Gonorrhea guide: Treatment and follow-up

On this page

• Management and treatment
  • Antimicrobial resistant gonorrhea: A challenge to treat
  • Treatment indications
  • Important considerations
  • Counselling
• Preferred treatment for uncomplicated NG infections
• Alternative treatments for uncomplicated NG infections
  • Alternative treatment for anogenital infections
  • Alternative treatment for pharyngeal infections
  • Cephalosporin allergy or resistance or severe non-IgE-mediated reaction to penicillins
  • Contraindications to macrolides and cephalosporins
  • Resistance to both cephalosporin and azithromycin with failure or contraindications to previously noted regimens
• Treatment for complicated NG infections
  • Epididymitis / epididymo-orchitis and pelvic inflammatory disease
  • Gonococcal ophthalmia and disseminated infections
  • Preferred initial therapy while awaiting consultation with an experienced colleague
  • Neonates
• Persistent and recurrent infection
• Treatment failure
• Follow-up
  • Test of cure
  • Screening for reinfection
• Reporting and partner notification
  • National/provincial/territorial notification
  • Partner notification
• References

Management and treatment

Antimicrobial resistant gonorrhea: A challenge to treat

Over time, treatment of gonorrhea has been complicated by the ability of Neisseria gonorrhoea (NG) to develop antimicrobial resistance (AMR). Optimal treatment is important to prevent long-term complications, decrease transmission, and slow the emergence and spread of AMR^{Footnote 1}. As a result, national gonococcal treatment recommendations have evolved over time.

AMR in gonorrhea in Canada is monitored by the Gonococcal Antimicrobial Surveillance Program in Canada (GASP-Canada) and the Enhanced Surveillance for Antimicrobial-resistant Gonorrhea (ESAG) system. In recent years, these surveillance systems have documented fluctuations in NG with decreased susceptibility to third-generation cephalosporins and resistance to azithromycin^{Footnote 2 Footnote 3}. GASP-Canada data has found that, since 2016, the national proportion of NG isolates resistant to azithromycin has exceeded 5%, which is the threshold identified by the World Health Organization to prompt a review of existing treatment recommendations^{Footnote 2 Footnote 4}. The most populated provinces demonstrated the greatest prevalence of NG isolates resistant to azithromycin^{Footnote 2}. Between 2017 and 2024, national surveillance has identified 13 cases of NG resistant to ceftriaxone (range of ceftriaxone minimum inhibitory concentration (MIC)=0.25-2.0 mg/L)^{Footnote 2 Footnote 5}. Antimicrobial stewardship is a priority for Canada, in particular for NG, to preserve antimicrobial effectiveness while promoting and protecting human health^{Footnote 6}.

Note: Final recommendations will be available after the completion of a review currently underway^{Footnote 1}. Consult the interim guidance from the National Advisory Committee on Sexually Transmitted and Blood-Borne Infections (NAC-STBBI) for more information: Interim Guidance for the treatment of uncomplicated gonococcal infections.

Treatment indications

Treat all cases confirmed by:

• Positive NAAT or culture results
• Gram-negative intracellular diplococci observed on male urethral smears

Consider treatment in the following suspected cases:

• If the partner has been found to have gonorrhea or if follow-up is not assured, treat for both gonococcal and chlamydial infection. For current treatment recommendations for chlamydia, refer to the Chlamydia and LGV Guide.
• In males, Gram-negative extracellular diplococci on a smear is an equivocal finding. If the person is at high risk of infection and follow-up is not assured, treatment for gonococcal infection should be provided while waiting for laboratory test results^{Footnote 7}.
• In males, a Gram stain showing polymorphonuclear leukocytes (PMNs) without diplococci suggests non-gonococcal urethritis (NGU) but does not rule out gonococcal infection. Refer to the following webpage for more information: STI-associated syndromes guide.

Note: Refer to local and provincial/territorial public health officials and guidelines for specific information about regional AMR patterns and specific recommendations.

