Gonorrhea guide: Treatment and follow-up

On this page

• Management and treatment
  • Treatment indications
  • Medication-specific considerations
    • Cephalosporins
    • Azithromycin
    • Doxycycline
• Treatment
  • Recommended treatment for uncomplicated anogenital and pharyngeal infection
  • Adults and youth nine years of age and over
  • Pregnancy or lactating people
  • HIV coinfection
• Alternative treatment in case of penicillins or cephalosporins allergy OR cephalosporins and/or macrolide resistance
  • Cephalosporins allergy or resistance or severe non-IgE-mediated reaction to penicillins
  • Quinolone treatment regimens
  • Contraindications to macrolides and cephalosporins
  • Resistance to both cephalosporin and azithromycin with failure or contraindications to previously noted regimens
• Complicated infection associated with N. gonorrhoeae
  • Epididymitis / epididymo-orchitis and PID
  • Ophthalmia and disseminated gonococcal infection (DGI) in adults and youth 9 years or older
  • Gonococcal infection in the neonates
• Persistent and recurrent infection
• Treatment failure
• Counselling related to treatment
• Follow-up
  • Test of cure
  • Screening for reinfection
• Reporting and partner notification
  • National/provincial/territorial notification
  • Partner notification
• References

Management and treatment

General advice

N. gonorrhoea is able to develop AMR, making successful treatment a challenge. Adults and adolescents should be treated with combination therapy^{Footnote 1}.

The use of two medications with different mechanisms of action is thought to improve treatment efficacy as well as to prevent or potentially delay the emergence and spread of antimicrobial-resistant gonorrhea.  

The appropriate combination therapy will depend on the site of infection (e.g., pharyngeal infection is harder to eradicate) and probability of resistance (e.g., more likely in gbMSM).

The recommended combination therapy includes a third generation cephalosporin with either azithromycin or doxycycline. Azithromycin is preferred over doxycycline, due to significant rates of tetracycline resistance and concerns about adherence with multiday treatment. This combination therapy is also effective for chlamydia, which is frequently associated with gonococcal infections^{Footnote 2Footnote 3Footnote 4Footnote 5}.

Avoid monotherapy in order to help prevent resistance. Monotherapy with azithromycin is not recommended due to macrolide resistance and treatment failures^{Footnote 6Footnote 7}.

Assess each case individually to guide decision-making and consult an experienced colleague or infectious disease specialist when necessary.

Choose treatment according to local epidemiologic data where available. Refer to local and P/T public health officials for specific information about AMR patterns in the region and follow P/T guidelines.

Treatment indications

Treat all cases confirmed by

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

Consider treatment in suspected cases as follows:

• If the partner has been found to have gonorrhea or if follow-up is not assured, treat for both gonococcal and chlamydial infection
• In males, extracellular Gram-negative 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 5}
• 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 STI-associated syndromes.

Note: Advise people and partners to abstain from unprotected sexual contact for at least seven days after treatment is complete and until signs and symptoms have resolved.

Medication-specific considerations

Cephalosporins

While an  estimated 10% of patients report a history of penicillin allergy, in reality, only less than one percent are truly allergic^{Footnote 8Footnote 9Footnote 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 11Footnote 12Footnote 13Footnote 14Footnote 15Footnote 16}.

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. 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).

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

Refer the health advisory issued by Health Canada about azithromycin and risk of cardiovascular complications and death.

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.

Doxycycline

Doxycycline is contraindicated in pregnant and lactating people.

Treatment

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

The treatment recommendations will be covered in the following sections:

• Recommendations for uncomplicated anogenital and pharyngeal infection in adults and youth
• Recommendations for alternative treatment in case of penicillins or cephalosporins allergy OR cephalosporin and/or macrolide resistance
• Recommendations for complicated infections associated with N. gonorrhoeae

Recommended treatment for uncomplicated anogenital and pharyngeal infection

Adults and youth nine years of age and over ^{Footnote 15Footnote 16Footnote 17Footnote 18Footnote 19Footnote 20Footnote 21Footnote 22Footnote 23Footnote 24Footnote 25Footnote 26}.

Indication/infection	Preferred treatment	Alternative treatment
Anogenital infection (urethral, endocervical, vaginal, rectal) in adults and youth ≥ 9 years of age	Ceftriaxone 250 mg IM in a single dose [A-l] PLUS azithromycin 1 g PO in a single dose [B-ll] OR Cefixime 800 mg PO in a single dose [A-l] PLUS azithromycin 1 g PO in a single dose [B-ll] Note: This regimen is considered an alternative therapy for gbMSM	If there is macrolide resistance or contraindication to macrolide use Ceftriaxone 250 mg IM in a single dose [A-l] PLUS doxycycline 100 mg PO BID x 7 days [B-III] OR Cefixime 800 mg PO in a single dose [A-l] PLUS doxycycline 100 mg PO BID x 7 days [B-III]
Pharyngeal infection in adults and youth ≥ 9 years of age	Ceftriaxone 250 mg IM in a single dose [A-l] PLUS azithromycin 1 g PO in a single dose [B-Ill]	Cefixime 800 mg PO in a single dose [A-l] PLUS azithromycin 1 g PO in a single dose [B-ll]

Note:

• There are geographic and population differences in AMR profiles. As such, the CGSTI may differ from P/T guidance. Specifically, oral cefixime is considered a first-line agent and there are separate treatment recommendations for gbMSM. Refer to the appropriate P/T guideline where available
• Gentamicin alternative route of administration: 240 mg IV infused over 30 minutes may be considered when the IM route is not feasible.
  Refer to the complete product monograph for prescribing information, monitoring of patient's kidney function, contraindications and adverse reactions (risk of nephrotoxicity)

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

Pregnancy or lactating people

Pregnant people should receive the same treatment (ceftriaxone or cefixime plus azithromycin) as other non-pregnant individuals and monitored for complications. In cases of cephalosporin allergy or other contraindications, consult with an infectious disease specialist^{Footnote 27}.

