Gonorrhea - Uncomplicated Anogenital Infection Management

Evaluation and Treatment of Sex Partners

Sex partners of sexually transmitted infection (STI) patients may be asymptomatic; thus, the importance of partner notification and management. Sex partners of STI patients are likely to be infected and should be offered treatment to prevent further STI transmission and reinfection. All partners who had sexual contact with the patient within 60 days of the diagnosis of infection should be evaluated and treated for both gonococcal and chlamydial infection. If a patient's previous sexual intercourse was >60 days before diagnosis, the latest sexual partner should be evaluated and treated.

For patients who present within 14 days of exposure, it is recommended to give epidemiological treatment. For those who present after 14 days of exposure, treat based on testing results. Patients and their sex partners should be instructed to abstain from sexual intercourse until they and their partners have completed the treatment. Continue abstinence for 7 days after a single-dose regimen or until the completion of a 7-day regimen.

Partner-delivered Therapy

In situations where concerns exist that the sex partners of a female patient with gonorrhea will not seek treatment, the patient may be the one to deliver therapy to their partners in the form of medication or a prescription. Partner-delivered therapy for gonorrhea should always include treatment for Chlamydia. The approach may not be permitted in some settings. 

All individuals diagnosed with gonorrhea require antimicrobial therapy, as the infection is highly transmissible and can lead to significant complications if left untreated even in those without symptoms. Treatment with the most effective agents will alleviate symptoms when present, prevent complications, reduce onward transmission, and potentially slow the emergence of antimicrobial resistance. Treatment of sexually transmitted infections (STIs) is challenging because antimicrobial susceptibility in many sexually transmitted pathogens changes rapidly, reducing the reliability of existing antibiotics.

An optimal therapeutic regimen for gonococcal infection should be highly effective across all anatomical sites; well tolerated, especially for patients with recurrent infections; and feasible to administer as a single dose at the point of care. Information about sexual behavior and recent travel history is important to ensure suitability of treatment given. Therapeutic regimens should achieve efficacy rates above 95%, as treatment failure carries important public health consequences by allowing continued transmission of the infection. Therapeutic choices should be guided by national or local antimicrobial resistance data whenever such information is available.

Given that resistance has emerged to all prior empiric first-line agents, select therapy based on local Neisseria gonorrhoeae susceptibility patterns and patient allergies (eg Penicillin); Ceftriaxone is the primary option in most settings. Many gonococcal isolates are now resistant to sulfonamides, penicillins, tetracyclines, and quinolones. Use Azithromycin sparingly due to high resistance potential. If local resistance data are unavailable or cephalosporin resistance is emerging with limited first-line alternative agents, consider dual therapy over monotherapy. Antibiotic selection for gonorrhea should also account for potential co-pathogens such as Chlamydia trachomatis and Mycoplasma genitalium, which can cause cervicitis in women and urethritis in men. Directly observed, single-dose therapy for N gonorrhoeae is recommended to enhance compliance. For adults and adolescents, including pregnant women, whose gonococcal infection persists despite treatment as shown by ongoing symptoms or a positive test, WHO advises assessing the possibility of reinfection or antimicrobial resistance to guide the next therapeutic choice.

Syndromic Management

In Areas Where Resources Allow for Lab Tests to Screen Women

Empiric therapy should be considered when the prevalence of Neisseria gonorrhoeae and Chlamydia trachomatis is high in the patient population and the patient is unlikely to return for treatment.

In Areas Where Lab Tests to Screen Women are Not Available

The justification for empiric treatment becomes stronger as the prevalence of gonorrheal and chlamydial infections in the patient population becomes higher. Patients with positive risk assessment and vaginal discharge should be offered treatment for gonococcal and chlamydial cervicitis.

Dual Therapy for Neisseria gonorrhoeae and Chlamydia trachomatis

Dual therapy is recommended for patients with N gonorrhoeae because co-infection with C trachomatis is common. In settings where 10-30% of gonococcal cases are co-infected with chlamydia, routine dual therapy is cost-effective since chlamydia treatment costs less than testing. A specific diagnosis may enhance partner notification, improve compliance with treatment, and decrease antibiotic exposure and expense. If the proper diagnostic tools are not available, patients should be treated for both infections.

Please see Chlamydia - Uncomplicated Anogenital Infection disease management chart for further information.