Important considerations

Cephalosporin use for people with penicillin allergies

While an estimated 10% of patients report a history of penicillin allergy, in reality, only less than one percent are truly allergic^{Footnote 8 Footnote 9 Footnote 10}. Approximately 80% of those with a penicillin allergy lose their sensitivity to it after 10 years^{Footnote 8}. Cross-reactivity between beta-lactam antibiotics, such as penicillins and cephalosporins, may arise, due to similarities in their chemical side-chain structures. The side-chain structures of cefixime and ceftriaxone differ from those of penicillin, hence there is a negligible risk of cross-reactivity. As such, it is considered safe to give cefixime or ceftriaxone to patients with an IgE-mediated reaction to penicillin (anaphylaxis, hives)^{Footnote 11 Footnote 12 Footnote 13 Footnote 14 Footnote 15 Footnote 16}.

Do not prescribe cefixime or ceftriaxone to persons with a history of allergy to cephalosporins or with severe non-IgE-mediated reactions to penicillins (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, interstitial nephritis or hemolytic anemia).

Advise the patient that the risk of a reaction to cefixime and ceftriaxone is low and it is similar to giving an antibiotic to an individual who does not have any drug allergies. If treatment should be initiated, ensure the setting has the capacity to respond to an IgE-mediated reaction with epinephrine.

Always take a comprehensive medical and allergy history and check with local jurisdiction for available guidelines or protocol for the assessment and management of penicillin allergy.

Azithromycin adverse drug events

Refer to the following health advisory issued by Health Canada about azithromycin and risk of cardiovascular complications and death: Zithromax/Zmax SR (azithromycin) health advisory.

There are significant gastrointestinal side effects associated with high dose azithromycin. Repeat dose if vomiting occurs within one-hour post-administration. Increasing drug resistance may impact effectiveness of this medication.

Gentamycin adverse drug events

Refer to the complete product monograph for prescribing information, monitoring of patient's kidney function, contraindications, and adverse reactions (risk of nephrotoxicity).

Children

Consult with a pediatric specialist or an experienced colleague and relevant clinical guidelines when a gonococcal infection is diagnosed in a child. Suspected sexual abuse of children must be reported to the local child protection agency.

Pregnant or lactating people

Pregnant people should be treated for uncomplicated NG infections with ceftriaxone 500 mg IM as a single dose and monitored for complications.

Alternative NG treatment regimens are not recommended in pregnancy. In cases of cephalosporin allergy or other contraindications, consult with an infectious disease specialist^{Footnote 17}.

Doxycycline is contraindicated in pregnant and lactating individuals. Combination therapy containing gentamycin is not recommended in pregnancy^{Footnote 1}. Available data suggest that azithromycin is safe and effective in pregnant people.

HIV coinfection

People with HIV infection should receive the same treatment as those without HIV infection.

Counselling

People diagnosed with gonorrhea and their partners should abstain from any sexual activity without barrier protection until treatment of the person and all current partners is complete (after completion of a multiple-dose treatment or for seven days after single-dose therapy) and symptoms have resolved.

Preferred treatment for uncomplicated NG infections

Uncomplicated Neisseria gonorrhoeae (NG) infections include urethritis, cervicitis, pharyngitis, and proctitis. Asymptomatic infections are common in the endocervical canal, and in pharyngeal and rectal sites in both men and women. Asymptomatic infections may also occur at the urethral site^{Footnote 18}.

The following treatment options are recommended in the absence of contraindication. Consult product monographs for contraindications and side effects.

Geographic and population differences in AMR profiles may lead to differences between PHAC's STBBI Guides for Health Professionals and provincial or territorial guidance. Refer to the appropriate provincial or territorial guideline where available.

Note: Preferred treatment for all uncomplicated NG infections consists of an interim recommendation. Final recommendations will be available after the completion of a review currently underway^{Footnote 1}. Consult the interim guidance from the National Advisory Committee on Sexually Transmitted and Blood-Borne Infections (NAC-STBBI) for more information: Interim Guidance for the treatment of uncomplicated gonococcal infections.