Notes:

• Doxycycline is contraindicated in pregnancy
• TOC is recommended in all cases
• 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.

Alternative treatment in case of penicillins or cephalosporins allergy OR cephalosporins and/or macrolides resistance

In case of documented allergy to penicillins/cephalosporins (refer to section above regarding medication-specific considerations cephalosporins) or resistance to macrolides, refer to the alternative treatment recommendations for adults and youth below.

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

Notes:

• This combination therapy is not recommended in pregnancy
• Gentamicin alternative route of administration: 240 mg IV infused over 30 minutes may be considered when the IM route is not feasible.

Quinolone treatment regimens

This combination therapy/regimen should only be used if quinolone susceptibility is demonstrated or regional/local quinolone resistance rates are under 5% and a TOC can be assured^{Footnote 29Footnote 3}.

Notes:

• This combination therapy is not recommended in pregnancy
• At the time of publication, gemifloxacin is not available on the Canadian market. Once available in the United States, it will be made accessible through Health Canada's Special Access Program (SAP)

Contraindications to macrolides and cephalosporins

This regimen is recommended for people with macrolide and cephalosporin-resistant N. gonorrhoeae, or a history of anaphylactic reaction to macrolides and cephasloporins or contraindications to cephalosporins.

Notes:

• If tetracycline resistance, use gentamicin only and TOC to be performed 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

Ertapenem has in-vitro activity but optimum dose/duration is undefined. Given the broad spectrum nature of this antimicrobial, use of this agent should be restricted to exceptional situations^{Footnote 35Footnote 36Footnote 37Footnote 38}.

Complicated infections associated with N. gonorrhoeae

Epididymitis / epididymo-orchitis and  PID

If epididymitis/epididymo-orchitis or PID (upper genital tract infection) are suspected, refer to STI-associated syndromes.

Gonococcal ophthalmia and disseminated infections in adults and youth 9 years or older^{Footnote 39Footnote 40}

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.

Situation/Infection	Preferred initial therapy while awaiting consultation with an experienced colleague
Arthritis	Ceftriaxone 2 g IV/IM daily for 7 days [A-II] PLUS azithromycin 1 g PO in a single dose x 1 dose [B-lll]
Meningitis	Ceftriaxone 2 g IV/IM daily for 10–14 days [A-II] PLUS azithromycin 1 g PO in a single dose x 1 dose [B-lll]
Endocarditis	Ceftriaxone 2 g IV/IM daily for 28 days [A-II] PLUS azithromycin 1 g PO in a single dose x 1 dose [B-lll]
Ophthalmia	Ceftriaxone 2 g IV/IM in a single dose [A-II] PLUS azithromycin 1 g PO in a single dose [B-lll]

Notes:

• This is the usual duration of therapy, but treatment may be extended with severe involvement of the eye^{Footnote 41}.
• 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

Gonococcal infection in the 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 Canadian Paediatric Society's article Preventing ophthalmia neonatorum for information about how to manage neonates born to birthing parents with untreated N gonorrhoeae infection.

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 intracellular Gram-negative 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 2-3 weeks post treatment  

Recommended management of cephalosporin treatment failures

• Notify public health authorities of  cephalosporin combination therapy treatment failures (i.e. cefixime 800 mg PO or ceftriaxone 250 mg IM plus azithromycin 1 g PO)
• Consult infectious disease specialist and local public health authorities to determine the appropriate antimicrobial agent according to susceptibility test results. 
• Once the person has completed the treatment, a TOC using culture should be performed three to seven days later. 

Counselling related to treatment

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.

Follow-up

Test of cure

TOC is recommended for all positive sites in all cases. Otherwise it is strongly recommended in the following situations:

• Persistent symptoms or signs post-therapy^{Footnote 4Footnote 42}
• Compliance to the prescribed treatment is suboptimal
• Extragenital (pharyngeal and rectal) infection^{Footnote 43}
• AMR to the administered therapy is documented^{Footnote 4Footnote 42}
• Case is linked to a treatment failure case who was treated with the same antibiotic^{Footnote 4}
• People undergoing therapeutic abortion^{Footnote 44}
• Alternate treatment was prescribed.

Consider follow-up testing for cases of PID if N. gonorrhoeae was initially isolated.

The use of culture (where available) is recommended. Take samples three to seven days after treatment.

If NAAT is the only choice for TOC, the test should not be done for two to three weeks after treatment^{Footnote 45Footnote 46} to avoid false positive results due to the presence of non-viable organisms.

Screening for reinfection

Repeat screening of people with a gonococcal infection is recommended six months post treatment, because of the risk of reinfection^{Footnote 47}.

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.

Local public health authorities should be promptly notified of suspected or confirmed treatment failures. The prompt notification of treatment failures will allow provincial and territorial (P/T) STI prevention and control programs to quickly identify emerging patterns of AMR in their jurisdictions. This will enable P/Ts to 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 4Footnote 42}.

Extend the length of time for partner notification

• 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)

Screen neonates born to birthing parents with gonorrhea, and treat as appropriate. Local public health authorities are available to assist with partner notification and help with referral for counselling, clinical evaluation, testing, treatment.

References