Approach

The main goal of treatment for gonorrhea 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 (such as mucopurulent discharge) consistent with gonorrhea 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, which are subject to periodic updates.[23] The CDC currently recommends dual therapy (i.e., two antimicrobials with different mechanisms of action). As patients infected with Neisseria gonorrhoeae are frequently coinfected with Chlamydia trachomatis, the regimen should cover both organisms. Metronidazole is added to the recommended drug regimen for people when there is a history of sexual abuse.

For all patients with gonorrhea, every effort should be made to ensure that the patients' sex partners from the preceding 60 days are evaluated and treated for N gonorrhoeae with a recommended regimen.[23] CDC: guidance on the use of expedited partner therapy in the treatment of gonorrhea external link opens in a new window [ Cochrane Clinical Answers logo ]

Uncomplicated gonococcal infection

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

  • First-line treatment is intramuscular ceftriaxone plus oral azithromycin, preferably given together under direct observation.[23] Azithromycin is preferred to doxycycline as the second antibiotic as it can be given as a single dose and the incidence of gonococcal resistance is higher with doxycycline; however, doxycycline may be used in patients who are allergic to azithromycin. A meta-analysis found that ceftriaxone had better efficacy for uncomplicated gonorrhea compared with other antibiotics.[67]

  • Oral cefixime plus azithromycin is a suitable alternative regimen if ceftriaxone is not available. However, cefixime has a lower response rate and reduced susceptibility compared with ceftriaxone when used for nongenital sites.[23] Other single-dose injectable cephalosporins that may be used in place of ceftriaxone include cefoxitin (administered with probenecid) and cefotaxime.

  • In patients who have a cephalosporin allergy, oral gemifloxacin or intramuscular gentamicin in a single dose plus a higher dose of azithromycin may be considered; however, gastrointestinal adverse effects may limit the use of these regimens. An infectious disease specialist should be consulted if there is known penicillin/cephalosporin allergy.

  • Pharyngeal infections are more difficult to treat than urogenital or anorectal infections. A test-of-cure is recommended 14 days after treatment if an alternative regimen is used for pharyngeal infections.[23] Use of an antiseptic mouthwash may help with clearance of pharyngeal infections.[68]

Gonococcal conjunctivitis

  • First-line treatment is intramuscular ceftriaxone plus oral azithromycin, preferably given together under direct observation.[23] Clinical studies have used a higher dose of ceftriaxone for gonococcal conjunctivitis than that used in other types of gonococcal infections.[69] There are no data for the use of oral cephalosporins in gonococcal conjunctivitis.

  • As gonococcal conjunctivitis is uncommon and data on treatment in adults is limited, an infectious disease specialist should be consulted.

Treatment failure

  • Persistent infection after treatment may be due to reinfection or resistance/treatment failure. Patients who have persistent symptoms after treatment should be retested by culture, and if these cultures are positive for gonococcus, isolates should be submitted for resistance testing.[23]

  • Persistent infections should be retreated with intramuscular ceftriaxone plus high-dose oral azithromycin, and an infectious disease specialist should be consulted.

  • Single-dose oral gemifloxacin or intramuscular gentamicin given with high-dose oral azithromycin can be used as an alternative regimen, particularly if resistance to cephalosporins is suspected. High-dose oral azithromycin is commonly accompanied by nausea and vomiting in patients.

  • A test-of-cure should be done 14 days after retreatment. Treatment failures should be reported to the CDC through the local or state health department within 24 hours of diagnosis.[23]

Complicated gonococcal infection

Pelvic inflammatory disease (PID)

PID is the most important complication of gonorrhea in women. It may develop in up to one third of women with gonorrhea and can lead to long-term sequelae even after resolution of infection.[40][41] The most common sequelae of PID are chronic pelvic pain (40%), tubal infertility (10.8%), and ectopic pregnancy (9.1%).[42][43]

Mild to moderate PID:

  • The recommended regimen is dual therapy with single-dose intramuscular ceftriaxone plus oral doxycycline for 14 days.[23]

  • Cefotaxime or cefoxitin (plus probenecid) may be used instead of ceftriaxone.

  • Metronidazole may be added if extended anaerobic coverage is required.

  • 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.[23][70]

  • 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.[71]

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.

  • Intravenous antibiotic therapy is required. Intravenous therapy with cefotetan or cefoxitin plus doxycycline, or clindamycin plus gentamicin, are the recommended first-line regimens.[23] Ampicillin/sulbactam plus doxycycline is a suitable alternative.

  • If the patient can take oral medication, oral doxycycline may be preferred to intravenous doxycycline to minimize pain associated with intravenous infusion.

  • Metronidazole is added if there is a tubo-ovarian abscess, or suspicion of any anaerobic organism or trichomonas involvement.

  • 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.[23]

Disseminated gonococcal infection (DGI)

DGI occurs in <3% of gonorrhea infections.[44] 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 hospitalized for initial therapy. Treatment of DGI should be undertaken with an infectious disease specialist. In cases of penicillin/cephalosporin allergy, desensitization may be required.

DGI (excluding meningitis and endocarditis):

  • The recommended first-line regimen is intravenous or intramuscular ceftriaxone plus oral azithromycin.[23] Cefotaxime plus azithromycin 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.

  • Arthrocentesis may be required if there is evidence of arthritis associated with gonorrhea infection.

DGI (meningitis and endocarditis):

  • The recommended first-line regimen is intravenous ceftriaxone plus oral azithromycin.[23]

  • Treatment for meningitis is continued for 10 to 14 days, and for endocarditis treatment is continued for at least 4 weeks.[23]

Epididymitis

Epididymitis occurs in <5% of men with gonorrhea.[39] 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 quinolone resistance, intramuscular ceftriaxone plus oral doxycycline is recommended for 10 days if epididymitis infection is suspected to be sexually transmitted (i.e., gonorrhea or chlamydia).[23] 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 quinolone therapy could be used, but it is important to rule out gonorrhea and chlamydia first.

Pregnant women

Intramuscular ceftriaxone plus azithromycin is the recommended first-line regimen in pregnant women, preferably given together under direct observation.[23][72] 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. Pregnant women treated with dual therapy (ceftriaxone and azithromycin) for gonorrhea do not require a test-of-cure. Women with pharyngeal gonorrhea treated with an alternative regimen should return 14 days after treatment for a test-of-cure using either culture or nucleic acid amplification test (NAAT).[72]

Complicated infection in pregnant women requires hospitalization and management by an experienced provider.

Neonates, infants, and children

Neonates with ophthalmia neonatorum should receive a single dose of intravenous/intramuscular ceftriaxone. Neonates with scalp abscesses or DGI (i.e., bacteremia, arthritis, or meningitis) should receive intravenous/intramuscular ceftriaxone or cefotaxime for 7 days (bacteremia, arthritis) or 10 to 14 days (meningitis).[23] 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. Those with complicated gonococcal infection should be treated with intravenous/intramuscular ceftriaxone for 7 days (bacteremia, arthritis), 10 days (meningitis), or 4 weeks (endocarditis).[23]

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

It is important to consider the possibility of sexual abuse in children with gonorrhea.[14] If suspected it should be reported and child protection procedures should be followed accordingly.

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