Preferred treatment for all uncomplicated NG infections

Notes:

• If C. trachomatis infection has not been excluded by a negative test, concurrent treatment for chlamydia is recommended. Refer to the following treatment recommendations from the Public Health Agency of Canada: Chlamydia and LGV Guide.
• A test of cure (TOC) is recommended for all positive NG sites in all cases. This is particularly important when regimens other than ceftriaxone 500 mg IM are used. Refer to the Test of cure section in the Gonorrhea Guide for more information on the timing for TOC.

Alternative treatments for uncomplicated NG infections

Note: The following alternative treatment options are currently under review by the NAC-STBBI. Continue referring to them until the completion of the review currently underway.

Consider alternative treatment options for uncomplicated NG infections in the following circumstances:

• If access to IM injection is not available
• If the individual refuses an injection
• If the individual is allergic to cephalosporins or has a history of severe non-IgE-mediated reactions to penicillins (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, interstitial nephritis or hemolytic anemia).

Refer to the Important Considerations section for additional information about specific therapeutic agents.

A test of cure (TOC) is recommended for all positive NG sites in all cases. This is particularly important when regimens other than ceftriaxone 500 mg IM are used. Refer to the Test of cure section in the Gonorrhea Guide for more information on the timing for TOC.

Alternative NG treatment regimens are not recommended in pregnancy. In cases of cephalosporin allergy or other contraindications, consult with an infectious disease specialist^{Footnote 17}.

Alternative treatment for anogenital infections

Notes:

• This regimen is recommended if there is macrolide resistance or contraindication to macrolide use.
• Doxycycline is contraindicated in pregnant and lactating individuals.

Alternative treatment for pharyngeal infections

Cephalosporin allergy or resistance or severe non-IgE-mediated reaction to penicillins

Notes:

• Consider administering gentamicin 240 mg IV infused over 30 minutes when IM route is not feasible.
• This combination therapy is not recommended in pregnancy.

Contraindications to macrolides and cephalosporins

Notes:

• This regimen is recommended for people with macrolide and cephalosporin-resistant N. gonorrhoeae, or a history of anaphylactic reaction to macrolides and cephalosporins or contraindications to cephalosporins.
• If tetracycline resistance, use gentamicin only and perform a test of cure after completion of treatment.
• This combination therapy is not recommended in pregnancy.

Resistance to both cephalosporin and azithromycin with failure or contraindications to previously noted regimens

Treatment for complicated NG infections

Complicated NG infections can be local (those that extend locally beyond the primary site of infection, such as epididymitis and pelvic inflammatory disease), or disseminated (systemic complications which may include arthritis-dermatitis syndrome and rarely endocarditis or meningitis^{Footnote 18}.)

Epididymitis / epididymo-orchitis and pelvic inflammatory disease

Refer to the following guide if epididymitis/epididymo-orchitis or pelvic inflammatory disease (upper genital tract infection) are suspected: STI-associated syndromes guide.

Gonococcal ophthalmia and disseminated infections in adults and youth 9 years or older^{Footnote 35 Footnote 36}

Consult an infectious diseases specialist for guidance on management.

Hospitalization is indicated for meningitis and as well as for initial management of other disseminated infections.

Preferred initial therapy while awaiting consultation with an experienced colleague

Situation	Adults and youth nine years of age and over
Arthritis	Ceftriaxone 2 g IV/IM daily for 7 days [A-II] PLUS Azithromycin 1 g PO in a single dose [B-III]
Meningitis	Ceftriaxone 2 g IV/IM daily for 10–14 days [A-II] PLUS Azithromycin 1 g PO in a single dose dose [B-III]
Endocarditis	Ceftriaxone 2 g IV/IM daily for 28 days [A-II] PLUS Azithromycin 1 g PO in a single dose dose [B-III]
Ophthalmia	Ceftriaxone 2 g IV/IM in a single dose [A-II] PLUS Azithromycin 1 g PO in a single dose [B-III]

Notes:

• For ophthalmia, treatment may be extended with severe involvement of the eye^{Footnote 37}.
• If there is macrolide resistance or contraindication to macrolide use, consider doxycycline 100 mg PO BID x 7 days.
• IM administration should only be considered if an IV line is not available.

