility of sexual abuse in children with gonorrhoea.[17][26] If suspected it should be reported and child protection procedures should be followed accordingly.

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