Cephalosporins

Ceftriaxone







Single-agent therapy with high-dose intramuscular (IM) Ceftriaxone is the preferred treatment. This is considered the most effective treatment for uncomplicated gonorrhea, in combination with a single oral dose of Azithromycin or 7-day regimen of Doxycycline as presumptive treatment of chlamydia. Doxycycline is used in patients allergic to or intolerant of Azithromycin. This may also be given in pregnant patients except for Doxycycline. This is an effective treatment for Neisseria gonorrhoeae infections at all sites.

Cefixime

Cefixime is currently not recommended as a first-line treatment option for patients with gonococcal infections due to evidence that showed increased minimum inhibitory concentrations that may predict the emergence of N gonorrhoeae resistance. Studies have shown that a 400-mg single oral dose does not provide sustained and high bactericidal levels as compared to a single intramuscular (IM) dose of Ceftriaxone. Cefixime also showed limited effectiveness in treating pharyngeal gonorrhea. This achieves a microbiologic cure in over 96% of uncomplicated urogenital or anorectal gonorrhea cases but is less effective than Ceftriaxone especially for pharyngeal infections, where earlier studies using a 400-mg dose showed high failure rates, leading to recommendations for higher dosing to boost plasma levels in response to rising N gonorrhoeae resistance to oral cephalosporins.

Cefixime may be given as an alternative agent if Ceftriaxone is not available or if the patient refuses or has contraindications to IM injection. The patient should be advised to return for a test of cure at the site of infection after 1 week. A combination of Cefixime plus Azithromycin is recommended when a test of cure is not possible or when an oropharyngeal infection is diagnosed.

Alternative agents

Alternative agents include single-dose cephalosporins (Cefotaxime, Ceftizoxime, Cefoxitin with Probenecid or Cefpodoxime). These have no advantage over Ceftriaxone or Cefixime in terms of efficacy or pharmacokinetics.

Gepotidacin

Gepotidacin is an inhibitor of bacterial gyrase and topoisomerase. This is effective for urogenital gonorrhea and shows in vitro activity even against strains resistant to other antibiotics. This is indicated for patients with uncomplicated urogenital gonorrhea who cannot receive Ceftriaxone or other alternatives, including those whose infections show reduced susceptibility to cephalosporins.

Macrolides

Azithromycin







Azithromycin is the preferred second antimicrobial agent in addition to Ceftriaxone irrespective of Chlamydia testing results. This is better than Doxycycline due to its convenience and increased compliance of single-dose therapy and lower prevalence of gonococcal resistance. This may be an option in persons known to have a severe allergy to cephalosporins; however, monotherapy for gonorrhea treatment is not recommended due to increasing gonococcal resistance. Azithromycin may be considered in pregnant women only if other drug alternatives are unavailable and if the isolate is determined to be susceptible.

Quinolones

Quinolones are no longer recommended for gonorrhea treatment in many areas due to increasing resistance rates. Quinolone-resistant Neisseria gonorrhoeae (QRNG) is common in parts of Europe, United States, the Middle East, Asia, and the Pacific. There are variations in the anti-gonococcal activity of individual quinolones, and it is necessary to use only the most active according to local resistance patterns. Quinolones may be used in areas where the prevalence of resistance is <5%. These may be given if an infection is known to be quinolone-sensitive prior to treatment. When quinolone resistance has been excluded, these may be given as alternative agents in patients with cephalosporin allergy or penicillin anaphylaxis.

Spectinomycin

Spectinomycin may be used as an alternative regimen in combination with a single oral dose of Azithromycin in patients allergic to cephalosporins or when Ceftriaxone is not available or in patients who are pregnant.

Zoliflodacin

Zoliflodacin is a new oral spiropyrimidinetrione antibiotic that blocks DNA synthesis and shows in vitro activity against Neisseria gonorrhoeae, including drug-resistant strains. This is indicated for patients with uncomplicated urogenital gonorrhea who cannot receive Ceftriaxone or other alternatives, including those whose infections show reduced susceptibility to cephalosporins.

Other Treatment Regimens

Injectable Gentamicin or oral Gamifloxacin combined with oral Azithromycin are new antibiotic regimens that have shown high rates of effectiveness in treating genital gonorrhea. This may be considered an option when Ceftriaxone cannot be given (eg severe allergic reaction or resistance). Adverse effects are mostly gastrointestinal. Other therapeutic agents currently being investigated for gonorrhea treatment include Ertapenem, Solithromycin, Delafloxacin, Sitafloxacin, and Avarofloxacin.