Neonates

Neonates born to birthing parents with untreated N. gonorrhoeae infection at the time of delivery should be tested and treated immediately without waiting for test results. They should be managed by or in consultation with a paediatric infectious disease specialist or an experienced colleague.

Refer to the following article from the Canadian Paediatric Society for information about how to manage neonates born to birthing parents with untreated N. gonorrhoeae infection: Preventing ophthalmia neonatorum.

Persistent and recurrent infection

Possible causes of persistent signs and symptoms after treatment:

• Failure to take the medication correctly (including vomiting within one hour of taking medication) or to finish the course of therapy
• Re-exposure
• Infection with other pathogen(s)
• Non-infective etiology
• Treatment failure or drug resistance

Treatment failure

Treatment failure is defined as absence of reported sexual contact during the post-treatment period AND one of the following:

• Presence of Gram-negative intracellular diplococci on microscopy in specimens taken at least 72 hours after completion of treatment
• Positive N. gonorrhoeae on culture taken at least 72 hours after completion of treatment
• Positive N. gonorrhoeae NAAT taken at least 3-4 weeks post treatment

Follow-up

Test of cure

A test of cure (TOC) is recommended for all positive sites in all cases. This is particularly important when regimens other than ceftriaxone 500 mg IM are used. Refer to the following table for more information on the timing for TOC^{Footnote 1}.

Situation	Choice of test and timing for test of cure
Asymptomatic individuals	Obtain NAAT three to four weeks after completion of treatment.
TOC is performed within three weeks after completion of treatment	Obtain culture at least three days after completion of treatment.
Treatment failure is suspected more than three weeks after treatment (e.g., when symptoms persist or recur after treatment)	Obtain both NAAT and culture.

Notes:

• For asymptomatic individuals, a NAAT should be performed three to four weeks after the completion of treatment because residual nucleic acids from dead bacteria may be responsible for positive results less than three weeks after treatment^{Footnote 1}.

Screening for reinfection

Repeat screening of people with a gonococcal infection is recommended six months post treatment, because of the risk of reinfection^{Footnote 38}.

Reporting and partner notification

National/provincial/territorial notification

Gonococcal infections are nationally notifiable and reportable by laboratories, physicians and designated health professionals to local public health authorities in all provinces and territories.

Promptly notify local public health authorities of suspected or confirmed treatment failures:

• Prompt notification of treatment failures allows provincial and territorial STI prevention and control programs to quickly identify emerging patterns of AMR in their jurisdictions.
• Provinces and territories can collaborate with the Public Health Agency of Canada to issue timely electronic alerts through the Canadian Network for Public Health Intelligence (CNPHI).

Partner notification

Case finding and partner notification are critical to the prevention and control of gonococcal infections. Notify, clinically assess, test, and provide empiric treatment to all sexual partners of the index case within 60 days prior to symptom onset or date of specimen collection (if the index case is asymptomatic). Empiric treatment is indicated regardless of clinical findings and without waiting for test results) ^{Footnote 39 Footnote 40}.

People diagnosed with gonorrhea and their partners should abstain from any sexual activity without barrier protection until treatment of the person and all current partners is complete (after completion of a multiple-dose treatment or for seven days after single-dose therapy) and symptoms have resolved.

Extend the length of time for partner notification in the following circumstances:

• To include additional time up to the date of treatment
• If the index case states there were no partners during the recommended trace-back period (notify last partner)
• If all partners traced test negative (notify the partner prior to the trace-back period)

Local public health authorities are available to assist with partner notification and help with referral for counselling, clinical evaluation, testing, treatment.